Unpredictable Threat Research Articles

Pipette-Free and Fully Integrated Paper Device Employing DNA Extraction, Isothermal Amplification, and Carmoisine-Based Colorimetric Detection for Determining Infectious Pathogens.

A pipette-free and fully integrated device that can be used to accurately recognize the presence of infectious pathogens is an important and useful tool in point-of-care testing, particularly when aiming to decrease the unpredictable threats posed by disease outbreak. In this study, a paper device is developed to integrate the three main processes required for detecting infectious pathogens, including DNA extraction, loop-mediated isothermal amplification (LAMP), and detection. All key reagents, including sodium dodecyl sulfate (SDS), NaOH, LAMP reagents, and carmoisine, are placed on the paper device. The paper device is operated simply via sliding and folding without using any bulky equipment, and the results can be directly observed by the naked eye. The optimized concentrations of sodium dodecyl sulfate (SDS), sodium hydroxide (NaOH), and carmoisine were found to be 0.1%, 0.1 M, and 0.5 mg/mL, respectively. The paper device was used to detect Enterococcus faecium at concentrations as low as 102 CFU/mL within 60 min. Also, E. faecium spiked in milk was successfully detected using the paper device, demonstrating the feasible application in real sample analysis.

Analisis Manajemen Pertahanan Indonesia dalam Menghadapi Post-Pandemic

Covid-19 is one of the unpredictable non-military threats. For approximately three years, Indonesia has experienced a transition period that has had an economic and social impact on people's lives. Thus, the country needs a strategy in dealing with these threats. Therefore, the state involves all policy stakeholders in various sectors related to handling Covid-19. This research aims to provide insight related to Indonesia's defense management in dealing with post-pandemic. The research method used is a qualitative approach. Data collection was conducted with FGDs of Defense University students and defense management experts. In addition, data collection is also carried out by literature studies. The results of this study show that for three years defense management in Indonesia in facing non-military threats of COVID-19 was carried out by strengthening the pentahelix element. Therefore, countries should face various threats with a universal defense strategy supported by a general state defense policy that has been considered holistically about what, how, who and what to do. The implications of this research can be used as a consideration for policymakers to continue to prioritize the pentahelix element in various non-military threats.
 
 

Strengthening Warfighter Resiliency Using Broad-Spectrum or Host-Directed Therapies within the Rapid Acquisition and Investigation of Drugs for Repurposing Program.

To maintain cadence with looming threats in a prolonged field-care environment, the broader medical countermeasure (MCM) enterprise must adopt new strategies for chemical, biological, radiological, and nuclear (CBRN)-addressing drug development. The Countering Emerging Threats - Rapid Acquisition and Investigation of Drugs for Repurposing (CET RAIDR) program within the Joint Program Manager for CBRN Medical is designed to rapidly tackle known, unknown, and emerging threats by utilizing late-stage or licensed therapeutics. The focus of the CET RAIDR effort is to bridge treatment gaps between threat identification and the implementation of licensed targeted MCMs, thereby strengthening warfighter resiliency. The repurposing approach conserves both time to market and funds by leveraging previous conventional development work as a launch point for repurposing efforts. The CET RAIDR program minimizes development and procurement costs by supplementing the military medical providers' toolbox with post-phase II therapies that demonstrate established safety and manufacturing processes, leading to a cost-sparing model for niche medicines (i.e., CBRN MCMs). SIGNIFICANCE STATEMENT: Countering Emerging Threats - Rapid Acquisition and Investigation of Drugs for Repurposing program candidates are selected based on several pillars: a proven human safety profile, the availability of tools and validated literature on the drug's mechanism of action, well defined assays, and/or animal models to demonstrate efficacy, as well as collaborations with willing and trusted industry partners. This broader repurposing approach to address the growing chemical, biological, radiological, and nuclear threat landscape will better safeguard the warfighter against well documented or unpredictable threats when a direct-acting medical countermeasure is unavailable or not yet conceived.

Fear-Conditioning to Unpredictable Threats Reveals Sex and Strain Differences in Rat Fear-Potentiated Startle (FPS).

Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies showed higher startle amplitudes and exaggerated fear reactivity to unpredictable vs. predictable threats in individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS studies use both sexes, a surprisingly limited number of rodent FPS studies use females. Here we investigate the effects of signal-threat contingency, signal-threat order and threat predictability on FPS in both sexes. We use a classic fear-conditioning protocol (100% contingency of cue and shock pairings, with forward conditioning such that the cue co-terminates with the shock) and compare it to modified fear-conditioning protocols (70% contingency; backward conditioning; or cue and shock un-paired). Although there are no sex differences in the startle amplitudes when corrected for body weight, females consistently demonstrate higher shock reactivity during fear-conditioning. Both sexes and strains demonstrate comparable levels of cued, non-cued, and contextual fear in the classic FPS and FPS following fear-conditioning with 70% contingency or backward order (cue co-starts with shock). However, in the classic FPS, Sprague-Dawley females show reduced proportion between cued fear and cue-elicited vigilant state than males. Lastly, a prominent sex difference is uncovered following unpredictable fear-conditioning (cue and shock un-paired), with Wistar, but not Sprague-Dawley, females showing significantly higher startle overall during the FPS recall, regardless of trial type, and higher contextual fear than males. This striking sex difference in processing unpredictable threats in rodent FPS might help to understand the mechanisms underlying higher incidence of PTSD in women.

보험범죄 대응체계에 관한 연구

“Insurance” is a mean of enabling modern people to lead a safe life that can experience unpredictable threats. However, sophisticated criminal methods using insurance are developing as they become corporate, internationalized, and organized. To prevent this, the Special Act on the Prevention of Insurance Frauds was enacted and implemented in 2016, but insurance crimes are on the rise in the number of people caught and the amount of damage. As reported in previous studies, the damage caused by insurance crimes affects the national economy as well as individuals. Various criminal justice agencies are paying attention to such growing measures to prevent insurance crimes, but general private institutions are also working to prevent insurance crimes by setting up special organizations. Among them, the Special Investigation Unit (SIU) is composed of insurance companies and is an institution that prevents and responds to insurance crimes at the forefront. Despite its importance, there are no studies in Korea that have dealt with the current status and problems of SIU in depth. Therefore, this study aims to analyze the significance of insurance crimes and the insurance crime room through literature review, and to explain the response system to insurance crimes, focusing on the SIU, an investigation team of private insurance companies in Korea, to efficiently investigate the current increase in insurance crimes. Based on these results, suggestions were made to establish an effective response system for insurance crimes.

Threat effects on cognitive systems: Testing links to aggression proneness.

The biobehavioral study of aggression has implications for expanding our understanding of transdiagnostic processes that increase risk for disinhibited behaviors. Toward this end, our study tested tenets from the process model of aggression (Verona & Bresin, 2015). First, we expected that the predictability of threat would differentially alter cognitive networks, including attentional alerting and executive control. Second, we examined the moderating effects of self- and informant reports of aggression on threat-related changes in cognitive functioning. Using event-related potential (ERP) measures of cognitive-attentional processes, 143 community individuals participated in a well-validated and translational threat manipulation (NPU) task (Schmitz & Grillon, 2012) while completing the Attention Network Test (Fan et al., 2002). Analyses revealed that relatively unpredictable threat quickened alerting-related reaction time, whereas predictable threat interfered with processing of flanker task stimuli. The results, however, failed to show reliable relationships between aggression proneness and threat-related cognitive alterations. The findings fit with a broader literature on cognitive and behavioral outputs of threat activation and provide fruitful avenues for better understanding threat-related aggression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Time-travelling pathogens and their risk to ecological communities.

Permafrost thawing and the potential 'lab leak' of ancient microorganisms generate risks of biological invasions for today's ecological communities, including threats to human health via exposure to emergent pathogens. Whether and how such 'time-travelling' invaders could establish in modern communities is unclear, and existing data are too scarce to test hypotheses. To quantify the risks of time-travelling invasions, we isolated digital virus-like pathogens from the past records of coevolved artificial life communities and studied their simulated invasion into future states of the community. We then investigated how invasions affected diversity of the free-living bacteria-like organisms (i.e., hosts) in recipient communities compared to controls where no invasion occurred (and control invasions of contemporary pathogens). Invading pathogens could often survive and continue evolving, and in a few cases (3.1%) became exceptionally dominant in the invaded community. Even so, invaders often had negligible effects on the invaded community composition; however, in a few, highly unpredictable cases (1.1%), invaders precipitated either substantial losses (up to -32%) or gains (up to +12%) in the total richness of free-living species compared to controls. Given the sheer abundance of ancient microorganisms regularly released into modern communities, such a low probability of outbreak events still presents substantial risks. Our findings therefore suggest that unpredictable threats so far confined to science fiction and conjecture could in fact be powerful drivers of ecological change.

