Pseudocapacitive Kinetics in Synergistically Coupled MoS2-Mo2N Nanowires with Enhanced Interfaces toward All-Solid-State Flexible Supercapacitors.

Pseudocapacitive kinetics in rationally engineered nanostructures can deliver higher energy and power densities simultaneously. The present report reveals a high-performance all-solid-state flexible symmetric supercapacitor (FSSC) based on MoS2-Mo2N nanowires deposited directly on stainless steel mesh (MoS2-Mo2N/SSM) employing DC reactive magnetron co-sputtering technology. The abundance of synergistically coupled interfaces and junctions between MoS2 nanosheets and Mo2N nanostructures across the nanocomposite results in greater porosity, increased ionic conductivity, and superior electrical conductivity. Consequently, the FSSC device utilizing poly(vinyl alcohol)-sodium sulfate (PVA-Na2SO4) hydrogel electrolyte renders an outstanding cell capacitance of 252.09 F·g-1 (44.12 mF·cm-2) at 0.25 mA·cm-2 and high rate performance within a wide 1.3 V window. Dunn's and b-value analysis reveals significant energy storage by surface-controlled capacitive and pseudocapacitive mechanisms. Remarkably, the symmetric device boosts tremendous energy density ∼10.36 µWh·cm-2 (59.17 Wh·kg-1), superb power density ∼6.5 mW·cm-2 (37.14 kW·kg-1), ultrastable long cyclability (∼93.7% after 10,000 galvanostatic charge-discharge cycles), and impressive mechanical flexibility at 60°, 90°, and 120° bending angles.

Use of Artificial Intelligence in the Diagnosis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common forms of cancer. Therefore, diagnosing the condition early and accurately is critical for improved patient outcomes and effective treatment. Recently, artificial intelligence (AI) algorithms such as support vector machine (SVM) and convolutional neural network (CNN) have demonstrated promise in medical image analysis. This paper, conducted from a systematic review perspective, aimed to determine the effectiveness of AI integration in CRC diagnosis, emphasizing accuracy, sensitivity, and specificity. From a methodological perspective, articles that were included were those that had been conducted in the past decade. Also, the articles needed to have been documented in English, with databases such as Embase, PubMed, and Google Scholar used to obtain relevant research studies. Similarly, keywords were used to arrive at relevant articles. These keywords included AI, CRC, specificity, sensitivity, accuracy, efficacy, effectiveness, disease diagnosis, screening, machine learning, area under the curve (AUC), and deep learning. From the results, most scholarly studies contend that AI is superior in medical image analysis, the development of subtle patterns, and decision support. However, while deploying these algorithms, a key theme is that the collaboration between medical experts and AI systems needs to be seamless. In addition, the AI algorithms ought to be refined continuously in the current world of big data and ensure that they undergo rigorous validation to provide more informed decision-making for or against adopting those AI tools in clinical settings. In conclusion, therefore, balancing between human expertise and technological innovation is likely to pave the way for the realization of AI's full potential concerning its promising role in improving CRC diagnosis, upon which there might be significant patient outcome improvements, disease detection, and the achievement of a more effective healthcare system.

A Novel Vibrating Capsule Treatment for Constipation: A Review of the Literature.

Constipation is a pretty common and sometimes complicated health condition around the world which is characterized by an inability to have regular bowel movements. In response to this worrying trend, various pharmacological and non-pharmacological interventions have been embraced to seek to produce promising outcomes, yet patient dissatisfaction continues to be reported. The main aim of this review paper was to determine the effectiveness and safety of the vibrating capsule in treating constipated patients. The key databases that were consulted to get articles on this subject include Google Scholar, Embase, and PubMed. Specific keywords were used in the database search to get the relevant articles. Based on the exclusion criterion, articles that were excluded include conference abstracts, commentaries, preclinical research articles, articles where full texts were inaccessible, and those that had been published in a language other than English. From the results, the safety profile of the vibrating capsule suggests that the intervention is generally well-tolerated, with only mild and transient side effects or adverse events noted, including abdominal discomfort and sensations of mild vibration. However, the impact of these adverse events (although mild to moderate) on the efficacy of the capsule remains unknown, an area requiring further scholarly attention in the future. Concerning the efficacy of the intervention, most studies were found to affirm that the vibrating capsule enhances the physiologic effects of meals and waking on bowel movements, but the need for providers in clinical environments to note the interplay between the number of vibrations and the effectiveness of the capsule or onset of complete spontaneous bowel movements could not be overemphasized. In conclusion, this paper established that the vibrating capsule is an effective and promising technology through which constipated patients could be treated while experiencing minimal or no adverse events, but future research efforts ought to seek to uncover the interplay between the mechanism of action of the capsule and any moderating role played by factors internal or external to patients, including their emotional, mental, and psychological statuses, as well as the type and quantity of food consumed before and after the vibration sessions.

