Selenium catalysis enables negative feedback organic oscillators.

The construction of materials regulated by chemical reaction networks requires regulatory motifs that can be stacked together into systems with desired properties. Multiple autocatalytic reactions producing thiols are known. However, negative feedback loop motifs are unavailable for thiol chemistry. Here, we develop a negative feedback loop based on the selenocarbonates. In this system, thiols induce the release of aromatic selenols that catalyze the oxidation of thiols by organic peroxides. This negative feedback loop has two important features. First, catalytic oxidation of thiols follows Michaelis-Menten-like kinetics, thus increasing nonlinearity for the negative feedback. Second, the strength of the negative feedback can be tuned by varying substituents in selenocarbonates. When combined with the autocatalytic production of thiols in a flow reactor, this negative feedback loop induces sustained oscillations. The availability of this negative feedback motif enables the future construction of oscillatory, homeostatic, adaptive, and other regulatory circuits in life-inspired systems and materials.

Dental hygiene clinical faculty attitudes and likelihood of working during the COVID-19 pandemic.

OBJECTIVE: To identify circumstances that influenced dental hygiene clinical faculty's likelihood of working during the COVID-19 pandemic, and to explore attitudes (responsibilities, personal issues, ethics, and policy statements) about working. METHODS: This cross-sectional study used a purposive sample of dental hygienists (n = 1710) employed in academic clinical settings that held full-time, part-time, or adjunct appointments. The Health Care Workers' Attitudes to Working During a Pandemic survey was utilized. Likelihood scores were calculated based on respondents more or less likely to work under differing circumstances. Frequencies of agreement for attitudes were developed. Correlations were explored between likelihood scores and demographic data. Answers to the open-ended questions were categorized and described. RESULTS: The response rate was 13.5% (225/1710). Only one-third of respondents had a likelihood score of 100%. Factors with the greatest impact on likelihood to work were personal protective equipment. Almost all respondents' attitudes of working indicated that their employer is responsible for providing PPE. Over 90% felt their main responsibility was to themselves/family. Correlation analyses resulted in no significant associations between likelihood scores and age, etc. Faculty are considering leaving their jobs because of pay cuts and/or not feeling safe. CONCLUSION: Likelihood of working for dental hygiene faculty represents several personal and ethical decisions. Most respondents want employers to be responsible for their on-the-job safety. In addition, personal and work-related issues were causes of unease. The pandemic has had far-reaching implications on day-to-day work of dental hygiene clinical faculty as well as on the long-term trajectories and views on employment in higher education.

Stirring-Free Scalable Electrosynthesis Enabled by Alternating Current.

Alternating current (AC) electrolysis is receiving increased interest as a versatile tool for mild and selective electrochemical transformations. This work demonstrates that AC can enable the concept of a stirring-free electrochemical reactor where the periodic switch of electrode polarity, inherent to AC, provides uniform electrolysis across the whole volume of the reactor. Such design implies a straightforward approach for scaling up electrosynthesis. This was demonstrated on the range of electrochemical transformations performed in three different RVC-packed reactors on up to a 50-mmol scale. Redox-neutral, oxidative, and reductive processes were successfully implemented using the suggested design and the applicable frequency ranges were further investigated for different types of reactions. The advantages of the AC-enabled design - such as the absence of stirring and a maximized surface area of the electrodes - provide the possibility for its universal application both for small-scale screening experimentation and large-scale preparative electrosynthesis without significant optimization needed in between.

Molecular subtypes of ALS are associated with differences in patient prognosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.

Supraspinatus Fatty Infiltration Correlation with Handgrip Strength, Shoulder Strength, and Validated Patient-Reported Outcome Measures in Patients with Rotator Cuff Tears.

