A comprehensive review of the applications of bacteriophage-derived endolysins for foodborne bacterial pathogens and food safety: recent advances, challenges, and future perspective.

Foodborne diseases are caused by food contaminated by pathogenic bacteria such as Escherichia coli, Salmonella, Staphylococcus aureus, Listeria monocytogenes, Campylobacter, and Clostridium, a critical threat to human health. As a novel antibacterial agent against foodborne pathogens, endolysins are peptidoglycan hydrolases encoded by bacteriophages that lyse bacterial cells by targeting their cell wall, notably in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have gained scientists' interest in recent years due to their selectivity, mode of action, engineering potential, and lack of resistance mechanisms. The use of endolysins for food safety has undergone significant improvements, which are summarized and discussed in this review. Endolysins can remove bacterial biofilms of foodborne pathogens and their cell wall-binding domain can be employed as a tool for quick detection of foodborne pathogens. We explained the applications of endolysin for eliminating pathogenic bacteria in livestock and various food matrices, as well as the limitations and challenges in use as a dietary supplement. We also highlight the novel techniques of the development of engineering endolysin for targeting Gram-negative bacterial pathogens. In conclusion, endolysin is safe and effective against foodborne pathogens and has no adverse effect on human cells and beneficial microbiota. As a result, endolysin could be employed as a functional bio-preservative agent to improve food stability and safety and maintain the natural taste of food quality.

The applications of animal models in phage therapy: An update.

The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies, phage therapy (PT) is promising. This review extensively summarizes preclinical PT approaches in various in-vivo models. PT has been evaluated in several recent clinical trials. However, there are still several unanswered concerns due to a lack of appropriate regulation and pharmacokinetic data regarding the application of phages in human therapeutic procedures. In this review, we also presented the current state of PT and considered how animal models can be used to adapt these therapies for humans. The development of realistic solutions to circumvent these constraints is critical for advancing this technology.

Accelerated LVAD pump thrombosis in COVID-19 patient: Case report and mini review.

BACKGROUND: Coronavirus (COVID-19) infection exposes patients with heart failure specially who are on mechanical support to a higher risk of morbidity and mortality. AIMS: To investigate the impact of COVID-19 infection on left ventricular assist device (LVAD) thrombosis in heart failure patients. MATERIALS & METHODS: We searched the medical electronic records, Medline, PubMed and Cochrane databases for; (LVAD) AND (thrombosis)) AND (covid-19)) AND (heart failure). We divided cases reported into, LVAD thrombosis with COVID-19 infection and compare them with LVAD thrombosis without COVID-19 infection. Demographic data, LVAD device, presentation, treatment and outcomes were reviewed in all the LVAD thrombosis patients. RESULTS: In addition to our case, 8 other cases of LVAD thrombosis associated with COVID and 9 cases of LVAD thrombosis without covid infection were found. Patients with Covid infection had worse presentation and outcomes (3 deaths VS. 1 death in non-covid group). DISCUSSION: In LVAD patients, pump malfunction due to thrombus development in the inflow cannula, device body, or outflow graft can result in hemodynamic instability, hemolysis and other life-threatening complications. COVID infection significantly increases the risk of mortality in LVAD patient by accelerating the pump thrombosis due to elevated levels of endothelial protein C receptor and thrombomodulin along with procoagulants such as factor VIII, P-selectin, and von Willebrand factor. CONCLUSION: Significant morbidity and mortality are attributed to LVAD thrombosis, which are exasperated by prothrombotic conditions created in COVID-19 infections.

Recent Advances in Sensors for Fire Detection.

Fire is indeed one of the major contributing factors to fatalities, property damage, and economic disruption. A large number of fire incidents across the world cause devastation beyond measure and description every year. To minimalize their impacts, the implementation of innovative and effective fire early warning technologies is essential. Despite the fact that research publications on fire detection technology have addressed the issue to some extent, fire detection technology still confronts hurdles in decreasing false alerts, improving sensitivity and dynamic responsibility, and providing protection for costly and complicated installations. In this review, we aim to provide a comprehensive analysis of the current futuristic practices in the context of fire detection and monitoring strategies, with an emphasis on the methods of detecting fire through the continuous monitoring of variables, such as temperature, flame, gaseous content, and smoke, along with their respective benefits and drawbacks, measuring standards, and parameter measurement spans. Current research directions and challenges related to the technology of fire detection and future perspectives on fabricating advanced fire sensors are also provided. We hope such a review can provide inspiration for fire sensor research dedicated to the development of advanced fire detection techniques.