Toward the Safe City Index Development: Infrastructure Security Indicators

Cities all over the world are suffering from various and multiple problems and crises that are estimated to increase if there are no practical and realistic solutions that reflect the real needs of the city. These solutions should be able to predict future challenges, despite the cities’ struggle to improve and enhance their economic, social, environmental, and security goals besides the strategies necessary to achieve them. Accordingly, many concepts have emerged to find solutions that help cities to overcome the challenges they face. Among these are the concepts of the resilient city, the safe city, the smart city, etc. Each concept has established its own index that provided a vision of how to solve problems and face challenges and crises in order to develop the city. Nevertheless, big gaps have appeared in cities with the spread of unpredicted challenges and threats inside them,. Accordingly, the cities’ authorities and local communities are obligated to comprehend how their cities are performing, where advancement is being made, or where failure appears in their systems after-shocks. The research seeks to develop the “infrastructure security pillar” within the safe city index, in particular. This is achieved through a thorough reviewing and crisscrossing of the infrastructure indicators in the safe, resilient, and smart city indexes. The research concludes subdivisions to the infrastructure security pillar presented by Ecosystem, Transportation, Energy, Water & sewage, Disasters & threats, and Security system. Each has its own extracted indicators based on the intersection of existing ones, as well as the modification and addition of others. This development helps to achieve integration between the prevailing concepts towards a safer city performance. This development can be used to assess safety parameters in existing cities.

Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders

BackgroundBiological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders compared with nonanxious control individuals, and in pharmacological challenge studies in healthy adults. However, little is known about how startle may change with treatment for anxiety disorders, and no data are available regarding alterations due to mindfulness meditation training. MethodsNinety-three individuals with anxiety disorders and 66 healthy individuals completed 2 sessions of the neutral, predictable, and unpredictable threat task, which employs a startle probe and the threat of shock to assess moment-by-moment fear and anxiety. Between the two testing sessions, patients received randomized 8-week treatment with either escitalopram or mindfulness-based stress reduction. ResultsAPS, but not FPS, was higher in participants with anxiety disorders compared with healthy control individuals at baseline. Further, there was a significantly greater decrease in APS for both treatment groups compared with the control group, with the patient groups showing reductions bringing them into the range of control individuals at the end of the treatment. ConclusionsBoth anxiety treatments (escitalopram and mindfulness-based stress reduction) reduced startle potentiation during unpredictable (APS) but not predictable (FPS) threat. These findings further validate APS as a biological correlate of pathological anxiety and provide physiological evidence for the impact of mindfulness-based stress reduction on anxiety disorders, suggesting that there may be comparable effects of the two treatments on anxiety neurocircuitry.

Don't worry, it won't be fine. Contributions of worry and anxious arousal to startle responses and event-related potentials in threat anticipation.

A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in these dimensions to differential neural response patterns in neuropsychological, imaging, and physiological studies. Differential effects of the anxiety dimensions might contribute to inconsistencies in prior studies that examined neural processes underlying anxiety, such as hypersensitivity to unpredictable threat. We investigated the association between trait worry (as a key component of anxious apprehension), anxious arousal, and the neural processing of anticipated threat. From a large online community sample (N = 1,603), we invited 136 participants with converging and diverging worry and anxious arousal profiles into the laboratory. Participants underwent the NPU-threat test with alternating phases of unpredictable threat, predictable threat, and safety, while physiological responses (startle reflex and startle probe locked event-related potential components N1 and P3) were recorded. Worry was associated with increased startle responses to unpredictable threat and increased attentional allocation (P3) to startle probes in predictable threat anticipation. Anxious arousal was associated with increased startle and N1 in unpredictable threat anticipation. These results suggest that trait variations in the anxiety dimensions shape the dynamics of neural processing of threat. Specifically, trait worry seems to simultaneously increase automatic defensive preparation during unpredictable threat and increase attentional responding to threat-irrelevant stimuli during predictable threat anticipation. The current study highlights the utility of anxiety dimensions to understand how physiological responses during threat anticipation are altered in anxiety and supports that worry is associated with hypersensitivity to unpredictable, aversive contexts.