Pseudocapacitive Storage in Molybdenum Oxynitride Nanostructures Reactively Sputtered on Stainless-Steel Mesh Towards an All-Solid-State Flexible Supercapacitor.

Exploiting pseudocapacitance in rationally engineered nanomaterials offers greater energy storage capacities at faster rates. The present research reports a high-performance Molybdenum Oxynitride (MoON) nanostructured material deposited directly over stainless-steel mesh (SSM) via reactive magnetron sputtering technique for flexible symmetric supercapacitor (FSSC) application. The MoON/SSM flexible electrode manifests remarkable Na+-ion pseudocapacitive kinetics, delivering exceptional ≈881.83 F g-1 capacitance, thanks to the synergistically coupled interfaces and junctions between nanostructures of Mo2N, MoO2, and MoO3 co-existing phases, resulting in enhanced specific surface area, increased electroactive sites, improved ionic and electronic conductivity. Employing 3D Bode plots, b-value, and Dunn's analysis, a comprehensive insight into the charge-storage mechanism has been presented, revealing the superiority of surface-controlled capacitive and pseudocapacitive kinetics. Utilizing PVA-Na2SO4 gel electrolyte, the assembled all-solid-state FSSC (MoON/SSM||MoON/SSM) exhibits impressive cell capacitance of 30.7 mF cm-2 (438.59 F g-1) at 0.125 mA cm-2. Moreover, the FSSC device outputs a superior energy density of 4.26 µWh cm-2 (60.92 Wh kg-1) and high power density of 2.5 mW cm-2 (35.71 kW kg-1). The device manifests remarkable flexibility and excellent electrochemical cyclability of ≈91.94% over 10,000 continuous charge-discharge cycles. These intriguing pseudocapacitive performances combined with lightweight, cost-effective, industry-feasible, and environmentally sustainable attributes make the present MoON-based FSSC a potential candidate for energy-storage applications in flexible electronics.

Directly Sputtered Molybdenum Disulfide Nanoworms Decorated with Binder-less VN and W2N Nanoarrays for Bendable Large-Scale Asymmetric Supercapacitor.

Considering the superior capacitive performance and rich redox kinetics, the two-dimensional (2D) layered molybdenum disulfide (MoS2) and transition metal nitrides (TMNs) have emerged as the latest set of nanomaterials. Direct incorporation of key materials vanadium nitride (VN) and tungsten nitride (W2N) into a MoS2 array has been achieved on cost-effective, bendable stainless steel (SS) foil via a reactive cosputtering route. Herein, we have utilized the synergistic effect of intermixed nanohybrids to develop a flexible asymmetric supercapacitor (FASC) device from MoS2-VN@SS (negative) and MoS2-W2N@SS (positive) electrodes. As-constructed FASC cell possesses a maximum operational potential of 1.80 V and an exceptional gravimetric capacitance of 200 F g-1 at a sweep rate of 5 mV s-1. The sustained capacitive performance mainly accounts for the synergism induced through unique interfacial surface architecture provided by MoS2 nanoworms and TMN conductive hosts. The sulfur and nitrogen edges ensure the transport channels to Li+/SO4-2 ions for intercalation/deintercalation into the composite nanostructured thin film, further promoting the pseudocapacitive behavior. Consequently, the supercapacitor cell exhibits a distinctive specific energy of 87.91 Wh kg-1 at 0.87 kW kg-1 specific power and a reduced open circuit potential (OCP) decay rate (∼42% self-discharge after 60 min). Moreover, the assembled flexible device exhibits nearly unperturbed electrochemical response even at bending at 165° angle and illustrates a commendable cyclic life-span of 82% after 20,000 charge-discharge cycles, elucidating advanced mechanical robustness and capacitance retentivity. The powering of a multicolor light-emitting diode (LED) and electronic digital watch facilitates the practical evidence to open up possibilities in next-generation state-of-the-art wearable and miniaturized energy storage systems.