Acinetobacter baumannii: More ways to die.

Acinetobacter baumannii is an important nosocomial and opportunistic pathogen. It causes infections worldwide, especially in intensive care units. It is clinically significant owing to its ability to persist for long periods on surfaces, as well as its resistance to multiple antibiotics. This pathogen has been reported to defy the available therapeutic options to combat it. In this dire circumstance, the need for new approaches to treating A. baumannii infections is undeniable. In this minireview, we summarize three important treatment options for controlling A. baumannii pathogen, including the use of bacteriophage / bacteriophage cocktails, phage-antibiotic combinations and resistance-driven fitness losses. It is hoped that, as resources to treat its infection expand, A. baumannii can become less scary.

A point-of-care SARS-CoV-2 test based on reverse transcription loop-mediated isothermal amplification without RNA extraction with diagnostic performance same as RT-PCR.

The global public health crisis and economic losses resulting from the current novel coronavirus disease (COVID-19) pandemic have been dire. The most used real-time reverse transcription polymerase chain reaction (RT-PCR) method needs expensive equipment, technical expertise, and a long turnaround time. Therefore, there is a need for a rapid, accurate, and alternative technique of diagnosis that is deployable at resource-poor settings like point-of-care. This study combines heat deactivation and a novel mechanical lysis method by bead beating for quick and simple sample preparation. Then, using an optimized reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to target genes encoding the open reading frame 8 (ORF8), spike and nucleocapsid proteins of the novel coronavirus, SARS-CoV-2. The test results can be read simultaneously in fluorometric and colorimetric readouts within 40 min from sample collection. We also calibrated a template transfer tool to simplify sample addition into LAMP reactions when pipetting skills are needed. Most importantly, validation of the direct RT-LAMP system based on multiplexing primers S1:ORF8 in a ratio (1:0.8) using 143 patients' nasopharyngeal swab samples showed a diagnostic performance of 99.30% accuracy, with 98.81% sensitivity and 100% selectivity, compared to commercial RT-PCR kits. Since our workflow does not rely on RNA extraction and purification, the time-to-result is two times faster than other workflows with FDA emergency use authorization. Considering all its strengths: speed, simplicity, accuracy and extraction-free, the system can be useful for optimal point-of-care testing of COVID-19.

Multidrug-resistant enteric bacteria in Nigeria and potential use of bacteriophages as biocontrol.

Enteric bacterial pathogens have been implicated in many cases of gastroenteritis in Nigeria, a West African country. This situation is worsened by some reports of the high prevalence of multidrug-resistant enteric bacteria. To better prepare for situations in which even antibiotics of last resort would fail to treat infections caused by these pathogens, attention should be paid to alternative antimicrobial strategies. Here, we summarize existing reports of multidrug-resistant enteric bacterial infections in Nigeria, and importantly present the use of bacteriophages (viruses of bacteria) as an attractive antimicrobial alternative to combat these pathogens. It is hoped that this review will encourage research into the use of lytic bacteriophages against multidrug-resistant enteric bacteria in Nigeria.

Intrinsic Antimicrobial Peptide Facilitates a New Broad-Spectrum Lysin LysP53 to Kill Acinetobacter baumannii In Vitro and in a Mouse Burn Infection Model.

