Neuromodulation Techniques for Headache Management.

This narrative review aims to summarize evidence regarding the current utilization and future applications of neuromodulation in patients with headaches, with special attention paid to migraine and chronic cluster headache. A search was conducted in PubMed in August of 2023 to survey the current literature on neuromodulation for the treatment of headache. In total, the search yielded 1989 results, which were further filtered to include only systematic reviews published between 2022 to 2023 to capture the most up-to-date and comprehensive research on this topic. The citation lists of these articles were reviewed to find additional research on neuromodulation and supplement the results presented in this paper with primary literature. Research on the use of neuromodulation for the treatment of headache has predominantly focused on four neuromodulation techniques: peripheral nerve stimulation (PNS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and spinal cord stimulation (SCS). Outcome measures reported in this article include impact on migraine and headache frequency and/or pain intensity, adverse effects of the neuromodulation technique, and associated costs, when available. We found that neuromodulation has developed utility as an alternative treatment for both chronic cluster headaches and migraines, with a reduction in frequency and intensity of headache most elucidated from the articles mentioned in this review.

High-Throughput Extracellular Matrix Proteomics of Human Lungs Enabled by Photocleavable Surfactant and diaPASEF.

The extracellular matrix (ECM) is a complex assembly of proteins that provide interstitial scaffolding and elastic recoil for human lungs. The pulmonary extracellular matrix is increasingly recognized as an independent bioactive entity, by creating biochemical and mechanical signals that influence disease pathogenesis, making it an attractive therapeutic target. However, the pulmonary ECM proteome ("matrisome") remains challenging to analyze by mass spectrometry due to its inherent biophysical properties and relatively low abundance. Here, we introduce a strategy designed for rapid and efficient characterization of the human pulmonary ECM using the photocleavable surfactant Azo. We coupled this approach with trapped ion mobility MS with diaPASEF to maximize the depth of matrisome coverage. Using this strategy, we identify nearly 400 unique matrisome proteins with excellent reproducibility that are known to be important in lung biology, including key core matrisome proteins.

Defining the Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy by Top-Down Proteomics.

Ischemic cardiomyopathy (ICM) is a prominent form of heart failure, but the molecular mechanisms underlying ICM remain relatively understudied due to marked phenotypic heterogeneity. Alterations in post-translational modifications (PTMs) and isoform switches in sarcomeric proteins play important roles in cardiac pathophysiology. Thus, it is essential to define sarcomeric proteoform landscape to better understand ICM. Herein, we have implemented a top-down liquid chromatography (LC)-mass spectrometry (MS)-based proteomics method for the identification and quantification of sarcomeric proteoforms in the myocardia of donors without heart diseases (n = 16) compared to end-stage ICM patients (n = 16). Importantly, quantification of post-translational modifications (PTMs) and expression reveal significant changes in various sarcomeric proteins extracted from ICM tissues. Changes include altered phosphorylation and expression of cardiac troponin I (cTnI) and enigma homologue 2 (ENH2) as well as an increase in muscle LIM protein (MLP) and calsarcin-1 (Cal-1) phosphorylation in ICM hearts. Our results imply that the contractile apparatus of the sarcomere is severely dysregulated during ICM. Thus, this is the first study to uncover significant molecular changes to multiple sarcomeric proteins in the LV myocardia of the end-stage ICM patients using liquid chromatography-mass spectrometry (LC-MS)-based top-down proteomics. Raw data are available via the PRIDE repository with identifier PXD038066.

VO Cluster-Stabilized H2O Adsorption on a TiO2 (110) Surface at Room Temperature.

We probe the adsorption of molecular H2O on a TiO2 (110)-(1 × 1) surface decorated with isolated VO clusters using ultrahigh-vacuum scanning tunneling microscopy (UHV-STM) and temperature-programmed desorption (TPD). Our STM images show that preadsorbed VO clusters on the TiO2 (110)-(1 × 1) surface induce the adsorption of H2O molecules at room temperature (RT). The adsorbed H2O molecules form strings of beads of H2O dimers bound to the 5-fold coordinated Ti atom (5c-Ti) rows and are anchored by VO. This RT adsorption is completely reversible and is unique to the VO-decorated TiO2 surface. TPD spectra reveal two new desorption states for VO stabilized H2O at 395 and 445 K, which is in sharp contrast to the desorption of water due to recombination of hydroxyl groups at 490 K from clean TiO2(110)-(1 × 1) surfaces. Density functional theory (DFT) calculations show that the binding energy of molecular H2O to the VO clusters on the TiO2 (110)-(1 × 1) surface is higher than binding to the bare surface by 0.42 eV, and the resulting H2O-VO-TiO2 (110) complex provides the anchor point for adsorption of the string of beads of H2O dimers.

Resistance of Mandibular Polyurethane Replicas to Fracture After Removal of Blocks From the Symphysis and Ramus.