Family study of the startle reflex and event-related potentials in anticipation of predictable and unpredictable threat in adolescents and their parents.

A heightened sensitivity to unpredictable threat has been identified as a potential transdiagnostic mechanism of psychopathology. The majority of supporting research has been conducted in adults, and it is unclear whether psychophysiological indicators of sensitivity to unpredictable threat are comparable in youth during developmental periods associated with increased risk for psychopathology. In addition, no studies have examined whether sensitivity to unpredictable threat is correlated between parents and their offspring. The present study examined defensive motivation (startle reflex) and attentional engagement (probe N100, P300) in anticipation of predictable and unpredictable threat in a sample of 15-year-old adolescents (N = 395) and a biological parent (N = 379). Adolescents, compared to their parents, demonstrated greater startle potentiation and probe N100 enhancement in anticipation of unpredictable threat. In addition, overall startle potentiation in anticipation of threat was correlated between the adolescents and their parents. Adolescence is a key developmental period characterized by heightened defensive motivation and attentional engagement in anticipation of both predictable and unpredictable threat. Sensitivity to threat might index is one mechanism of vulnerability that is at least partially shared between parents and their offspring.

Rapid and Green Methods for Qualitative Classification of Polygonati Rhizoma and Polygonati Odorati Rhizoma Using a Handheld near Infrared Instrument

The confusing use of Polygonati Rhizoma (PR) and Polygonati Odorati Rhizoma (POR) poses an unpredictable threat to the health of consumers. Sensitive, nondestructive, rapid, and multicomponent techniques for their detection are sought after. In this study, a low-cost, short-wavelength (898–1668 nm), and handheld near-infrared (NIR) spectrometer combined with multivariate spectral evaluation methods was used to establish calibration models for identifying PR and POR. NIR spectra were treated with a standard normal variate (SNV) before performing chemometric approaches. Then principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were tested for calibration model development. The PCA results showed that spectral differences existed between the two herbs. However, the evaluation techniques could not separate them with the required accuracy. The PLS-DA calibration model, on the other hand, could separate the two herbs according to their spectral information with the prediction accuracy of >98.3%. Thus, it has been proven that a rapid, green, and low-cost method to support on-site and practical inspection through a handheld NIR instrument has been established to identify PR and POR and ensure the safety of the clinical medication.

Altered bed nucleus of the stria terminalis and amygdala responses to threat in combat veterans with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to potential, unpredictable threat and engages the bed nucleus of the stria terminalis (BNST). The BNST has been implicated in PTSD, but the role of the BNST in combat veterans with PTSD has yet to be examined. Identifying alterations in BNST responses to unpredictable threat could provide important new targets for treatment. The current study examined whether veterans with PTSD have altered BNST or amygdala responses (function and connectivity) to unpredictable and predictable threat. The fMRI task involved viewing predictable threat cues followed by threat images, predictable neutral cues followed by neutral images, and unpredictable threat cues followed by either a threat or neutral image. Participants included 32 combat-exposed veterans with PTSD and 13 combat-exposed controls without PTSD. Across all conditions, veterans with PTSD had heightened BNST activation and displayed stronger BNST and amygdala connectivity with multiple fear and anxiety regions (hypothalamus, hippocampus, insula, ventromedial prefrontal cortex) relative to controls. In contrast, combat controls showed a pattern of stronger connectivity during neutral conditions (e.g., BNST-vmPFC), which may suggest a neural signature of resilience to developing PTSD, ηp 2 = .087-.527, ps < .001. These findings have implications for understanding fear and anxiety networks that may contribute to the development and maintenance of PTSD.

Understanding Nonattendance among Women Invited to a Cardiovascular Preventive Initiative