Introduction: The purpose of this study was to investigate the relationships between supraspinatus atrophy on magnetic resonance imaging (MRI) and other objective parameters in patients with rotator cuff tears. It was hypothesized that high-grade supraspinatus fatty infiltration would be correlated negatively with handgrip strength, shoulder strength, and patient-reported outcome measures (PROMs). Methods: Patients with MRI-proven rotator cuff tears treated by a single sports medicine fellowship-trained orthopaedist at a single institution underwent comprehensive preoperative evaluation including bilateral handgrip and shoulder strength measurements with dynamometers and multiple online questionnaires from the Surgical Outcomes SystemTM (Arthrex, Naples, FL). Available shoulder MRIs were reviewed to grade supraspinatus fatty infiltration severity according to the 5-tier Goutallier system and an alternate 3-tier classification scheme. Difference analysis and Spearman (rho) rank order correlation were applied to the collected data to define the relationships between supraspinatus fatty infiltration and key variables including handgrip strength, shoulder strength, and scores derived from the shoulder PROMs. Results: Ninety of the 121 patients enrolled in the study had shoulder MRIs available for review. There was no correlation found between supraspinatus fatty infiltration and handgrip strength, shoulder abduction strength, or any of the seven common shoulder PROM scores evaluated. There was statistically significant, albeit weak, correlation between MRI-derived fatty infiltration and shoulder external rotation strength. Conclusions: Contrary to the hypothesis, high-grade supraspinatus fatty infiltration is largely unrelated to and should not be considered predictive of handgrip strength, shoulder strength, or common shoulder PROM scores.

The Reliability and Validity of Gluteal Endurance Measures (GEMs).

BACKGROUND: The gluteals have unique morphology related to muscle endurance, including moderate fiber sizes and a majority of Type I endurance fibers. Evidence suggests gluteal endurance is related to low back pain, running kinematics, balance, posture, and more. However, reliable and valid measures specific to gluteal endurance are lacking in the literature. HYPOTHESIS/PURPOSE: The purpose of this study was to examine the intra- and inter-rater reliability of two gluteal endurance measures (GEMs) for clinical use. It also aimed to examine validity for the two measures by using electromyography (EMG), recording reasons for task failure, and analyzing differences between demographic groups. STUDY DESIGN: Cross-Sectional. METHODS: Sixty-eight males and females with and without recurrent low back pain aged 18-35 years were recruited from a university population. Electromyography electrodes were placed on subjects' gluteus maximus and gluteus medius, and each subject performed three trials of GEM-A (abduction endurance) and GEM-B (bridging endurance). Hold times, EMG median frequency (MF) data, and subjective reasons for task failure were analyzed. RESULTS: Both GEMs demonstrated high intra-rater reliability (ICC = 0.87-0.94) and inter-rater reliability (ICC = 0.99). Mean hold times were 104.83 ± 34.11 seconds for GEM-A (abduction endurance) and 81.03 ± 24.79 seconds for GEM-B (bridging endurance). No statistically significant difference was found between subjects with and without recurrent LBP. Median frequency data validated the onset of gluteal fatigue during both measures. Posterolateral hip (gluteal) fatigue was reported as the primary reason for task failure in 93% and 86% of subjects for GEM-A and GEM-B, respectively. CONCLUSION: This seminal study of GEM-A (abduction endurance) and GEM-B (bridging endurance) found both measures to be reliable and valid measures of gluteal endurance. Further examination of the GEMs in samples with different types of LBP or hip pain is recommended. LEVEL OF EVIDENCE: 3.

Automated microscope-independent fluorescence-guided micropipette.

Glass micropipette electrodes are commonly used to provide high resolution recordings of neurons. Although it is the gold standard for single cell recordings, it is highly dependent on the skill of the electrophysiologist. Here, we demonstrate a method of guiding micropipette electrodes to neurons by collecting fluorescence at the aperture, using an intra-electrode tapered optical fiber. The use of a tapered fiber for excitation and collection of fluorescence at the micropipette tip couples the feedback mechanism directly to the distance between the target and electrode. In this study, intra-electrode tapered optical fibers provide a targeted robotic approach to labeled neurons that is independent of microscopy.

A Metabolomic Approach for Predicting Diurnal Changes in Cortisol.

Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods: We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results: The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion: This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time.

Survey instrument development and validation to measure technology adoption in dental hygiene clinical environments.

