Tribally-led mobile outreach: improving access to harm reduction services in one rural reservation community.

American Indian and Alaska Native populations in the United States face significant disparities related to opioid use disorder and opioid-related mortality. Inequitable access to medications and harm reduction strategies due to structural, societal, and geographical factors prevent Tribal communities from obtaining needed services, and further contribute to the opioid epidemic. One Tribal Healing Center in the Rocky Mountain region identified mobile outreach to build upon existing opioid prevention, treatment, and harm reduction efforts.

Protein analysis using capillary electrophoresis coupled to mass spectrometry through vibrating sharp-edge spray ionization.

Capillary electrophoresis (CE) interfaced to mass spectrometry (MS) with electrospray ionization typically incorporates acidic additives or organic solvents to assist in ionization. Vibrating sharp-edge spray ionization (VSSI) is a voltage-free method to interface CE and MS that does not require these additives, making it appealing for protein analyses. CE-VSSI nanoflow sheath separations are performed with low ionic strength aqueous solutions in the sheath to reduce suppression.

Prospective evaluation of NGS-based sequencing in epilepsy patients: results of seven NASGE-associated diagnostic laboratories.

Background: Epilepsy is one of the most common and disabling neurological disorders. It is highly prevalent in children with neurodevelopmental delay and syndromic diseases. However, epilepsy can also be the only disease-determining symptom.

Documenting tribal community readiness to support substance abuse prevention.

Documenting community readiness to support substance abuse prevention in tribal communities is needed to maximize the impact of prevention programming. Semi-structured interviews with 26 tribal community members from Montana and Wyoming served as the primary data source for this evaluation. The Community Readiness Assessment was used to guide the interview process, analysis, and results.

Amplified Gliosis and Interferon-Associated Inflammation in the Aging Brain following Diffuse Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with chronic psychiatric complications and increased risk for development of neurodegenerative pathology. Aged individuals account for most TBI-related hospitalizations and deaths. Nonetheless, neurobiological mechanisms that underlie worsened functional outcomes after TBI in the elderly remain unclear.

Chronic Cortical Inflammation, Cognitive Impairment, and Immune Reactivity Associated with Diffuse Brain Injury Are Ameliorated by Forced Turnover of Microglia.

Traumatic brain injury (TBI) is associated with an increased risk of cognitive, psychiatric, and neurodegenerative complications that may develop after injury. Increased microglial reactivity following TBI may underlie chronic neuroinflammation, neuropathology, and exaggerated responses to immune challenges. Therefore, the goal of this study was to force turnover of trauma-associated microglia that develop after diffuse TBI and determine whether this alleviated chronic inflammation, improved functional recovery and attenuated reduced immune reactivity to lipopolysaccharide (LPS) challenge.

The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature.

This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied.

Retrieval of vector integration sites from cell-free DNA.

Gene therapy (GT) has rapidly attracted renewed interest as a treatment for otherwise incurable diseases, with several GT products already on the market and many more entering clinical testing for selected indications. Clonal tracking techniques based on vector integration enable monitoring of the fate of engineered cells in the blood of patients receiving GT and allow assessment of the safety and efficacy of these procedures. However, owing to the limited number of cells that can be tested and the impracticality of studying cells residing in peripheral organs without performing invasive biopsies, this approach provides only a partial snapshot of the clonal repertoire and dynamics of genetically modified cells and reduces the predictive power as a safety readout.

Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients.

Background: Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency.

Objective: In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene.

Methods: For genetic analysis, we performed Whole Exome Sequencing (WES) or targeted sequencing by means of Next-generation sequencing (NGS) for some of the patients.

Refractory and Fatal Presentation of Severe Autoimmune Hemolytic Anemia in a Child With the DNASE1L3 Mutation Complicated With an Additional DOCK8 Variant.

Various autoimmune diseases may be associated with primary immune deficiencies. We reported a case with a loss-of-function mutation in DNASE1L3, a gene described previously in families with systemic lupus erythematosus. In addition, the patient showed a novel homozygous missense variant in DOCK8, a gene known to be responsible for the hyper-IgE recurrent infection syndrome (HIES).

A Feasibility Evaluation of the Urban Native Youth Leaders Program.

Urban American Indian and Alaska Native (AI/AN) youth represent a unique and growing population in the United States. Culture and participation in cultural activities is associated with resilience; however, urban AI/AN youth often report limited access to their culture. This paper presents results from a mixed-method feasibility evaluation of the Native Youth Leaders (NYL) program, a culturally-grounded youth program for urban AI youth.