Graphene oxide-coated Ag-TiO2 hybrid nanocomposites for superior photocatalytic activity.

Graphene oxide (GO) has now emerged as one of the most promising materials in different areas such as photocatalysis, adsorption, and energy storage due to its high surface area, unique layered structure, etc. Among various types of precursors, anthracite coal has attracted a lot of attention nowadays as it affords GO a high concentration of sp2 carbons resulting in high conductivity and superior absorbance in the visible region. In this report, we have prepared GO-TiO2 nanocomposites as it is supposed to possess high photocatalytic activity owing to facile electron transmission from the conduction band of TiO2 to the GO surface resulting in a much lower degree of electron-hole pair recombination. To boost the photocatalytic activity further, TiO2 was coated with Ag nanoparticles as well. These hybrid structures were characterized by different analytical techniques, for example, XRD, HR-TEM, SEM, and Raman spectroscopy. The XRD pattern of these composites consists of characteristic peaks corresponding to GO, TiO2, and Ag. The HR-TEM studies confirm the presence of GO layers, cube-shaped TiO2, and spherical Ag nanoparticles. Phenol and 4-nitrophenol have been used as model pollutants to evaluate the photooxidation efficiencies under both UV and visible light irradiation. Under UV irradiation, the GO/Ag-TiO2 ternary nanocomposite shows better photooxidation efficiency (62%) compared to Ag-TiO2 (38%), GO-TiO2 (9%), GO (17%), and TiO2 (8%) toward phenol degradation. The GO/Ag-TiO2 is also having the highest photocatalytic activity toward the removal of phenol under visible light irradiation (34%). The ternary heterostructure (85%) also possesses superior photooxidation activity compared to Ag-TiO2 (44%) and GO-TiO2 (71%) toward the degradation of p-nitrophenol under UV light radiation for 60 min. The above observation reveals that the cooperative effect of Ag, TiO2, and GO is playing a crucial role to result in the high photooxidation activity of the GO/Ag-TiO2 hetero-nanocomposites.

Effects of chemical cues and prior experience on predator avoidance in crayfish.

Multisensory stimuli provide organisms with information to assess the threat present in the surroundings. Olfactory cues show dominance over other sensory modalities in the aquatic environment. The impact of chemical predator cues combined with experiences gained (learning) in species without previous contact is not fully understood. We investigated the foraging and shelter-seeking behaviour of naïve and experienced marbled crayfish Procambarus virginalis juveniles in response to the chemical signals of pumpkinseed Lepomis gibbosus alone and in combination with alarm chemicals produced by preyed-upon conspecifics. Naïve and experienced (previously exposed to pumpkinseed predation) juveniles were stocked in an arena with shelter and feed and exposed (1) to water from a tank containing a predator actively feeding on conspecifics, (2) water from a tank with predator only and (3) water only as control. Crayfish exposed to the combined stimuli avoided the inlet zone and gravitated to shelter zone of the arena to a greater extent than did those exposed to predator-only cues and the control. Regardless of the treatment, experienced crayfish showed significantly reduced interest in feeding. Our findings imply that crayfish response to threat-associated odours with the greatest potency when visual or tactile cues are present, while previous encounters with predators may make them more cautious.

Effect of psychoactive substances on cardiac and locomotory activity of juvenile marbled crayfish Procambarus virginalis.

Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are classified as emerging pollutants for a variety of aquatic organisms. To determine the effects of environmentally relevant levels of psychoactive compounds on non-target organisms, we analyzed cardiac and locomotory activity in early developmental stages of marbled crayfish Procambarus virginalis. Responses to sertraline, methamphetamine, and a mixture of citalopram, oxazepam, sertraline, tramadol, venlafaxine, and methamphetamine at a concentration of 1 µg L-1 of each compound were assessed. On day four of exposure, cardiac activity was recorded for 5 min, and on day eight, locomotory activity was recorded for 15 min. There was a significant increase (p < 0.01) in heart rate in methamphetamine-exposed and Mix-exposed juveniles compared to the unexposed control and there was significant difference (p < 0.01) in proportion of time (activity %) was observed with sertraline-exposed, whereas velocity, and distance moved did not significantly differ (p > 0.05) in exposed and control animals. These findings revealed that low concentrations of chemicals and their mixtures can modify the physiological state of aquatic animals without outward manifestations (activity, distance moved, and velocity). Aquatic animals can be impacted earlier than is visible, but effects can potentially lead to substantial changes in populations and in ecosystem processes. Additional research to investigate chemical combinations, exposure systems, and organism physiological and molecular responses may provide evidence of broad impact of environmental pharmaceuticals.

Trustability for Resilient Internet of Things Services on 5G Multiple Access Edge Cloud Computing.

Billions of Internet of Things (IoT) devices and sensors are expected to be supported by fifth-generation (5G) wireless cellular networks. This highly connected structure is predicted to attract different and unseen types of attacks on devices, sensors, and networks that require advanced mitigation strategies and the active monitoring of the system components. Therefore, a paradigm shift is needed, from traditional prevention and detection approaches toward resilience. This study proposes a trust-based defense framework to ensure resilient IoT services on 5G multi-access edge computing (MEC) systems. This defense framework is based on the trustability metric, which is an extension of the concept of reliability and measures how much a system can be trusted to keep a given level of performance under a specific successful attack vector. Furthermore, trustability is used as a trade-off with system cost to measure the net utility of the system. Systems using multiple sensors with different levels of redundancy were tested, and the framework was shown to measure the trustability of the entire system. Furthermore, different types of attacks were simulated on an edge cloud with multiple nodes, and the trustability was compared to the capabilities of dynamic node addition for the redundancy and removal of untrusted nodes. Finally, the defense framework measured the net utility of the service, comparing the two types of edge clouds with and without the node deactivation capability. Overall, the proposed defense framework based on trustability ensures a satisfactory level of resilience for IoT on 5G MEC systems, which serves as a trade-off with an accepted cost of redundant resources under various attacks.

Global scenario of Plasmodium vivax occurrence and resistance pattern.

Malaria caused by Plasmodium vivax is comparatively less virulent than Plasmodium falciparum, which can also lead to severe disease and death. It shows a wide geographical distribution. Chloroquine serves as a drug of choice, with primaquine as a radical cure. However, with the appearance of resistance to chloroquine and treatment has been shifted to artemisinin combination therapy followed by primaquine as a radical cure. Sulphadoxine-pyrimethamine, mefloquine, and atovaquone-proguanil are other drugs of choice in chloroquine-resistant areas, and later resistance was soon reported for these drugs also. The emergence of drug resistance serves as a major hurdle to controlling and eliminating malaria. The discovery of robust molecular markers and regular surveillance for the presence of mutations in malaria-endemic areas would serve as a helpful tool to combat drug resistance. Here, in this review, we will discuss the endemicity of P. vivax, a historical overview of antimalarial drugs, the appearance of drug resistance and molecular markers with their global distribution along with different measures taken to reduce malaria burden due to P. vivax infection and their resistance.

In-situsputtered 2D-MoS2nanoworms reinforced with molybdenum nitride towards enhanced Na-ion based supercapacitive electrodes.

We report the fabrication of binder-free, low-cost and efficient hybrid supercapacitive electrode based on the hexagonal phase of two-dimensional MoS2nanoworms reinforced with molybdenum nitride nanoflakes deposited on stainless steel (SS) substrate using reactive magnetron sputtering technique. The hybrid nanostructured MoS2-Mo2N/SS thin film working electrode delivers a high gravimetric capacitance (351.62 F g-1at 0.25 mA cm-2) investigated in 1 M Na2SO4aqueous solution. The physisorption/intercalation of sodium (Na+) ions in electroactive sites of MoS2-Mo2N composite ensures remarkable electrochemical performance. The deposited porous nanostructure with good electrical conductivity and better adhesion with the current collector demonstrates a high-energy density of 82.53 Wh kg-1in addition to a high-power density of 24.98 kW kg-1. Further, excellent capacitance retention of 93.62% after 4000 galvanostatic charge-discharge cycles elucidated it as a promising candidate for realizing high-performance supercapacitor applications.