Antimicrobial resistance-related infections of Gram-negative pathogens pose a huge threat to global public health. Lysins, peptidoglycan hydrolases from bacteriophages, are expected as an alternative weapon against drug-resistant bacteria. In the present study, we report a new lysin LysP53 from Acinetobacter baumannii phage 53. Bioinformatic analysis revealed that LysP53 contains a positively charged N-terminal region and a putative peptidase catalytic domain. In vitro biochemical experiments showed that LysP53 is active against multiple antibiotic-resistant Gram-negative bacteria, including A. baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, with a reduction of 5 logs in viable A. baumannii number after exposure to 100 µg/mL LysP53 for 1 h. Further studies showed that LysP53 contains a functional antimicrobial peptide, i.e., N-terminal 33 aa, with a comparable spectrum of activity to LysP53. In an A. baumannii-associated mouse model of burn infection, a single dose of 14 µg/mouse LysP53 (57.6 µM) showed higher decolonization efficacy than 4 µg/mouse minocycline- (874 µM; p < 0.05) and buffer-treated groups (p <0.001), leading to a bacterial reduction of 3 logs. Our findings collectively establish that LysP53 could be a promising candidate in the treatment of topical infections caused by multiple Gram-negative pathogens.

Expanding the Utilization of Rectal Spacer Hydrogel for Larger Prostate Glands (>80 cc): Feasibility and Dosimetric Outcomes.

PURPOSE: The Hydrogel Spacer Prospective Randomized Pivotal Trial achieved mean rectoprostatic spacing of 12.6 mm resulting in lowering of rectal V70 from 12.4% (without spacer) to 3.3% (with spacer) in patients with glands up to 80 cm3. The value of this approach in patients with larger glands is inadequately established. This study assesses the feasibility and dosimetric outcomes of perirectal spacing in patients with prostate cancer with larger glands (>80 cm3). METHODS AND MATERIALS: Between January 2017 and December 2019, 33 patients with prostate glands >80 cm3 (mean 108.1 cm3; range, 81.1-186.6 cm3) were treated, 15 with glands >80 to 100 cm3 and 18 >100 cm3. Median follow-up was 10 months (range, 3-26). The median international prostate symptom score was 9 (range, 1-18). Hydrogel was placed under local anesthesia in all cases. Treatment modality included intensity modulated radiation therapy in 15 and proton therapy (PT) in 18 patients. Treatment targeted the prostate plus seminal vesicles in 21 patients and 12 also had elective nodal irradiation. Conventional fractionation (CF) to 78 Gy in 39 fractions was used in 16 and moderate hypofractionation (HF) to 70 Gy in 28 fractions in 17 patients. RESULTS: In the CF group, mean rectum (r) V75, 70, 60, 50 was 0.87%, 2.25%, 5.61%, and 10.5%, respectively. For glands >80 to 100 cm3 and >100 cm3, rV70 was 2.55% and 2%, respectively. In HF patients, mean rV65, 63, 60, and 50 was 1.67%, 2.3%, 3.4%, and 8.6%. For glands >80 to 100 cm3 and >100 cm3, rV63 was 2% and 2.56%, respectively. Overall, the mean midgland rectoprostatic hydrogel separation was 9.3 mm (range, 4.7-19.4 mm). All patients tolerated treatment well; no acute grade 2 or higher adverse gastrointestinal events were observed. CONCLUSIONS: Hydrogel placement is feasible in prostate glands larger than 80 cm3 with favorable dosimetric outcomes.

Anomalous Behavior Detection Framework Using HTM-Based Semantic Folding Technique.

Upon the working principles of the human neocortex, the Hierarchical Temporal Memory model has been developed which is a proposed theoretical framework for sequence learning. Both categorical and numerical types of data are handled by HTM. Semantic Folding Theory (SFT) is based on HTM to represent a data stream for processing in the form of sparse distributed representation (SDR). For natural language perception and production, SFT delivers a solid structural background for semantic evidence description to the fundamentals of the semantic foundation during the phase of language learning. Anomalies are the patterns from data streams that do not follow the expected behavior. Any stream of data patterns could have a number of anomaly types. In a data stream, a single pattern or combination of closely related patterns that diverges and deviates from standard, normal, or expected is called a static (spatial) anomaly. A temporal anomaly is a set of unexpected changes between patterns. When a change first appears, this is recorded as an anomaly. If this change looks a number of times, then it is set to a "new normal" and terminated as an anomaly. An HTM system detects the anomaly, and due to continuous learning nature, it quickly learns when they become the new normal. A robust anomalous behavior detection framework using HTM-based SFT for improving decision-making (SDR-ABDF/P2) is a proposed framework or model in this research. The researcher claims that the proposed model would be able to learn the order of several variables continuously in temporal sequences by using an unsupervised learning rule.

