Oscillatory Coupling Between Neural and Cardiac Rhythms.

Oscillations serve a critical role in organizing biological systems. In the brain, oscillatory coupling is a fundamental mechanism of communication. The possibility that neural oscillations interact directly with slower physiological rhythms (e.g., heart rate, respiration) is largely unexplored and may have important implications for psychological functioning. Oscillations in heart rate, an aspect of heart rate variability (HRV), show remarkably robust associations with psychological health. Mather and Thayer proposed coupling between high-frequency HRV (HF-HRV) and neural oscillations as a mechanism that partially accounts for such relationships. We tested this hypothesis by measuring phase-amplitude coupling between HF-HRV and neural oscillations in 37 healthy adults at rest. Robust coupling was detected in all frequency bands. Granger causality analyses indicated stronger heart-to-brain than brain-to-heart effects in all frequency bands except gamma. These findings suggest that cardiac rhythms play a causal role in modulating neural oscillations, which may have important implications for mental health.

Task-based default mode network connectivity predicts cognitive impairment and negative symptoms in first-episode schizophrenia.

Individuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in "source monitoring" have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self-generated and externally generated events is disrupted. Source monitoring abnormalities in SZ have additionally been linked to impairments in selective attention and inhibitory processing, which are reliably observed via the N100 component of the event-related brain potential elicited during an auditory paired-stimulus paradigm. Given overlapping constructs associated with DMN connectivity and N100 in SZ, the present investigation evaluated relationships between these measures of disorder-related dysfunction and sought to clarify the nature of task-based DMN function in SZ. DMN connectivity and N100 measures were assessed using EEG recorded from SZ during their first episode of illness (N = 52) and demographically matched healthy comparison participants (N = 25). SZ demonstrated less evoked theta-band connectivity within DMN following presentation of pairs of identical auditory stimuli than HC. Greater DMN connectivity among SZ was associated with better performance on measures of sustained attention (p = .03) and working memory (p = .09), as well as lower severity of negative symptoms, though it was not predictive of N100 measures. Together, present findings provide EEG evidence of lower task-based connectivity among first-episode SZ, reflecting disruptions of DMN functions that support cognitive processes. Attentional processes captured by N100 appear to be supported by different neural mechanisms.

Does format matter? A naturalistic study of digital and provider-led cognitive behavioral therapy for insomnia implemented in a healthcare system.

OBJECTIVES: Cognitive Behavioral Therapy for Insomnia (CBTi) is a first-line treatment for a prevalent and impairing disorder. Digital CBTi programs increase access to internet-based self-directed care. However, the clinical effect of offering different forms of CBTi in a healthcare setting is not clearly understood. This study examines treatment engagement and clinical outcomes for individuals referred to either digital or provider-led CBTi. METHODS: Over two years, providers at a Veterans Health Administration (VHA) facility referred patients to digital CBTi with telephone coaching support or traditional provider-led CBTi. Characteristics of those referred, proportions engaging in and completing treatment, as well as insomnia severity were compared among those referred to each format. RESULTS: Providers referred 139 individuals to digital CBTi, 340 to provider-led CBTi, and 14 to both formats. Individuals referred to digital CBTi were older with less severe insomnia. Despite lower levels of program engagement and completion in the digital CBTi cohort, measures of insomnia symptom change were similar between the groups. CONCLUSIONS: This is the first study to evaluate both digital and provider-led evidence-based treatments for insomnia disorder simultaneously deployed in a healthcare setting. While engagement in digital CBTi lagged that for provider-led CBTi, offering both formats may expand access to different groups, while fostering similar outcomes.

Robotic Surgery for Stone Disease.

PURPOSE OF REVIEW: To evaluate recent literature regarding the role of robotic technology in the treatment of nephrolithiasis with particular attention to complex technical procedures. RECENT FINDINGS: Robotic platforms including single-port robotics have been widely adopted in urological practice for the treatment of both malignant and benign conditions and has led to an expansion of the utilization of robot-assisted surgery to tackle challenging clinical scenarios such as bladder neck reconstruction, upper urinary tract reconstruction, and more recently complex stone disease. Presently, the American Urological Association guidelines on the surgical management of stones advise against using robotic, open, or laparoscopic techniques as a first-line approach for most patients with stone disease with the exception for patients with anatomical abnormalities, large or complex stones, or patients requiring a concomitant reconstructive operation. Clinicians have demonstrated the safety and feasibility of surgical robotics in the treatment of stone disease for a variety of operations including robotic pyeloplasty, pyelolithotomy, ureterolithotomy, and surgical interventions in urinary diversions as well as novel technologies for robotic ureteroscopy and percutaneous access. Numerous clinicians have demonstrated the safety and feasibility of using robot-assisted surgery to treat nephrolithiasis, mainly in complex renal anatomy. Further research is necessary to identify the best candidates for utilization of robotics in complex stone disease, and further technological developments will continue to further advance the use of these platforms in the treatment of nephrolithiasis.

Applying a Primary Health Care Approach to Closing the Human Resource for Health Gaps for Immunization.