BACKGROUND: When block grafts are harvested intraorally, the donor sites may act as stress concentrators and alter the structural integrity of the mandible. PURPOSE: The study aimed to compare displacement and load failure between intact polyurethane mandibular replicas and similar replicas from which blocks were taken at the symphysis or the ramus. It also aimed to identify trends of load failure. MATERIALS AND METHODS: Thirty-five mandibular replicas were tested to failure with an electromagnetic material testing unit. The variables evaluated in this investigation were maximal load, displacement at maximal load, and fracture location. RESULTS: Statistically significant differences in maximal load were detected between groups (P = 0.0008). Differences between fracture locations were also statistically significant (P < 0.0001). The mandibles from which blocks were removed at the symphysis were significantly more likely to break at a lower maximal load than were the control mandibles (P = 0.0010) or the mandibles from which blocks were removed at the ramus (P = 0.0162). They were also more likely than the control group to break at a lower displacement at maximal load (P = 0.0145). CONCLUSIONS: Location of the donor site significantly influences the structural integrity of mandibular replicas. In addition, the donor site significantly affects the location of mandibular fractures.

Catalytic oxidation of methanol to formaldehyde by mass-selected vanadium oxide clusters supported on a TiO2(110) surface.

We report the results of a systematic study of the catalytic activity of mass-selected vanadium oxide clusters deposited on rutile TiO2 surfaces under ultrahigh vacuum (UHV) conditions. Our results show that supported V, VO, and VO2 clusters are not catalytically active for the oxidative dehydrogenation of methanol to formaldehyde but can be made catalytically active by postoxidation. In addition, we found that the postoxidized VO/TiO2 produces the most formaldehyde. Scanning tunneling microscopy (STM) imaging of the postoxidized VO/TiO2 reveals isolated clusters with height and width indicative of VO3 bound to the TiO2 surface. Our results are consistent with previous density functional theory (DFT) calculations that predict that VO3 will be produced by postoxidation of VO and that VO3/TiO2 is an active catalyst.

Gene-Z: a device for point of care genetic testing using a smartphone.

By 2012, point of care (POC) testing will constitute roughly one third of the $59 billion in vitro diagnostics market. The ability to carry out multiplexed genetic testing and wireless connectivity are emerging as key attributes of future POC devices. In this study, an inexpensive, user-friendly and compact device (termed Gene-Z) is presented for rapid quantitative detection of multiple genetic markers with high sensitivity and specificity. Using a disposable valve-less polymer microfluidic chip containing four arrays of 15 reaction wells each with dehydrated primers for isothermal amplification, the Gene-Z enables simultaneous analysis of four samples, each for multiple genetic markers in parallel, requiring only a single pipetting step per sample for dispensing. To drastically reduce the cost and size of the real-time detector necessary for quantification, loop-mediated isothermal amplification (LAMP) was performed with a high concentration of SYTO-81, a non-inhibiting fluorescent DNA binding dye. The Gene-Z is operated using an iPod Touch, which also receives data and carries out automated analysis and reporting via a WiFi interface. This study presents data pertaining to performance of the device including sensitivity and reproducibility using genomic DNA from Escherichia coli and Staphylococcus aureus. Overall, the Gene-Z represents a significant step toward truly inexpensive and compact tools for POC genetic testing.

Antipsychotic treatment of adolescent dual diagnosis patients.

BACKGROUND: A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients. METHODS: A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms "addiction," "adolescence," "childhood," "dual diagnosis," "schizophrenia," and "substance abuse." Results were limited to English-language articles. RESULTS: Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events. CONCLUSION: There is a great need for more research and use of available data to develop safe and effective treatment guidelines for childhood and adolescent dual diagnosis patients. When appropriate decisions are made regarding treatment of patients with comorbid schizophrenia and chemical dependence, both conditions may benefit with increased remission.

Application of the Three Rs to challenge assays used in vaccine testing: tenth report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement.

This report aims to facilitate the implementation of the Three Rs (reduction, refinement and replacement) in the testing of vaccines for regulatory and other purposes. The focus is predominantly on identification of reduction and refinement opportunities in batch potency testing but the principles described are widely applicable to other situations that involve experimental infections of animals. The report should also help to interpret the requirements of the European Pharmacopoeia with regard to the use of alternative tests, humane endpoints and other refinements. Two specific worked examples, for batch potency testing of Clostridium chauvoei and canine leptospira, with recommendations for harmonisation of international test requirements for these and other vaccines, are provided as appendices online.

Acceleration risk in student fighter pilots: preliminary analysis of a management program.

Despite advances in G-protection, F-16 student pilots continue to demonstrate G-performance inadequacies. The G-Risk Indicator Management (GRIM) Program was introduced at Luke Air Force Base in 2000 to facilitate early detection of G-related problems and to aid in the establishment of tailored ground training programs designed to enhance a student's performance under G. Assessment of anthropomorphic data, previous G-performance, anaerobic fitness, and centrifuge qualification scores comprise the initial assessment in the GRIM Program. Observations from these assessments are used to qualitatively determine the level of risk for the student. In the absence of any historical controls, no conclusions could be drawn with regards to the overall efficiency of the GRIM program. Significant differences were found between groups for anaerobic test scores, centrifuge scores, and gradebook comments. The results from this non-experimental study suggest the need for future studies to better determine the validity of G-risk indicators.