Nucleosome fibre topology guides transcription factor binding to enhancers.

Cellular identity requires the concerted action of multiple transcription factors (TFs) bound together to enhancers of cell-type-specific genes. Despite TFs recognizing specific DNA motifs within accessible chromatin, this information is insufficient to explain how TFs select enhancers. Here we compared four different TF combinations that induce different cell states, analysing TF genome occupancy, chromatin accessibility, nucleosome positioning and 3D genome organization at the nucleosome resolution.

Improving Turnaround Times for Routine Antimicrobial Sensitivity Testing Following European Committee on Antimicrobial Susceptibility Testing Methodology in Patients with Bacteraemia.

: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated with increased mortality and increased antibiotic resistance, highlighting the need for more rapid turnaround times for AST.

Comparing self-report medication data from a longitudinal study on intellectual disability and national dispensing records.

Background: Medication data are a valuable resource in epidemiological studies. As the most common data collection method of medication data is self-report, it is important to understand the accuracy of this in comparison with other methods such as dispensing records. The aim of this study was to compare the agreement between two different sources of medication data of older adults with intellectual disability (ID).

Point-of-Care Ultrasound Track in an Academic Family Medicine Department.

Introduction: Point-of-care ultrasound (POCUS) is increasingly being employed in family medicine. Residency tracks can be an effective way to increase mastery in a specific subdiscipline for interested residents, but no studies exist on the implementation of a POCUS track in family medicine. We address this gap in the literature by assessing POCUS use by POCUS track residents compared to non-POCUS track residents and faculty in an academic family medicine department.

NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models.

Objective: Ovarian cancer is a lethal gynaecological malignancy with unsatisfactory 5 year survival rates of 30-50 %. Cell immunotherapy is a promising new cancer treatment where immune cells, such as Natural Killer (NK) cells, are administered to enable the patient to fight cancer through direct cytotoxicity. NK cells orchestrate an adaptive immune response by enabling the release of tumour antigens.

Relationship between anti-seizure medication and behaviors that challenge in older persons with intellectual disability and epilepsy: a review.

Introduction: There is increased focus on the negative impact of the overprescribing of medication, specifically psychotropic medication, including anti-seizure medications (ASM), in people with Intellectual Disability (ID). This is particularly important for the older adult population, where multi-morbidity and polypharmacy are more common. ASMs are associated with psychiatric and behavioral adverse effects.

OPTIMA-ID: development and validation of a medicine optimization tool for older adults with intellectual disability.

Background: Older people (i.e. ≥40 years) with intellectual disability have unique medication needs and may experience high levels of potentially inappropriate prescribing.

Blood Cancer Network Ireland (BCNI) and National Cancer Registry Ireland (NCRI) collaboration: challenges and utility of an Enhanced Blood Cancer Outcomes Registry (EBCOR) pilot.

Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up.

Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival.

Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee.

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies.

Steroid-free combination of 5-azacytidine and venetoclax for the treatment of multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy that, despite an unprecedented increase in overall survival, lacks truly risk-adapted or targeted treatments. A proportion of patients with MM depend on BCL-2 for survival, and, recently, the BCL-2 antagonist venetoclax has shown clinical efficacy and safety in t(11;14) and BCL-2 overexpressing MM. However, only a small proportion of MM patients rely on BCL-2 (approx.

Psychotropic medicines' prevalence, patterns and effects on cognitive and physical function in older adults with intellectual disability in Ireland: longitudinal cohort study, 2009-2020.

Background: The frequent prescribing of psychotropics and high prevalence of polypharmacy among older adults with intellectual disabilities require close monitoring.

Aims: To describe change in prevalence, predictors and health outcomes of psychotropic use during the four waves (2009/2010, 2013/2014, 2016/2017, 2019/2020) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA).

Method: Eligible participants were adults (≥40 years) with intellectual disabilities who participated in all four waves of IDS-TILDA and who reported medication use for the entire period.

Who speaks my language? Linguistic diversity among people living in Australian residential aged care facilities.

