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Serotonin is an important neurotransmitter that plays a major role in many aspects of neuroscience. Fast-scan cyclic voltammetry measures fast in vivo serotonin dynamics using carbon fiber microelectrodes. More recently, fast-scan controlled-adsorption voltammetry (FSCAV) has been developed to measure slower, minute-to-minute changes in ambient extracellular serotonin. We have previously demonstrated that FSCAV measurements of basal serotonin levels give critical information regarding brain physiology and disease. In this work, we revealed the presence of low-periodicity fluctuations in serotonin levels in mouse hippocampi, measured in vivo with FSCAV. Using correlation analyses, we found robust evidence of oscillations in the basal serotonin levels, which had a period of 10 min and were not present in vitro. Under control conditions, the oscillations did not differ between male and female mice, nor do they differ between mice that underwent a chronic stress paradigm and those in the control group. After the acute administration of a selective serotonin reuptake inhibitor, we observed a shift in the frequency of the oscillations, leading us to hypothesize that the newly observed fluctuations were transporter regulated. Finally, we optimized the experimental parameters of the FSCAV to measure at a higher temporal resolution and found more pronounced shifts in the oscillation frequency, along with a decreased oscillation amplitude. We postulate that this work may serve as a potential bridge for studying serotonin/endocrine interactions that occur on the same time scale.

The sensitivity of zinc (Zn(II)) detection using fast-scan cyclic voltammetry (FSCV) with carbon fiber microelectrodes (CFMEs) is low compared to other neurochemicals. We have shown previously that Zn(II) plates to the surface of CFME's and we speculate that it is because of the abundance of oxide functionality on the surface. Plating reduces sensitivity over time and causes significant disruption to detection stability. This limited sensitivity and stability hinders Zn(II) detection, especially in complex matrices like the brain. To address this, we developed plasma-treated gold fiber microelectrodes (AuMEs) which enable sensitive and stable Zn(II) detection with FSCV. Typically, gold fibers are treated using corrosive acids to clean the surface and this step is important for preparing the surface for electrochemistry. Likewise, because FSCV is an adsorption-based technique, it is also important for Zn(II) to adsorb and desorb to prevent irreversible plating. Because of these requirements, careful optimization of the electrode surface was necessary to render the surface for Zn(II) adsorption yet strike a balance between attraction to the surface vs. irreversible interactions. In this study, we employed oxygen plasma treatment to activate the gold fiber surface without inducing significant morphological changes. This treatment effectively removes the organic layer while functionalizing the surface with oxygen, enabling Zn(II) detection that is not possible on untreated gold surfaces. Our results demonstrate significantly improved Zn(II) detection sensitivity and stability on AuME compared to CFME's. Overall, this work provides an advance in our understanding of Zn(II) electrochemistry and a new tool for improved metallotransmitter detection in the brain. [ABSTRACT FROM AUTHOR]

The realm of analytical chemistry continues to struggle with defining and evaluating the limit of detection in analytical methods in the sense that a multitude of definitions, criteria, caveats, and methods have been proposed, developed, and adopted across disciplines. The last decade has seen a surge in the growth of electrochemical methods and studies in the field of forensic science and forensic chemistry. While many disciplines within forensic science have established method validation guidelines, the historical and current lack of electrochemical methods within forensic laboratories throughout the United States has left a major gap in knowledge, inhibiting the adoption and utilization of electrochemistry, which may serve as a powerful tool in many subdisciplines of forensics. As such, this work begins this discussion by focusing first on the limit of detection (LOD), with application toward both qualitative and quantitative methods. Both inorganic (ferrocyanide and lead) and organic (diphenylamine, naltrexone, and acetaminophen) target analytes were analyzed via two common voltammetry methods: cyclic voltammetry and square-wave voltammetry. The LOD for each analyte was estimated and/or calculated following a variety of literature-described methods and compared. The accuracy and reliability of these LOD characteristics based on the experimental data is described herein along with suggestions and recommendations. This manuscript is intended to compare the resulting LOD values from various methods and provide a starting point for the incorporation of electrochemistry into the forensic science laboratory, beginning a focused discussion on the development of validation guidelines and parameters needed for the adoption of this technology in forensic laboratories in order to meet the standards required by the criminal justice system. [ABSTRACT FROM AUTHOR]

