Now showing items 1-20 of 2657

    • Inflammatory and Cognitive Effects of COVID-19 Infection in Schizophrenia

      Kulaga, Stephanie S.; Glassman, Matthew; Dougherty, Shawna; Pan, Yezhi; Chen, Shuo; Sathyasaikumar, Korrapati V.; Shriver, Mallory; Marx, Kristen; Liu, Fang, M.S.; August, Sharon; et al. (2024-04-04)
    • Combined Cognitive and Sensorimotor Assessment Can Enhance the Detection of Cognitive Changes

      Yin, Wei; Oppizzi, Giovanni; Hur, Soh-Hyun; Zhang, Li-Qun (2024-05-06)
    • A KATP channel-Dependent Electrical Signaling Network Links Capillary Pericytes to Arterioles During Neurovascular Coupling

      Isaacs, Dominic P.; Xiang, Liuruimin; Hariharan, Ashwini; Longden, Thomas A. (2024-04-05)
      The brain has evolved mechanisms to dynamically modify local blood flow, thus enabling the timely delivery of energy substrates and the rapid clearance of byproducts in response to the highly fluctuating metabolic demands of cognition and behavior. Several such neurovascular coupling mechanisms have been identified, but vascular signal transduction and transmission mechanisms that enable acute dilation of penetrating arterioles remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of neurovascular coupling. However, the relatively sparse spatial arrangement of arterioles contrasts with the vast plexus of capillaries, and recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the contractile state of mural cells on upstream vessels. Thin-strand pericyte processes cover around 90% of the capillary bed but their specific contributions to blood flow control are not understood. We hypothesized that thin-strand pericytes could play a role in sensing and transmitting blood flow control signals from neurons back to the electromechanical controller of blood flow , upstream PA and contractile pericytes. We first wondered whether we could probe for the existence of a functional vascular relay between pericytes and arterioles using focal optogenetics. To do this we developed a mouse line expressing ArchT-EGFP optically driven proton pump in mural cells (shown below). We targted pericytes in this mouse with focal 561 nm laser to excite ArchT while monitoring the feeding PA for dynamics. After observing evidence for a functional electrical network coupling pericyte-ArchT activation to PA dilation we moved on to determine if this system operated in a physiological scenario. We assayed neurovascular coupling in several mouse models, including awake mice receiving whisker stimulus and anesthetized Thy1-ChR2-EYFP mice where we excited the cortex with 488 nm point-scanning. We found using a conditional expressed dominant negative KATP channel in mural cells (pericytes and smooth muscle cells) that the initial phase of the bi-phasic response to sensory stimulation was diminished. Next we physically disrupted pericytes via laser ablation, which reduced the PA dilation associated with an optogenetic impulse in neural activity. The effect of laser ablation was lost with the inclusion of glibenclamide in the agar, implicating the pericyte KATP channel specifically in mediating a component of neurovascular coupling in mouse cortex
    • Xylazine-positive prevalence among people receiving medications for opioid use disorder: exploratory data from three urban settings in the Northeast

      Leeman, Alejandro Villar; Fitzsimons, Heather; Greenblatt, Aaron D.; Ringwala, Aditi; Liu, Tracy; Zimmermann, Hannah; Konova, Anna; Tofighi, Babak; Murphy, Sean; Rotrosen, John; et al. (2024-05-06)
    • Effective NAION neuroregenerative treatment using TXA127

      Bernstein, Steven L.; Woo, Kwang Min; Guo, Yan, M.D.; Mehrabyan, Zara (2024-05-04)
      Current approaches to treatment of nonarteritic anterior ischemic optic neuropathy (NAION) rely on early retinal ganglion cell (RGC) neuroprotection. However, current neuroprotective approaches have been ineffective when administered late (>1d) after induction in rodent and primate NAION models. This is particularly problematic clinically, since nearly all patients are diagnosed at least a day post-symptom onset. We report on the success of a new neuroregenerative approach using TXA127, a pharmaceutical formulation of angiotensin (1-7) currently in Phase II for ischemic stroke.
    • Vasoactive Intestinal Peptide alters TCR proximal signaling in naïve T cells

