Caregiver ECHO: A Model for Delivering Virtual Behavior Management Education to Families of Children With Neurodevelopmental Disorders.

Children with neurodevelopmental disorders (NDD) are at high risk of challenging behavior, yet families experience consistent barriers to affordable parent education in behavior management. This study tested the efficacy of a caregiver-focused Extensions of Community Health Outcomes (ECHO) program in delivering behavior management education and support to caregivers of children with NDD. A pre-post design was used to evaluate impact on 30 caregivers' behavioral knowledge, self-efficacy in managing challenging behavior, empowerment, and negative emotional reactions to challenging behavior.

Environmentally sustainable opportunities for health systems: Metered-dose inhaler prescribing, dispensing, use and waste at a tertiary academic centre.

Background: The Canadian health sector's carbon footprint is among the highest in the world and is responsible for 4.6% of Canada's total greenhouse gas emissions, a quarter of which is linked to pharmaceuticals, with metered-dose inhalers (MDIs) contributing disproportionally high amounts.

Objectives: To describe MDI prescribing, dispensing, use and waste patterns at a Canadian tertiary care academic hospital.

A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation.

Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques.

Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations.

Different Patterns of Care and Survival Outcomes in Transplant-Centre Managed Patients with Early-Stage HCC: Real-World Data from an Australian Multi-Centre Cohort Study.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes.

ECHO Autism Washington: Autism Diagnostic Evaluations in Primary Care.

() is a telementoring learning model to increase community capacity for autism-related health care. Seventy-seven pediatric providers (mostly primary care, seeing exclusively Medicaid patient populations) enrolled in 1 year of . Analysis of self-report surveys showed a significant increase in autism diagnoses made by ECHO providers after 1 year, (1, 65) = 7.

Environmentally sustainable opportunities for health systems: metered-dose inhaler prescribing, dispensing, usage, and waste at The Ottawa Hospital.

Background: The carbon footprint of Canada's health sector is among the worst in the world, responsible for 4·6% of Canada's total greenhouse gas emissions. A quarter of emissions from Canada's health sector are linked to pharmaceuticals, including metered dose inhalers (MDIs). MDIs use propellants, such as hydrofluorocarbons, which act as greenhouse gas emissions and contribute to the health-care sector's overall carbon footprint.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study.

Snack Talk: Effects of a Naturalistic Visual Communication Support on Increasing Conversation Engagement for Adults with Disabilities.

Adults with intellectual and developmental disabilities frequently experience poor life outcomes, with individuals reporting lower levels of social support, relationships, gainful employment, and satisfaction in their quality of life. To ameliorate these outcomes, social skills and social communication interventions aligned with the needs of adults are warranted. This study examined the efficacy of Snack Talk, a supplemental naturalistic visual communication support, with five adults with intellectual and developmental disabilities.

Visual Supports to Increase Conversation Engagement for Preschoolers With Autism Spectrum Disorder During Mealtimes: An Initial Investigation.

The diversity of children within the preschool classroom is dramatically changing as children with autism spectrum disorder are increasingly included within it. To engage in the benefits of inclusion, social skills are needed. Yet, children with autism commonly experience difficulties in this area.

Keeping Teachers Engaged during Non-Instructional Times: An Analysis of the Effects of a Naturalistic Intervention.

As the prevalence of autism continues to rise, early childhood programs continue to evolve to meet the needs of children across a spectrum of abilities. To do this, strategies and supports are needed for teachers to engage with children who experience difficulties across developmental domains. Snack Talk, a naturalistic visual communication intervention, focuses on increases in conversation engagement for children with autism and related disabilities during mealtimes.

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.

Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.

The CCR5-specific antibody Leronlimab is being investigated as a novel immunotherapy that can suppress HIV replication with minimal side effects. Here we studied the virological and immunological consequences of Leronlimab in chronically CCR5-tropic HIV-1 infected humans (n = 5) on suppressive antiretroviral therapy (ART) and in ART-naïve acutely CCR5-tropic SHIV infected rhesus macaques (n = 4). All five human participants transitioned from daily combination ART to self-administered weekly subcutaneous (SC) injections of 350 mg or 700 mg Leronlimab and to date all participants have sustained virologic suppression for over seven years.

Identification and Characterization of Antigen-Specific CD8 T Cells Using Surface-Trapped TNF-α and Single-Cell Sequencing.

CD8 T cells are key mediators of antiviral and antitumor immunity. The isolation and study of Ag-specific CD8 T cells, as well as mapping of their MHC restriction, has practical importance to the study of disease and the development of therapeutics. Unfortunately, most experimental approaches are cumbersome, owing to the highly variable and donor-specific nature of MHC-bound peptide/TCR interactions.

Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.

In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIV. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition.

Terumo spectra optia leukapheresis of cynomolgus macaques for hematopoietic stem cell and T cell collection.

Macaques are physiologically relevant animal models of human immunology and infectious disease that have provided key insights and advanced clinical treatment in transplantation, vaccinology, and HIV/AIDS. However, the small size of macaques is a stumbling block for studies requiring large numbers of cells, such as hematopoietic stem cells (HSCs) for transplantation, antigen-specific lymphocytes for in-depth immunological analysis, and latently-infected CD4+ T-cells for HIV cure studies. Here, we provide a detailed protocol for collection of large numbers of HSCs and T-cells from cynomolgus macaques as small as 3 kg using the Terumo Spectra Optia apheresis system, yielding an average of 5.

Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.

Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder.

Expression, purification and preliminary crystallographic analysis of O-acetylhomoserine sulfhydrylase from Mycobacterium tuberculosis.

The gene product of the open reading frame Rv3340 from Mycobacterium tuberculosis is annotated as encoding a probable O-acetylhomoserine (OAH) sulfhydrylase (MetC), an enzyme that catalyzes the last step in the biosynthesis of methionine, which is an essential amino acid in bacteria and plants. Following overexpression in Escherichia coli, the M. tuberculosis MetC enzyme was purified and crystallized using the hanging-drop vapor-diffusion method.

Plant protein proteinase inhibitors: structure and mechanism of inhibition.

This review outlines known examples of the three-dimensional structures of protein proteinase inhibitors from plants. Three families of enzymes, serine proteinases, carboxypeptidases and cysteine proteinases, are targeted by at least a dozen inhibitor families, with the majority of them adopting the standard mechanism of inhibition towards the serine proteinases. All of the inhibitors discussed maintain compact and stable inhibitory domains that bind to the active site of their target proteinases and prevent access to the substrate molecules.

Crystal structure of β-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone.

β-Hexosaminidases (β-hex) are a group of glycosyl hydrolase isozymes that break down neutral and sialylated glycosphingolipids in the lysosomes, thereby preventing their buildup in neuronal cells. Some mutants of β-hex have decreased folding stability that results in adult-onset forms of lysosomal storage diseases. However, prevention of the harmful accumulation of glycolipids only requires 10% of wild-type activity.

Effects of methamphetamine on sexual performance and compulsive sex behavior in male rats.

Rationale: Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of human immunodeficiency virus. Currently, there is a lack of studies investigating the effects of Meth on maladaptive sexual behavior under controlled experimental settings in animal studies.

Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.

ATP-citrate lyase (ACLY) catalyzes the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, coupled with the hydrolysis of ATP. In humans, ACLY is the cytoplasmic enzyme linking energy metabolism from carbohydrates to the production of fatty acids. In situ proteolysis of full-length human ACLY gave crystals of a truncated form, revealing the conformations of residues 2-425, 487-750, and 767-820 of the 1101-amino acid protein.