Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production.

Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2-/- mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS.

Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins.

The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of subcellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs in both mouse and Drosophila cells, and Mbnl-dependent translation and protein secretion were observed for a subset of mRNAs with Mbnl-dependent localization. These findings hold several new implications for DM pathogenesis.

A large-scale binding and functional map of human RNA-binding proteins.

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.

Predicting Out-of-Hospital Cardiac Arrest in the General Population Using Electronic Health Records.

BACKGROUND: The majority of out-of-hospital cardiac arrests (OHCAs) occur among individuals in the general population, for whom there is no established strategy to identify risk. In this study, we assess the use of electronic health record (EHR) data to identify OHCA in the general population and define salient factors contributing to OHCA risk. METHODS: The analytical cohort included 2366 individuals with OHCA and 23 660 age- and sex-matched controls receiving health care at the University of Washington. Comorbidities, electrocardiographic measures, vital signs, and medication prescription were abstracted from the EHR. The primary outcome was OHCA. Secondary outcomes included shockable and nonshockable OHCA. Model performance including area under the receiver operating characteristic curve and positive predictive value were assessed and adjusted for observed rate of OHCA across the health system. RESULTS: There were significant differences in demographic characteristics, vital signs, electrocardiographic measures, comorbidities, and medication distribution between individuals with OHCA and controls. In external validation, discrimination in machine learning models (area under the receiver operating characteristic curve 0.80-0.85) was superior to a baseline model with conventional cardiovascular risk factors (area under the receiver operating characteristic curve 0.66). At a specificity threshold of 99%, correcting for baseline OHCA incidence across the health system, positive predictive value was 2.5% to 3.1% in machine learning models compared with 0.8% for the baseline model. Longer corrected QT interval, substance abuse disorder, fluid and electrolyte disorder, alcohol abuse, and higher heart rate were identified as salient predictors of OHCA risk across all machine learning models. Established cardiovascular risk factors retained predictive importance for shockable OHCA, but demographic characteristics (minority race, single marital status) and noncardiovascular comorbidities (substance abuse disorder) also contributed to risk prediction. For nonshockable OHCA, a range of salient predictors, including comorbidities, habits, vital signs, demographic characteristics, and electrocardiographic measures, were identified. CONCLUSIONS: In a population-based case-control study, machine learning models incorporating readily available EHR data showed reasonable discrimination and risk enrichment for OHCA in the general population. Salient factors associated with OCHA risk were myriad across the cardiovascular and noncardiovascular spectrum. Public health and tailored strategies for OHCA prediction and prevention will require incorporation of this complexity.

A systematic framework for selecting gene-condition pairs for inclusion in newborn sequencing panels: Early Check implementation.

PURPOSE: Research is underway worldwide to investigate the feasibility, acceptability, and utility of sequencing-based newborn screening. Different methods have been used to select gene-condition pairs for screening, leading to highly inconsistent gene lists across studies. METHODS: Early Check developed and utilized actionability-based frameworks for evaluating gene-condition pairs for inclusion in newborn panels (Panel 1 - high actionability, Panel 2 - possible actionability). A previously developed framework, the Age-based Semi Quantitative Metric (ASQM), was adapted. Increasing ASQM scores, with a maximum of 15, suggest greater actionability. Wilcoxon tests were performed to compare Panel 1 gene-condition pairs on the Recommended Uniform Screening Panel (RUSP) to non-RUSP pairs. RESULTS: In our first round of assessment, Early Check identified 178 gene-condition pairs for inclusion in Panel 1 and 29 for Panel 2. Median ASQM scores of RUSP conditions on Panel 1 was 12 (range 4 to 15) and non-RUSP was 13 (range 9 to 15). Median scores for Panel 2 was 10 (range 6 to 14). CONCLUSION: The Early Check frameworks provide a transparent, semiquantitative, and reproducible methodology for selecting gene-condition pairs for NBS sequencing pilot studies that may inform future integration of genomic sequencing into population-level NBS. Collaborative efforts among newborn sequencing studies to establish shared criteria is needed to enhance cross-study comparisons.

Boosting efficiency in the endoscopy suite: integrating team workflows improves productivity and minimizes cost.