      Adebamowo, Adedola; Rosenberg, Kenneth, M.D., Ph.D.; Singh, Nevil J. (2024-05-01)
      Communication between the nervous and immune systems is critical for regulating the immune response. Neuropeptides have been observed to exert modulatory effects on many different lymphocyte subsets. In mouse models, we found peripheral T cells expressed a set of 26 neurotransmitter receptors and exhibited distinct patterns across T cell subsets. The Vasoactive Intestinal Peptide receptor (VIPR1) had an intriguing pattern with high expression in naïve peripheral CD4 T cells and none in Tregs. Upon T cell receptor (TCR) stimulation, VIPR1 expression rapidly declines, suggesting endogenous VIP primarily affects resting naïve T cells. Functionally, treatment with VIP dampened the early activation of naïve T cells, as measured by reductions in proliferative responses and IL-2 secretion in response to antigenic stimulation. Mechanistically, VIP-exposure directly affected signaling via the TCR. Although the early events in the signaling cascade, such as the phosphorylation of ZAP70 was intact, downstream activation of ERK was reduced. Endogenous VIP has a very short lifespan and therefore localized production is likely to impact naïve T cell activation. To map the cellular sources of VIP we generated strains of VIP-lineagetracing mice. Preliminary analysis shows strong expression in multiple neurons. These data suggest that VIP secreted by neurons has the potential to influence T cell response in a broad manner at the early stage of an immune response.
    • Echogenicity Enhances Risk Assessment of Lesions on MP-MRI for Clinically Significant Prostate Cancer

      Wegner, Garret; Khan, Amir; Panagos, MIchael; Wang, Shu; Van Besien, Alexa J.; Naslund, Michael; Siddiqui, M. Minhaj; Panagos, Michael (2024-05-03)
      Multiparametric Magnetic Resonance Imaging (MP-MRI)/ ultrasound fusion guided biopsy (targeted biopsy) is emerging as an alternative diagnostic tool for Prostate cancer (PCa) in addition to historically used Transrectal Ultrasound-guided (TRUS) biopsy. Echogenicity observed during the fusion of MRI and ultrasound images may be associated with the detection of clinically significant prostate cancer in targeted biopsy of MP-MRI lesions.
    • Evaluating the Impact of the New CKD-EPI Creatinine Equation (2021) for eGFR on the Management of Muscle Invasive Bladder Cancer

      Khan, Amir; Siddiqui, M. Minhaj (2024-05-06)
      The estimated glomerular filtration rate (eGFR) equation had been historically calculated inclusive of a race coefficient. However, in September 2021, the NKF and the American Society of Nephrology Task Force announced a new race-free calculation for eGFR due to criticism around racial disparities. Aspects of treatment decisions for muscle-invasive bladder cancer (MIBC) such as cisplatin-based neoadjuvant chemotherapy (NAC) eligibility depend on eGFR due to potential nephrotoxic effects.
    • Documenting Psychosocial Problems in Children’s Electronic Health Records

      Dubowitz, Howard; Kressly, Susan J. (American Medical Association (AMA), 2023-09-01)
    • Initial Medical Assessment of Possible Child Sexual Abuse: History, History, History

      Dubowitz, Howard; Finkel, Martin; Feigelman, Susan; Lyon, Thomas (Elsevier, 2024)
      Primary care professionals (PCPs) can play a valuable role in the initial assessment of possible child sexual abuse (CSA), an all too prevalent problem. PCPs, however, are often reluctant to conduct these assessments. The goal of this paper is to help PCPs be more competent and comfortable playing a limited but key role. This is much needed as there may be no need for further assessment and also because of a relative paucity of medical experts in this area. While some children present with physical problems, the child's history is generally the critical information. This article therefore focuses on practical guidance regarding history-taking when CSA is suspected, incorporating evidence from research on forensic interviewing. We have been mindful of the practical constraints of a busy practice and the role of the public agencies in fully investigating possible CSA. The approach also enables PCPs to support children and their families.
    • Validation of the Swedish version of the safe environment for every kid (SEEK) parent screening questionnaire

