Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers.

Background: S-pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β-blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5-hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that S-pindolol can reverse weight loss and improve fat-free mass in patients with cancer-related weight loss. A comparative phase I bioavailability study of S-pindolol and racemic pindolol was performed to support the development of S-pindolol in cancer cachexia.

Vogt-Koyanagi-Harada-Like Uveitis Secondary to Pembrolizumab in Metastatic Gastric Cancer: A Case Report and Review of the Literature.

Introduction: Vogt-Koyanagi-Harada (VKH) disease is a multisystem syndrome characterized by uveitis and exudative retinal detachments in the absence of ocular trauma or surgery. Neurological and cutaneous manifestations can also occur. Prior case reports have associated immune checkpoint inhibitors with a VKH-like disease.

Pre-Emptive Pharmacogenetic Testing in the Acute Hospital Setting: A Cross-Sectional Study.

Background: Pharmacogenetic guided prescribing can be used to improve the safety and effectiveness of medicines. There are several approaches by which this intervention might be implemented in clinical practice, which will vary depending on the health system and clinical context.

Aim: To understand the clinical utility of panel-based pharmacogenetic testing in patients admitted acutely to hospital and to establish variables which predict if an individual might benefit from the intervention.

Irregular breakfast eating in type 2 diabetes mellitus is associated with greater social jetlag and poorer metabolic health.

Circadian disruption, arising from conflict between internal circadian time and behavioural sleep-wake and fasting-feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus.

Knowledge and practice of foot self-care behaviours in Irish diabetes patients with high-risk feet.

Background: Diabetic foot disease is associated with significant morbidity and mortality. Patients at high risk of developing diabetic foot disease can reduce their risk, however, by practicing appropriate foot self-care behaviours. Despite this fact, and often despite education regarding appropriate foot care, patients frequently engage in risky foot care practices which place them at risk of foot ulceration.

Orbital Complication in the Setting of Cocaine Use: A Case Report and Review of Literature.

Orbital cellulitis is a common ophthalmologic consultation and has numerous risk factors; however, one that is seldomly encountered is chronic cocaine use. We describe a case of a 63-year-old man with a history of HIV and cocaine use who presented with OD pain, proptosis, and blurred vision. CT imaging revealed extensive erosions throughout the nasal septum, bilateral turbinates, ethmoid sinuses, and loss of the right medial orbital wall.

Pharmacogenetics Clinical Decision Support Systems for Primary Care in England: Co-Design Study.

Background: Pharmacogenetics can impact patient care and outcomes through personalizing the selection of medicines, resulting in improved efficacy and a reduction in harmful side effects. Despite the existence of compelling clinical evidence and international guidelines highlighting the benefits of pharmacogenetics in clinical practice, implementation within the National Health Service in the United Kingdom is limited. An important barrier to overcome is the development of IT solutions that support the integration of pharmacogenetic data into health care systems.

The impact of machine learning on the prediction of diabetic foot ulcers - A systematic review.

Introduction: Globally, diabetes mellitus poses a significant health challenge as well as the associated complications of diabetes, such as diabetic foot ulcers (DFUs). The early detection of DFUs is important in the healing process and machine learning may be able to help inform clinical staff during the treatment process.

Methods: A PRISMA-informed search of the literature was completed via the Cochrane Library and MEDLINE (OVID), EMBASE, CINAHL Plus and Scopus databases for reports published in English and in the last ten years.

Functional analysis of protein interactions using coupled bi-fluorescence complementation/GFP nanobody techniques.

Transcription factors (TFs) form homo- or hetero-dimeric DNA binding complexes along with associated co-regulators that can have transcriptional repressor or activator functions. Defining the specific composition of the complexes is therefore key to understanding their biological role. Here, we utilized bimolecular fluorescence complementation (BiFC) to visualize the formation of defined TF dimers and associated co-regulators derived from the activator protein-1 (AP-1) and myocyte enhancer factor 2 (MEF2) families.

Genomics and insurance in the United Kingdom: increasing complexity and emerging challenges.

