Survey of GP registrars' training experience and confidence in managing children and adolescents with mental health conditions in primary care.

Objectives: The aim of this study is to assess General Practitioner (GP) trainees' training experience, and confidence in assessing and managing children and adolescents with common mental health conditions in primary care in Ireland.

Methods: An online anonymous questionnaire was distributed to third and fourth year GP registrars enrolled in the Irish College of General Practitioners training schemes. The online questionnaire evaluated participants' training experiences and confidence levels in key areas of child and adolescent mental health in primary care.

Cell-cell interactome of the hematopoietic niche and its changes in acute myeloid leukemia.

The bone marrow (BM) is a complex microenvironment, coordinating the production of billions of blood cells every day. Despite its essential role and its relevance to hematopoietic diseases, this environment remains poorly characterized. Here we present a high-resolution characterization of the niche in health and acute myeloid leukemia (AML) by establishing a single-cell gene expression database of 339,381 BM cells.

Knowledge gap in a cross section of Irish general practitioners prescribing denosumab for osteoporosis.

Background: Denosumab is commonly used by general practitioners (GPs) in Ireland to treat osteoporosis though drug holidays are not recommended with rebound bone loss and risk of vertebral fractures if stopped. We aimed to investigate GP practice and knowledge regarding denosumab including use and reasons for use, therapy duration, blood monitoring and recommended vitamin D status/calcium intake on treatment, staff administering, methods of recall, delays in receiving injections, management of and awarenes of guidelines if stopped, reasons for stopping and concerns about same.

Methods: GPs were contacted (n = 846) by email and invited to complete an online anonymous survey comprising 25 questions in January 2022.

Concurrent transposon engineering and CRISPR/Cas9 genome editing of primary CLL-1 chimeric antigen receptor-natural killer cells.

Background: Natural killer (NK) cell genome editing promises to enhance the innate and alloreactive anti-tumor potential of NK cell adoptive transfer. DNA transposons are versatile non-viral gene vectors now being adapted to primary NK cells, representing important tools for research and clinical product development.

Aims And Methods: We set out to generate donor-derived, primary chimeric antigen receptor (CAR)-NK cells by combining the TcBuster transposon system with Epstein-Barr virus-transformed lymphoblastoid feeder cell-mediated activation and expansion.

Recreating the Bone Marrow Microenvironment to Model Leukemic Stem Cell Quiescence.

The main challenge in the treatment of acute myeloid leukemia (AML) is relapse, as it has no good treatment options and 90% of relapsed patients die as a result. It is now well accepted that relapse is due to a persisting subset of AML cells known as leukemia-initiating cells or leukemic stem cells (LSCs). Hematopoietic stem cells (HSCs) reside in the bone marrow microenvironment (BMM), a specialized niche that coordinates HSC self-renewal, proliferation, and differentiation.

Hematopoietic versus leukemic stem cell quiescence: Challenges and therapeutic opportunities.

Hematopoietic stem cells (HSC) are responsible for the production of mature blood cells. To ensure that the HSC pool does not get exhausted over the lifetime of an individual, most HSCs are in a state of quiescence with only a small proportion of HSCs dividing at any one time. HSC quiescence is carefully controlled by both intrinsic and extrinsic, niche-driven mechanisms.

Repression of Mcl-1 expression by the CDC7/CDK9 inhibitor PHA-767491 overcomes bone marrow stroma-mediated drug resistance in AML.

Acute myeloid leukaemia (AML) is an aggressive cancer with 50-75% of patients relapsing even after successful chemotherapy. The role of the bone marrow microenvironment (BMM) in protecting AML cells from chemotherapeutics and causing consequent relapse is increasingly recognised. However the role that the anti-apoptotic Bcl-2 proteins play as effectors of BMM-mediated drug resistance are less understood.

Generic substitution of antiretrovirals: patients' and health care providers' opinions.

There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs).

The Janus Face of Death Receptor Signaling during Tumor Immunoediting.

Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family.