The oxygen gradient across the intestine influences intestinal physiology and the microbial environment of the microbiome. The microbiome releases metabolites that communicate with enterochromaffin cells, neuronal cells, and resident immune cells to facilitate the bidirectional communication across the gut–brain axis. Measuring communication between various cell types within the intestine could provide essential information about key regulators of gut and brain health; however, the microbial environment of the intestine is heavily dependent on the physiological oxygen gradient that exists across the intestinal wall. Likewise, there exist a need for methods which enable real-time monitoring of intestinal signaling ex vivo yet this remains challenging due to the inability to adequately culture intestinal tissue ex vivo while also exposing the appropriate locations of the intestine for probe insertion and monitoring. Here, we designed and fabricated a 3D printed microfluidic device to maintain the oxygen gradient across precision cut murine intestinal slices with the capability to couple to external neurochemical recording techniques. The gradient is maintained from outlets below while allowing access to the slice from above for detection with fast scan cyclic voltammetry (FSCV) and carbon-fiber microelectrodes. A series of 11 outlet ports were designed to lay underneath the slice which were connected to channels to deliver oxygenated vs. deoxygenated media. Outlet ports were designed in an oval shape where deoxygenated media was delivered to the center of the slice and oxygenated media is delivered to the outer portion of the slice to mimic the location of oxygen across the intestine. An oxygen sensitive fluorescent dye, tris(2,2′-bipyridyl)dichlororuthenium(II), was used to characterize the tunability of the gradient. Viability of the tissue was confirmed by both fluorescence microscopy and FSCV. Additionally, we measured simultaneous serotonin and melatonin signaling with FSCV in the intestine for the first time. Overall, this chip provides a significant advance in our ability to culture intestinal slices ex vivo with the added benefit of direct access for measurements and imaging. [ABSTRACT FROM AUTHOR]

Multiple analytical techniques for the screening of fentanyl‐related compounds exist. High discriminatory methods such as GC–MS and LC–MS are expensive, time‐consuming, and less amenable to onsite analysis. Raman spectroscopy provides a rapid, inexpensive alternative. Raman variants such as electrochemical surface‐enhanced Raman scattering (EC‐SERS) can provide signal enhancements with 1010 magnitudes, allowing for the detection of low‐concentration analytes, otherwise undetected using conventional Raman. Library search algorithms embedded in instruments utilizing SERS may suffer from accuracy when multicomponent mixtures involving fentanyl derivatives are analyzed. The complexing of machine learning techniques to Raman spectra demonstrates an improvement in the discrimination of drugs even when present in multicomponent mixtures of various ratios. Additionally, these algorithms are capable of identifying spectral features difficult to detect by manual comparisons. Therefore, the goal of this study was to evaluate fentanyl‐related compounds and other drugs of abuse using EC‐SERS and to process the acquired data using machine learning—convolutional neural networks (CNN). The CNN was created using Keras v 2.4.0 with Tensorflow v 2.9.1 backend. In‐house binary mixtures and authentic adjudicated case samples were used to evaluate the created machine‐learning models. The overall accuracy of the model was 98.4 ± 0.1% after 10‐fold cross‐validation. The correct identification for the in‐house binary mixtures was 92%, while the authentic case samples were 85%. The high accuracies achieved in this study demonstrate the advantage of using machine learning to process spectral data when screening seized drug materials comprised of multiple components. [ABSTRACT FROM AUTHOR]

Applications and advances in surface-enhanced Raman spectroscopy (SERS) have grown over the last several years, demonstrating improvements in sensitivity and selectivity. Applications for SERS-related techniques have been explored in many analytical disciplines including forensic applications. Drug chemistry and toxicology may benefit from the growth of SERS since many methods have demonstrated high sensitivity, potential for quantitative analysis, and portable instrumentation for onsite testing. SERS techniques have been developed using many substrates including nanoparticles and colloids; microfluidic devices; paper-based substrates; electrodes; and wearable/flexible devices. These methods take advantage of the SERS phenomenon, providing more potential applications for Raman analysis and overcoming the traditional challenges of the technique. This is desirable for forensic drug chemistry applications which require screening and confirmatory approaches and analysis of mixtures with low weight percent contributions of analytes, as well as forensic toxicology, where matrix interferences, sensitivity requirements, and a growing introduction of novel drug entities pose challenges. Several chemometric approaches have been applied to Raman data to improve identification, classification, and quantification. These advances position SERS for incorporation into forensic chemistry laboratories. While some SERS applications are available commercially, widespread use of SERS in practicing forensic laboratories remains limited. Due to the requirements for use of analytical techniques in the courtroom, future studies for SERS should revolve around the assessment of validation parameters common in other analytical methods. SERS techniques that are rapid, simple, and inexpensive may be more quickly adapted for forensic testing, where use as advanced screening techniques is a clear avenue of research. This article is categorized under: Forensic Chemistry and Trace Evidence > Controlled and Emerging Drug Compounds Toxicology > New Psychoactive Substances Forensic Chemistry and Trace Evidence > Emerging Technologies and Methods. [ABSTRACT FROM AUTHOR]