Objectives: Australia's migration programs mean that an increasing number of people living in residential aged care (RAC) were born in a non-main English-speaking country (NMESC) and have a preferred language other than English (LOTE). This study describes the number of such residents in aged care facilities in Australia and discusses the implications for their care.

Methods: This study presents a secondary analysis of the Australian Institute of Health and Welfare (AIHW) National Aged Care Data Clearinghouse 2020-2021 to examine the country of birth and preferred language of people living in RAC in each state and territory and the number of residents who are lone speakers of their language in their facility.

PSGL-1 decorated with sialyl Lewis promotes high affinity binding of myeloma cells to P-selectin but is dispensable for E-selectin engagement.

Dissemination of multiple myeloma into the bone marrow proceeds through sequential steps mediated by a variety of adhesion molecules and chemokines that eventually results in the extravasation of malignant plasma cells into this protective niche. Selectins are a class of C-type lectins that recognize carbohydrate structures exposed on blood borne cells and participate in the first step of the extravasation cascade, serving as brakes to slow down circulating cells enabling them to establish firm adhesion onto the endothelium. Myeloma cells enriched for the expression of selectin ligands present an aggressive disease in vivo that is refractory to bortezomib treatment and can be reverted by small molecules targeting E-selectin.

A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery.

Objective: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia.

Background: Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality.

Methods: From a prospective consecutive cohort (n=150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2-6, 24, and 48 h).

The adverse effects of long-term exposure to anticholinergics among people with intellectual disabilities: a scoping review.

Older adults with intellectual disability are exposed to a higher anticholinergic burden compared to general older adults. This is due to a higher rate of both mental and neurological disorders among people with intellectual disability. The use of medications with a high anticholinergic burden is associated with adverse effects including daytime dozing, constipation and higher dependence level in the Barthel index for measuring activities of daily living.

Care of Cancer Survivors: Distress and Mental Health.

In 2022, it was estimated that 18.1 million US adults were cancer survivors. By 2032, this number is projected to increase to 22.

Adoptive Immunotherapy and High-Risk Myeloma.

Despite significant improvements in the treatment of multiple myeloma (MM), it remains mostly incurable, highlighting a need for new therapeutic approaches. Patients with high-risk disease characteristics have a particularly poor prognosis and limited response to current frontline therapies. The recent development of immunotherapeutic strategies, particularly T cell-based agents have changed the treatment landscape for patients with relapsed and refractory disease.

Targeting stromal cell sialylation reverses T cell-mediated immunosuppression in the tumor microenvironment.

Immunosuppressive tumor microenvironments (TMEs) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSCs), precursors to cancer-associated fibroblasts (CAFs), promote tumor progression by enhancing immune cell suppression in colorectal cancer (CRC). Hyper-sialylation of glycans promotes immune evasion in cancer through binding of sialic acids to their receptors, Siglecs, expressed on immune cells, which results in inhibition of effector functions.

Sialofucosylation Enables Platelet Binding to Myeloma Cells via P-Selectin and Suppresses NK Cell-Mediated Cytotoxicity.

Multiple myeloma (MM) is a plasma cell disorder that develops in the bone marrow (BM) and is characterized by uncontrolled proliferation and the ability to disseminate to different sites of the skeleton. Sialofucosylated structures, particularly Sialyl Lewis a/x (SLe), facilitate the homing of MM cells into the BM, leading to resistance to bortezomib in vivo. Platelets have been shown to play an important role in tumor metastasis.

The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014.

Introduction: Often misperceived as solely a dental disease, periodontitis is a chronic condition characterized by inflammation of the support structures of the tooth and associated with chronic systemic inflammation and endothelial dysfunction. Despite affecting almost 40% of US adults 30 years of age or older, periodontitis is rarely considered when quantifying the multimorbidity (the presence of 2 or more chronic conditions in an individual) burden for our patients. Multimorbidity represents a major challenge for primary care and is associated with increasing health care expenditure and increased hospitalizations.