antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan-mastoparan ...nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR)
.
Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. The complex was assessed for interactions and stability through molecular dynamic simulation (MDS). Binding pocket analysis was used to assess the protease-peptide interface. Mast-Cs NC were prepared by the ionic gelation method. Mast-Cs NC were evaluated in vitro and in vivo for their therapeutic efficacy against drug-resistant clinical
.
MDS for 100 ns showed stable bonds between chitosan and mastoparan; the first at chitosan oxygen atom-46 and mastoparan isoleucine carbon atom with a distance of 2.77 Å, and the second between oxygen atom-23 and mastoparan lysine nitrogen atom with a distance of 2.80 Å, and binding energies of -3.6 and -7.4 kcal/mol, respectively. Mast-Cs complexes approximately 156 nm in size, with +54.9 mV zeta potential and 22.63% loading capacity, offered >90% encapsulation efficiency and were found to be geometrically incompatible with binding pockets of various proteases. The MIC
of Mast-Cs NC was significantly lower than that of chitosan (4 vs 512 μg/mL, respectively,
<0.05), with noticeable bacterial damage upon morphological analysis. In a BALB/c mouse sepsis model, a significant reduction in bacterial colony count in the Mast-Cs treated group was observed compared with chitosan and mastoparan alone (
<0.005). Mast-Cs maintained good biocompatibility and cytocompatibility.
Novel mastoparan-loaded chitosan nanoconstructs signify a successful strategy for achieving a synergistic bactericidal effect and higher therapeutic efficacy against MDR clinical
isolates. The Mast-Cs nano-drug delivery system could work as an alternative promising treatment option against MDR
.
The rGO-supported C@Nd2O3 photocatalyst was designed and fabricated via a facile chemical approach, and ultrasound radiations, aiming to enhance the photocatalytic performance of a novel composite. ...Crystal structure, surface morphology, and chemical composition of as-synthesized samples were carried out through analytical techniques like UV, XRD, FT-IR, and FESEM. Physical investigation confirms the synthesis of nano-sized material formation. Methylene blue (MB) dye, an organic waste contaminant, in water under UV/simulated solar illumination was used as the benchmark reaction to assess the photocatalytic performance of C@Nd2O3/rGO. The synergism of ternary composite C@Nd2O3/rGO exhibited greater photocatalytic activity than C@Nd2O3. The photocatalytic efficiency of C@Nd2O3/rGO was found to be greatly increased by the impregnation of C@Nd2O3 over rGO sheets, as evidenced by the elimination of 90.93% of the dye under 60 min exposure to UV light. Eventually, the mechanism and pathway for methylene blue dye degradation by UV photocatalysis over C@Nd2O3/rGO composite was also proposed. Major oxidative species involved in the photocatalytic degradation of MB dye include superoxide radicals (O2−•), hydroxyl radicals (HO•), and holes (h+). The increased photocatalytic activity may be attributed to the creation of heterojunction, high charge separation and low recombination rate of photoinduced e− - h+ couples. It was established from obtained results that hydroxyl radicals generated in C@Nd2O3/rGO composite play a major role during photocatalysis. In photochemical applications, the synthesized photocatalyst is anticipated to be a promising material system.
•rGO supported C@Nd2O3 photocatalyst was designed and prepared via facile route.•Prepared catalyst was characterized by XRD, FTIR and SEM.•Impregnation of C@Nd2O3 over rGO sheets showed of >90% dye degradation.
The pandemic situation with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from China has endangered human lives. Coronavirus disease 2019 (COVID-19) is presented with ...asymptomatic, mild, or severe pneumonia-like symptoms. COVID-19 patients with diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), hypertension, malignancies, HIV, and other comorbidities could develop a life-threatening situation. SARS-CoV-2 utilizes ACE-2 receptors found at the surface of the host cells to get inside the cell. Certain comorbidities are associated with a strong ACE-2 receptor expression and higher release of proprotein convertase that enhances the viral entry into the host cells. The comorbidities lead to the COVID-19 patient into a vicious infectious circle of life and are substantially associated with significant morbidity and mortality. The comorbid individuals must adopt the vigilant preventive measure and require scrupulous management. In this review, we rigorously focused on the impact of common morbidities in COVID-19 patients and recapitulated the management strategies with recent directions. We found limited resources describing the association of comorbidities in COVID-19; however, our review delineates the broader spectrum of comorbidities with COVID-19 patients.