Analysis of gunshot residue currently lacks effective screening methods that can be implemented in real time at the crime scene. Historically, SEM‐EDS has been the standard for analysis; however, advances in technology have brought portable instrumentation to the forefront of forensic science disciplines, including the screening of GSR. This study proposes electrochemical methods with disposable screen‐printed carbon electrodes for GSR screening at the laboratory and points of care due to their rapid, cost‐efficient, and compact platform. GSR residues were extracted from typical aluminum/carbon adhesive collection stubs and analyzed via square‐wave anodic stripping voltammetry. Benchtop and portable electrochemical instruments were compared for the assessment and classification of authentic shooter samples by monitoring a panel of inorganic and organic GSR elements and compounds including lead, antimony, copper, 2,4‐dinitrotoluene, diphenylamine, nitroglycerin, and ethyl centralite. The evaluation included the assessment of figures of merit and performance measures from quality controls, nonshooter, and shooter data sets. Samples collected from the hands of 200 background individuals (nonshooters), and shooters who fired leaded ammunition (100) and lead‐free ammunition (50) were analyzed by the benchtop and portable systems with accuracies of 95.7% and 96.5%, respectively. The findings indicate that electrochemical methods are fast, sensitive, and specific for the identification of inorganic and organic gunshot residues. The portable potentiostat provided results comparable with the benchtop system, serving as a proof‐of‐concept to transition this methodology to crime scenes for a practical and inexpensive GSR screening that could reduce backlogs, improve investigative leads, and increase the impact of gunshot residues in forensic science. [ABSTRACT FROM AUTHOR]

Serotonin is an important neurotransmitter that plays a major role in many aspects of neuroscience. Fast-scan cyclic voltammetry measures fast in vivo serotonin dynamics using carbon fiber microelectrodes. More recently, fast-scan controlled-adsorption voltammetry (FSCAV) has been developed to measure slower, minute-to-minute changes in ambient extracellular serotonin. We have previously demonstrated that FSCAV measurements of basal serotonin levels give critical information regarding brain physiology and disease. In this work, we revealed the presence of low-periodicity fluctuations in serotonin levels in mouse hippocampi, measured in vivo with FSCAV. Using correlation analyses, we found robust evidence of oscillations in the basal serotonin levels, which had a period of 10 min and were not present in vitro. Under control conditions, the oscillations did not differ between male and female mice, nor do they differ between mice that underwent a chronic stress paradigm and those in the control group. After the acute administration of a selective serotonin reuptake inhibitor, we observed a shift in the frequency of the oscillations, leading us to hypothesize that the newly observed fluctuations were transporter regulated. Finally, we optimized the experimental parameters of the FSCAV to measure at a higher temporal resolution and found more pronounced shifts in the oscillation frequency, along with a decreased oscillation amplitude. We postulate that this work may serve as a potential bridge for studying serotonin/endocrine interactions that occur on the same time scale. [ABSTRACT FROM AUTHOR]

Progressive vision loss and neurocognitive impairment are early and frequent presentations in CLN3 disease. This highlights neurodevelopmental functioning as critical to the disease, but limits the neuropsychological test repertoire. We evaluated the convergent validity of the Vineland Adaptive Behavior Scales as a potential outcome measure. In a prospective observational study of 22 individuals (female:male 11:11; 6–20 years‐old) with a molecular diagnosis of CLN3, we used generalized linear models and Spearman correlations to quantify the relationship of the adaptive behavior composite (ABC) standard score with established outcomes of verbal IQ (VIQ) and disease severity (Unified Batten Disease Rating Scale, UBDRS) scores. We analyzed ABC changes in 1‐year follow‐up data in a subset of the same cohort (n = 17). The ABC and VIQ, both standard scores, exhibited a strong positive correlation in cross‐sectional data (r = 0.81). ABC and UBDRS scores were strongly and positively correlated in cross‐sectional data (rrange = 0.87–0.93). Participants' ABC scores decreased slightly over the 1‐year follow‐up period (mean change, 95% CI: −5.23, −2.16). The convergent validity of the Vineland‐3 for use in CLN3 is supported by its relationships with the established outcomes of VIQ and UBDRS. Future longitudinal research, including replication in other cohorts and evaluation of sensitivity to change, will be important to establish utility of the Vineland‐3 for monitoring change in CLN3. [ABSTRACT FROM AUTHOR]

