The metabolic consequences of 'yo-yo' dieting are markedly influenced by genetic diversity.

Background: Weight loss can improve the metabolic complications of obesity. However, it is unclear whether insulin resistance persists despite weight loss and whether any protective benefits are preserved following weight regain (weight cycling). The impact of genetic background on weight cycling is undocumented.

Direct activation of PI3K in osteoblasts and osteocytes strengthens murine bone through sex-specific actions on cortical surfaces.

Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. While one formation is increased by removing the PI3K inhibitor (phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)), the effect of direct PI3K activation in the osteoblast lineage has not been reported.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

Purpose: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles.

Methods: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137).

Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy.

Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors.

Understanding REM Sleep Behavior Disorder through Functional MRI: A Systematic Review.

Neuroimaging studies in rapid eye movement sleep behavior disorder (RBD) can inform fundamental questions about the pathogenesis of Parkinson's disease (PD). Across modalities, functional magnetic resonance imaging (fMRI) may be better suited to identify changes between neural networks in the earliest stages of Lewy body diseases when structural changes may be subtle or absent. This review synthesizes the findings from all fMRI studies of RBD to gain further insight into the pathophysiology and progression of Lewy body diseases.

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

Background: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.

Methods: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity.

Geographic and racial variability in kidney, cardiovascular and safety outcomes with canagliflozin: A secondary analysis of the CREDENCE randomized trial.

Aim: To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups.

Materials And Methods: A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end-stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes.

Early onset metastatic colorectal cancer in Australia.

Background: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP).

Methods: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry.

'The Reports of My Death Are Greatly Exaggerated'-Evaluating the Effect of Necrosis on Promoter Methylation Testing in High-Grade Glioma.

(1) Background: (O-6-methylguanine-DNA methyltransferase) promoter methylation remains an important predictive biomarker in high-grade gliomas (HGGs). The influence of necrosis on the fidelity of promoter (p) hypermethylation testing is currently unknown. Therefore, our study aims to evaluate the effect of varying degrees of necrosis on p status, as determined by pyrosequencing, in a series of primary and recurrent HGGs; (2) Methods: Within each case, the most viable blocks (assigned as 'true' MGMTp status) and the most necrotic block were determined by histopathology review.

Osteoporosis screening in Australian community pharmacies: A mixed methods study.

Issues Addressed: Osteoporosis and poor bone health impact a large proportion of the Australian population, but is drastically underdiagnosed and undertreated. Community pharmacies are a strategic location for osteoporosis screening services due to their accessibility and the demographic profile of customers. The aim of this study was to develop, implement and evaluate a community pharmacy health promotion service centred on encouraging consumers to complete an anonymous osteoporosis screening survey called Know Your Bones.

Bone metabolism in diabetes: a clinician's guide to understanding the bone-glucose interplay.

Skeletal fragility is an increasingly recognised, but poorly understood, complication of both type 1 and type 2 diabetes. Fracture risk varies according to skeletal site and diabetes-related characteristics. Post-fracture outcomes, including mortality risk, are worse in those with diabetes, placing these people at significant risk.

An Update on the Adult-Onset Hereditary Cerebellar Ataxias: Novel Genetic Causes and New Diagnostic Approaches.

The hereditary cerebellar ataxias (HCAs) are rare, progressive neurologic disorders caused by variants in many different genes. Inheritance may follow autosomal dominant, autosomal recessive, X-linked or mitochondrial patterns. The list of genes associated with adult-onset cerebellar ataxia is continuously growing, with several new genes discovered in the last few years.

Evaluating possible 'next day' impairment in insomnia patients administered an oral medicinal cannabis product by night: a pilot randomized controlled trial.

Cannabis and its major constituents, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo.

Characterisation of Symptom and Polysomnographic Profiles Associated with Cardiovascular Risk in a Sleep Clinic Population with Obstructive Sleep Apnoea.

Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure).

Short tandem repeat expansions in are absent in cohorts of familial and sporadic amyotrophic lateral sclerosis patients of European ancestry.

In patients of Asian ancestry, a heterozygous CGG repeat expansion of >100 units in is the cause of oculopharyngodistal myopathy type 1 (OPDM1). Repeat lengths of between 61 and 100 units have been associated with rare amyotrophic lateral sclerosis (ALS) cases of Asian ancestry, although with unusually long disease duration and without significant upper motor neuron involvement. This study sought to determine whether CGG repeat expansions were also present in ALS patients of European ancestry.

From ownership to custodianship of tumor biopsy tissue in genomic testing: a mixed methods study of patient views.

Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n = 397) completed a questionnaire prior to undergoing MP (n = 356/397).

Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations.

Plasma Lipidomic Profiling Identifies Elevated Triglycerides as Potential Risk Factor in Chemotherapy-Induced Peripheral Neuropathy.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN.

An Approach to Evaluate the Costs and Outputs of Academic Biobanks.

Academic biobanks commonly report sustainability challenges, which may be exacerbated by a lack of information on biobank value. To better understand the costs and supported outputs that contribute to biobank value, we developed a systematic, generalizable methodology to determine biobank inputs and publications arising from biobank-supported research. We then tested this in a small cohort ( = 12) of academic cancer biobanks in New South Wales, Australia.