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Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via promotion of microglial M1 polarization and activation of the NLRP3 inflammasome
Get PDFBackground: Studies have shown that activation of microglia is the main mechanism of neuropathic pain. The Kv1.3 channel is a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of microglial cells. As such, it may be involved in the processes of neuropathic pain, however, whether Kv1.3 plays a role in neuroinflammation following peripheral nerve injury is unclear. Methods: The spared nerve injury model (SNI) was used to establish neuropathic pain. Western blot and immunofluorescence were used to examine the effect of Kv1.3 in the SNI rats. PAP-1, a Kv1.3 specific blocker was administered to alleviate neuropathic pain in the SNI rats. Results: Neuropathic pain and allodynia occurred after SNI, the levels of M1 (CD68, iNos) and M2 (CD206, Arg-1) phenotypes were up-regulated in the spinal cord, and the protein levels of NLRP3, caspase-1 and IL-1β were also increased. Pharmacological blocking of Kv1.3 with PAP-1 alleviated hyperpathia induced by SNI. Meanwhile, intrathecal injection of PAP-1 reduced M1 polarization and decreased NLRP3, caspase-1, and IL-1β expressions of protein levels. Conclusion: Our research indicates that the Kv1.3 channel in the spinal cord contributes to neuropathic pain by promoting microglial M1 polarization and activating the NLRP3 inflammasome
Deploying Man-In-the-Middle attack on IoT devices connected to Long Range Wide Area Networks (LoRaWAN)
Get PDFAdvancements in research and innovation on Smart IoT technology have provided quality of life to physical and visually impaired users. However, deploying Man-In-the-Middle (MITM) attacks on IoT devices that use Long Range Wide Area Networks (LoRaWAN) has increased exponentially due to the high user demand and increased access to the internet. As a result, there is a high probability of user data being exploited, especially on visually impaired user IoT devices, by penetrating the network devices leading to cyberattacks such as remote access, extortion, sabotage, and loss of internet access. This paper explores the methods used by threat actors to deploy MITM attacks on IoT devices that use LoRaWAN to detect vulnerabilities, understand attack patterns and assist in understanding human factors in cyber security. The contribution of this paper is threefold: First, we review the existing attacks on IoT devices and their impact on visually impaired users. Secondly, we implement a MITM attack using an open-source tool to exploit the LoRaWAN to determine the vulnerabilities. Finally, we recommend a control mechanism to improve security. The results show that the MITM attack can be replicated on devices, demonstrating the importance of creating more robust security to prevent information or identity theft without the user's permission
Intermediate Levels of Predation and Nutrient Enrichment Enhance the Activity of Ibuprofen-Degrading Bacteria
Get PDFWater is the most indispensable natural resource; yet, organic pollution of freshwater sources is widespread. In recent years, there has been increasing concern over the vast array of emerging organic contaminants (EOCs) in the effluent of wastewater treatment plants (WWTPs). Several of these EOCs are degraded within the pore space of riverbeds by active microbial consortia. However, the mechanisms behind this ecosystem service are largely unknown. Here, we report how phosphate concentration and predator–prey interactions drive the capacity of bacteria to process a model EOC (ibuprofen). The presence of phosphate had a significant positive effect on the population growth rate of an ibuprofen-degrading strain. Thus, when phosphate was present, ibuprofen removal efficiency increased. Moreover, low and medium levels of predation, by a ciliated protozoan, stimulated bacterial population growth. This unimodal effect of predation was lost under high phosphate concentration, resulting in the flattening of the relationships between predator density and population growth of ibuprofen degraders. Our results suggest that moderate nutrient and predation levels promote the growth rate of bacterial degraders and, consequently, the self-purifying capability of the system. These findings enhance our understanding of the mechanisms by which riverbed communities drive the processing of EOCs
Dowels effectiveness investigation between ultra high performance fiber reinforced concrete and reinforced concrete