: Dahl M et al. (2022), conducted a study to analysis of women’s reasons for refusing cardiovascular screening aiming to achieve a profound understanding of nonattendance by conducted a semi-structured interviews using Anton sky’s theory of sense of coherence as a theoretical frame work. Totally 1984 women who are born in 1936, 1941, 1946, 1951 and lived in Denmark were invited to participate in a cardiovascular screening programmed, only 74.3% participated in the study. Result showed that nonattendance was rooted in the women’s s social role as caregiver and their individual inner logics, which attested to a line of reasoning without critical reflection. A self-imposed caring role provided the women with meaningfulness in their daily lives, a role they were unwilling to risk by participating. As such, accepting screening was perceived as an unpredictable threat to upholding their social role. Inner logics were used as a strategy to keep life unchanged and uphold their identity. Women who felt healthy, found meaningfulness in relying on their own interpretation of their health status and thus considered screening unnecessarily. Moreover, nonattendance was related to the balance between personal resources and daily caring demands. Conclusion sScreening must be emotionally and cognitively meaningful for women to attend. This study contributed with valuable knowledge on what constitutes public acceptability in relation to cardiovascular preventive initiatives, making it relevant to healthcare professionals and policymakers alike. Involving targeted invitees in designing the screening initiative is likely to facilitate acceptability and encourage participation.

Phenotypic heterogeneity in the bacterial oxidative stress response is driven by cell-cell interactions

Genetically identical bacterial cells commonly display different phenotypes. This phenotypic heterogeneity is well known for stress responses, where it is often explained as bet hedging against unpredictable environmental threats. Here, we explore phenotypic heterogeneity in a major stress response of Escherichia coli and find it has a fundamentally different basis. We characterize the response of cells exposed to hydrogen peroxide (H2O2) stress in a microfluidic device under constant growth conditions. A machine-learning model reveals that phenotypic heterogeneity arises from a precise and rapid feedback between each cell and its immediate environment. Moreover, we find that the heterogeneity rests upon cell-cell interaction, whereby cells shield each other from H2O2 via their individual stress responses. Our work shows how phenotypic heterogeneity in bacterial stress responses can emerge from short-range cell-cell interactions and result in a collective phenotype that protects a large proportion of the population.

Threat effects on attention networks in individuals with a history of externalizing behaviors.

Research identifying the biobehavioral processes that link threat exposure to cognitive alterations can inform treatments designed to reduce perpetration of stress-induced aggression. The present study attempted to specify the effects of relatively predictable versus unpredictable threat on two attention networks, attentional alerting and executive control. In a sample of adults (n=74, 35% identifying as women, Mage=32.85) with high rates of externalizing behaviors (e.g., substance use, criminal/legal system involvement, aggressivity), we measured event-related brain activity during an attention network test that manipulated cognitive systems activation under relatively unpredictable and predictable threat conditions. Results showed that threat exposure alters attentional alerting and executive control. The predictable threat condition, relative to unpredictable threat, increased visual alerting (N1 amplitude to alert vs. no alert cue conditions) and decreased attention to the task (P3 amplitude to subsequent task-relevant flankers, but these effects did not survive adjusting for multiple tests. In contrast, overall threat and unpredictable threat conditions were associated with faster response time to alert cue (versus no cue) and poorer conflict processing, operationalized as flanker N2 reductions and slower response time to incongruent (versus congruent) flanker trials. These results expand what is known about threat-related modulation of cognition in a sample of individuals with histories of externalizing behaviors.

A novel subdivision of the bed nucleus of stria terminalis in monkey, rat, and mouse brains.

The bed nucleus of stria terminalis (BST) is a critical structure that mediates sustained vigilant responses to contextual, diffuse, and unpredictable threats. Dysfunction of the BST could lead to excessive anxiety and hypervigilance, which are often observed in posttraumatic stress disorder and anxiety disorders. Vigilance of potential future threats from the external environment is a basic brain function and probably requires rapid and/or short neural circuits, which enable both quick detection of the potential threats and fast adaptive responses. However, the BST in literature does not appear to receive spatial information directly from earlier visual or spatial processing structures. In this study, a novel subdivision of the BST is uncovered in monkey, rat, and mouse brains based on the human equivalent and is found in mouse to receive direct inputs from the ventral lateral geniculate nucleus and pretectal nucleus as well as from the spatial processing structures such as subiculum, presubiculum, and medial entorhinal cortex. This new subdivision, termed spindle-shaped small cell subdivision (BSTsc), is located between the known BST and the anterior thalamus. In addition to the unique afferent connections and cell morphology, the BSTsc also displays unique molecular signature (e.g., positive for excitatory markers) compared with other BST subdivisions, which are mostly composed of inhibitory GABAergic neurons. The BSTsc appears to have largely overlapping efferent projections with other BST subdivisions such as the projections to the amygdala, hypothalamus, nucleus accumbens, septum, and brainstem. Together, the present study suggests that the BSTsc is poised to serve as a shortcut bridge directly linking spatial information from the environment to vigilant adaptive internal responses.

Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos

The use of clinical psychoactive drugs often poses unpredictable threats to fetal development. Catechol-O-methyltransferase (COMT) is a key enzyme that regulates dopamine metabolism and a promising target for modulation of cognitive functions. Opicapone, a newly effective third-generation peripheral COMT inhibitor, is used for the treatment of Parkinson's disease (PD) and possibly to improve other dopamine-related disorders such as alcohol use disorder (AUD) and obsessive-compulsive disorder (OCD). The widespread use of opicapone will inevitably lead to biological exposure and damage to the human body, such as affecting fetal development. However, the effect of opicapone on embryonic development remains unknown. Here, zebrafish larvae were used as an animal model and demonstrated that a high concentration (30 μM) of opicapone exposure was teratogenic and lethal, while a low concentration also caused developmental delay such as a shortened body size, a smaller head, and reduced locomotor behaviors in zebrafish larvae. Meanwhile, opicapone treatment specifically increased the level of dopamine (DA) in zebrafish larvae. The depletion response of the total glutathione level (including oxidized and reduced forms of glutathione) and changed antioxidant enzymes activities in zebrafish larvae suggest oxidative damage caused by opicapone. In addition, enhanced glutathione metabolism and cytokine-cytokine receptor interaction were found in zebrafish larvae treated with opicapone, indicating that opicapone treatment caused an oxidation process and immune responses. Our results provide a new insight into the significant developmental toxicity of opicapone in zebrafish larvae.

Revisiting due diligence in cyberspace: crafting international law’s arsenal against transboundary Botnets

Abstract The emergence of cyberspace has been followed by increasingly unpredictable threats to cybersecurity, including Botnets, which have been frequently exploited in cyber-criminal activities affecting dozens or hundreds of States at once. In existing scholarship, many reasons have informed growing support for the promise of ‘due diligence’ obligations in regulating transboundary cyber operations. We affirm this position through a study of the specific context of Botnets, although bringing much-needed caution and complexity to the discourse. We offer a comprehensive account of the standard of conduct expected of States in detecting, mitigating and preventing Botnet-linked harms under due diligence; as well as to pursue cyber capacity building toward discharging these obligations. In so doing, we problematize and elaborate on the nature of due diligence as an obligation of conduct, therefore accounting for differential State capacities against Botnet-linked harms. The paper involves attempts to unpack a coherent conception of due diligence, appreciating the spectrum of obligations that it demands, and demonstrating these nuances through an appraisal of good practices adopted by States and private actors against Botnets. Consequently, we provide a unique holistic account of how States and their law enforcement could practically understand the conduct expected of them when faced with transboundary Botnets on a case-to-case basis. In the end, while underscoring potential dilemmas within this legal regime that may be faced by target States, as also its unresolved questions, we submit that due diligence is indeed the most appropriate candidate to act as a legal arsenal against transboundary Botnets.

Vaccine development for zoonotic viral diseases caused by positive‑sense single‑stranded RNA viruses belonging to the Coronaviridae and Togaviridae families (Review).

Outbreaks of zoonotic viral diseases pose a severe threat to public health and economies worldwide, with this currently being more prominent than it previously was human history. These emergency zoonotic diseases that originated and transmitted from vertebrates to humans have been estimated to account for approximately one billion cases of illness and have caused millions of deaths worldwide annually. The recent emergence of severe acute respiratory syndrome coronavirus-2 (coronavirus disease 2019) is an excellent example of the unpredictable public health threat causing a pandemic. The present review summarizes the literature data regarding the main vaccine developments in human clinical phase I, II and III trials against the zoonotic positive-sense single-stranded RNA viruses belonging to the Coronavirus and Alphavirus genera, including severe acute respiratory syndrome, Middle east respiratory syndrome, Venezuelan equine encephalitis virus, Semliki Forest virus, Ross River virus, Chikungunya virus and O'nyong-nyong virus. That there are neither vaccines nor effective antiviral drugs available against most of these viruses is undeniable. Therefore, new explosive outbreaks of these zoonotic viruses may surely be expected. The present comprehensive review provides an update on the status of vaccine development in different clinical trials against these viruses, as well as an overview of the present results of these trials.