Interleukin-18, IL-18 binding protein and IL-18 receptor expression in asthma: a hypothesis showing IL-18 promotes epithelial cell differentiation.

OBJECTIVE: In asthma, genome-wide association studies have shown that interleukin-18 (IL-18) receptor 1 gene (IL-18R1) and sputum IL-18 are increased during exacerbations. However, the role of the IL-18 axis in bronchial epithelial function is unclear. To investigate IL-18, IL-18 binding protein (BP) and IL-18R expression in bronchial biopsies and sputum samples from patients with asthma, and to determine its functional role using in vitro bronchial epithelial cells. METHODS: The expression of IL-18, IL-18BP and IL-18Rα was examined in subjects with asthma and healthy controls in bronchial biopsies by immunohistochemistry and IL-18 and IL-18BP release in sputum. In epithelial cells, the mRNA and protein expression of IL-18, IL-18BP, IL-18Rα and IL-18Rß was assessed by qPCR, flow cytometry, Western blotting and immunofluorescence respectively. IL-18 function in epithelial cells was examined by intracellular calcium, wound repair, synthetic activation and epithelial differentiation changes. RESULTS: In biopsies from subjects with asthma, the IL-18 expression was not different in the lamina propria compared with controls but was decreased in the epithelium. In contrast, the IL-18BP was decreased in the lamina propria in asthma and was absent in the bronchial epithelium. IL-18 was released in sputum with IL-18BP elevated in patients with asthma. The IL-18Rα expression was not different between health and disease. In vitro, IL-18-stimulated bronchial epithelial cells increased intracellular calcium, wound repair, metabolic activity, morphological changes and epithelial cellular differentiation. CONCLUSION: In asthma, the dynamic interaction between IL-18, its cognate receptor and natural inhibitor is complex, with differences between airway compartments. Upregulation of IL-18 can promote epithelial activation and cellular differentiation.

Functional bipolar resistive switching in AlN/Ni-Mn-In based magnetoelectric heterostructure.

This report explores the influence of temperature on resistive switching characteristics in the AlN/Ni-Mn-In magnetoelectric (ME) heterostructure-based resistive random access memory (ReRAM) device. The fabricated Cu/AlN/Ni-Mn-In/Si device exhibits a sharp transition from a high resistance state (HRS) to low resistance state (LRS) at a SET voltage. The rupture of the filament from its weakest point at a RESET voltage turn the device back to its HRS. The stable bipolar resistive switching behavior is described by the current-voltage (I-V) characteristic. The HRS and LRS are explained by the trap-controlled space charge limited conduction mechanism and a well-known Ohmic conduction mechanism, respectively. The temperature-dependent resistance has been observed to further confirm the conduction mechanism in HRS and LRS. The current conduction in LRS is explained by an analytical model based on copper metallic filament formation via Cu+migration from the top to the bottom electrode. A significant change in the SET voltage has been observed with the decrease in temperature. This variation in the SET voltage is explained via strain-mediated coupling in interfacially connected AlN/Ni-Mn-In ME heterostructure. The fabricated device displays an appreciable OFF/ON ratio of the order ∼3 × 103with good endurance and retention of ∼1000 cycles and ∼900 s, respectively. A slight variation (<40%) in SET and RESET voltages has been observed for total endurance cycles. This study demonstrates the importance of ME heterostructure for futuristic tuneable ReRAM applications.

Fibrocyte localisation to the ASM bundle in asthma: bidirectional effects on cell phenotype and behaviour.