BACKGROUND AND AIMS: Inefficiencies in the endoscopy suite cause frustration for physicians, hospital administrators, staff, and patients. Turnover time (TOT), the time between one case ending and another beginning, is subjectively disproportionate between various team members. We aimed to define perceptions of TOT and target steps within the process to improve efficiency. METHODS: This was a prospective cohort study at a tertiary center outpatient endoscopy unit. Phase I aimed to identify the TOT process components based on time stamps in the electronic medical record (N = 686). We defined gastroenterologist perceived TOT (pTOT), anesthesia pTOT, and standard TOT (sTOT). TOT length was calculated for each subgroup. Patient transport was identified as an intervenable target. In Phase II, the task of patient transport moved from the anesthesiology team to endoscopy nurses. Mean TOT and proportion of cases with sTOT <15 minutes' preintervention (n = 2192) and postintervention (n = 292) were compared. RESULTS: Seven key TOT components were identified that explain variations in pTOT. Average anesthesia pTOT was 15 minutes, whereas average gastroenterologist pTOT was 34 minutes (25.9% vs 57.2% of case length; P = .0007). In Phase II, mean sTOT improved from 18.51 to 14.25 minutes (P < .0001), and proportion of sTOT within 15 minutes improved from 41.79% to 58.90% (P < .0001). This intervention saved 45 minutes per room per day, allowing for a revenue potential of more than $300,000 per year per procedure room. CONCLUSIONS: This study defines variations in TOT and shows that finding imbalances and sharing the workload significantly cuts costs and improves the overall efficiency of the different subgroups in the turnover process.

Scope-of-Practice Expansions Associated with Reduced Racial Disparities in Pediatric Mental Health Care.

To examine the association between scope-of-practice (SoP) regulations and racial disparities in pediatric mental health services. We used the National Survey of Children's Health (2016-2020; n = 33,790) to examine racial disparities in unmet mental health care needs and receipt of mental health medication between states with and without SoP expansions for psychologists and nurse practitioners (NP). Our primary outcomes were (1) unmet mental health care needs and (2) receipt of mental health medication. We examined heterogeneous treatment effects of SoP expansion on the outcomes using logistic regression with interaction terms between SoP expansion and race/ethnicity. We estimated population-level racial disparities for both outcomes stratified by SoP expansion to identify differences in racial disparities. The psychologist SoP expansion-associated reduction in unmet need was 15.8 percentage-points (CI= -25.3, -6.2) larger for Other-race children than for White children. The psychologist SoP expansion-associated increase in medication was 5.1%-points (CI=. 0.8, 9.4) larger for Black children and 5.6%-points (CI = 0.5, 10.8) for Other-race children. No differences were found for NP SoP expansion. Racial disparities in both outcomes were lower in psychologist SoP expansion states but varied in NP SoP states. Expanded SoP was generally associated with lower racial disparities in pediatric mental health care access.

Comparison of direct and indirect soil organic carbon prediction at farm field scale.

To advance sustainable and resilient agricultural management policies, especially during land use changes, it is imperative to monitor, report, and verify soil organic carbon (SOC) content rigorously to inform its stock. However, conventional methods often entail challenging, time-consuming, and costly direct soil measurements. Integrating data from long-term experiments (LTEs) with freely available remote sensing (RS) techniques presents exciting prospects for assessing SOC temporal and spatial change. The objective of this study was to develop a low-cost, field-based statistical model that could be used as a decision-making aid to understand the temporal and spatial variation of SOC content in temperate farmland under different land use and management. A ten-year dataset from the North Wyke Farm Platform, a 20-field, LTE system established in southwestern England in 2010, was used as a case study in conjunction with an RS dataset. Linear, additive and mixed regression models were compared for predicting SOC content based upon combinations of environmental variables that are freely accessible (termed open) and those that require direct measurement or farmer questionnaires (termed closed). These included an RS-derived Ecosystem Services Provision Index (ESPI), topography (slope, aspect), weather (temperature, precipitation), soil (soil units, total nitrogen [TN], pH), and field management practices. Additive models (specifically Generalised Additive Models (GAMs)) were found to be the most effective at predicting space-time SOC variability. When the combined open and closed factors (excluding TN) were considered, significant predictors of SOC were: management related to ploughing being the most important predictor, soil unit (class), aspect, and temperature (GAM fit with a normalised RMSE = 9.1%, equivalent to 0.4% of SOC content). The relative strength of the best-fitting GAM with open data only, which included ESPI, aspect, and slope (normalised RMSE = 13.0%, equivalent to 0.6% of SOC content), suggested that this more practical and cost-effective model enables sufficiently accurate prediction of SOC.

Pediatric Mental Health Care and Scope-of-Practice Expansions.

