-
Cureus Jun 2024Background Point-of-care ultrasound (POCUS) has been disruptive to many experienced emergency physicians as it requires competence in a new physical skill, real-time...
Background Point-of-care ultrasound (POCUS) has been disruptive to many experienced emergency physicians as it requires competence in a new physical skill, real-time image interpretation, and navigation of novel software for submission to the electronic health record (EHR). Incomplete documentation of a performed POCUS study used for clinical decision-making represents a potential medicolegal liability, may expose the patient to repetitive or potentially unnecessary imaging, and is a missed opportunity for reimbursement. Identifying effective facilitators of ED POCUS documentation completion requires additional investigation. Methods In the first part of this mixed-methods study, eligible attending physicians were stratified into levels of use ("high"/"low"/"never") based on recent POCUS documentation performance. Semi-structured interviews were conducted with high and low utilizers to explore their perceptions of the POCUS submission workflow and their receptivity to various proposed interventions. Qualitative data were analyzed using a thematic analysis that explored perceived usefulness and usability. The second part of the study consisted of two intervention phases. First, physicians achieving minimum POCUS documentation numbers were rewarded with additional shift scheduling flexibility. In the second phase, the intervention that garnered the most interview support, daily documentation reminder emails, was implemented. The primary outcome was the individual POCUS documentation rates calculated as all studies submitted divided by all studies performed (submitted plus unsubmitted) per month. Provider-level monthly data was aggregated into a departmental rate. Results Interviews were conducted with 12 physicians, six from the highest and six from the lowest documentation quartiles. Both groups supported the same two proposed interventions: reminder emails ranked first, then monetary rewards ranked second. High utilizers emphasized the clinical utility of POCUS, whereas low utilizers expressed concerns over "double billing" and exposure to medicolegal liability with uncertain scan interpretations. For low utilizers, a documentation decision could be dependent on the performing resident physician's displayed confidence. Both groups voiced frustration with the need to use a separate program, Qpath (Telexy Healthcare, Inc, Maple Ridge, British Columbia, Canada), for POCUS documentation. During intervention phase one, the aggregate departmental documentation rate increased from 44.6% to 60.1% with the introduction of the schedule request incentive. This improvement was seen across all documentation quartiles. The departmental rate remained stable and did not improve further following the addition of the daily documentation reminder emails in intervention phase two. When reminder emails ceased yet the day-off request incentive continued, the departmental rate did not drop. Conclusions The implementation of a non-financial shift scheduling incentive correlated with the largest increase in departmental POCUS documentation rate. Interviewees incorrectly predicted that email reminders would be the most influential intervention highlighting a mismatch between physician perception and effective drivers of behavior change. Further investigation may focus on determining the size and longevity of the isolated impact of a schedule request incentive, as one might expect diminishing marginal utility.
PubMed: 38966489
DOI: 10.7759/cureus.61675 -
Cureus Jun 2024Introduction The evolution of computer-aided design/computer-aided manufacturing (CAD/CAM) systems has heightened the significance of digital models in dentistry,...
Introduction The evolution of computer-aided design/computer-aided manufacturing (CAD/CAM) systems has heightened the significance of digital models in dentistry, particularly for fabricating prostheses like inlays, crowns, and bridges. While digital dentistry offers enhanced speed and precision, the initial investment in intraoral scanners may pose a barrier for some clinicians. Extraoral or lab scanners, however, offer a viable alternative, reducing laboratory time and providing accurate prostheses fit, though challenges such as reflective surfaces and availability of scanning sprays persist, impacting scanning quality and operator technique. Optical scanning using laboratory scanners is a routine practice in today's age of digital dentistry. Often these require powder opacification to record fine details. There are numbered studies on the accuracy of scanning sprays. Materials and methods Ten casts, poured with type 4 dental stone (Elite Rock, Zhermack, Italy) with single implants, were used for the purpose of this study. Each cast was scanned by two different operators, using both mediums. It was scanned using an extraoral scanner (E4, 3Shape, Copenhagen, Denmark). Operator A used easy scan (Alphadent, Korea), followed by zirconia dust (Upcera, Guangdong, China), whereas operator B used zirconia dust first. Digital models within each group were superimposed individually to measure precision. Results Easy scan operator 1 and zirconia dust operator 1 differ by 0.16000 (p = 0.0802). In scenario 2, easy scan operator 2 and zirconia dust operator 2 differ by 0.21900 (p = 0.0212) . Operator type significantly affects performance, emphasizing the need to account for operator variability in relevant contexts. The trueness values obtained for zirconia dust and easy scan among both operators were statistically insignificant. Conclusion Zirconia dust can be reliably used for extraoral scanning of abutments in place of optical scanning sprays.