This article identifies issues relating to the use of genetics and genomics in risk-rated insurance that may challenge existing regulatory models in the UK and elsewhere. We discuss three core issues: (1) As genomic testing advances, and results are increasingly relevant to guide healthcare across an individual's lifetime, the distinction between diagnostic and predictive testing that the current UK insurance code relies on becomes increasingly blurred. (2) The emerging category of pharmacogenetic tests that are predictive only in the context of a specific prescribing moment.

Public preferences for pharmacogenetic testing in the NHS: Embedding a discrete choice experiment within service design to better meet user needs.

Aims: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines-a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service.

Methods: Members of the UK population were surveyed via an online panel company.

FoxP1 Represses MEF2A in Striated Muscle.

Myocyte enhancer factor 2 (MEF2) proteins are involved in multiple developmental, physiological, and pathological processes in vertebrates. Protein-protein interactions underlie the plethora of biological processes impacted by MEF2A, necessitating a detailed characterization of the MEF2A interactome. A nanobody based affinity-purification/mass spectrometry strategy was employed to achieve this goal.

A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation.

Thematic Daily Sleep Routine Analysis of Adults Not in Employment Living with Type 2 Diabetes Mellitus.

Background: Day-to-day variations in sleep timing have been associated with poorer glycemic control in type 2 diabetes mellitus, although the factors that influence this sleep timing variability are poorly understood.

Methods: Daily routines of sleep in a sample of seventeen adults with type 2 diabetes mellitus who were either retired or not currently working were examined qualitatively through the application of semi-structured interviews and a thematic analysis of the resulting transcripts.

Results: Four themes were identified: "Consistent Sleeping Patterns", "Fluctuating Sleep Timing", "Night-Time Disruptions" and "Lasting Effort Needed with Type Two Diabetes Mellitus".

Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

Aim: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity.

Design: An interpretive, descriptive, qualitative interview study.

Methods: Data were collected using semi-structured interviews undertaken between January and November 2020.

Klinefelter syndrome presenting as metastatic bilateral breast cancer: missed diagnostic opportunities.

Klinefelter syndrome (KS) is the most common cause of primary hypogonadism in male patients; however, the diagnosis of KS is frequently delayed or missed. This delay can lead to undesirable outcomes for patients, especially considering that individuals with KS have a higher risk of developing specific malignancies, including breast cancer, non-Hodgkin's lymphoma and mediastinal germ cell tumours. We present a case of a male patient in his 60s, where the established diagnosis of metastatic bilateral breast cancer prompted us to investigate and subsequently confirm a diagnosis of KS.

Small is Powerful: Demonstration of the Impact of Nanoformed Piroxicam in a Controlled Clinical Study.

Purpose: New solutions are needed to enable the efficient use of poorly water-soluble drugs. Therefore, we aimed to demonstrate that decreasing particle size with a solution-to-particle method known as nanoforming can improve dissolution and thus bioavailability.

Methods: Piroxicam, a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID), was used as a model compound.

Development of a point-of-care genetic test for effective treatment of ischaemic stroke: an early model-based cost-effectiveness analysis.

People who have experienced a stroke are at high risk of recurrent strokes. Clopidogrel is prescribed to people who have had a non-cardioembolic stroke. There is evidence that clopidogrel is not effective for patients with loss-of-function alleles.

Introduction to pharmacogenetics.

There is considerable interindividual variability in the effectiveness and safety of medicines. Although the reasons for this are multifactorial, it is well recognised that genetic changes impacting the absorption or metabolism of these drugs play a significant contributory role. Understanding how these pharmacogenetic variants impact response to medicines, and leveraging this knowledge to guide prescribing, could have significant benefits for patients and health services.

Metastatic lacrimal/salivary gland duct adenocarcinoma.

In this report, we present a case of a patient with a 30-year history of orbital asymmetry who presented with metastatic human epidermal growth factor receptor 2 () positive lacrimal/salivary gland ductal adenocarcinoma. The patient was treated with chemoradiotherapy and trastuzumab. Tumours of lacrimal gland origin are rare, and unfortunately can frequently present in late stage.