OBJECTIVES: Airway hyper-responsiveness and persistent airflow obstruction contribute to asthma pathogenesis and symptoms, due in part to airway smooth muscle (ASM) hypercontractility and increased ASM mass. Fibrocytes have been shown to localise to the ASM in asthma however it is not known whether fibrocytes localise to the ASM in nonasthmatic eosinophilic bronchitis (NAEB) and chronic obstructive pulmonary disease (COPD). In addition, the potential consequences of fibrocyte localisation to ASM as regards asthma pathophysiology has not been widely studied. METHODS: Fibrocytes and proliferating cells were enumerated in ASM in bronchial tissue using immunohistochemistry. The effects of primary ASM and fibrocytes upon each other in terms of phenotype and behaviour following co-culture were investigated by assessing cell number, size, apoptotic status, phenotype and contractility in in vitro cell-based assays. RESULTS: Increased fibrocyte number in the ASM was observed in asthma versus NAEB, but not NAEB and COPD versus controls, and confirmed in asthma versus controls. ASM proliferation was not detectably different in asthmatics versus healthy controls in vivo. No difference in proliferation, apoptotic status or size of ASM was seen following culture with/without fibrocytes. Following co-culture with ASM from asthmatics versus nonasthmatics, fibrocyte smooth muscle marker expression and collagen gel contraction were greater. Following co-culture, fibrocyte CD14 expression was restored with the potential to contribute to asthma pathogenesis via monocyte-mediated processes dependent on the inflammatory milieu. CONCLUSION: Further understanding of mechanisms of fibrocyte recruitment to and/or differentiation within the ASM may identify novel therapeutic targets to modulate ASM dysfunction in asthma.

Pathophysiological regulation of lung function by the free fatty acid receptor FFA4.

Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein-coupled receptor family, FFA4, that responds to free circulating fatty acids including dietary omega-3 fatty acids found in fish oils. We show that FFA4, although usually associated with metabolic responses linked with food intake, is expressed in the lung where it is coupled to Gq/11 signaling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated at least in part by the release of the prostaglandin E2 (PGE2) that subsequently acts on EP2 prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. In acute and chronic ozone models of pollution-mediated inflammation and house dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, a response that was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was similar to that observed in mice, and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation ex vivo. Our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, has in vivo efficacy and might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.

ST2 expression and release by the bronchial epithelium is downregulated in asthma.

BACKGROUND: The airway epithelium plays an important role in wound repair, host defense and is involved in the immunopathogenesis of asthma. Genome wide association studies have described associations between ST2/Interleukin (IL)-33 genes in asthma, but its role in bronchial epithelium is unclear. METHODS: ST2 expression was examined in subjects with asthma and healthy controls in bronchial epithelium from biopsies (n = 27 versus n = 9) and brushings (n = 34 versus n = 20) by immunohistochemistry and RNA-Seq. In human primary bronchial epithelial cells ST2 mRNA and protein expression were assessed by qPCR, flow cytometry, Western blotting, and immunofluorescence. IL-33 function in epithelial cells was examined by intracellular calcium measurements, wound healing assays, and synthetic activation by gene array and ELISA. RESULTS: Bronchial epithelial ST2 protein expression was significantly decreased in biopsies in subjects with asthma compared to healthy controls (P = .039). IL1RL1 gene expression in bronchial brushes was not different between health and disease. In vitro primary bronchial epithelial cells expressed ST2 and IL-33 stimulation led to an increase in intracellular calcium, altered gene expression, but had no effect upon wound repair. Epithelial cells released sST2 spontaneously, which was reduced following stimulation with TNFα or poly-IC. Stimulation by TNFα or poly-IC did not affect the total ST2 expression by epithelial cell whereas surface ST2 decreased in response to TNFα, but not poly-IC. CONCLUSION: In asthma, bronchial epithelium protein expression of ST2 is decreased. Our in vitro findings suggest that this decrease might be a consequence of the pro-inflammatory environment in asthma or in response to viral infection.

The Impact of Open versus Closed Catheter Access System of Central Venous Catheter on Infection Prevention in Critically Ill Patients: A Comparative Evaluation.