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes.

The rapid spread and emergence of multidrug-resistant Acinetobacter baumannii and other pathogenic Gram-negative bacteria spurred scientists and clinicians to look for alternative therapeutic agents to conventional antibiotics. In the present study, an A. baumannii bacteriophage p54 was isolated and characterized. Morphological and genome analysis revealed that bacteriophage p54 belongs to Myoviridae family with a genome size of 165,813 bps. A novel endolysin, namely LysAB54, showing low similarity with other well-known related endolysins, was cloned, expressed, and characterized from the bacteriophage p54. LysAB54 showed significant bactericidal activity against multidrug-resistant A. baumannii and other Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, in the absence of outer membrane permeabilizers. Based on all those observations, LysAB54 could represent a potential agent for the treatment of multidrug-resistant Gram-negative superbugs.

Epidemiology of coronaviruses, genetics, vaccines, and scenario of current pandemic of coronavirus diseases 2019 (COVID-19): a fuzzy set approach.

Human coronaviruses (HCoVs) are associated with a range of respiratory complications. In the last two decades, three major outbreaks have been reported due to HCoVs including the current pandemic. In December 2019, a newly emerged virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan city, China. This paper presents a detailed review of the literature and discusses the uncertain spread of coronavirus disease 2019 (COVID-19) using fuzzy set as classical set theory logic to measure uncertainty and vagueness of COVID-19 in China. Our findings show that both infection and death rate touched the peak (normal fuzzy sets) and have shown a decline. The graphs are not convex, which shows that there remains much uncertainty in the spread of COVID-19. Effective vaccines are clearly needed to control and prevent the COVID-19 pandemic.

Phage-Encoded Endolysins.

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

Hyponatremia: An Overlooked Risk Factor Associated With Adverse Outcomes After Cardiac Surgery.

BACKGROUND: Hyponatremia is an unrecognized risk factor for adverse outcomes after cardiac surgery. We sought to study the prevalence of preoperative hyponatremia and its impact on short-term and long-term outcomes after cardiac surgery. METHODS: Patients who had coronary artery bypass graft, valve, or coronary artery bypass graft and valve procedures from 2000 to 2016 and available preoperative serum sodium values within 30 days of the index procedure were included in the study. The effect of preoperative sodium on short-term and long-term outcomes was analyzed as a continuous and binary (hyponatremia [Na+ <135 mEq/L] versus no hyponatremia) predictor variable in multivariable regression models. RESULTS: Preoperative hyponatremia was present in 9.9% of 16,238 patients with available sodium levels. Comorbidities were more common in patients with hyponatremia. Hyponatremia was independently associated with operative mortality (odds ratio [OR] = 1.80; 95% confidence interval [CI], 1.38-2.34; P < .001), long-term mortality (hazard ratio = 1.31; 95% CI, 1.21-1.40; P < .001), longer postoperative length of stay (hazard ratio = 1.35; 95% CI, 1.28-1.43; P < .001), renal failure (OR = 1.52; 95% CI, 1.20-1.93; P < .001), prolonged ventilation use (OR = 1.52; 95% CI, 1.30-1.78; P < .001), and stroke or transient ischemic attack (OR = 1.48; 95% CI, 1.09-2.02; P = .013). Severity of hyponatremia, as measured by sodium level, was similarly associated with increased risk for death and postoperative complications. CONCLUSIONS: Preoperative hyponatremia is relatively common and is associated with adverse short-term and long-term outcomes after cardiac surgery. Preoperative hyponatremia can be used independently from standard risk factors to identify high-risk patients for cardiac surgery.

Encapsulation and Delivery of Therapeutic Phages.