Get PDFIn the present study, the performance of Reinforced Concrete (RC) beams which were strengthened with Ultra High Performance Fiber Reinforced Concrete (UHPFRC) and dowels at the interface was investigated. RC beams with a length of 2.2 m strengthened with UHPFRC layers at the tensile side. Before the application of the layers, the interface between RC and UHPFRC was roughened. During the testing, the interface slips between UHPFRC and RC were recorded using Linear Variable Differential Transformers (LVDTs). The beams were tested under four-point flexural test. The results of the present study indicated that the dowels at the interface reduce the slips at the interface, delay the formation of cracks and result in higher load carrying capacity
Cell and body tissue physiology
No full textThis article discusses cell and tissue physiology and provides a basic review of their structure, function, and life cycle. Altered physiology is explored using clinical scenarios to give context to the aetiology of tumorigenesis
Editorial
Get PDFUrban communities around the world depend on the critical services provided by infrastructure systems to be resilient in the face of natural hazards and man-made shocks such as earthquake, climate change, landslide, population growth, urbanisation, fire, war and pandemic diseases. Therefore, infrastructure needs to both be resilient itself, and to ensure that the services contribute to urban resilience. Any type of failure of infrastructure can cause numerous issues from financial damages to social disruption and disaster events such as human loss and spread of viral diseases due to lack or failure of services in urban infrastructure. These services include potable water, access to safe and reliable energy provision, ability to connect to work and society through communications networks. To enhance resilience of urban infrastructure, interventions are needed at all stages of the infrastructure life cycle from policy and planning through to operation and maintenance of existing systems. Analysis and monitoring are essential tools for decision making both to understand the response to potential shocks and stresses, and to evaluate the performance of potential interventions. This can involve authorities and policy makers or can be actively engaged with local communities and can be effectively contributed by private investors and public organisations to financially support final decision making. Appropriate intervention strategies such as renewable energy, water reuse (Landa-Cansigno et al., 2020), smart schemes (Behzadian et al., 2018) can cover a range of options through new technologies/services/processes that will lead to better coping capacity or faster recovery after failure from extreme events and disruptions
Philosophy and the clinic: stigma, respect and shame
Get PDFSince its foundation in 2010, the annual philosophy thematic edition of this journal has been a forum for authors from a wide range of disciplines and backgrounds, enabling contributors to raise questions of an urgent and fundamental nature regarding the most pressing problems facing the delivery and organization of healthcare. Authors have successfully exposed and challenged underlying assumptions that framed professional and policy discourse in diverse areas, generating productive and insightful dialogue regarding the relationship between evidence, value, clinical research and practice. These lively debates continue in this thematic edition, which includes a special section on stigma, shame and respect in healthcare. Authors address the problems with identifying and overcoming stigma in the clinic, interactional, structural and phenomenological accounts of stigma and the ‘stigma-shame nexus’. Papers examine the lived experience of discreditation, discrimination and degradation in a range of contexts, from the labour room to mental healthcare and the treatment of ‘deviancy’ and ‘looked-after children’. Authors raise challenging questions about the development of our uses of language in the context of care, and the relationship between stigma, disrespect and important analyses of power asymmetry and epistemic injustice. The relationship between respect, autonomy and personhood is explored with reference to contributions from an important conference series, which includes analyses of shame in the context of medically unexplained illness, humour, humiliation and obstetric violence
An emerging lineage of uropathogenic extended spectrum β-lactamase Escherichia coli ST127
Get PDFUropathogenic Escherichia coli (UPEC) is one of the most common causes of urinary tract infections. Here we report for the first time the whole genome sequencing (WGS) and analysis of four extended-spectrum beta-lactamase (ESBL) UPEC sequence type (ST) 127 isolates recovered from patients in five hospitals in Armenia between January to August 2019. Phylogenetic comparison revealed that our isolates were closely related to each other by the core and accessory genomes despite being isolated from different regions and hospitals in Armenia. We identified unique genes in our isolates and in a closely related isolate recovered in France. The unique genes (hemolysin E virulence gene, lactate utilisation operon lutABC and endonuclease restriction modification operon