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Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.

Given the ongoing dilemma for college counseling centers to meet steady increases in demand for services, this study outlines the implementation of an adapted stepped care model in a university counseling center. Our adapted model focused, as do other stepped care models, on treatment planning and lower-intensity interventions, with the addition of the intensive therapy option being provided on a weekly basis. We adopted our stepped care model across a large center and hypothesized that after implementation we would be able to serve a similar number of clients as our previous model and that treatment outcomes for these clients would improve. Descriptive data and regression analyses demonstrated support for our hypotheses, including an increased likelihood of clinically significant improvement for clients postimplementation. Implications for adapting service delivery models using practice-based evidence are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of Dicer1. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity, and exemplifies how lineage-specific TEs can facilitate evolutionary turnover and divergence of innate immune regulatory networks.

Treatment of painful diabetic peripheral neuropathy (PDPN) is challenging and often limited by drug tolerability and adverse effects. This review article focuses on the high-dose (8%) capsaicin patch that allows for improved efficacy and reduced application frequency in comparison to low-dose capsaicin formulations. Systemic absorption is minimal resulting in fewer systemic side effects than first-line oral medications. There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for adverse effects from oral medication, polypharmacy or inadequate pain relief from first-line therapies.Treatment of nerve pain in the feet and other regions due to nerve damage from diabetes is challenging, often due to the unwanted side effects of medications. This review article focuses on the high-dose (8%) capsaicin patch, which can be applied directly to the feet. It is more potent than the low-dose formulations, allowing patients to apply it less often while also working more effectively compared with low-dose capsaicin creams. Because it acts directly on the skin, there are fewer systemic side effects such as drowsiness or urinary retention. There is evidence that capsaicin patch treatment is safe and provides pain relief for several weeks. More large studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for side effects from oral medications or inadequate pain relief from first-line medications.

Objective: To explore the detection of cortical responses to continuous speech using a single EEG channel. Particularly, to compare detection rates and times using a cross-correlation approach and parameters extracted from the temporal response function (TRF).Design: EEG from 32-channels were recorded whilst presenting 25-min continuous English speech. Detection parameters were cross-correlation between speech and EEG (XCOR), peak value and power of the TRF filter (TRF-peak and TRF-power), and correlation between predicted TRF and true EEG (TRF-COR). A bootstrap analysis was used to determine response statistical significance. Different electrode configurations were compared: Using single channels Cz or Fz, or selecting channels with the highest correlation value.Study sample: Seventeen native English-speaking subjects with mild-to-moderate hearing loss.Results: Significant cortical responses were detected from all subjects at Fz channel with XCOR and TRFCOR. Lower detection time was seen for XCOR (mean ¼ 4.8 min) over TRF parameters (best TRF-COR, mean ¼ 6.4 min), with significant time differences from XCOR to TRF-peak and TRF-power. Analysing multiple EEG channels and testing channels with the highest correlation between envelope and EEG reduced detection sensitivity compared to Fz alone.Conclusions: Cortical responses to continuous speech can be detected from a single channel with recording times that may be suitable for clinical application.

Over the past years, a wide range of studies have provided evidence of asymmetry in the response of static and dynamic cerebral autoregulation (CA) during increasing and decreasing pressure challenges. The main message is that CA is stronger during transient increases of arterial blood pressure rather than decreases. Here we do not argue against the presence of CA asymmetry but we seek to raise questions regarding the measurement of the effect and whether this effect needs to be taken into account, especially in clinical settings.

Background The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. Objectives Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. Methods Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. Results Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. Conclusions The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