PubMed: 38966468
DOI: 10.7759/cureus.61633 -
Frontiers in Cell and Developmental... 2024Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires...
PURPOSE
Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation.
METHODS
Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9-39 weeks. Charge balanced, biphasic, current pulses (100 μA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3-34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed.
RESULTS
All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation.
CONCLUSION
Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.
PubMed: 38966426
DOI: 10.3389/fcell.2024.1422764 -
Frontiers in Nutrition 2024Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential...
BACKGROUND
Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear.
PURPOSE
The purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification.
METHODS
Search for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets.
RESULTS
In RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking.
CONCLUSION
This study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.
PubMed: 38966421
DOI: 10.3389/fnut.2024.1404123 -
Frontiers in Nutrition 2024Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle... (Review)
Review
BACKGROUND AND AIMS
Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance.
METHODS
We performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course.
RESULTS
Growing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized.
CONCLUSION
Omega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.
PubMed: 38966419
DOI: 10.3389/fnut.2024.1414132 -
Wellcome Open Research 2023Globally, more than half of women take medicines whilst breastfeeding. Data concerning the exposure of the breastfed infant to drugs and any related risks are sparce....
BACKGROUND
Globally, more than half of women take medicines whilst breastfeeding. Data concerning the exposure of the breastfed infant to drugs and any related risks are sparce. Lactation studies are only rarely performed close to licensing for medicines anticipated to be widely used in women of childbearing age. Medicines taken by breastfeeding mothers on tuberculosis (TB) treatment can be transferred to the breastfed infant. Potential effects of anti-tuberculosis medicines on nursing infants are not well understood. Similarly, women face mental health challenges while taking medications, including postpartum depression, hence the need to assess the psychological behavior of a breastfeeding woman. Potential risks are the development of adverse drug effects in the breastfed infant and selection for resistance, whereas potential benefits might include exposure to potentially prophylactic concentrations of the drug. Pharmacokinetic studies are therefore necessary to understand this situation fully.
METHODS
This study will enroll 20 mothers receiving first-line anti-tuberculosis medicines, together with their breastfed infants, with the aim of characterizing the breastmilk transfer of the medicines from the mother to the infants. Samples of maternal blood, breastmilk, and breastfeeding infant's blood will be obtained at specific time points for bioanalysis of drug concentrations. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach. Additionally, the study will assess the psychological status of breastfeeding women and the well-being of their infants. Maternal depression is linked to long-term negative consequences for the infant's physiological regulation, poor growth-promoting setting for the infants, and inappropriate interactive conduct, characterized by low compassion, constrained range of emotional expression, and varying provision of the infant's budding engagement.
CONCLUSIONS
This study will provide the first systematic characterization of mother-to-infant transfer of first-line anti-tuberculosis medicines through breast milk. A mathematical pharmacokinetics model characterizing plasma-to-breastmilk transfer of rifampicin, isoniazid, ethambutol, and pyrazinamide will be developed and used to characterize infant exposure through breast milk. Our findings will contribute towards treatment optimization in breastfeeding and provide a framework to foster other lactation pharmacokinetic studies.
PubMed: 38966399
DOI: 10.12688/wellcomeopenres.19113.3 -
Chemical Science Jul 2024Reaction optimization and characterization depend on reliable measures of reaction yield, often measured by high-performance liquid chromatography (HPLC). Peak areas in...
Reaction optimization and characterization depend on reliable measures of reaction yield, often measured by high-performance liquid chromatography (HPLC). Peak areas in HPLC chromatograms are correlated to analyte concentrations by way of calibration standards, typically pure samples of known concentration. Preparing the pure material required for calibration runs can be tedious for low-yielding reactions and technically challenging at small reaction scales. Herein, we present a method to quantify the yield of reactions by HPLC without needing to isolate the product(s) by combining a machine learning model for molar extinction coefficient estimation, and both UV-vis absorption and mass spectra. We demonstrate the method for a variety of reactions important in medicinal and process chemistry, including amide couplings, palladium catalyzed cross-couplings, nucleophilic aromatic substitutions, aminations, and heterocycle syntheses. The reactions were all performed using an automated synthesis and isolation platform. Calibration-free methods such as the presented approach are necessary for such automated platforms to be able to discover, characterize, and optimize reactions automatically.