To examine the association between psychologist and nurse practitioner scope-of-practice (SoP) regulations and pediatric mental health service access. A nationally representative sample of children with mental health needs was identified using 5 years of National Survey of Children's Health (2016-2020). Utilization was measured in two ways: (1) unmet mental health care needs and (2) receipt of mental health medication. Expanded SoP for psychologists and nurse practitioners was measured based on the child's state of residence and the year of the survey. The associations between both SoP expansion and both outcomes were assessed using logistic regression models adjusted for multiple covariates. The probability of having unmet mental health needs was 5.4 percentage points lower (95% CI - 0.102, - 0.006) for children living in a state with psychologist SoP expansion; however, there was no significant difference in unmet mental health needs between states with and without NP SoP expansion. The probability of receiving a mental health medication was 2.0 percentage points higher (95% CI 0.007, 0.034) for children living in a state with psychologist SoP expansion. Conversely, the probability of receiving a mental health medication was 1.5 percentage points lower (95% CI - 0.023, - 0.007) for children living in a state with NP SoP expansion. Expanded SoP for psychologists is associated with improved access to pediatric mental health care in terms of both unmet need and receiving medication. Expanded SoP for NPs, however, was not associated with unmet need and lower receipt of medication.

Factors Associated with Substance Use Disorder among High-Need Adolescents and Young Adults in North Carolina.

Background: Prevalence of substance use disorders (SUD) is high among adolescents and young adults (AYAs) with complex medical needs. Little is known about risk factors for SUD in this population. Methods: This retrospective cohort study used electronic health record data from a large academic hospital system (2015-2019) to identify adolescents (aged 10-17) and young adults (aged 18-27) with intellectual/developmental disorders, psychiatric conditions, or complex medical conditions. Logistic regression was used to identify demographic, clinical, and neighborhood-level risk factors associated with SUD in this population. Results: A total of 149 adolescents and 536 young adults had a SUD diagnosis (6.7% and 20.6%, respectively). Among adolescents, notable risk factors for SUD included age (adjusted odds ratio [aOR] = 1.42, 95% confidence interval [CI] = [1.31, 1.54]), Hispanic ethnicity (aOR = 2.10, 95% CI = [1.10, 3.99]), additional psychoactive medication classes (aOR = 1.27, 95% CI = [1.11, 1.46]), and living in a "high" child opportunity index (COI) (aOR = 2.06, 95% CI [1.02, 4.14]) or a "very high" COI (aOR = 3.04, 95% CI [1.56,5.95]) area. Among young adults, notable risk factors included being male (aOR = 2.41, 95% CI [1.91, 3.05]), being Black (aOR = 1.64, 95% CI [1.28, 2.09]), and additional non-psychoactive (aOR = 1.07, 95% CI [1.03, 1.11]) or psychoactive medication classes (aOR = 1.17, 95% CI [1.07, 1.28]). Limitations: These descriptive analyses are limited to one large academic hospital system in North Carolina and may not be representative of all high-need AYAs in the state. Conclusions: Several demographic, clinical, and neighborhood risk factors are associated with SUD in high-need AYAs.

New model integrates innate responses, PML-NB formation, epigenetic control and reactivation from latency.

The dynamic nature of interactions between invading viral pathogens and their hosts has fascinated scientists for several decades. The well-known capacity of herpes simplex virus (HSV) to establish life-long infections in humans reflects a dynamic balance between maintaining a latent state in which viral genomes are silenced and re-entry into the lytic phase during reactivation. Silencing of the viral genome has been shown to be a function of innate immune signalling, intrinsic cellular antiviral mechanisms and epigenetic repression. Thus, although many important observations have been made identifying cellular processes that contribute to the repression of the viral genome and latency, the field has lacked an understanding of how these factors work together. In this issue of EMBO Reports, Suzich et al (2021) present convincing evidence that brings together individual observations into a cohesive model that explains many of these outstanding mysteries. Here, we will review the background data that lead to this outstanding piece of work.

Identification and Characterization of Synthetic Nicotine Product Promotion and Sales on Instagram Using Natural Language Processing.