Reliable Identification of fentanyl and fentanyl analogs present In seized drug samples Is Imperative to the safety of first responders and laboratory personnel and informs the future analysis process and handling procedures. The electrochemical-surface enhanced Raman spectroscopy (EC-SERS) method developed in this work allows the in-situ preparation of the SERS substrate providing a rapid, efficient, and accurate approach to detect fentanyl, even at low percent by weight concentrations common in seized drugs. Optimization of the electrochemical potentials suitable for the SERS substrate preparation and adsorption of the analyte was achieved using multi-pulse amperometric detection. This method demonstrated large enhancement of the SERS response. This method was applied to six fentanyl analogs with substitutions to the amide group, representing small changes in the fentanyl core structure. Identification of these analogs through differences in the EC-SERS spectra was evident. Interference studies incorporating analytes frequently encountered with fentanyl including heroin, cocaine, methamphetamine, naltrexone, and naloxone were assessed and found to offer limited to no interference. The limits of detection of the fentanyl compounds were in the low to mid nanograms per milliliter range, with the most sensitive compound detected at 10ng/ml. Application of the method to simulated drug mixtures was performed to determine fit-for-purpose. In all mixtures with fentanyl as the minor contributor, fentanyl was correctly identified, including mixture samples comprised of 5 and 1% fentanyl. This approach represents the first in-situ EC-SERS analysis of fentanyl and its analogs and provides accurate and efficient screening for fentanyl in seized drug samples. [ABSTRACT FROM AUTHOR]

Centrally acting skeletal muscle relaxants (CASMR) are widely prescribed as adjuncts for acute and chronic pain. Given the recent interest in multimodal analgesia and reducing opioid consumption, there has been an increase in its use for perioperative/postoperative pain control. The mechanism of action, pharmacodynamics, and pharmacokinetics of these drugs vary. Their use has been studied in a wide range of operative and non-operative settings. The best evidence for the efficacy of CASMRs is in acute, nonoperative musculoskeletal pain and, in the operative setting, in patients undergoing total knee arthroplasty and abdominal surgery, including inguinal herniorrhaphy and hemorrhoidectomy. The risk of complications and side effects, coupled with the limited evidence of efficacy, should prompt careful consideration of individual patient circumstances when prescribing CASMRs as part of perioperative pain management strategies.

Abstract Background Psoriasis is a common autoimmune dermatologic condition which has a pronounced negative impact on patient quality of life and disease burden. Currently, there are a number of treatments available for psoriasis, with differences in efficacy, mechanism of action, mode of administration, adverse effects, and tolerability. However, a reliable, validated patient-reported instrument to address patient expectations and of psoriasis treatment has not been developed. This project was undertaken with the aim of developing a fit-for-purpose self-reported instrument to inform patient expectations and preferences of psoriasis treatments. Methods Two studies, both utilizing qualitative and quantitative methods, were conducted in patients within the entire spectrum of psoriasis severity. In Study 1, a group concept mapping (GCM) exercise was conducted with dermatologists and moderate-to-severe psoriasis patients to identify concepts important in the treatment of psoriasis. In Study 2, a preliminary Treatment Acceptability Questionnaire (TAQ) was developed using GCM-derived concepts from Studies 1 and 2, followed by cognitive debriefing (CD) telephone interviews of the preliminary TAQ. In Study 2, another GCM exercise was conducted with mild and newly diagnosed psoriasis patients. Psychometric analyses were performed on the TAQ to evaluate validity and reliability. Results The Study 1 GCM exercise generated 43 concepts from moderate-to-severe psoriasis patients (n = 20) and dermatologists (n = 10). In Study 2, 37 GCM concepts were generated from mild and newly diagnosed psoriasis patients (n = 20). From the 2 GCM exercises, 28 concepts were selected to form the preliminary TAQ; CD interviews indicated strong understanding and relevance of TAQ items among patients with disease ranging from mild to severe. The final TAQ consisted of 20 items; psychometric analysis demonstrated strong validity and reliability of the TAQ. Conclusions The TAQ is a novel psychometrically validated patient-reported instrument to inform healthcare providers of patients’ expectations of and preferences for treatment of their psoriasis and can help in shared decision making between patients and physicians.