Early 'Aryans' and their neighbors outside and inside India.

Data from archaeology, linguistics, population genetics, and from early Vedic texts, which deal with religion, mythology and rituals, have to be assembled and closely compared in order to gain a comprehensive picture of the early 'Aryans'. Such interdisciplinary dialogue is necessary in order to establish areas of overlap of data. This paper attempts to indicate a western Central Asian origin of the Indo-Aryan speakers, in the steppe belt near the Urals, from where they moved, via the Inner Asian Mountain belt and Bactria, into India.

Preventing Substance Use in American Indian Youth: The Case for Social Support and Community Connections.

Aims: This study explored the relationship between social support, community connections, self-esteem, and culture on misuse in American Indian youth.

Methods: The study team developed a culturally-responsive 16-question survey for American Indian youth ages 12-20 living in six American Indian communities in the Great Plains Region of the United States. The study was grounded in primary socialization theory and variables were explored using regression models.

Alpha-Amino-Beta-Carboxy-Muconate-Semialdehyde Decarboxylase Controls Dietary Niacin Requirements for NAD Synthesis.

NAD is essential for redox reactions in energy metabolism and necessary for DNA repair and epigenetic modification. Humans require sufficient amounts of dietary niacin (nicotinic acid, nicotinamide, and nicotinamide riboside) for adequate NAD synthesis. In contrast, mice easily generate sufficient NAD solely from tryptophan through the kynurenine pathway.

Is culturally based prevention effective? Results from a 3-year tribal substance use prevention program.

American Indian youth substance use is a major public health concern. To date, there has been limited evaluation of American Indian youth substance use prevention programs. Evaluation of prevention programs is necessary to understand the aspects of programming that are effective or not effective.

A review of tribal best practices in substance abuse prevention.

Unlabelled: American Indian youth experience higher rates of substance use than non-American Indian youth. Researchers, clinicians, and treatment programs embrace evidence-based practices (EBPs) and practice based evidence (PBE) as a primary method for addressing substance abuse and advancing behavioral health. However, less is known about the use of tribal best practices (TBPs) and how they are implemented in American Indian substance use prevention contexts.

Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.

We identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, we identified three homozygous loss-of-function mutations in SMARCD2. Using mice and zebrafish as model systems, we showed that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells.

Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations.

Background: Myb-like, SWIRM, and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood.

Objectives: We sought to investigate the clinical, cellular, and molecular features in 2 siblings presenting with progressive bone marrow failure (BMF), immunodeficiency, and developmental aberrations.

CLINICAL FEATURES AND GENETIC ANALYSIS OF SIX PATIENTS WITH WISKOTT-ALDRICH SYNDROME REPORTING TWO NOVEL MUTATIONS: EXPERIENCE OF ERCIYES UNIVERSITY, KAYSERI, TURKEY.

Aim: The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by micro-thrombocytopenia, eczema, and recurrent infections. We aimed to share our experience with six children with WAS, including two patients with two novel mutations.

Material And Method: We present phenotypical and laboratory description of six patients with WAS.

Gene therapy for Wiskott-Aldrich syndrome--long-term efficacy and genotoxicity.

Wiskott-Aldrich syndrome (WAS) is characterized by microthrombocytopenia, immunodeficiency, autoimmunity, and susceptibility to malignancies. In our hematopoietic stem cell gene therapy (GT) trial using a γ-retroviral vector, 9 of 10 patients showed sustained engraftment and correction of WAS protein (WASP) expression in lymphoid and myeloid cells and platelets. GT resulted in partial or complete resolution of immunodeficiency, autoimmunity, and bleeding diathesis.

Gene therapy for Wiskott-Aldrich Syndrome-Long-term reconstitution and clinical benefits, but increased risk for leukemogenesis.

Wiskott-Aldrich-Syndrome (WAS) is a rare X-linked recessive disease caused by mutations of the WAS gene. It is characterized by immunodeficiency, autoimmunity, low numbers of small platelets (microthrombocytopenia) and a high risk of cancer, especially B cell lymphoma and leukemia.

Afghan Hindu Kush: where Eurasian sub-continent gene flows converge.

Despite being located at the crossroads of Asia, genetics of the Afghanistan populations have been largely overlooked. It is currently inhabited by five major ethnic populations: Pashtun, Tajik, Hazara, Uzbek and Turkmen. Here we present autosomal from a subset of our samples, mitochondrial and Y- chromosome data from over 500 Afghan samples among these 5 ethnic groups.