INTRODUCTION: There has been a rapid proliferation of synthetic nicotine products in recent years, despite newly established regulatory authority and limited research into its health risks. Previous research has implicated social media platforms as an avenue for nicotine product unregulated sales. Yet, little is known about synthetic nicotine product content on social media. We utilized natural language processing to characterize the sales of synthetic nicotine products on Instagram. METHODS: We collected Instagram posts by querying Instagram hashtags (e.g., "#tobaccofreenicotine) related to synthetic nicotine. Using BERT, collected posts were categorized into thematically related topic clusters. Posts within topic clusters relevant to study aims were then manually annotated for variables related to promotion and selling (e.g., cost discussion, contact information for offline sales). RESULTS: A total of 7,425 unique posts were collected with 2,219 posts identified as related to promotion and selling of synthetic nicotine products. Nicotine pouches (52.9%, n=1174), ENDS (30.6%, n=679), and flavored e-liquids (14.1%, n=313) were most commonly promoted. 16.1% (n=345) of posts contained embedded hyperlinks and 5.8% (n=129) provided contact information for purported offline transactions. Only 17.6% (n=391) of posts contained synthetic nicotine specific health warnings. CONCLUSIONS: In the United States, synthetic nicotine products can only be legally marketed if they have received premarket authorization from the FDA. Despite these prohibitions, Instagram appears to be a hub for potentially unregulated sales of synthetic and "tobacco-free" products. Efforts are needed by platforms and regulators to enhance content moderation and prevent unregulated online sales of existing and emerging synthetic nicotine products. IMPLICATIONS: There is limited clinical understanding of synthetic nicotine's unique health risks and how these novel products are changing over time due to regulatory oversight. Despite synthetic nicotine specific regulatory measures, such as the requirement for premarket authorization and FDA warning letters issued to unauthorized sellers, access to and promotion of synthetic nicotine is widely occurring on Instagram, a platform with over 2 billion users and one that is popular among youth and young adults. Activities include direct-to-consumer sales from questionable sources, inadequate health warning disclosure, and exposure with limited age restrictions, all conditions necessary for the sale of various tobacco products. Notably, the number of these Instagram posts increased in response to the announcement of new FDA regulations. In response, more robust online monitoring, content moderation, and proactive enforcement is needed from platforms who should work collaboratively with regulators to identify, report, and remove content in clear violation of platform policies and federal laws. Regulatory implementation and enforcement should prioritize digital platforms as conduits for unregulated access to synthetic nicotine products and other future novel and emerging tobacco products.

Acute Mania and Psychosis in the Context of Primary Adrenal Insufficiency: A Systematic Review of the Literature.

BACKGROUND: Given the sparse nature of acute mania or psychosis in primary adrenal insufficiency (PAI), physicians may not be aware of the association of these two entities. OBJECTIVE: To conduct a systematic review of the literature for the purpose of identifying all studies reporting mania and/or psychosis in individuals with PAI. METHOD: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the PubMed, Embase, and Web of Science databases from June 22, 1970 to June 22, 2021, for the purpose of identifying all studies reporting instances of mania or psychosis associated with PAI. RESULTS: We identified nine case reports featuring nine patients (M age = 43.3 years, male = 44.4%) over eight countries that fit our inclusion/exclusion criteria. Eight (89%) of the patients had experienced psychosis. Manic and/or psychotic symptom resolution was achieved in 100% of the cases, of which steroid replacement therapy was efficacious in seven (78%) cases and was sufficient in six (67%). CONCLUSION: Acute mania and psychosis in the context of PAI is a very rare presentation of an already uncommon disease. Resolution of acute psychiatric change is reliably achieved with the correction of underlying adrenal insufficiency.

Academic cardiac electrophysiologists' perspectives on sleep apnea care.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) is an important, modifiable risk factor in the pathophysiology of arrhythmias including atrial fibrillation (AF). The purpose of the study was to evaluate cardiac electrophysiologists' (EPs) perception of OSAS. METHODS: We designed a 27-item online Likert scale-based survey instrument entailing several domains: (1) relevance of OSAS in EP practice, (2) OSAS screening and diagnosis, (3) perception on treatments for OSAS, (4) opinion on the OSAS care model. The survey was distributed to 89 academic EP programs in the USA and Canada. While the survey instrument questions refer to the term sleep apnea (SA), our discussion of the diagnosis, management, and research on the sleep disorder is more accurately described with the term OSAS. RESULTS: A total of 105 cardiac electrophysiologists from 49 institutions responded over a 9-month period. The majority of respondents agreed that sleep apnea (SA) is a major concern in their practice (94%). However, 42% reported insufficient education on SA during training. Many (58%) agreed that they would be comfortable managing SA themselves with proper training and education and 66% agreed cardiac electrophysiologists should become more involved in management. Half of EPs (53%) were not satisfied with the sleep specialist referral process. Additionally, a majority (86%) agreed that trained advanced practice providers should be able to assess and manage SA. Time constraints, lack of knowledge, and the referral process are identified as major barriers to EPs becoming more involved in SA care. CONCLUSIONS: We found that OSAS is widely recognized as a major concern for EP. However, incorporation of OSAS care in training and routine practice lags. Barriers to increased involvement include time constraints and education. This study can serve as an impetus for innovation in the cardiology OSAS care model.

