Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

A Lightweight Authentication Scheme for a Network of Unmanned Aerial Vehicles (UAVs) by Using Physical Unclonable Functions

A network of agents constituted of multiple unmanned aerial vehicles (UAVs) is emerging as a promising technology with myriad applications in the military, public, and civil domains. UAVs’ power, memory, and size constraints, ultra-mobile nature, and non-trusted operational environments make them susceptible to various attacks, including physical capturing and cloning attacks. A robust and resilient security protocol should be lightweight and resource-efficient in addition to providing protection against physical and tampering threats. This paper proposes an authentication protocol for a UAV-based multi-agent system robust against various threats and adversaries, including strong resistance against cloning and physical attacks. The proposed protocol is based on a physical unclonable function (PUF), a well-known hardware security primitive that is utilized for low-cost authentication and cryptographic key generation. The analysis of the proposed approach shows that it provides strong protection against various attacks, including tampering and cloning, and exhibits scalability and energy efficiency

A Lightweight Authentication Scheme for a Network of Unmanned Aerial Vehicles (UAVs) by Using Physical Unclonable Functions

A network of agents constituted of multiple unmanned aerial vehicles (UAVs) is emerging as a promising technology with myriad applications in the military, public, and civil domains. UAVs’ power, memory, and size constraints, ultra-mobile nature, and non-trusted operational environments make them susceptible to various attacks, including physical capturing and cloning attacks. A robust and resilient security protocol should be lightweight and resource-efficient in addition to providing protection against physical and tampering threats. This paper proposes an authentication protocol for a UAV-based multi-agent system robust against various threats and adversaries, including strong resistance against cloning and physical attacks. The proposed protocol is based on a physical unclonable function (PUF), a well-known hardware security primitive that is utilized for low-cost authentication and cryptographic key generation. The analysis of the proposed approach shows that it provides strong protection against various attacks, including tampering and cloning, and exhibits scalability and energy efficiency

C2S2-LOOP: Circular Chessboard-Based Secure Source Location Privacy Model Using ECC-ALO in WSN

Source location privacy (SLP) is a serious issue in wireless sensor networks (WSN) since Eavesdroppers tries to determine the source location. Hunting Animals in Forest is considered as an example for SLP. Many conventional schemes have been proposed for SLP in WSN, namely, Random Walk Routing, and Fake Messages Transmission, which cause critical issues (less safety period, packet delivery latency, and high energy consumption). Furthermore, the security analysis is not properly investigated in any previous work. In this paper, we propose a new model called the circular chessboard-based secure source location privacy model (C2S2-LOOP) with the following tasks: key generation, network topology management (clustering), intercluster routing (travel plan), and data packets encryption. All sensor nodes are deployed in a circular chessboard (Circular Field) and the key generation (PUK,SEK) is invoked using elliptic curve cryptography (ECC) with Ant Lion Optimization algorithm, which mitigate the issues of conventional ECC. Then, the network topology is managed using clustering where residual energy of the nodes is used for Cluster Head (CH) selection. Intercluster routing is implemented using packet traversing using clockwise and anticlockwise directions, which are mainly concerned with establishing a secure route between the source to the destination node. To ensure data security, we present the Chaotic Artificial Neural Network (C-ANN) in which encryption is executed. Assume that CH near to the source node has a high trust value, then it traverses (clock-wise) real packets towards sink node and similarly in the left side region (anticlockwise), fake packets are transmitted. Network simulations (OMNeT++) are evaluated and compared with the previous approaches, and finally, our proposed scheme concludes that it maintains not only source node location privacy (large safety period) and also reduces energy consumption by more than 40% and latency by more than 35%

An Effective Knowledge-Based Modeling Approach towards a “Smart-School Care Coordination System” for Children and Young People with Special Educational Needs and Disabilities

There is a significant need for a computer-aided modeling, effective information analysis and ontology knowledge base models to support both special needs children and care providers. As this research work correlated to the symmetry scope, it proposes an innovative generic smart knowledge-based “School Care Coordination System” (SCCS), which is established on a novel holistic six-layered data management model. The development of the Smart-SCCS adopts a methodology of ontology engineering to transform the given theoretical unstructured special educational needs and disabilities (SEND) code of practice into a comprehensive knowledge representation and reasoning system. The intended purpose is to deliver a system that can coordinate and bring together education, health and social care services into a single application to meet the needs of children and young people (CYP) with SEND. Moreover, it enables coordination, integration and monitoring of education, health and social care activities between different actors (formal, informal and CYP in the education sector) involved in the school care process network to provide personalized care interventions based on a predefined care plan. The developed ontology knowledge-based model has been proven efficient and solved the enormous difficulties faced by schools and local authorities on a daily basis. It enabled the coordination of care and integration of information for CYP from different departments in health, social care and education. The developed model has received significant attention with great feedback from all the schools and the local authorities involved, showing its efficiency and robustness