      Engström, Maria; Lindqvist, Sara; Janson, Staffan; Feldman, Inna; Dubowitz, Howard; Lucas, Steven (Springer Science and Business Media LLC, 2023-10-12)
      Background: Psychosocial risk factors in the home may impair children's health and development and increase the risk of maltreatment. The Safe Environment for Every Kid (SEEK) model was developed to provide pediatric primary care professionals with a structured way to identify common psychosocial problems. The SEEK model includes use of the Parent Screening Questionnaire (SEEK-PSQ) at routine preventive child health visits, discussion with parents about their responses and, when indicated, referral to relevant services. The SEEK-PSQ has not previously been available in Swedish. The aim of the present study was to evaluate the psychometric properties of an adapted Swedish version of the SEEK-PSQ (PSQ-S). Methods: This study is part of a cluster-randomised controlled trial of SEEK in the Swedish child health services. To validate the PSQ-S, parents (n = 852) with children 0-18 months of age were invited to complete a survey including the PSQ-S as well as evidence-based standardized instruments for the targeted psychosocial risk factors: economic worries, depressive symptoms, parental stress, alcohol misuse and intimate partner violence (IPV). Baseline data from 611 (72%) parents were analysed regarding sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each risk factor. Results: As a whole, the PSQ-S had a sensitivity of 93%, specificity of 52%, PPV of 67% and NPV of 87%. For mothers and fathers combined, sensitivity was 80% for economic worries, 89% for depressive symptoms, 78% for parental stress, 47% for intimate partner violence (IPV) and 70% for alcohol misuse. Specificity was highest for IPV and alcohol misuse (91%) and lowest for depressive symptoms (64%). NPV values were high (81-99%) and PPV values were low to moderate (22-69%) for the targeted problems. Sensitivity was higher for mothers compared to fathers for economic worries, depressive symptoms and IPV. This difference was particularly evident for IPV (52% for mothers, 27% for fathers). Conclusion: The SEEK-PSQ-S demonstrated good psychometric properties for identifying economic worries, depressive symptoms, parental stress and alcohol misuse but low sensitivity for IPV. The PSQ-S as a whole showed high sensitivity and NPV, indicating that most parents with or without the targeted psychosocial risk factors were correctly identified.
    • Assessment of Adoption and Early Implementation Barriers and Facilitators of the Safe Environment for Every Kid (SEEK) Model

      Palinkas, Lawrence A.; Belanger, Rosemarie; Newton, Stacey; Saldana, Lisa; Landsverk, John; Dubowitz, Howard (Elsevier, 2023)
      Objective: Although the use of interventions for screening for social determinants of health of families in pediatric primary care clinics has increased in the past decade, research on the barriers and facilitators of implementing such interventions has been limited. We explored barriers, facilitators, and the mechanisms clarifying their roles in the adoption and implementation of the Safe Environment for Every Kid (SEEK) model, an approach for strengthening families, promoting children's health and development, and preventing child maltreatment. Methods: A total of 28 semistructured interviews were completed with 9 practice champions, 11 primary care professionals, 5 behavioral health professionals, and 3 nursing/administrative staff representing 12 pediatric primary care practices participating in a larger randomized control trial of implementing SEEK. Results: We identified several barriers and facilitators in the stages of SEEK's adoption and early implementation. Barriers associated with outer and inner setting determinants and poor innovation-organization fit declined in importance over time, while facilitators associated with SEEK characteristics increased in importance based on participants' responses. Barriers and facilitators were linked by mechanisms of comparison and contrast of burdens and benefits, and problem-solving to address limited capacity with available resources. Conclusions: Any screening for and addressing social determinants of health demands greater attention to adoption and implementation mechanisms and the processes by which primary care professionals assess and utilize facilitators to address barriers. This occurs in a context defined by perceived burdens and benefits of innovation adoption and implementation, the capacity of the practice, and changes in perception with experiencing the innovation.
    • Addressing Adverse Childhood Experiences in Primary Care: Challenges and Considerations

      Dubowitz, Howard; Finkelhor, David; Zolotor, Adam; Kleven, Jennifer; Davis, Neal (American Academy of Pediatrics (AAP), 2022-03-10)
      This article draws attention to the overlapping literature on social determinants of health and adverse childhood experiences, and the growing clinical interest in addressing them to promote children's and parents' health and well-being. We address important considerations and suggest solutions for leaders and practitioners in primary care to address social determinants of health/adverse childhood experiences. Priorities include: begin with a few prevalent conditions for which there are helpful resources; focus on conditions that are current or recent and where parents may be more apt to engage in services; focus initially on families with children aged <6 given the frequency of well-child visits and the especially strong relationships between primary care professionals and parents during this period; ensure training of primary care professionals and staff to help them play this role competently and comfortably; and have good referral processes to facilitate additional evaluation or help.
    • Neglect in Childhood, Problem Behavior in Adulthood

