Biomarkers.

Background: Age-related neurodegenerative disorders (NDDs) continuum includes late-onset Alzheimer's disease (LOAD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) exhibit shared and distinct clinicopathological characteristics. Each of the different NDDs is characterized by a complex genetic etiology and although numerous loci have been identified via GWAS, and the causal genes and the specific neuronal and glial cell subtypes through which they exert their pathogenic effects are yet to be fully elucidated. We aimed to untangle the genetic complexity of NDDs, and to identify shared and distinct biological pathways and disease driver cell-subtypes across NDDs.

Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.

Introduction: Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) represent a spectrum of neurodegenerative disorders (NDDs). Here, we performed the first direct comparison of their transcriptomic landscapes.

Methods: We profiled the whole transcriptomes of NDD cortical tissue by snRNA-seq.

Breakthrough cancer pain management: mixed-methods study of health care professionals.

Objectives: Knowledge gaps in defining, diagnosing, educating health practitioners and treatment options hinder breakthrough cancer pain (BtCP) management. A systematic review revealed a lack of clarity on health professional derived definitions, management strategies and professional development for BtCP. The current study aimed to explore the perspectives of multidisciplinary health professionals by seeking to understand how they define, identify, treat and manage BtCP, barriers to management and professional development requirements.

Attitudes toward Voluntary Assisted Dying for people in prison in Australia.

End-of-life care options in Australia, recently including Voluntary Assisted Dying (VAD), are available to people in prison. Little is known about how the public perceives this right. We aimed to identify the attitudes of the public by conducting a qualitative content analysis of comments across four Australian online news media outlets discussing the first case of a person in prison being granted VAD (a sexual offender).

Advancing insights into virus-induced neurodevelopmental disorders through human brain organoid modelling.

Human neurodevelopment is a complex process vulnerable to disruptions, particularly during the prenatal period. Maternal viral infections represent a significant environmental factor contributing to a spectrum of congenital defects with profound and enduring impacts on affected offspring. The advent of induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) human brain organoids has revolutionised our ability to model prenatal viral infections and associated neurodevelopmental disorders.

Make the Right Call: formative evaluation for a water safety programme for adults in Western Australia.

Background: Preventing drowning in adults is a complex, multifaceted injury prevention issue. The adult drowning rate in Australia is continuing to rise. In 2023, more than half of those who drowned were aged over 45 years.

Engaging with Culturally and Linguistically Diverse Communities to Promote Palliative Care That Exceeds Expectation.

Introduction: Given longstanding barriers that obstruct integrated palliative care, particularly for culturally and linguistically diverse communities, this article demonstrates a way to engage with Syrian, Bhutanese and African communities to learn about brilliant palliative care with and from members of these communities.

Methods: This study involved the methodology of POSH-VRE, which combines positive organisational scholarship in healthcare (POSH) with video-reflexive ethnography (VRE). Members of the Syrian, Bhutanese, and African communities (n = 14) participated in a focus group or an interview to consider understandings of palliative care; conceptualisations of a good death; how and why palliative care was typically enacted in their communities; the associated effects; as well as the relationship between culturally and linguistically diverse communities and public palliative care services.

Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia.

Variation in the non-coding genome represents an understudied mechanism of disease and it remains challenging to predict if single nucleotide variants, small insertions and deletions, or structural variants in non-coding genomic regions will be detrimental. Our approach using complementary RNA-seq and targeted long-read DNA sequencing can prioritize identification of non-coding variants that lead to disease via alteration of gene splicing or expression. We have identified a patient with primary ciliary dyskinesia with a pathogenic coding variant on one allele of the SPAG1 gene, while the second allele appears normal by whole exome sequencing despite an autosomal recessive inheritance pattern.

Important antimicrobial dosing considerations for transitions of care: Focus on thrice-weekly dosing in hemodialysis.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Supportive care 2030 movement: towards unifying ambitions for global excellence in supportive cancer care-an international Delphi study.

Background: Supportive care to ensure optimal quality of life is an essential component of cancer care and symptom control across the lifespan. Ongoing advances in cancer treatment, increasing toxicity from many novel treatment regimes, and variations in access to care and cancer outcomes across the globe and resource settings present significant challenges for supportive care delivery. To date, no overarching framework has been developed to guide supportive care development worldwide.

Efficacy of the Enteroadsorbent Silicol®gel in Adults with Irritable Bowel Syndrome Subtypes IBS-D or Mixed: Observational Open-Label Study.