Extracellular ATP targets Arabidopsis RIBONUCLEASE 1 to suppress mycotoxin stress-induced cell death

Extracellular ATP is a purinergic signal with important functions in regulating plant growth and stress-adaptive responses, including programmed cell death. While signalling events proximate to receptor activation at the plasma membrane have been characterised, downstream protein targets and the mechanism of cell death activation/regulation are unknown. We designed a proteomic screen to identify ATP-responsive proteins in Arabidopsis cell cultures exposed to mycotoxin stress via fumonisin B1 (FB1) application. Arabidopsis RIBONUCLEASE 1 (RNS1) was identified by the screen and transgenic plants overexpressing native RNS1showed greater susceptibility to FB1, while a gene knockout rns1 mutant and antisense RNS1 transgenic plants were resistant to FB1-induced cell death. Native RNS1 complemented rns1 mutants and restored cell death response to FB1, while a catalytically inactive version of the ribonuclease could not. The FB1 resistance of salicylic acid-depleted nahG-expressing plants was abolished by transformation with native RNS1, but not the catalytically dead version. The mechanism of FB1-induced cell death is activation of RNS1-dependent RNA cleavage, which is blocked by ATP via RNS1 suppression, or enhanced by salicylic acid (SA) through induction of RNS1 expression. Our study reveals RNS1 as a previously unknown convergence point of ATP and SA signalling in the regulation of stress-induced cell death

Fluoroquinolones as Tyrosinase Inhibitors; Enzyme Kinetics and Molecular Docking Studies to Explore Their Mechanism of Action

The binding of fluoroquinolones, the most commonly prescribed antibiotics, with melanin is well explored. However, their binding patterns and exact mechanism of interaction with tyrosinase, a key enzyme in melanogenesis, are not explored yet. Thus, in the present study, seven fluoroquinolone drugs were selected to characterize their interactions with the tyrosinase enzyme: ciprofloxacin, enoxacin sesquihydrate, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gemifloxacin. The results confirmed that all the drugs execute excellent enzyme activity, with an inhibition range from IC50 = 28 ± 4 to 50 ± 1.9 μM, outperforming the standard hydroquinone (IC50 = 170 μM). Later, kinetic studies revealed that all the drugs showed irreversible, but mixed-type, tyrosinase inhibition, with a preferentially competitive mode of action. Further, 2D and 3D docked complexes and binding analyses confirmed their significant interactions in the active region of the target enzyme, sufficient for the downstream signaling responsible for the observed tyrosinase inhibition. Thus, this is the first report demonstrating their mechanism of tyrosinase inhibition, critical for melanin-dependent responses, including toxicity

Process optimization, antioxidant, antibacterial, and drug adjuvant properties of bioactive keratin microparticles derived from porcupine (Hystrix indica) quills

A structural protein called keratin is often employed in the medical industry to create medication carriers. Process improvement, antioxidant, antibacterial, and adjuvant drug studies of synthetic bioactive keratin microparticles made from lipids and keratin derived from porcupine (Hystrix indica) quills are the main objectives of this study. After coating the keratin microparticles with lipids which were obtained from the same porcupine quills, the bioactive keratin microparticles were produced. The response surface technique was applied to optimize the conditions for extraction of the keratin protein and sizing of the keratin microparticles. An infrared spectroscopy was used to analyze the chemical shifts in compositions of keratin microparticles while the optical microscopy was used to measure the size of the keratin microparticles. The results of this work revealed that a yield 27.36 to 42.25% of the keratin protein could be obtained from porcupine quills. The keratin microparticles were sized between 60.65 and 118.87 µm. Through response surface optimization, mercaptoethanol and urea were shown to be the main variables which positively affected the yield and the size of the keratin protein. The lipid stacking on the keratin microparticles’ surface was confirmed by infrared spectroscopy. The 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) assay confirmed the keratin microparticle’s antioxidant activity of 29.83%. Compared to lipid alone, the antibacterial properties of the keratin microparticles against Escherichia coli—a gram-negative—and Staphylococcus aureus—a gram-positive—bacteria enhanced by up to 55% following the coating of the microparticles with the lipids. The pharmacological action against these bacterial species was further improved by the lipid-loaded erythromycin that was carried on the surface of keratin microparticles. This work has demonstrated the design and uses of the keratin microparticles obtained from porcupine quills for clinical applications