Delivery of therapeutic compounds to the site of action is crucial. While many chemical substances such as beta-lactam antibiotics can reach therapeutic levels in most parts throughout the human body after administration, substances of higher molecular weight such as therapeutic proteins may not be able to reach the site of action (e.g. an infection), and are therefore ineffective. In the case of therapeutic phages, i.e. viruses that infect microbes that can be used to treat bacterial infections, this problem is exacerbated; not only are phages unable to penetrate tissues, but phage particles can be cleared by the immune system and phage proteins are rapidly degraded by enzymes or inactivated by the low pH in the stomach. Yet, the use of therapeutic phages is a highly promising strategy, in particular for infections caused by bacteria that exhibit multi-drug resistance. Clinicians increasingly encounter situations where no treatment options remain available for such infections, where antibiotic compounds are ineffective. While the number of drug-resistant pathogens continues to rise due to the overuse and misuse of antibiotics, no new compounds are becoming available as many pharmaceutical companies discontinue their search for chemical antimicrobials. In recent years, phage therapy has undergone massive innovation for the treatment of infections caused by pathogens resistant to conventional antibiotics. While most therapeutic applications of phages are well described in the literature, other aspects of phage therapy are less well documented. In this review, we focus on the issues that are critical for phage therapy to become a reliable standard therapy and describe methods for efficient and targeted delivery of phages, including their encapsulation.

Detection of Potentially Compromised Computer Nodes and Clusters Connected on a Smart Grid, Using Power Consumption Data.

Monitoring what application or type of applications running on a computer or a cluster without violating the privacy of the users can be challenging, especially when we may not have operator access to these devices, or specialized software. Smart grids and Internet of things (IoT) devices can provide power consumption data of connected individual devices or groups. This research will attempt to provide insides on what applications are running based on the power consumption of the machines and clusters. It is therefore assumed that there is a correlation between electric power and what software application is running. Additionally, it is believed that it is possible to create power consumption profiles for various software applications and even normal and abnormal behavior (e.g., a virus). In order to achieve this, an experiment was organized for the purpose of collecting 48 h of continuous real power consumption data from two PCs that were part of a university computer lab. That included collecting data with a one-second sample period, during class as well as idle time from each machine and their cluster. During the second half of the recording period, one of the machines was infected with a custom-made virus, allowing comparison between power consumption data before and after infection. The data were analyzed using different approaches: descriptive analysis, F-Test of two samples of variance, two-way analysis of variance (ANOVA) and autoregressive integrated moving average (ARIMA). The results show that it is possible to detect what type of application is running and if an individual machine or its cluster are infected. Additionally, we can conclude if the lab is used or not, making this research an ideal management tool for administrators.

Biosafety and biosecurity approaches to restrain/contain and counter SARS-CoV-2/COVID-19 pandemic: a rapid-review.

Emergence and reemergence of infectious diseases pose significant public health risks that are continuously haunting human civilization in the past several decades. Such emerging pathogens should be considered as a high threat to humans, animals, and environmental health. The year 2020 was welcomed by another significant virus from family Coronaviridae called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19). The disease was first reported in the city of Wuhan, Hubei province, China. Within a short time, this disease attained the status of the Public Health Emergency of International Concern. Presently, COVID-19 has spread to more than 150 countries, therefore, the World Health Organization (WHO) called it a pandemic. The Chinese government, along with WHO, other health agencies, and many nations, are monitoring the current situation closely to analyze the impact of SARS-CoV-2/COVID-19 on humans, animals, and environmental health. In the context of the current situation, biosafety and biosecurity measure that focus on One Health aspects of the disease outbreaks and the SARS-CoV-2 spread are of great importance to restrain this pathogen. Along with these efforts, standard precaution and control measures should also be taken at personal and community level to prevent the spreading of any contagion diseases, including COVID-19. Researchers are putting their very high efforts to develop suitable vaccines and therapeutics/drugs to combat COVID-19. This review aims to highlight the importance of biosafety, biosecurity, One Health approach, and focusing on recent developments and the ways forward to prevent and control COVID-19 in a useful way.