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Amanda C Brodeur,1–3 Anna M Roberts-Pilgrim,3 Kimberlee L Thompson,1 Craig L Franklin,4 Charlotte L Phillips2,3 1Department of Biomedical Sciences, Missouri State University, Springfield, MO, USA; 2Department of Child Health, University of Missouri, Columbia, MO, USA; 3Department of Biochemistry, University of Missouri, Columbia, MO, USA; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Abstract: The glomerulofibrotic Col1a2-deficient mouse model demonstrates glomerular homotrimeric type I collagen deposition in mesangial and subendothelial spaces. In this report, we investigate the role of transforming growth factor β1 (TGF-β1) in myofibroblast activation and epithelial–mesenchymal transition (EMT) in this glomerulopathy. Immunohistochemical analyses of glomerular α-sma, desmin, vimentin, and proliferating cell nuclear antigen demonstrated parietal epithelial cell proliferation and EMT in late stages of the glomerulopathy in the Col1a2-deficient mice. Glomerular TGF-β1 RNA and protein were not elevated in 1- and 3-month-old mice as determined by quantitative reverse transcriptase-polymerase chain reaction and protein immunoassay analyses. To investigate further whether TGF-β1 plays a role in the glomerulopathy outside of the 1- and 3-month time periods, the Col1a2-deficient mice were bred with Smad3 knockout mice. If the glomerular fibrosis in the Col1a2-deficient mice is mediated by the TGF-β1/Smad3 transcription pathway, it was hypothesized that the resultant Col1a2-deficient/Smad3-deficient mice would exhibit attenuated glomerular homotrimer deposition. However, the Col1a2-deficient/Smad3-deficient kidneys were similarly affected as compared to age-matched Col1a2-deficient kidneys, suggesting that homotrimeric type I collagen deposition in the Col1a2-deficient mouse is independent of TGF-β1/Smad3 signaling. Deposition of homotrimeric type I collagen appears to be the initiating event in this glomerulopathy, providing evidence that EMT and myofibroblast activation occur following initiation, consistent with a secondary wound-healing response independent of TGF-β1. Keywords: renal pathology, glomerulofibrosis, myofibroblast, homotrimeric type I collagen

Craig L Phillips,1–3 Denise M O'Driscoll4,51Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia; 2National Health and Medical Research Council Center for Integrated Research and Understanding of Sleep, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia; 3Discipline of Sleep Medicine, Sydney Medical School, University of Sydney, Sydney, Australia; 4Monash Lung and Sleep, Monash Medical Centre, Monash University, Melbourne, Australia; 5Department of Medicine, Southern Clinical School, Monash University, Melbourne, AustraliaAbstract: Obstructive sleep apnea (OSA) is increasingly being recognized as a major health burden with strong focus on the associated cardiovascular risk. Studies from the last two decades have provided strong evidence for a causal role of OSA in the development of systemic hypertension. The acute physiological changes that occur during apnea promote nocturnal hypertension and may lead to the development of sustained daytime hypertension via the pathways of sympathetic activation, inflammation, oxidative stress, and endothelial dysfunction. This review will focus on the acute hemodynamic disturbances and associated intermittent hypoxia that characterize OSA and the potential pathophysiological mechanisms responsible for the development of hypertension in OSA. In addition the epidemiology of OSA and hypertension, as well as the role of treatment of OSA, in improving blood pressure control will be examined.Keywords: obstructive sleep apnea, hypertension, intermittent hypoxia, ambulatory blood pressure, sympathetic activation

Despite the fundamental importance of soil temperature for Earth's carbon and energy budgets, ecosystem functioning, and agricultural production, studies of climate change impacts on soil processes have mainly relied on air temperatures, assuming they are accurate proxies for soil temperatures. We evaluated changes in soil temperature, moisture, and air temperature predicted over the 21st century from 14 Earth system models. The model ensemble predicted a global mean soil warming of 2.3 ± 0.7 and 4.5 ± 1.1 °C at 100-cm depth by the end of the 21st century for RCPs 4.5 and 8.5, respectively. Soils at 100 cm warmed at almost exactly the same rate as near-surface (~1 cm) soils. Globally, soil warming was slightly slower than air warming above it, and this difference increased over the 21st century. Regionally, soil warming kept pace with air warming in tropical and arid regions but lagged air warming in colder regions. Thus, air warming is not necessarily a good proxy for soil warming in cold regions where snow and ice impede the direct transfer of sensible heat from the atmosphere to soil. Despite this effect, high-latitude soils were still projected to warm faster than elsewhere, albeit at slower rates than surface air above them. When compared with observations, the models were able to capture soil thermal dynamics in most biomes, but some failed to recreate thermal properties in permafrost regions. Particularly in cold regions, using soil warming rather than air warming projections may improve predictions of temperature-sensitive soil processes.

