Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma.

Introduction: Memantine is used for neurocognitive protection in patients undergoing cranial radiotherapy for central nervous system tumors and is reported to be well-tolerated.

Case Report: Presented is a case of memantine-induced altered mental status requiring an intensive care unit admission. An 18-year-old male with relapsed, progressive medulloblastoma presented with severe altered mental status shortly after the first fraction of palliative whole brain radiotherapy.

Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia.

Improving Guideline-Congruent Care for Chemotherapy-Induced Nausea and Vomiting Prophylaxis in Pediatric Oncology Patients.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon.

A nanoscale DNA force spectrometer capable of applying tension and compression on biomolecules.

Single molecule force spectroscopy is a powerful approach to probe the structure, conformational changes, and kinetic properties of biological and synthetic macromolecules. However, common approaches to apply forces to biomolecules require expensive and cumbersome equipment and relatively large probes such as beads or cantilevers, which limits their use for many environments and makes integrating with other methods challenging. Furthermore, existing methods have key limitations such as an inability to apply compressive forces on single molecules.

The Impact of Individual and Parental American Indian Boarding School Attendance on Chronic Physical Health of Northern Plains Tribes.

This study investigated the relationship of American Indian boarding school attendance and chronic physical health. We hypothesized boarding school attendance would be associated with an increased number of chronic physical health problems. We also examined the relationship between boarding school attendance and the 15 chronic health problems that formed the count of the chronic health conditions.

Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant.

Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant.

The relationship of five boarding school experiences and physical health status among Northern Plains Tribes.

Purpose: American Indian (AI) boarding school attendance is related to poor physical health status; however, little is known about how specific aspects of this experience contribute to poor health. Five experiences (age of first attendance, limited family visits, forced church attendance, prohibition on practicing AI culture and traditions, and punishment for use of AI language) may be independently associated with physical health status in adulthood. We expected the effect to be greater for those who began boarding school at older ages.

National Overview of Medication-Assisted Treatment for American Indians and Alaska Natives With Substance Use Disorders.

Objective: American Indians and Alaska Natives (AI/ANs) experience higher rates of substance use disorders and less access to high-quality care compared with other racial-ethnic groups. The objective of this study was to better understand the use of medication-assisted treatment (MAT) of substance use disorders for AI/ANs and barriers to broader implementation.

Methods: Representatives of 192 substance abuse treatment programs completed a survey about their use of MAT.

Clindamycin-associated acute generalized exanthematous pustulosis.

What Is Known And The Objective: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous reaction that usually occurs following medication exposure. Clindamycin has rarely been linked to dermatologic side effects, including AGEP.

Case Summary: This report details the case of a patient who developed AGEP with vancomycin and clindamycin use.

Correlates of Motivational Interviewing Use Among Substance Use Treatment Programs Serving American Indians/Alaska Natives.

Motivational interviewing (MI) offers a treatment modality that can help meet the treatment needs of American Indians/Alaska Natives (AI/ANs) with substance use disorders. This report presents results from a national survey of 192 AI/AN substance abuse treatment programs with regard to their use of MI and factors related to its implementation, including program characteristics, workforce issues, clinician perceptions of MI, and how clinicians learned about MI. Sixty-six percent of programs reported having implemented the use of MI in their programs.

AMERICAN INDIAN AND ALASKA NATIVE BOYS: EARLY CHILDHOOD RISK AND RESILIENCE AMIDST CONTEXT AND CULTURE.

American Indian and Alaska Native (AIAN) adolescent and adult men experience a range of health disparities relative to their non-AIAN counterparts and AIAN women. Given the relatively limited literature on early development in tribal contexts, however, indicators of risk during early childhood specific to AIAN boys are not well-known. The current article reviews sources of strength and challenge within AIAN communities for AIAN children in general, including cultural beliefs and practices that support development, and contextual challenges related to socioeconomic and health disparities and historical trauma affecting the AIAN population as a whole.

A National Study of American Indian and Alaska Native Substance Abuse Treatment: Provider and Program Characteristics.

American Indians and Alaska Natives (AIANs) experience major disparities in accessing quality care for mental health and substance use disorders. There are long-standing concerns about access to and quality of care for AIANs in rural and urban areas including the influence of staff and organizational factors, and attitudes toward evidence-based treatment for addiction. We conducted the first national survey of programs serving AIAN communities and examined workforce and programmatic differences between clinics located in urban/suburban (n=50) and rural (n=142) communities.

Characterization of PCS1055, a novel muscarinic M4 receptor antagonist.

Identification of synthetic ligands selective for muscarinic receptor subtypes has been challenging due to the high sequence identity and structural homology among the five muscarinic acetylcholine receptors. Here, we report the pharmacological characterization of PCS1055, a novel muscarinic M4 receptor antagonist. PCS1055 inhibited radioligand [(3)H]-NMS binding to the M4 receptor with a Ki=6.