hsdMSR) were identified in three separate genomic regions adjacent to prophage genes, including one region containing the TonB-dependent iron siderophore receptor gene ireA, which was only found in 5 other ST127 isolates from the European Nucleotide Archive (ENA). We further identified that these isolates possessed unique virulence and metabolic genes and harboured antibiotic resistance genes, including ESBL genes blaCTX-M-3 (n=3), blaCTX-M-236 (n=1) and blaTEM-1 (n=1), in addition to a quinolone resistance protein gene qnrD1 (n=1), which was absent in ST127 isolates obtained from ENA. Moreover, a plasmid replicon gene IncI2 (n=1) was unique to ARM88 of the Armenian isolates. Our findings demonstrate that at the time of this study E. coli ST127 was a cause of urinary tract infections in patients in different regions of Armenia, with a possibility of cross-country transmission between Armenia and France
Methicillin resistant staphylococci isolated from goats and their farm environments in Saudi Arabia genotypically linked to known human clinical isolates: a pilot study
Get PDFWe conducted a pilot whole genome sequencing (WGS) study to characterize the genotypes of nine methicillin resistant staphylococci (MRS) isolates recovered from goats and their farm environments in Eastern Province, Saudi Arabia, between November 2019 to August 2020. Seven out of nine isolates were methicillin resistant Staphylococcus aureus (MRSA), and two were methicillin resistant Staphylococcus epidermidis (MRSE). All MRSA isolates possessed genotypes previously identified to infect humans, including isolates harboring ST6-SCCmec IV-t304 (n = 4), ST5-SCCmec VI- t688 (n = 2) and ST5-SCCmec V-t311 (n = 1). 2 MRSA isolates possessed plasmids that were genetically similar to those identified in S. aureus isolates recovered from humans and poultry. In contrast, plasmids found in three MRSA isolates and one MRSE isolate were genetically similar to those recovered from humans. All MRSA isolates harbored the host innate modulate genes sak and scn previously associated with human infections. The genotypes of MRSE isolates were determined as ST35, a well-known zoonotic sequence type and ST153, which has been associated with humans. However, the MRSE isolates were untypeable due to extra ccr complexes identified in their SCCmec elements. Moreover, we identified in ST153 isolate SCCmec element also harbored the Arginine Catabolic Mobile Element (ACME) IV. All MRS isolates were phenotypically resistant to trimethoprim-sulfamethoxazole, an antibiotic for the decolonization of MRS. Three isolates carried antibiotic resistance genes in their SCCmec elements that were not previously described, including those encoding fusidic acid resistance (fusC) and trimethoprim resistance (dfrC) incorporated in the MRSA SCCmec VI.
IMPORTANCE Our findings demonstrate a possible cross-transmission of methicillin resistant staphylococci between goats and their local environments and between goats and humans. Due to ever increasing resistance to multiple antibiotics, the burden of MRS has a significant impact on livestock farming, public health, and the economy worldwide. This study highlights that implementing a holistic approach to whole genome sequencing surveillance in livestock and farm environments would aid our understanding of the transmission of methicillin resistant staphylococci and, most importantly, allow us to implement appropriate infection control and hygiene practices
3D migration depth focus velocity analysis of hand-held ground penetrating radar
Get PDFHand-held ground penetrating radar (GPR) systems have been widely applied to landmine detections during recent decades. The accuracy of an imaging result by migration for a hand-held GPR is strongly related to the accuracy of subsurface velocity distribution obtained from multi offset data. For shallow targets like landmines, the hyperbolas are usually not distinct in 2D slices and are masked by the surface reflections. In this article, we propose a 3D migration depth focus velocity analysis method for hand-held GPRs to estimate the background velocity of the subsurface. This method is performed based on the images generated by migrations. The objective function is defined as the proportion of the target on the depth slice containing the target. After migrating a GPR radargram with different velocities, the background velocity, which minimizes the objective function, can be determined by comparing the imaging results by migration using different velocities. To test the proposed method, we apply this procedure to experimental GPR data collected with an advanced landmine imaging system (ALIS) in the laboratory. Subsequently, the velocity of the background is obtained, 3D diffraction migration with the obtained velocity achieves subsurface imaging with high quality. The accurate position and depth of the target are obtained from the optimal migration image