      Dubowitz, Howard; Roesch, Scott; Lewis, Terri; Thompson, Richard; English, Diana; Kotch, Jonathan B. (SAGE Publications, 2022-02-13)
      Few studies have reported problem behaviors in adulthood related to the timing of child neglect. The objective was to examine the relationship between classes of child neglect and later behavior. The sample included 473 participants from the prospective Longitudinal Studies of Child Abuse and Neglect (LONGSCAN); their mean age was 23.8 years. They completed an online survey regarding behaviors and experiences in early adulthood. Neglect was assessed via Child Protective Services (CPS) and self-reports of neglect. Latent class analysis (LCA) identified three classes: Late Neglect, Chronic Neglect, and Limited Neglect. There were significant differences between Limited and Late Neglect regarding later intimate partner aggression and violence (IPAV) and psychological distress, and among all classes for criminal behavior. High-risk youth experiencing neglect beginning in mid-adolescence appear especially vulnerable to later criminal behavior, psychological distress, and IPAV. Those working with such youth can help ensure that their needs are adequately met, to prevent or mitigate problems in adulthood.
    • Adolescent Neglect and Health Risk

      Kobulsky, Julia M.; Villodas, Miguel; Yoon, Dalhee; Wildfeuer, Rachel; Steinberg, Laurence; Dubowitz, Howard (SAGE Publications, 2021-10-19)
      This study examined relationships between adolescent neglect and abuse and later health risk in a sample of 1050 youth (53% female, 56% Black, and 24% White) from the Longitudinal Studies of Child Abuse and Neglect. At age 16, the youth reported any adolescent exposure to neglect and physical, sexual, and emotional abuse. At age 18, they reported risk behaviors (delinquency, substance use, and sexual behavior) and emotional and behavioral problems (externalizing and internalizing problems, suicidality). Control variables were childhood maltreatment (self-reports and early childhood child protective services reports), risk behaviors and emotional and behavioral problems at age 16, and demographics. Analysis confirmed a 5-factor model of adolescent neglect (Exposure to Risk, Inadequate Monitoring, Inattention to Basic Needs, Permitting Misbehavior, and Inadequate Support). Inadequate Support and Exposure to Risk were associated with more substances used; Exposure to Risk was also associated with delinquency and suicidality. Adolescent emotional abuse was associated with not using a condom use and internalizing and externalizing problems. Findings underscore the importance of preventing or addressing neglect during adolescence.
    • Social determinants of health, personalized medicine, and child maltreatment

      Lane, Wendy G.; Dubowitz, Howard (Springer Science and Business Media LLC, 2021)
      This review begins with a brief summary of the importance of child maltreatment as a major public health problem, given its prevalence and the substantial human and economic costs involved. The focus then shifts to consideration of personalized medicine and child maltreatment, including genetic and genomics factors, as well as the role of social determinants of health. Research on epigenetics related to child abuse and neglect is presented, followed by that pertaining to a few specific social factors, such as poverty, parental depression and substance use, and domestic (or intimate partner) violence. The review ends with a discussion of interventions to help address social determinants of health with brief descriptions of several model programs, and thoughts concerning the role of personalized medicine in addressing child maltreatment in the foreseeable future. IMPACT: This paper synthesizes knowledge on social determinants of health and advances in genetics and genomics related to the prevention of child maltreatment. It provides examples of model approaches to addressing the prevention of child maltreatment in primary care practices.
    • Public policy and parent-child aggression: Considerations for reducing and preventing physical punishment and abuse

      McGuier, Elizabeth A.; Kolko, David J.; Dubowitz, Howard (Elsevier, 2022)
      Parent-child physical aggression, including both physical punishment and abuse, remains a prevalent problem in the United States. In this paper, we briefly review the prevalence and harms of parent-child aggression and discuss changes in social norms and policies over the past several decades. Then, we discuss broad social policies influencing risk for parent-child physical aggression, policies relevant to reducing and preventing physical abuse, and policies relevant to reducing and preventing physical punishment. We close by considering future directions to strengthen research and evaluation and accelerate progress toward ending parent-child physical aggression.