Use of evidence-based treatments in substance abuse treatment programs serving American Indian and Alaska Native communities.

Background: Research and health surveillance activities continue to document the substantial disparities in the impacts of substance abuse on the health of American Indian and Alaska Native (AI/AN) people. While Evidence-Based Treatments (EBTs) hold substantial promise for improving treatment for AI/ANs with substance use problems (as they do for non-AI/ANs), anecdotal reports suggest that their use is limited. In this study, we examine the awareness of, attitudes toward, and use of EBTs in substance abuse treatment programs serving AI/AN communities.

Design and synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as selective and potent muscarinic M₁ agonists.

The observation that cholinergic deafferentation of circuits projecting from forebrain basal nuclei to frontal and hippocampal circuits occurs in Alzheimer's disease has led to drug-targeting of muscarinic M1 receptors to alleviate cognitive symptoms. The high homology within the acetylcholine binding domain of this family however has made receptor-selective ligand development challenging. This work presents the synthesis scheme, pharmacokinetic and structure-activity-relationship study findings for M1-selective ligand, LY593093.

Decreased mental health care utilization following a psychosocial intervention in caregivers of hematopoietic stem cell transplant patients.

Caregivers are known to experience increased morbidity when compared to noncaregivers. Does an intervention targeting caregiver distress affect their health care utilization? One hundred forty-eight caregivers of allogeneic hematopoietic stem cell transplant patients were randomized to treatment as usual (TAU) or a psychoeducation, paced respiration, and relaxation (PEPRR) intervention. Assessments of caregivers' service utilization were collected at baseline and 1, 3, and 6 months post-transplant.

Toddler socioemotional behavior in a northern plains Indian tribe: associations with maternal psychosocial well-being.

M.C. Sarche, C.

Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites.

In this study, we characterized a muscarinic acetylcholine receptor (mAChR) potentiator, LY2119620 (3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide) as a novel probe of the human M2 and M4 allosteric binding sites. Since the discovery of allosteric binding sites on G protein-coupled receptors, compounds targeting these novel sites have been starting to emerge. For example, LY2033298 (3-amino-5-chloro-6-methoxy-4-methyl-thieno(2,3-b)pyridine-2-carboxylic acid cyclopropylamid) and a derivative of this chemical scaffold, VU152100 (3-amino-N-(4-methoxybenzyl)-4,6-dim​ethylthieno[2,3-b]pyridine carboxamide), bind to the human M4 mAChR allosteric pocket.

Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors.

The M(4) receptor is a compelling therapeutic target, as this receptor modulates neural circuits dysregulated in schizophrenia, and there is clinical evidence that muscarinic agonists possess both antipsychotic and procognitive efficacy. Recent efforts have shifted toward allosteric ligands to maximize receptor selectivity and manipulate endogenous cholinergic and dopaminergic signaling. In this study, we present the pharmacological characterization of LY2119620 (3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy] thieno[2,3-b]pyridine-2-carboxamide), a M(2)/M(4) receptor-selective positive allosteric modulator (PAM), chemically evolved from hits identified through a M4 allosteric functional screen.

Religio-Spiritual Participation in Two American Indian Populations.

Following a previous investigation of religio-spiritual beliefs in American Indians, this article examined prevalence and correlates of religio-spiritual participation in two tribes in the Southwest and Northern Plains (N = 3,084). Analysis suggested a "religious profile" characterized by strong participation across three traditions: aboriginal, Christian, and Native American Church. However, sociodemographic variables that have reliably predicted participation in the general American population, notably gender and age, frequently failed to achieve significance in multivariate analyses for each tradition.

Multilevel context of depression in two American Indian tribes.

Objective: Depression is a major debilitating disease. For American Indians living in tribal reservations, who endure disproportionately high levels of stress and poverty often associated with depression, determining the patterns and correlates is key to appropriate clinical assessment and intervention development. Yet little attention has been given to the cultural context of correlates for depression, including the influence of family, cultural traditions or practices, or community conditions.

Lifetime prevalence of posttraumatic stress disorder in two American Indian reservation populations.

Posttraumatic stress disorder (PTSD) has been found to be more common among American Indian populations than among other Americans. A complex diagnosis, the assessment methods for PTSD have varied across epidemiological studies, especially in terms of the trauma criteria. Here, we examined data from the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) to estimate the lifetime prevalence of PTSD in two culturally distinct American Indian reservation communities, using two formulas for calculating PTSD prevalence.

Trauma and conditional risk of posttraumatic stress disorder in two American Indian reservation communities.

Purpose: To determine conditional risk of posttraumatic stress disorder (PTSD) in two culturally distinct American Indian reservation communities.

Method: Data derived from the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project, a cross-sectional population-based survey that was completed between 1997 and 2000. This study focused on 1,967 participants meeting the DSM-IV criteria for trauma exposure.