Prediction of Sudden Cardiac Death: Looking Beyond Ejection Fraction.

PURPOSE OF REVIEW: Sudden cardiac death (SCD) is a major public health burden accounting for 15-20% of global mortality. Contemporary guidelines for SCD prevention are centered around the presence of low left ventricular ejection fraction, although the majority of SCD accrues in those not meeting contemporary criteria for SCD prevention. The goal of this review is to elaborate on the contemporary landscape of SCD prediction tools and further highlight gaps and opportunities in SCD prediction and prevention. RECENT FINDINGS: There have been considerable advancements in both non-invasive and invasive measures for SCD risk prediction including clinical morbidities, electrocardiographic measures, cardiac imaging (nuclear, magnetic resonance, computed tomography), serum biomarkers, genetics, and invasively assessed electrophysiological characteristics. Novel methodological approaches including application of machine learning, incorporation of competing risk, and use of computational modeling have underscored a future of personalized risk prediction. SCD remains a vital public health challenge. Emerging methods highlight opportunities to improve SCD prediction in the majority of those at risk who do not meet contemporary criteria for SCD prevention therapies. Future efforts will need to focus on easily deployed, multi-parametric risk models that enrich for SCD risk and not for competing mortality.

Developing Predictive Models to Anticipate Shunt Complications in 33,248 Pediatric Patients with Shunted Hydrocephalus Utilizing Machine Learning.

INTRODUCTION: Hydrocephalus is a common pediatric neurosurgical pathology, typically treated with a ventricular shunt, yet approximately 30% of patients experience shunt failure within the first year after surgery. As a result, the objective of the present study was to validate a predictive model of pediatric shunt complications with data retrieved from the Healthcare Cost and Utilization Project (HCUP) National Readmissions Database (NRD). METHODS: The HCUP NRD was queried from 2016 to 2017 for pediatric patients undergoing shunt placement using ICD-10 codes. Comorbidities present upon initial admission resulting in shunt placement, Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining criteria, and Major Diagnostic Category (MDC) at admission classifications were obtained. The database was divided into training (n = 19,948), validation (n = 6,650), and testing (n = 6,650) datasets. Multivariable analysis was performed to identify significant predictors of shunt complications which were used to develop logistic regression models. Post hoc receiver operating characteristic (ROC) curves were created. RESULTS: A total of 33,248 pediatric patients aged 6.9 ± 5.7 years were included. Number of diagnoses during primary admission (OR: 1.05, 95% CI: 1.04-1.07) and initial neurological admission diagnoses (OR: 3.83, 95% CI: 3.33-4.42) positively correlated with shunt complications. Female sex (OR: 0.87, 95% CI: 0.76-0.99) and elective admissions (OR: 0.62, 95% CI: 0.53-0.72) negatively correlated with shunt complications. ROC curve for the regression model utilizing all significant predictors of readmission demonstrated area under the curve of 0.733, suggesting these factors are possible predictors of shunt complications in pediatric hydrocephalus. CONCLUSION: Efficacious and safe treatment of pediatric hydrocephalus is of paramount importance. Our machine learning algorithm delineated possible variables predictive of shunt complications with good predictive value.

Characterization of high intensity progressive ultrasound beams in air at 300 kHz.

The majority of reported measurements on high intensity ultrasound beams in air are below 40 kHz and performed on standing waves inside of a guide. Here, experimental characterization of high intensity progressive and divergent sound beams in air at 300 kHz are presented. Measurements in this frequency range are challenging. Accurate characterization of high intensity sound beams requires a measurement bandwidth at least ten times the beam's primary frequency, as high intensity soundwaves steepen and form shocks and, therefore, contain significant signal power at harmonic frequencies. Hence, a measurement bandwidth of at least 3 MHz is required. Calibrated measurement microphones are generally not available in this frequency range. This limitation has been overcome by using a hydrophone with a calibrated response from 250 kHz to 20 MHz. A narrowband piezoelectric transducer is used as the source in this study, and it is capable of generating tone burst waveforms centered at 300 kHz with 160 dB sound pressure level surface pressure. Cumulative wave steepening and shock formation are observed in on-axis measurements. The source's surface vibration profile is measured using a scanning laser Doppler vibrometer, and the vibration profile is imported into a numerical wide-angle Khokhlov-Zabolotskaya-Kuznetsov simulation for comparison against measured on-axis waveforms.

