Electrostatic microfiltration (EM) enriches and recovers viable microorganisms at low-abundance in large-volume samples and enhances downstream detection.

Rapid and sensitive detection of pathogens in various samples is crucial for disease diagnosis, environmental surveillance, as well as food and water safety monitoring. However, the low abundance of pathogens (<10 CFU) in large volume (1 mL-1 L) samples containing vast backgrounds critically limits the sensitivity of even the most advanced techniques, such as digital PCR. Therefore, there is a critical need for sample preparation that can enrich low-abundance pathogens from complex and large-volume samples. This study develops an efficient electrostatic microfiltration (EM)-based sample preparation technique capable of processing ultra-large-volume (≥500 mL) samples at high throughput (≥10 mL min-1). This approach achieves a significant enrichment (>8000×) of extremely-low-abundance pathogens (down to level of 0.02 CFU mL-1, i.e., 10 CFU in 500 mL). Furthermore, EM-enabled sample preparation facilitates digital amplification techniques sensitively detecting broad pathogens, including bacteria, fungi, and viruses from various samples, in a rapid (≤3 h) sample-to-result workflow. Notably, the operational ease, portability, and compatibility/integrability with various downstream detection platforms highlight its great potential for widespread applications across diverse settings.

A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells.

The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale out of cell-therapy manufacturing.

Interactions between a dsDNA Oligonucleotide and Imidazolium Chloride Ionic Liquids: Effect of Alkyl Chain Length, Part I.

Ionic liquids (ILs) have become nearly ubiquitous solvents and their interactions with biomolecules has been a focus of study. Here, we used the fluorescence emission of DAPI, a groove binding fluorophore, coupled with molecular dynamics (MD) simulations to report on interactions between imidazolium chloride ([Imn,1]+) ionic liquids and a synthetic DNA oligonucleotide composed entirely of T/A bases (7(TA)) to elucidate the effects ILs on a model DNA duplex. Spectral shifts on the order of 500-1000 cm-1, spectral broadening (~1000 cm-1), and excitation and emission intensity ratio changes combine to give evidence of an increased DAPI environment heterogeneity on added IL. Fluorescence lifetimes for DAPI/IL solutions yielded two time constants 0.15 ns (~80% to 60% contribution) and 2.36-2.71 ns for IL up to 250 mM. With DNA, three time constants were required that varied with added IL (0.33-0.15 ns (1-58% contribution), ~1.7-1.0 ns (~5% contribution), and 3.8-3.6 ns (94-39% contribution)). MD radial distribution functions revealed that π-π stacking interactions between the imidazolium ring were dominant at lower IL concentration and that electrostatic and hydrophobic interactions become more prominent as IL concentration increased. Alkyl chain alignment with DNA and IL-IL interactions also varied with IL. Collectively, our data showed that, at low IL concentration, IL was primarily bound to the DNA minor groove and with increased IL concentration the phosphate regions and major groove binding sites were also important contributors to the complete set of IL-DNA duplex interactions.

Discontinuation of Chronic Opiate Therapy After Successful Spinal Cord Stimulation Is Highly Dependent Upon the Daily Opioid Dose.

OBJECTIVES: The aim of this study was to determine if any of the factors recorded on a standard clinical history of a patient considered for spinal cord stimulation (SCS) would be associated with reduction or cessation of opioids following implantation. DESIGN: Retrospective, single academic center. METHODS: Patients included in the chart analysis underwent implantation of percutaneous SCS devices from 1999 to 2015 with follow-up until the end of September 2018. Patients who achieved at least an average of 50% pain reduction were included for analysis of daily opioid intake. Patients were then divided into 4 groups that included no opioid use, stable opioid daily dose, weaned opioid dose, and complete cessation of opioids. Statistical methods were used to analyze for associations between opioid intake after SCS insertion and usual elements of a clinical history, including adjuvant medications, numeric pain rating, past medical history, psychiatric illness, substance abuse, employment, and smoking history. RESULTS: In a group of 261 patients who had undergone implantation, 214 met the criteria for analysis and had a median age of 50 years, with majority having the diagnoses of failed back surgery syndrome and complex regional pain syndrome. The only factor that was associated with complete cessation of opioid use was a median dose of 30 mg of morphine per day (P < 0.01) and was observed in 15% of subjects who used opioids preoperatively. CONCLUSION: The elimination of opioid dependence following initiation of SCS therapy is highly dependent on the daily dose.

Building psychosocial programming in geriatrics fellowships: a consortium model.

Geriatric psychosocial problems are prevalent and significantly affect the physical health and overall well-being of older adults. Geriatrics fellows require psychosocial education, and yet to date, geriatrics fellowship programs have not developed a comprehensive geriatric psychosocial curriculum. Fellowship programs in the New York tristate area collaboratively created the New York Metropolitan Area Consortium to Strengthen Psychosocial Programming in Geriatrics Fellowships in 2007 to address this shortfall. The goal of the Consortium is to develop model educational programs for geriatrics fellows that highlight psychosocial issues affecting elder care, share interinstitutional resources, and energize fellowship program directors and faculty. In 2008, 2009, and 2010, Consortium faculty collaboratively designed and implemented a psychosocial educational conference for geriatrics fellows. Cumulative participation at the conferences included 146 geriatrics fellows from 20 academic institutions taught by interdisciplinary Consortium faculty. Formal evaluations from the participants indicated that the conference: a) positively affected fellows' knowledge of, interest in, and comfort with psychosocial issues; b) would have a positive impact on the quality of care provided to older patients; and c) encouraged valuable interactions with fellows and faculty from other institutions. The Consortium, as an educational model for psychosocial learning, has a positive impact on geriatrics fellowship training and may be replicable in other localities.

Biofeedback and dance performance: a preliminary investigation.

Alpha-theta neurofeedback has been shown to produce professionally significant performance improvements in music students. The present study aimed to extend this work to a different performing art and compare alpha-theta neurofeedback with another form of biofeedback: heart rate variability (HRV) biofeedback. Twenty-four ballroom and Latin dancers were randomly allocated to three groups, one receiving neurofeedback, one HRV biofeedback and one no intervention. Dance was assessed before and after training. Performance improvements were found in the biofeedback groups but not in the control group. Neurofeedback and HRV biofeedback benefited performance in different ways. A replication with larger sample sizes is required.

The effects of alpha/theta neurofeedback on personality and mood.

Alpha/theta neurofeedback has been shown to be successful both in treating addictions and in enhancing artistry in music students. How its effects are mediated are not yet clear. The present study aimed to test the hypothesis that alpha/theta neurofeedback works inter alia by normalising extreme personality and raising feelings of well being. 12 participants with high scores for Withdrawal (as measured by the PSQ) were given either alpha/theta neurofeedback or mock feedback and their personality and mood were assessed. Withdrawal scores on the PSQ-80 were not found to change in either group but significant effects were found for the Profile Of Mood States (POMS), with real feedback producing higher overall scores than mock feedback (P = 0.056). Real feedback caused participants to feel significantly more energetic (P < 0.01) than did mock feedback. Sessions of real feedback made participants feel more composed (P < 0.01), agreeable (P < 0.01), elevated (P < 0.01) and confident (P < 0.05), whilst sessions of mock feedback made participants feel more tired (P < 0.05), yet composed (P < 0.01). These findings suggest that, whilst 9 sessions of alpha/theta neurofeedback was insufficient to change personality, improvements in mood may provide a partial explanation for the efficacy of alpha/theta neurofeedback.