BACKGROUND: Use of Central Venous Catheters (CVC) can be associated with increased incidence of Catheter-Related Bloodstream Infections (CRBSIs). The present study assessed the impact of open versus closed catheter access system of CVC on infection prevention in critically sick patients admitted in the Intensive Care Unit (ICU). MATERIALS AND METHODS: After obtaining ethical clearance and consent of relatives of the patients admitted in ICU of our institute, the present study was carried out as a randomized, prospective, double-blind trial with parallel group design (of 200 patients in each group). In study group (Group I), closed catheter access system (Luer access split septum) was used, while open access (three-way) system was used in the control group. Among clinical parameters, if any patient developed fever, his/her blood, urine, and tracheal secretions were sent for culture and sensitivity. Collected data were analyzed using descriptive and inferential statistics. RESULTS: Demographic profile was similar in both the groups. Significant clinical and statistical differences were observed in blood culture values (χ2 = 58.30, df = 1, p < 0.001) as well as Total Leukocyte Counts (TLC) on day 1, 4, and 8 (F2,260= 80.61, p < 0.001). However, no statistically significant (t390= 0.90, p = 0.367) difference was found in the duration of hospital stay among patients in both the groups despite significant differences in various clinical parameter. CONCLUSION: Luer access split septum connectors along with appropriate training of the nursing personals decrease CRBSI.

DP2 antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment.

Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D2 type 2 receptor (DP2) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP2 in airway smooth muscle cells. We report that the DP2 antagonist fevipiprant reduced airway smooth muscle mass in bronchial biopsies from patients with asthma who had participated in a previous randomized placebo-controlled trial. We developed a computational model to capture airway remodeling. Our model predicted that a reduction in airway eosinophilia alone was insufficient to explain the clinically observed decrease in airway smooth muscle mass without a concomitant reduction in the recruitment of airway smooth muscle cells or their precursors to airway smooth muscle bundles that comprise the airway smooth muscle layer. We experimentally confirmed that airway smooth muscle migration could be inhibited in vitro using DP2-specific antagonists in an airway smooth muscle cell culture model. Our analyses suggest that fevipiprant, through antagonism of DP2, reduced airway smooth muscle mass in patients with asthma by decreasing airway eosinophilia in concert with reduced recruitment of myofibroblasts and fibrocytes to the airway smooth muscle bundle. Fevipiprant may thus represent a potential therapy to ameliorate airway remodeling in asthma.

Combined administration of anti-IL-13 and anti-IL-17A at individually sub-therapeutic doses limits asthma-like symptoms in a mouse model of Th2/Th17 high asthma.

BACKGROUND: Recent studies have demonstrated that Th2 responses have the ability to antagonize Th17 responses. In mouse models of allergic asthma, blockade of Th2-effector cytokines results in elaboration of Th17 responses and associated increases in pulmonary neutrophilia. While these can be controlled by simultaneous blockade of Th17-associated effector cytokines, clinical trials of anti-IL-17/IL-17RA blocking therapies have demonstrated increased of risk of bacterial and fungal infections. Identification of minimally effective doses of cytokine-blocking therapies with the goal of reducing the potential emergence of infection-related complications is a translationally relevant goal. OBJECTIVE: In the current report, we examine whether combined blockade of IL-13 and IL-17A, at individually sub-therapeutic levels, can limit the development of allergic asthma while sparing expression of IL-17A-associated anti-microbial effectors. METHODS: House dust mite was given intratracheally to A/J mice. Anti-IL-13 and anti-IL-17A antibodies were administered individually, or concomitantly at sub-therapeutic doses. Airway hyper-reactivity, lung inflammation, magnitude of Th2- and Th17-associated cytokine production and expression of IL-13- and IL-17A-induced genes in the lungs was assessed. RESULTS: Initial dosing studies identified sub-therapeutic levels of IL-13 and IL-17A blocking mAbs that have a limited effect on asthma parameters and do not impair responses to microbial products or infection. Subsequent studies demonstrated that combined sub-therapeutic dosing with IL-13 and IL-17A blocking mAbs resulted in significant improvement in airway hyperresponsiveness (AHR) and expression of IL-13-induced gene expression. Importantly, these doses neither exacerbated nor inhibited production of Th17-associated cytokines, or IL-17A-associated gene expression. CONCLUSION: This study suggests that combining blockade of individual Th2 and Th17 effector cytokines, even at individually sub-therapeutic levels, may be sufficient to limit disease development while preserving important anti-microbial pathways. Such a strategy may therefore have reduced potential for adverse events associated with blockade of these pathways.