This perspective is focused on the evidence on human resources for health (HRH) solutions for immunization, as a part of a primary health care (PHC) approach.. In the wake of the COVID-19 pandemic and 50 years since the Expanded Program on Immunization (EPI) clocks 50 years since its inception. was initiated, evidence and experience demonstrate the significant HRH gaps in many countries and globally, and how countries are seeking innovative ways of closing them with limited resources. The aim of this perspective article is to highlight the growing gap between the needs and the realities related to health workforce for PHC, including immunization, and to call for increasing the visibility of HRH within global and national immunization agendas. This perspective highlights key guidelines and tools to improve HRH, such as integrating immunization and primary health care, addressing the mental health needs of the health workforce, addressing gender-related issues, rationalizing the roles and composition of PHC workforce teams, and meeting the surge requirements related to health emergencies.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Fluorescence-guided radical prostatectomy.

Robotic-assisted laparoscopic radical prostatectomy represents one of the most common operations in urologic oncology and involves several critical technical steps including pelvic lymph node dissection, cavernous nerve sparing and vesicourethral anastomosis. The quality of performing these steps is linked to functional and oncological outcomes. Indocyanine green [ICG] is a non-radioactive, water-soluble compound which allows for enhanced visualization with near-infrared fluorescence of both anatomical structures and vasculature during complex abdominal operations such as prostatectomy. During the last decade, several investigators have examined the value and role of ICG fluorescence during prostatectomy. In this review, we sought to evaluate the body of evidence for fluorescence-guided robotic prostatectomy as well as assess potential future areas of investigation with this technology.

Associations between physiological responses to social-evaluative stress and daily functioning in first-episode schizophrenia.

Schizophrenia (SZ) is associated with impaired adaptive functioning, including difficulties managing the demands of independent living, work, school, and interpersonal relationships. Prior studies have linked the physiological stress response with less effective coping in daily life. Differences in stress-response tendencies may also support heterogeneity in daily functioning in SZ. The present study examined two established measures of the stress response in patients with first-episode SZ. Salivary cortisol was included as an index of hypothalamic-pituitary-adrenal response. Vagal suppression (VS), a measure of stress-related reduction in heart rate variability, was used to assess parasympathetic flexibility. Greater cortisol response and VS to social-evaluative stress were predicted to be associated with better functioning in SZ over and above relationships with social cognition and neurocognition, two well-established predictors of functional outcome. Thirty-eight first-episode SZ outpatients and 29 healthy comparison subjects (HC) provided social cognitive, neurocognitive, and physiological measurements before and after the Trier Social Stress Test (TSST). Although SZ and HC did not differ on VS to the TSST, patients exhibited significant associations between VS and functioning across all four domains of the Role Functioning Scale. Furthermore, greater VS predicted more effective functioning with friends, beyond the contributions associated with social cognition and neurocognition, and strengthened the positive effects of higher levels of social cognition on independent living/self-care. VS elicited by social-evaluative stress in the laboratory may reflect stress-response tendencies in daily life that are relevant for daily functioning in first-episode SZ.

Schizophrenia, smoking status, and performance on the matrics Cognitive Consensus Battery.

Cognitive deficits and high rates of nicotine dependence are consistently documented in the schizophrenia literature. However, there is currently no consensus about how regular smoking influences cognition in schizophrenia or which cognitive domains are most affected by chronic smoking. Previous studies have also failed to disambiguate the effects of chronic nicotine from those of acute exposure. The current study uses a novel approach to testing nicotine addicted patients at a time-point between acute enhancement and withdrawal and implements the MATRICS Cognitive Consensus Battery (MCCB) to compare the overall cognitive performance of regular smokers (n=40) and nonsmokers (n=36) with schizophrenia. Controlling for age, gender, and education, smokers with schizophrenia were significantly more impaired on a visual learning task, the Brief Visuospatial Memory Test-Revised (BVMT-R), than their nonsmoking peers. Among smokers, smoking behavior (i.e., exhaled carbon monoxide levels of smokers) predicted BVMT-R T score; greater smoking was associated with more impaired visual learning. Negative symptom severity was not predictive of greater visual learning deficits in smokers or nonsmokers. Future longitudinal research will be required to determine if there is a dose-response relationship between chronic nicotine and visual learning impairment in patients at various stages of psychotic illness.

The Domino Effects of Federal Research Funding.

The extent to which federal investment in research crowds out or decreases incentives for investment from other funding sources remains an open question. Scholarship on research funding has focused on the relationship between federal and industry or, more comprehensively, non-federal funding without disentangling the other sources of research support that include nonprofit organizations and state and local governments. This paper extends our understanding of academic research support by considering the relationships between federal and non-federal funding sources provided by the National Science Foundation Higher Education Research and Development Survey. We examine whether federal research investment serves as a complement or substitute for state and local government, nonprofit, and industry research investment using the population of research-active academic science fields at U.S. doctoral granting institutions. We use a system of two equations that instruments with prior levels of both federal and non-federal funding sources and accounts for time-invariant academic institution-field effects through first differencing. We estimate that a 1% increase in federal research funding is associated with a 0.411% increase in nonprofit research funding, a 0.217% increase in state and local research funding, and a 0.468% increase in industry research funding, respectively. Results indicate that federal funding plays a fundamental role in inducing complementary investments from other funding sources, with impacts varying across academic division, research capacity, and institutional control.