Rationale: Dyslipidemia is common in Obstructive Sleep Apnea (OSA). Postprandial lipidemia (PPL) is a strong marker of cardiovascular risk. Evidence that OSA treatment improves PPL is lacking. Objectives: To investigate the effect of continuous positive airway pressure (CPAP) treatment on postprandial lipidemia (PPL) in patients with obstructive sleep apnea (OSA) in the upper moderate or severe range. Methods: In this randomized, placebo-controlled crossover trial, we compared the effects of 2 months each of therapeutic and placebo CPAP on PPL. Measurements and Main Results: PPL was determined from the area under the 24-hour triglyceride concentration curve (TAG-AUC(24)) using seven blood samples drawn across both the wake and sleep periods. Secondary outcomes were the difference in other 24-hour lipid profiles. Thirty-eight eligible patients were randomly assigned to a treatment order and 29 patients completed the trial. CPAP reduced PPL compared with placebo with a mean TAG-AUC(24) difference of -357 mmol/L/d (95% confidence interval [CI], -687.3 to -26.8; P = 0.035). During both the CPAP and placebo studies, TAG levels peaked during both wakefulness (2:00 p.m.) and sleep (3:00 a.m.). Both peaks were lower during CPAP than placebo: 2:00 p.m., -0.49 mmol/L (95% CI, -0.74 to -0.24; P < 0.0005) and 3:00 a.m., -0.40 mmol/L (95% CI, -0.65 to -0.15; P = 0.002). Moreover, mean 24-hour total cholesterol was -0.19 mmol/L lower on CPAP (95% CI, -0.27 to -0.11; P < 0.00001). Conclusions: This randomized trial demonstrated that treatment of severe OSA with CPAP improves postprandial TAG and total cholesterol levels. These effects may reduce the risk for cardiovascular events. The results imply that the association between OSA and cardiovascular disease may, in part, be caused by direct effects on dyslipidemia. Clinical trial registered with the Australian and New Zealand Clinical Trials Registry at www.anzctr.org.au (ACTRN 12605000066684). [ABSTRACT FROM AUTHOR]

The clinical course of a 10-year-old female patient who presented with hematuria, proteinuria, and hypertension is described. Four months after being diagnosed with acute glomerulonephritis, the child was referred to a pediatric nephrologist due to persistent hematuria and unresolved proteinuria. A renal biopsy was performed due to the persistent urinary abnormalities and a family history of renal failure. The renal biopsy demonstrated pathological findings characteristic of membranoproliferative glomerulonephritis type II. The child was treated with an antihypertensive agent and steroids. Despite poor prognostic clinical and pathological features, she has minimal urinary abnormalities, normal renal function, and normal blood pressure on antihypertensive medication six years after the diagnosis of membranoproliferative glomerulonephritis type II. [ABSTRACT FROM AUTHOR]

The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as 'ever' or 'never' smokers and doing 'low,' 'moderate,' or 'high' level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examines the association of disability and social interaction, measured as in-person contact with non-household members and home confinement, and identifies sociodemographic, socioeconomic, and health-related factors that modify this relationship. METHODS: Participants were 1,002 moderately to severely disabled community-dwelling women aged 65 and older from the Women's Health and Aging Study, identified by screening an age-stratified random sample of Medicare beneficiaries in Baltimore, Maryland. Logistic regression models were used to estimate the odds of low social interaction associated with disability and each independent modifier. RESULTS: In a typical week, 23% did not visit with anyone residing outside their households and 17% did not leave their homes. In addition to and independent of disability level, older age, not completing high school, having a driver in the home, hearing difficulties and incontinence were associated with low social contact; older age and African American race were related to home confinement. African American women living alone are especially vulnerable to home confinement. DISCUSSION: Physical disability is not necessarily socially disabling, as many of the most severely disabled in our study had at least daily social interaction. Improvements in social interaction appear possible through more effective management of certain health conditions and attention to potential sociocultural barriers. [ABSTRACT FROM AUTHOR]