PURPOSE: This pilot study aimed to develop and test a comprehensive assessment instrument, through an examination of measurement properties, to evaluate relationships between faculty technology adoption and age, level of education, teaching experience, technology anxiety, perceived technology integration barriers, and technology available in dental hygiene (DH) clinical environments. Focus was to acquire instrument validity with emphasis on test content, internal structure, and response processes. METHODS: The survey was developed based on expert review, pretesting, and survey piloting in 2018. Three content experts evaluated face and traditional content validity. Eleven DH faculty with diverse clinical experiences were recruited for pretesting to comment on item definitions and language. The instrument was pilot tested among DH faculty with full-time, part-time, and clinical appointments at institutions located in the Mid-West. Psychometric properties of the questionnaire were evaluated with frequency analysis and scale responses detailed. RESULTS: Evaluation by experts and faculty members refined definitions, language, and response options for the seventy-item response scale. Forty-three DH faculty completed the online pilot. The 4 sections subjected to factor analysis showed excellent factor loading. Internal consistency was satisfactory. Frequency analysis showed an array of perceived abilities and technological integration in the educational environment. CONCLUSION: Findings suggest that respondents found the survey easy to complete and understand. The survey appears to be a valid measure of technology adoption among DH faculty of differing experiences. The survey will now be disseminated to a larger group of DH faculty.

Side-viewing photoacoustic waveguide endoscopy.

Side-viewing hollow optical waveguides allow for minimally invasive endoscopy by concentrically guiding light and sound for photoacoustic generation and detection. Here, we characterize the side-viewing photoacoustic waveguide (PWG) endoscope by scanning 7.2 µm diameter carbon fiber threads within phantom tissues and animal tissues. Photoacoustic signals are carried along the 5.5 and 10.0 cm length of the PWG with minimal attenuation. Thus, this technology enables 360°, deep-tissue photoacoustic imaging. Photoacoustic signals were identified up to 8.0 mm from the PWG imaging window in an optically clear medium. The outer diameter of this device is measured as just over 1.0 mm, with the potential to be further miniaturized due to its unique design. The PWG is an ideal candidate for a myriad of pre-clinical and clinical applications where typical photoacoustic endoscopy systems are impractical, due to their size. Presented here, is the first side-viewing photoacoustic waveguide endoscope.

Young Adults Performance of Unipedal Dynamic Balance with Various Footwear Conditions.

Wearing barefoot-style (minimalist) shoes is suggested as a transition between wearing shoes and barefoot running. Some sources equate wearing Vibram FiveFingers™(VFFs), a brand of barefoot shoes, with running/walking barefoot. Static and dynamic balance exercises are recommended. Little information is available on the effects barefoot shoes may have on dynamic balance. This study's purpose was to examine dynamic balance when participants wore VFFs, athletic shoes, or went barefoot (BF). To test dynamic balance, participants used a modified version of the Star Excursion Balance Test (SEBT), in which the reaching leg followed only three spokes of the test: the anterior, posteromedial and posterolateral. For the timed test, participants touched down as quickly as possible in both directions using all 8 spokes. Thirty participants (ages 24.1+/-3.71 years) without lower extremity injury or experience wearing minimalist shoes were tested using the modified SEBT and a timed test wearing VFFs™, athletic shoes, or BF. Three trials for each footwear were completed for three reaching positions: anterior, posterolateral, posteromedial. The timed test measured (seconds) one counterclockwise and one clockwise direction of the 8-spoke figure. A repeated measures analysis of variance determined if any differences existed between footwear type and studied variables. Anterior reach was significantly greater when wearing shoes than with VFF or BF. Posteromedial reach was greater with shoes than BF. Time trials were not significantly different. Because no difference was found in any measured variables between VFF and BF, the results suggest wearing VFFS™ provided similar dynamic balance as going barefoot.

Ovarian Cancer Detection Using Photoacoustic Flow Cytometry.

Many studies suggest that the enumeration of circulating tumor cells (CTCs) may show promise as a prognostic tool for ovarian cancer. Current strategies for the detection of CTCs include flow cytometry, microfluidic devices, and real-time polymerase chain reaction (RT-PCR). Despite recent advances, methods for the detection of early ovarian cancer metastasis still lack the sensitivity and specificity required for clinical translation. Here, a novel method is presented for the detection of ovarian circulating tumor cells by photoacoustic flow cytometry (PAFC) utilizing a custom three dimensional (3D) printed system, including a flow chamber and syringe pump. This method utilizes folic acid-capped copper sulfide nanoparticles (FA-CuS NPs) to target SKOV-3 ovarian cancer cells by PAFC. This work demonstrates the affinity of these contrast agents for ovarian cancer cells. The results show NP characterization, PAFC detection, and NP uptake by fluorescence microscopy, thus demonstrating the potential of this novel system to detect ovarian CTCs at physiologically relevant concentrations.

Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS.

Urinary metabolomics offers a non-invasive means of obtaining information about the system-wide biological health of a patient. Untargeted metabolomics approaches using one-dimensional gas chromatography (GC) are limited due to the chemical complexity of urine, which poorly detects co-eluting low-abundance analytes. Metabolite detection and identification can be improved by applying comprehensive two-dimensional GC, allowing for the discovery of additional viable biomarkers of disease. In this work, we applied comprehensive two-dimensional GC coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) to the analysis of urine samples collected daily across 28-days from 10 healthy female subjects for a personalized approach to female reproductive health monitoring. Through this analysis, we identified 935 unique volatile metabolites. Two statistical methods, a modified T-statistic and Wilcoxon Rank Sum, were applied to analyze differences in metabolome abundance on ovulation days as compared to non-ovulation days. Four metabolites (2-pentanone, 3-penten-2-one, carbon disulfide, acetone) were identified as statistically significant by the modified T-statistic but not the Rank Sum, after a false-discovery rate of 0.1 was set using a Benjamini-Hochberg correction. Subsequent analyses by boxplot indicated that the putative volatile metabolic biomarkers for fertility are expressed in increased or decreased abundance in urine on the day of ovulation. Individual analysis of metabolome expression across 28-days revealed some subject-specific features, which suggest a potential for long-term, personalized fertility monitoring using metabolomics.

Photoacoustic Flow System for the Detection of Ovarian Circulating Tumor Cells Utilizing Copper Sulfide Nanoparticles.

The development of cell-specific photoacoustic (PA) contrast agents within systems of fluidic flow provides opportunities for the accurate detection of early stage cancer metastasis. Despite the promise of exogenous contrast agents for use in clinical settings, applications are currently limited by both material biocompatibility and target specificity. In this study, folic acid functionalized copper sulfide nanoparticles (FA-CuS NPs) are synthesized to enable ovarian-cancer-specific binding and PA detection in a custom flow system. Folate receptors, known to be overexpressed on the surface of ovarian cancer cells, have remained an ideal candidate for specific targeting through functionalization on nanoparticles and other contrast agents. In combination with copper sulfide nanoparticles' strong absorbance in the near-infrared (NIR), these FA-CuS NPs are an ideal contrast agent capable of being detected by photoacoustic flow cytometry. For the first time, this study shows a potential PA contrast agent to accurately identify ovarian circulating tumor cells in flow.

Effects of Pelvic and Core Strength Training on High School Cross-Country Race Times.

Clark, AW, Goedeke, MK, Cunningham, SR, Rockwell, DE, Lehecka, BJ, Manske, RC, and Smith, BS. Effects of pelvic and core strength training on high school cross-country race times. J Strength Cond Res 31(8): 2289-2295, 2017-There is only limited research examining the effect of pelvic and core strength training on running performance. Pelvic and core muscle fatigue is believed to contribute to excess motion along frontal and transverse planes which decreases efficiency in normal sagittal plane running motions. The purpose of this study was to determine whether adding a 6-week pelvic and core strengthening program resulted in decreased race times in high school cross-country runners. Thirty-five high school cross-country runners (14-19 years old) from 2 high schools were randomly assigned to a strengthening group (experimental) or a nonstrengthening group (control). All participants completed 4 standardized isometric strength tests for hip abductors, adductors, extensors, and core musculature in a test-retest design. The experimental group performed a 6-week pelvic and core strengthening program along with their normal training. Participants in the control group performed their normal training without additional pelvic and core strengthening. Baseline, 3-week, and 6-week race times were collected using a repeated measures design. No significant interaction between experimental and control groups regarding decreasing race times and increasing pelvic and core musculature strength occurred over the 6-week study period. Both groups increased strength and decreased overall race times. Clinically significant findings reveal a 6-week pelvic and core stability strengthening program 3 times a week in addition to coach led team training may help decrease race times.