Published studies have shown differences in types and underlying mechanisms of stroke between different regions of the world. There is a lack of published literature describing the characteristics of ...acute stroke in Saudi Arabia. The aim of this study was to identify different types and associated risk factors among acute stroke patients in Saudi Arabia. In this descriptive study, records of 500 patients with acute stroke were included. Acute stroke was classified as ischemic stroke, intracerebral hemorrhage, cerebral venous sinus thrombosis or subarachnoid hemorrhage. The TOAST classification was used to categorize ischemic stroke. Ischemic stroke was found to be the most common type (86.6%). The patients included comprised 326 (65.2%) males and 174 (34.8%) females. Small vessel occlusive disease was the most common etiology of ischemic stroke. The males had a lower mean age than the females (p=0.00). The results of our study are largely in agreement with published literature, although a few differences emerged which need to be verified through further prospective multicenter studies.
The Kommerell diverticulum (KD) is an extremely rare developmental abnormality of the aorta related to an aberrant subclavian artery (ASCA). The objective of our study was to review the natural ...history of KD and ASCA using our single-center experience in diagnosing and managing KD and ASCA.
A retrospective review of the Yale radiological database from January 1999 to December 2016 was performed. Only patients with KD/ASCA and a computed tomography (CT) scan of the chest were selected for review. The primary goal was to examine the natural history of KD and ASCA and the secondary goals were to review the management and outcomes of those patients treated for KD and ASCA.
There were 75 patients with KD/ASCA identified, with a mean age of 63 ± 19 years; 49 were female (65%). On CT scans, left- and right-sided aortas were present in 47 (63%) and 28 (37%) patients. A right ASCA or a left ASCA were present in 47 (63%) and 28 (37%) patients. Six patients were symptomatic on presentation. Symptoms included dysphagia, chest or back pain, and emboli to the fingers. The mean KD diameter was 21.8 ± 6.0 mm and the distance to the opposite aortic wall (DAW) was 48.3 ± 10.8 mm. Sixty-six patients were followed for a mean of 31.7 ± 32.5 months. One patient ruptured without repair. Nine patients underwent operative intervention, including eight open and one endovascular repair. Complications from operative intervention included ischemic stroke with hemorrhagic transformation, deep vein thrombosis and pneumonia. The mean growth rate for KD and DAW was 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year, respectively. On multivariable regression analysis, hypertension was a predictor of growth of DAW (P = .03).
KD is uncommon and shows a female predominance. The diverticulum grows, albeit slowly (KD and DAW growth rates of 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year). Most patients are asymptomatic, but dysphagia, chest/back pain, and distal emboli may occur. Rupture is rare. Symptomatic patients should be operated. Asymptomatic patients can be followed with serial CT scans.
The aim of this article is to investigate the unsteady natural convection flow of Maxwell fluid with fractional derivative over an exponentially accelerated infinite vertical plate. Moreover, slip ...condition, radiation, MHD and Newtonian heating effects are also considered. A modern definition of fractional derivative operator recently introduced by Caputo and Fabrizio has been used to formulate the fractional model. Semi analytical solutions of the dimensionless problem are obtained by employing Stehfest’s and Tzou’s algorithms in order to find the inverse Laplace transforms for temperature and velocity fields. Temperature and rate of heat transfer for non-integer and integer order derivatives are computed and reduced to some known solutions from the literature. Finally, in order to get insight of the physical significance of the considered problem regarding velocity and Nusselt number, some graphical illustrations are made using Mathcad software. As a result, in comparison between Maxwell and viscous fluid (fractional and ordinary) we found that viscous (fractional and ordinary) fluids are swiftest than Maxwell (fractional and ordinary) fluids.
Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. ...Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.
Exact general solutions for the dynamics of an incompressible viscous fluid with non-integer order derivative without singular kernel are established using the integral transforms. These solutions, ...which are organized in simple forms in terms of exponential and trigonometric functions, can be conveniently engaged to obtain known solutions from the literature. The control of the new non-integer order derivative on the velocity of the fluid moreover a comparative study with an older model, is analyzed for some flows with practical applications. The non-integer order derivative with non-singular kernel is more appropriate for handling mathematical calculations of obtained solutions. It is also more reliable for numerical computations.
The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.
We performed a randomized, ...double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses.
We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval CI, 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo.
Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).
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