A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope.

INTRODUCTION: Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs. MATERIALS AND METHODS: We performed a retrospective chart review of all adult patients who underwent initial DBS implantation at Stanford Hospital between November 14, 2012, and November 9, 2020. Operative details, perioperative antibiotics, comorbidities, and postoperative complications were extracted for all patients. Univariate and multivariate logistic regression were used to identify factors associated with SSIs within three months of surgery, and interrupted time-series analysis was performed to assess whether the departmental adoption of the antibacterial envelope led to a reduction in IPG SSIs. RESULTS: Of 344 patients who underwent initial IPG implantation with the antibacterial envelope, one developed an SSI within three months of surgery (0.3%), compared with six of 204 patients (2.9%) who underwent the same procedure without the antibacterial envelope (odds ratio: 0.10, 95% CI: 0.01-0.80, p = 0.031). Univariate logistic regression revealed that the antibacterial envelope and 2000-mg intravenous cefazolin perioperatively were associated with reduced SSI risk, whereas no other factors reached statistical significance. After adjusting for comorbidities, no association remained statistically significant. Interrupted time-series analysis showed a reduction in SSIs after 2016, but the effect was not significant. CONCLUSIONS: The adoption of antibacterial envelopes was found to reduce IPG SSIs at the univariate level, but this association did not remain significant after controlling for confounding variables including perioperative antibiotic administration. Although encouraging, this study does not conclusively establish that the use of antibacterial pouches in patients who underwent initial DBS implantation reduces the incidence of IPG SSIs. Future prospective studies that control for confounding variables are necessary to determine the efficacy of antibacterial envelopes in reducing post-DBS infections at the IPG site before clear recommendations can be made.

Soybean (Glycine max) INFOGEST Colonic Digests Attenuated Inflammatory Responses Based on Protein Profiles of Different Varieties.

Soybean compounds have been established to modulate inflammation, but less is known about how whole soybean compositions work together after digestion. The objective was to evaluate and compare the anti-inflammatory responses of different soybean varieties under simulated gastrointestinal digestion, with additional consideration of the glycinin:ß-conglycinin ratio (GBR). Soybean colonic digests (SCD) inhibited cyclooxygenase (COX)-2 (25-82%), 5-lipoxidase (LOX) (18-35%), and inducible nitric oxide (iNOS) (8-61%). Varieties 88, GN3, and 93 were the most effective inhibitors. SCD (1 mg/mL) of varieties 81 and GN1 significantly (p < 0.05) reduced nitrite production by 44 and 47%, respectively, compared to lipopolysaccharide (LPS)-stimulated macrophages. SCD effectively reduced pro-inflammatory cytokine interleukin (IL)-6 (50 and 80% for 96 and GN1, respectively). Western blot results showed a decrease in the expression of iNOS, p65, and p50. The GBR was in the range of 0.05-1.57. Higher ratio correlated with higher production of IL-1ß (r = 0.44) and tumor necrosis factor-alpha (TNF-α, r = 0.56). Inflammatory microarray results showed a significant decrease in expression of markers granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-6 in cells treated with GN1 SCD compared to LPS. The results suggested that SCD exerted its anti-inflammatory potential through nuclear factor kappa B (NF-κΒ) pathway inhibition by decreasing the levels of NF-κB-dependent cytokines and subunits, and inhibition of pro-inflammatory enzyme activity.

Therapeutic techniques and session impact: A practice-research network study in private practice.

Objective: This study investigated the relationship between therapeutic techniques and session impact, by examining the replicability of findings observed in a university-based training clinic (Boswell et al., 2010) in another practice-oriented setting: private practice.Method: N = 8 therapists completed session-level assessments of their technique use for N = 38 clients. The same client sample completed session-level assessments of session outcome. Technique-outcome associations were examined with multilevel models.Results: As in Boswell et al., common factors were associated with positive session impact. For clients who received higher average common factor techniques (relative to their own therapist's caseload), session impact was the poorest in sessions with higher behavioral change techniques use (relative to the client's own average). Moreover, clients with the lowest average common factor techniques (relative to their therapist's caseload) reported better session impact in sessions that involved a higher degree of session-level behavioral change techniques (relative to their own average).Conclusion: In line with Boswell et al., therapists should be mindful of the consistency of their routine technique use between- and within-clients, and this can be aided through collection of their own practice-oriented data.