Background: Irritable bowel syndrome (IBS) is a common chronic gut-brain interaction disorder with limited effective treatment options. Intestinal adsorbents have a high adsorption capacity for gut irritants and may provide nonpharmacological alternatives.

Objectives: This post marketing study is aimed at providing up-to-date evidence to support the safety and efficacy in normal use of an established medical device for IBS treatment.

Engaging Community Health Workers in the Centers for Disease Control and Prevention's COVID-19 Public Health Response to Address Health Disparities and Build Community Resilience.

In 2021, the Centers for Disease Control and Prevention's (CDC) National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) funded community health workers (CHWs) for COVID Response and Resilient Communities (CCR). CCR is a 3-year, $350 million initiative to implement CHW strategies aimed at reducing COVID-19 impacts, building resilience, and improving health equity by addressing health-related social needs. This paper describes the CCR initiative and experiences to date, underscoring CHWs' critical role in CDC's pandemic response.

B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting.

Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is characterized by a failure of the germinal center response, a process involving the proliferation and positive selection of antigen-specific B cells. Here, we describe how DOCK8-deficient B cells are blocked at a light-zone checkpoint in the germinal centers of immunized mice, where they are unable to respond to T cell-dependent survival and selection signals and consequently differentiate into plasma cells or memory B cells. Although DOCK8-deficient B cells can acquire and present antigen to initiate activation of cognate T cells, integrin up-regulation, B cell-T cell conjugate formation, and costimulation are insufficient for sustained B cell and T cell activation when antigen availability is limited.

Opioid analgesic dose and route conversion ratio studies: a scoping review to inform an eDelphi guideline.

Background: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries.

A qualitative study of Samoan cancer patients' experiences.

Methods: This qualitative interview study was part of a larger study that interviewed19 participants recruited among patients with cancer registered with Samoa Cancer Society, or patients recently discharged from the main tertiary hospital in Samoa. Interview transcripts were reviewed, and the research team identified the key palliative-care-related themes.

Results: Analysis led to the generation of the following key themes: living with pain; resource constraints; support from family and faith; and interactions with healthcare professionals.

Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.

The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution.

Searching for choice and control: Western Australian service provider experiences of health, housing and migration.

This research aimed to inform approaches to increase access to secure housing and improve mental health outcomes for migrants from culturally and linguistically diverse backgrounds (hereafter migrants) who are generally invisible in health and social policy and service provision in Western Australia. We used semi-structured, in-depth interviews (n = 11) and interpretative phenomenological analysis to explore service provider experiences and perspectives of issues impacting service provision and the needs of migrants in this context. Five superordinate themes reveal complex experiences for both service providers and the migrants with whom they work.

The operationalisation of recovery colleges: A scoping review.

Background: Recovery Colleges (RCs) represent an approach to enhancing mental wellbeing through education, lived experience and co-production. Despite their increasing presence, scant literature explores the operationalisation of RCs and their embodiment of co-production principles. The aim of this scoping review was to investigate the operationalisation of RCs and their application of co-production in RCs located in high-income countries over the past decade.

Survivorship Care for People Affected by Advanced or Metastatic Cancer: MASCC-ASCO Standards and Practice Recommendations.

Purpose: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared with those with early-stage disease or those nearing the end of life. These Multinational Association for Supportive Care in Cancer (MASCC)-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer.

Methods: A MASCC-ASCO expert panel was formed.

Survivorship care for people affected by advanced or metastatic cancer: MASCC-ASCO standards and practice recommendations.

Purpose: People with advanced or metastatic cancer and their caregivers may have different care goals and face unique challenges compared to those with early-stage disease or those nearing the end-of-life. These MASCC-ASCO standards and practice recommendations seek to establish consistent provision of quality survivorship care for people affected by advanced or metastatic cancer.

Methods: An expert panel comprising MASCC and ASCO members was formed.

Machine learning methods for predicting guide RNA effects in CRISPR epigenome editing experiments.

CRISPR epigenomic editing technologies enable functional interrogation of non-coding elements. However, current computational methods for guide RNA (gRNA) design do not effectively predict the power potential, molecular and cellular impact to optimize for efficient gRNAs, which are crucial for successful applications of these technologies. We present "launch-dCas9" (machine LeArning based UNified CompreHensive framework for CRISPR-dCas9) to predict gRNA impact from multiple perspectives, including cell fitness, wildtype abundance (gauging power potential), and gene expression in single cells.