The increasing demand for rapid methods to identify both inorganic and organic gunshot residues (IGSR and OGSR) makes electrochemical methods, an attractive screening tool to modernize current practice. Our research group has previously demonstrated that electrochemical screening of GSR samples delivers a simple, inexpensive, and sensitive analytical solution that is capable of detecting IGSR and OGSR in less than 10 min per sample. In this study, we expand our previous work by increasing the number of GSR markers and applying machine learning classifiers to the interpretation of a larger population data set. Utilizing bare screen‐printed carbon electrodes, the detection and resolution of seven markers (IGSR; lead, antimony, and copper, and OGSR; nitroglycerin, 2,4‐dinitrotoluene, diphenylamine, and ethyl centralite) was achieved with limits of detection (LODs) below 1 µg/mL. A large population data set was obtained from 395 authentic shooter samples and 350 background samples. Various statistical methods and machine learning algorithms, including critical thresholds (CT), naïve Bayes (NB), logistic regression (LR), and neural networks (NN), were utilized to calculate the performance and error rates. Neural networks proved to be the best predictor when assessing the dichotomous question of detection of GSR on the hands of shooter versus nonshooter groups. Accuracies for the studied population were 81.8 % (CT), 88.1% (NB), 94.7% (LR), and 95.4% (NN), respectively. The ability to detect both IGSR and OGSR simultaneously provides a selective testing platform for gunshot residues that can provide a powerful field‐testing technique and assist with decisions in case management. [ABSTRACT FROM AUTHOR]

The increasing demand for rapid methods to identify both inorganic and organic gunshot residues (IGSR and OGSR) makes electrochemical methods, an attractive screening tool to modernize current practice. Our research group has previously demonstrated that electrochemical screening of GSR samples delivers a simple, inexpensive, and sensitive analytical solution that is capable of detecting IGSR and OGSR in less than 10 min per sample. In this study, we expand our previous work by increasing the number of GSR markers and applying machine learning classifiers to the interpretation of a larger population data set. Utilizing bare screen‐printed carbon electrodes, the detection and resolution of seven markers (IGSR; lead, antimony, and copper, and OGSR; nitroglycerin, 2,4‐dinitrotoluene, diphenylamine, and ethyl centralite) was achieved with limits of detection (LODs) below 1 µg/mL. A large population data set was obtained from 395 authentic shooter samples and 350 background samples. Various statistical methods and machine learning algorithms, including critical thresholds (CT), naïve Bayes (NB), logistic regression (LR), and neural networks (NN), were utilized to calculate the performance and error rates. Neural networks proved to be the best predictor when assessing the dichotomous question of detection of GSR on the hands of shooter versus nonshooter groups. Accuracies for the studied population were 81.8 % (CT), 88.1% (NB), 94.7% (LR), and 95.4% (NN), respectively. The ability to detect both IGSR and OGSR simultaneously provides a selective testing platform for gunshot residues that can provide a powerful field‐testing technique and assist with decisions in case management. [ABSTRACT FROM AUTHOR]

Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans’ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars. A total of four assessments were administered: one every two months for a total duration of six months. The average number of completed assessments across all participants was 3.70 (SD = 0.75) with 159 participants (84.13%) completing all four timepoints. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.

Abstract Extended‐release liposomal bupivacaine is frequently used in surgical infiltration for postoperative pain control. The manufacturer recommends against subsequent local anesthetics within 96 hours. We administered epidural bupivacaine one day after local liposomal bupivacaine infiltration for staged hemipelvectomy without symptoms of LAST. Further pharmacokinetic and clinical safety studies are needed.

Abstract Background There is an increasing amount of literature describing the pathogenesis of coronavirus disease 2019 (COVID-19) pneumonia and its associated complications. Historically, a small pneumothorax has been shown to be successfully treated without chest tube insertion, but this management has yet to be proven in COVID-19 pneumonia patients. In addition, pneumothorax in an intubated patient with high positive end-expiratory pressure (PEEP) provides additional uncertainty with pursuing non-operative management. Case presentation In this series we report four cases of patients with respiratory distress who tested positive for COVID-19 via nasopharyngeal swab and developed ventilator-induced pneumothoraces which were successfully managed with observation alone. Conclusions Management of patients with COVID-19 pneumonia on positive pressure ventilation who develop small stable pneumothoraces can be safely observed without chest tube insertion.