A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate.

This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer-a device that is more available than the combination BHB/glucometer. Strategies that use a "3D pop-up"-that is, large-scale changes in 3D structure and fluidic paths-by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.

From the bench to the field in low-cost diagnostics: two case studies.

Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field--the processes intended to evaluate operation and performance under realistic conditions--are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments.

Effects of wearing athletic shoes, five-toed shoes, and standing barefoot on balance performance in young adults.

BACKGROUND/PURPOSE: Almost all research using participants wearing barefoot-style shoes study elite runners or have participants with a history of barefoot style shoe training run on a treadmill when shod or barefoot. Wearing barefoot-style shoes is suggested as a method of transition between shod and barefoot running. Static and dynamic balance exercises also are recommended. However, little information is available on the effects five-toed barefoot style shoes have on static balance. The purpose of this study was to examine balance of subjects barefoot, wearing Vibram FiveFingers™ barefoot-style shoes, and regular athletic shoes with eyes closed when using the Biodex Balance System-SD™. STUDY DESIGN: This was a repeated measures study. METHODS: Forty nine participants aged 18-30 years without lower extremity injury or experience wearing barefoot-style shoes were tested for static balance on the Biodex Stability System™ with their eyes closed while wearing Vibram FiveFingers™, athletic shoes, or barefoot. Three trials of 10 seconds for each footwear type were completed. Repeated measures analysis of variance with Bonferroni's correction was used to analyze the degrees of sway in the anterior-posterior and medial lateral directions. An overall stability index was also calculated by the Biodex. RESULTS: For anterior-posterior and overall indices, differences were found between all conditions. Participants wearing athletic shoes demonstrated the smallest anterior-posterior stability index (least sway) and spent the most time in the innermost concentric circular zone. Medial-lateral indices were not different for any condition. CONCLUSIONS: Wearing Vibram FiveFingers™ provided better overall and anterior-posterior static balance than going barefoot. While differences between Vibram FiveFingers™ and barefoot are significant, results may reflect statistical significance rather than any clinical difference in young, uninjured individuals. CLINICAL RELEVANCE: It would appear that Vibram FiveFingers™ mimic going barefoot and may be a bridge for exercising in preparation for barefoot exercise. LEVEL OF EVIDENCE: 3B.

Polymerization-based signal amplification for paper-based immunoassays.

Diagnostic tests in resource-limited settings require technologies that are affordable and easy to use with minimal infrastructure. Colorimetric detection methods that produce results that are readable by eye, without reliance on specialized and expensive equipment, have great utility in these settings. We report a colorimetric method that integrates a paper-based immunoassay with a rapid, visible-light-induced polymerization to provide high visual contrast between a positive and a negative result. Using Plasmodium falciparum histidine-rich protein 2 as an example, we demonstrate that this method allows visual detection of proteins in complex matrices such as human serum and provides quantitative information regarding analyte levels when combined with cellphone-based imaging. It also allows the user to decouple the capture of analyte from signal amplification and visualization steps.

Folding analytical devices for electrochemical ELISA in hydrophobic R(H) paper.

This work describes a device for electrochemical enzyme-linked immunosorbent assay (ELISA) designed for low-resource settings and diagnostics at the point of care. The device is fabricated entirely in hydrophobic paper, produced by silanization of paper with decyl trichlorosilane, and comprises two zones separated by a central crease: an embossed microwell, on the surface of which the antigen or antibody immobilization and recognition events occur, and a detection zone where the electrodes are printed. The two zones are brought in contact by folding the device along this central crease; the analytical signal is recorded from the folded configuration. Two proof-of-concept applications, an electrochemical direct ELISA for the detection of rabbit IgG as a model antigen in buffer and an electrochemical sandwich ELISA for the detection of malarial histidine-rich protein from Plasmodium falciparum (Pf HRP2) in spiked human serum, show the versatility of this device. The limit of detection of the electrochemical sandwich ELISA for the quantification of Pf HRP2 in spiked human serum was 4 ng mL(-1) (10(2) pmol L(-1)), a value within the range of clinically relevant concentrations.