Blockade of Tyrosine Kinase, LCK Leads to Reduction in Airway Inflammation through Regulation of Pulmonary Th2/Treg Balance and Oxidative Stress in Cockroach Extract-Induced Mouse Model of Allergic Asthma

Asthma is one of the most common inflammatory diseases affecting the airways. Approximately 300 million individuals suffer from asthma around the world. Allergic immune responses in the asthmatic airways are predominantly driven by Th2 cells and eosinophils. Lymphocyte-specific protein tyrosine kinase (LCK) is a non-receptor tyrosine kinase which regulates several key intracellular events through phosphorylation of its substrates. Some of the intracellular signaling pathways activated by LCK phosphorylation help in differentiation of Th2 cells which secrete allergic cytokines that amplify airway inflammation. Therefore, this investigative study was designed to determine the role of LCK in a cockroach extract (CE)-induced airway inflammation murine model of allergic asthma. Further, the effect of a pharmacological LCK inhibitor, A-770041, on allergic airway inflammation and key intracellular pathways in CD4+ T cells was assessed. Our data exhibit that there is an activation of LCK during allergic airway inflammation as depicted by increased p-LCK levels in CD4+ T cells. Activated LCK is involved in the activation of ITK, PLC-γ, GATA3, NFkB, and NFATc1. Activated LCK is also involved in the upregulation of Th2 related cytokines, such as IL-4/IL-5/IL-13 and oxidative stress, and the downregulation of Treg cells. Furthermore, utilization of LCK inhibitor causes the reduction in p-LCK, PLC-γ, GATA3, and NFATc1 as well as Th2 cytokines and oxidative stress. LCK inhibitor causes upregulation of Treg cells in allergic mice. LCK inhibitor also caused a reduction in CE-induced airway inflammation and mucus secretion. Therefore, the inhibition of LCK signaling could be a fruitful approach to adjust allergic airway inflammation through the attuning of Th2/Treg immune responses. This study could lead to the design of newer treatment options for better management of allergic inflammation in asthma

Anti-Inflammatory Potentials of β-Ketoester Derivatives of N-Ary Succinimides: In Vitro, In Vivo, and Molecular Docking Studies

Inflammation, being a well-known and complex pathological condition, is always a challenge to the human health. This research work was designed for a rationale-based anti-inflammatory study on β-ketoester derivatives of N-ary succinimides. The compounds (A–D) were synthesized by organocatalytic Michael addition. The compounds were initially screened for in vitro 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-2) assays. For the in vivo activity, carrageenan-induced paw edema and arachidonic acid-induced ear edema tests were used. Furthermore, different in vivo pathways such as prostaglandins E2, histamine, leukotriene, and bradykinin were studied. The results were supported with molecular docking studies. Among the compounds, D (ethyl 1-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-2-oxocyclohexane-1-carboxylate) at a concentration of 1000 μg/ml showed significant inhibitory effects of 83.67% and 78.12% against COX-2 and 5-LOX in comparison to celecoxib and zileuton, respectively. Similarly, compound D also showed excellent in vivo anti-inflammatory potential. Amongst all the compounds, D demonstrated excellent (55.92 ± 2.95%) anti-inflammatory potential at maximum tested dose (100 mg/kg) which accomplished the highest significance at 4 h following the carrageenan insertion and stayed considerable (∗∗∗P<0.001) till the 5th hour of test sample injection. Compound D also exhibited excellent percent inhibition (63.81 ± 2.24%) at the highest dose in arachidonic acid-induced ear inflammation. On the basis of in vivo and in vitro results, compound D was subjected to various inflammation-causing agents such as histamine, prostaglandins E2, bradykinin, and leukotriene via the mouse paw edema test. Compound D revealed moderate effect (28.10 ± 1.64%) against histamine-induced paw edema while nonsignificant result (9.72 ± 3.125%) was marked for the bradykinin pathway. Compound D showed significance against edematogenic consequence of prostaglandin E2 (56.28–72.03%) and leukotriene (55.13 ± 2.25%) induced inflammation. In summary, our findings recommended that compound D possesses double acting anti-inflammatory properties inhibiting both COX and LOX pathways. Binding orientations and energy values computed via docking simulations support the results of the experimental in vitro evaluation