Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

Psychostimulant Medications for Physical Function and Spasticity in Children With Cerebral Palsy: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations. OBJECTIVE: The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP. METHODS: This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure-66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test. RESULTS: The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024. CONCLUSIONS: The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53728.

Hemodynamic performance evaluation of neonatal ECMO double lumen cannula using fluid-structure interaction.

Extra corporeal membrane oxygenation (ECMO) is an artificial oxygenation facility, employed in situations of cardio-pulmonary failure. Some diseases i.e., acute respiratory distress syndrome, pulmonary hypertension, corona virus disease (COVID-19) etc. affect oxygenation performance of the lungs thus requiring the need of artificial oxygenation. Critical care teams used ECMO technique during the COVID-19 pandemic to support the heart and lungs of COVID-19 patients who had an acute respiratory or cardiac failure. Double Lumen Cannula (DLC) is one of the most critical components of ECMO as it resides inside the patient and, connects patient with external oxygenation circuit. DLC facilitates delivery and drainage of blood from the patient's body. DLC is characterized by delicate balance of internal and external flows inside a limited space of the right atrium (RA). An optimal performance of the DLC necessitates structural stability under biological and hemodynamic loads, a fact that has been overlooked by previously published studies. In the past, many researchers experimentally and computationally investigated the hemodynamic performance of DLC by employing Eulerian approach, which evaluate instantaneous blood damage without considering blood shear exposure history (qualitative assessment only). The present study is an attempt to address the aforementioned limitations of the previous studies by employing Lagrangian (quantitative assessment) and incorporating the effect of fluid-structure interaction (FSI) to study the hemodynamic performance of neonatal DLC. The study was performed by solving three-dimensional continuity, momentum, and structural mechanics equation(s) by numerical methods for the blood flow through neonatal DLC. A two-way coupled FSI analysis was performed to analyze the effect of DLC structural deformation on its hemodynamic performance. Results show that the return lumen was the most critical section with maximum pressure drop, velocity, shear stresses, and blood damage. Recirculation and residence time of blood in the right atrium (RA) increases with increasing blood flow rates. Considering the structural deformation has led to higher blood damage inside the DLC-atrium system. Maximum Von-Mises stress was present on the side edges of the return lumen that showed direct proportionality with the blood flow rate.

Fabrication of Low-Cost Resistance Temperature Detectors and Micro-Heaters by Electrohydrodynamic Printing.

EHD printing is an advanced deposition technology that is commonly utilized for the direct manufacture of electrical devices. In this study, meander-type resistive electrodes consisting of silver nanoparticles were printed directly on rigid glass and flexible polyethylene terephthalate (PET) substrates. High-resolution patterns of ≈50 µm linewidth were successfully printed on untreated surfaces utilizing a bigger nozzle of 100 µm inner diameter after improving the experimental settings. The manufactured electrodes were evaluated and used as Resistance Temperature Detectors (RTDs) and micro-heaters in a systematic manner. The temperature sensors performed well, with a Temperature Coefficient of Resistivity (TCRs) of 11.5 ×10-3/°C and 13.3 ×10-3/°C, for glass and PET substrates, respectively, throughout a wide temperature range of 100 °C and 90 °C. Furthermore, the RTDs had a quick response and recovery time, as well as minimal hysteresis. The electrodes' measured sensitivities as micro-heaters were 3.3 °C/V for glass and 6.8 °C/V for PET substrates, respectively. The RTDs were utilized for signal conditioning in a Wheatstone bridge circuit with a self-heating temperature of less than 1 °C as a practical demonstration. The micro-heaters have a lot of potential in the field of soft wearable electronics for biomedical applications, while the extremely sensitive RTDs have a lot of potential in industrial situations for temperature monitoring.

A Biophysical and Computational Study of Concanavalin A Immobilized Zinc Oxide Nanoparticles.

BACKGROUND: Con A, a lectin extract from jackbean Canavalia ensiformis is known for its agglutination activity. ZnO nanoparticles promote the faster electron transfer between the lectin immobilized and the target cells. Hence, Con A immobilized on ZnO nanoparticles will agglutinate cells more effectively than the native protein. OBJECTIVES: Concanavalin A (Con A), a lectin was immobilized on the hexagonal zinc oxide (ZnO) nanoparticles to monitor its activity on RBCs and lymphocytes. METHODS: The immobilization of Con A and zinc oxide nanoparticles has been studied by molecular docking, microscopic and genotoxicity assessment techniques. RESULTS: Qualitative assessment using various techniques like atomic force microscopy, scanning electron microscopy and X-ray diffraction showed minor changes in morphology of Con A and ZnO nanoparticles. FT-IR spectroscopy confirmed the linking of Con A amino groups with ZnO nanoparticles. Con A immobilized nanoparticles in contrast to native lectin showed minor changes in hemagglutination activity as confirmed by pH dependence studies using fluorimetry. Con Aimmobilized nanoparticles retained the agglutination activity, this can be indicative of their potential application in detection of virus transformed and neoplastic cells. The Con A immobilized ZnO nanoparticles did not induce any significant but minor damage to whole cell DNA as revealed from comet assay or plasmid DNA. CONCLUSION: Con A immobilized on ZnO nanoparticles showed minor changes in the structure of ZnO nanoparticles and in the conformational of native Con A. However, Con A immobilized ZnO nanoparticles interestingly, showed pH resistance and better hemagglutination activity as well as minor DNA damage to whole cell lymphocytes. Thus, this novel bioaffinity support has prospective clinical implications.

Galectins-A Potential Target for Cardiovascular Therapy.

Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell-cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of ß-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.

Analysis of Passive Mixing in a Serpentine Microchannel with Sinusoidal Side Walls.

Sample mixing is difficult in microfluidic devices because of laminar flow. Micromixers are designed to ensure the optimal use of miniaturized devices. The present study aims to design a chaotic-advection-based passive micromixer with enhanced mixing efficiency. A serpentine-shaped microchannel with sinusoidal side walls was designed, and three cases, with amplitude to wavelength (A/λ) ratios of 0.1, 0.15, and 0.2 were investigated. Numerical simulations were conducted using the Navier⁻Stokes equations, to determine the flow field. The flow was then coupled with the convection⁻diffusion equation to obtain the species concentration distribution. The mixing performance of sinusoidal walled channels was compared with that of a simple serpentine channel for Reynolds numbers ranging from 0.1 to 50. Secondary flows were observed at high Reynolds numbers that mixed the fluid streams. These flows were dominant in the proposed sinusoidal walled channels, thereby showing better mixing performance than the simple serpentine channel at similar or less mixing cost. Higher mixing efficiency was obtained by increasing the A/λ ratio.