PubMed: 38966367
DOI: 10.1039/d4sc01881h -
Journal of Scientific Computing 2024We introduce an -version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while...
We introduce an -version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and -version a priori error analysis of the proposed method, by deriving suitable -approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented.
PubMed: 38966341
DOI: 10.1007/s10915-024-02569-3 -
JAC-antimicrobial Resistance Aug 2024Antimicrobial resistance is a growing concern and claims over 1 million lives per year. The discovery of new antimicrobial drugs is expensive and often generates low...
OBJECTIVES
Antimicrobial resistance is a growing concern and claims over 1 million lives per year. The discovery of new antimicrobial drugs is expensive and often generates low profitability, with very low success rates. One way to combat this is by the improvement of known antimicrobials, such as antimicrobial peptides (AMPs). The aim of this study was to improve the antimicrobial activities of two known AMPs, UyCT3 and indolicidin, with the use of peptide libraries and growth curves.
METHODS
Peptide permutation libraries were synthesized for two AMPs, indolicidin and UyCT3, which included 520 peptides. These peptides were subsequently tested against MG1655-K12, to which subsequent peptide design was performed, then tested against three clinically Gram-negative relevant drug-resistant isolates. Best-performing candidates were subjected to a haemolysis assay for toxicity validation.
RESULTS
Single amino acid permutations of UyCT3 and indolicidin were sufficient to inhibit growth of MG1655-K12, and subsequent generations of peptide design were able to inhibit growth of clinical isolates at concentrations as low as 5 µM. Our best-performing AMP, UyCT3, was not seen to be toxic towards sheep RBCs.
CONCLUSIONS
The efficacy of the AMPs improved with the use of our peptide library technology, whereby an AMP was found that inhibited bacterial growth of clinical Gram-negative isolates 4-fold better than its WT counterpart.
PubMed: 38966332
DOI: 10.1093/jacamr/dlae096 -
JAC-antimicrobial Resistance Aug 2024The rise of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) in low- and middle-income countries limits treatment options, leading to the frequent use...
A proof-of-principle study for the point-of-care detection of ESBL (CTX-M) by NG-Test CTX-M MULTI lateral flow assay in urine samples using a simplified method for use in a resource-limited setting.
BACKGROUND
The rise of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) in low- and middle-income countries limits treatment options, leading to the frequent use of broad-spectrum antibiotics. Reducing time-to-result for a urinary infection can facilitate correct antibiotic treatment and support antimicrobial and diagnostic stewardship measures. This study compared two simplified enrichment methods for detecting CTX-M directly from urine specimens.
METHODS
Two enrichment methods, namely centrifugation of 2 mL urine and filtration of 1 mL urine using the DirecTool adaptor, were compared using 20 culture-positive urine samples (20 suspected ESBL-E and 20 non-ESBL-E). CTX-M production was detected using a lateral flow assay (LFA), NG-Test CTX-MMULTI. The presence of genes was confirmed by whole-genome sequencing (WGS).
RESULTS
The results of both enrichment methods were identical, with a sensitivity of 87.5% and a specificity of 100%. In 19/20 (95%) of the urine samples, the results of the CTX-M LFA were identical with the phenotypic confirmation and WGS. Both methods could detect ESBL-E bacteriuria with ≥10 cfu/mL. All ESBL-E-negative samples were identified accurately. Both enrichment methods yielded negative results in one ESBL-E-positive (CTX-M-15) sample despite phenotypic and genotypic confirmation of ESBL production. High leukocyte count (>500 cells/µL), the presence of boric acid or polymicrobial samples did not appear to impact the performance of both enrichment methods.
CONCLUSIONS
Our study underscores the feasibility of directly detecting CTX-M in urine. Simplified enrichment methods, particularly with a filtration kit, enhance the assay's practicality, rendering it suitable for use in primary care, emergency departments or remote laboratories without sophisticated equipment.
PubMed: 38966331
DOI: 10.1093/jacamr/dlae103