Introduction/Aims The development and persistence of neurological symptoms following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is referred to as “long‐haul” syndrome. We aimed to determine whether small fiber neuropathy (SFN) was associated with SARS‐CoV‐2 infection. Methods We retrospectively studied the clinical features and outcomes of patients who were referred to us between May 2020 and May 2021 for painful paresthesia and numbness that developed during or after SARS‐CoV‐2 infection and who had nerve conduction studies showing no evidence of a large fiber polyneuropathy. Results We identified 13 patients, Eight women and five men with age ranging from 38–67 y. Follow‐up duration ranged from 8 to 12 mo. All patients developed new‐onset paresthesias within 2 mo following SARS‐CoV‐2 infection, with an acute onset in seven and co‐existing autonomic symptoms in seven. Three patients had pre‐existing but controlled neuropathy risk factors. Skin biopsy confirmed SFN in six, all of whom showed both neuropathy symptoms and signs, and two also showed autonomic dysfunction by autonomic function testing (AFT). Of the remaining seven patients who had normal skin biopsies, six showed no clinical neuropathy signs and one exhibited signs and had abnormal AFT. Two patients with markedly reduced intraepidermal nerve fiber densities and one with normal skin biopsy had severe and moderate coronavirus disease 2019 (COVID‐19); the remainder experienced mild COVID‐19 symptoms. Nine patients received symptomatic neuropathy treatment with paresthesias controlled in seven (77.8%). Discussion Our findings suggest that symptoms of SFN may develop during or shortly after COVID‐19. SFN may underlie the paresthesias associated with long‐haul post‐COVID‐19 symptoms.

Objectives: the primary objective of this study was to train and test machine learning algorithms to be able to detect accurately whether EEG data contains an auditory brainstem response (ABR) or not and recommend suitable machine learning methods. In addition, the performance of the best machine learning algorithm was compared with that of prominent statistical detection methods.Design: four machine learning algorithms were trained and evaluated using nested k-fold cross-validation: a random forest, a convolutional long short-term memory network, a stacked ensemble, and a multilayer perceptron. The best method was evaluated on a separate test set and compared with conventional detection methods: Fsp, Fmp, q-sample uniform scores test, and Hotelling’s T2 test. The models were trained and tested on simulated data that were generated based on recorded ABRs collected from 12 normal-hearing participants and no-stimulus EEG data from 15 participants. Simulation allowed the ground truth of the data (“response present” or “response absent”) to be known.Results: the sensitivity of the best machine learning algorithm, a stacked ensemble, was significantly greater than that of the conventional detection methods evaluated. The stacked ensemble, evaluated using a bootstrap approach, consistently achieved a high and stable level of specificity across ensemble sizes.Conclusions: the stacked ensemble model presented was more effective than conventional statistical ABR detection methods and the alternative machine learning approaches tested. The stacked ensemble detection method may have potential both in automated ABR screening devices as well as in evoked potential software, assisting clinicians in making decisions regarding a patient’s ABR threshold. Further assessment of the model’s generalizability using a large cohort of subject recorded data, including participants of different ages and hearing status, is a recommended next step.

Transposable elements (TEs) are abundant in the genome, and specific insertions may be co-opted to act as coding or noncoding functional elements. CRISPR-based genome editing technologies enable functional studies of TE insertions in cell lines. Here, we describe the use of CRISPR-Cas9 to create and validate genetic knockouts of TEs in mammalian cell lines.

Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an IFN-inducible enhancer of Dicer1 and the nearby Serpina3f and Serpina3g genes. The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity and exemplifies how lineage-specific TEs can facilitate evolutionary divergence of innate immune regulatory networks.

Introduction A conduction block at a noncompressible site warrants further investigation. Methods and materials A 36-year-old woman with a history of Hodgkin lymphoma and chemotherapy-induced polyneuropathy developed bilateral hand numbness and paresthesias. Workup revealed bilateral carpal tunnel syndrome and an apparent superimposed conduction block of the median nerve in the forearm. Given the history of cancer, there was concern for an infiltrative or an immune-mediated process. Results Neuromuscular ultrasound demonstrated that the median nerve descended the upper extremity along an atypical path, deep along the posteromedial aspect of the upper arm, and relatively medially in the forearm. Ultrasound-directed nerve stimulation revealed there was no conduction block. This anatomical variant has been rarely described and has not been reported previously to mimic conduction block or been documented via ultrasound. Conclusions This case demonstrates that neuromuscular ultrasound may supplement the electrodiagnostic study and limit confounding technical factors because of rare anatomic variation.

Neuropathic pain is common in the geriatric population. Diagnosis requires a thorough history and physical examination to differentiate it from other types of pain. Once diagnosed, further workup is required to elucidate the cause, including potential reversible causes of neuropathy. When treating neuropathic pain in the elderly, it is important to consider patients' comorbidities and other medications to avoid drug-drug interactions and iatrogenic effects given the physiologic changes of drug metabolism in the elderly. Nonsystemic therapies and topical medications should be considered. Systemic medications should be started at low dose and titrated up slowly with frequent monitoring for adverse effects.