The organizational principles of nephronal segments are based on longstanding anatomical and physiological attributes that are closely linked to the homeostatic functions of the kidney. Novel molecular approaches have recently uncovered layers of deeper signatures and states in tubular cells that arise at various timepoints on the spectrum between health and disease. For example, a dedifferentiated state of proximal tubular cells with mesenchymal stemness markers is frequently seen after injury. The persistence of such a state is associated with failed repair. Here, we introduce a novel analytical pipeline applied to highly multiplexed spatial protein imaging to characterize proximal tubular subpopulations and neighborhoods in reference and disease human kidney tissue. The results were validated and extended through integration with spatial and single cell transcriptomics. We demonstrate that, in reference tissue, a large proportion of S1 and S2 proximal tubular epithelial cells express THY1, a mesenchymal stromal and stem cell marker that regulates differentiation. Kidney disease is associated with loss of THY1 and transition towards expression of PROM1, another stem cell marker shown recently to be linked to failed repair. We demonstrate that the trajectory of proximal tubular cells to THY1 expression is clearly distinct from that of PROM1, and that a state with PROM1 expression is associated with niches of inflammation. Our data support a model in which the interplay between THY1 and PROM1 expression in proximal tubules associates with their regenerative potential and marks the timeline of disease progression.

Background and Purpose: Obstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia., Methods: Older adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index-3% (REM-ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high-resolution hippocampus T2 scans. We determined whether the relationship between REM-ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non-REM sleep to determine whether the effects were REM-specific., Results: Although there was not a direct effect of REM-ODI on verbal learning (p > 0.05) or memory (p > 0.05), mediation analyses showed a significant indirect effect of high REM-ODI on poorer verbal learning (β = -0.09, 95% confidence interval [CI] = -0.238 to -0.005) and memory (β = -0.100, 95% CI = -0.255 to -0.005), which was mediated by CA1 volume. These associations were absent in non-REM sleep (p > 0.05)., Conclusions: Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Osteogenesis imperfecta (OI) is a rare heritable connective tissue disorder of skeletal fragility with an incidence of roughly 1:15,000. Approximately 85% of the pathogenic variants responsible for OI are in the type I collagen genes, COL1A1 and COL1A2, with the remaining pathogenic OI variants spanning at least 20 additional genetic loci that often involve type I collagen post-translational modification, folding, and intracellular transport as well as matrix incorporation and mineralization. In addition to being the most abundant collagen in the body, type I collagen is an important structural and extracellular matrix signaling molecule in multiple organ systems and tissues. Thus, OI disease-causing variants result not only in skeletal fragility, decreased bone mineral density (BMD), kyphoscoliosis, and short stature, but can also result in hearing loss, dentinogenesis imperfecta, blue gray sclera, cardiopulmonary abnormalities, and muscle weakness. The extensive genetic and clinical heterogeneity in OI has necessitated the generation of multiple mouse models, the growing awareness of non-skeletal organ and tissue involvement, and OI being more broadly recognized as a type I collagenopathy.This has driven the investigation of mutation-specific skeletal and extra-skeletal manifestations and broadened the search of potential mechanistic therapeutic strategies. The purpose of this review is to outline several of the extra-skeletal manifestations that have recently been characterized through the use of genetically and phenotypically heterogeneous mouse models of osteogenesis imperfecta, demonstrating the significant potential impact of OI disease-causing variants as a collagenopathy (affecting multiple organ systems and tissues), and its implications to overall health., Competing Interests: Declarations. Conflicts of interest: Tara K. Crawford, Brittany N. Lafaver, and Charlotte L. Phillips have declared no conflict of interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Obstructive sleep apnea (OSA) is highly prevalent among older adults and has been associated with cognitive decline and dementia risk. The suitability of screening tools for detecting OSA in memory clinic settings is unclear., Objective: To evaluate the utility and validity of the STOP-Bang questionnaire (SBQ) and pulse oximeter as a screening tool, compared to gold-standard polysomnography (PSG) in older adults attending a memory clinic., Methods: Participants aged over 50 with new onset cognitive/mood concerns attended a memory clinic, then completed the SBQ, oximetry, and PSG. The SBQ and oximetry's accuracy in detecting moderate-severe and severe OSA was evaluated using receiver operating curves. Intraclass correlation and Bland-Altman plots compared the oximeter's adjusted oxygen desaturation index (ODI-Ox) and PSG's apnea-hypopnea index (AHI-PSG)., Results: Of 194 participants (mean age = 65.6, 64 males) who completed PSG, 184 completed the SBQ, and 138 completed oximetry. SBQ demonstrated limited performance for moderate-severe OSA (sensitivity = 52%, specificity = 62%, AUC = 0.600) and severe OSA (sensitivity = 18%, specificity = 87%, AUC = 0.577). Oximetry was satisfactory for moderate-severe OSA (sensitivity = 67%, specificity = 73%, AUC = 0.769) and severe OSA (sensitivity = 50%, specificity = 88%, AUC = 0.730). The diagnostic performance was improved with new cut-offs at ODI-Ox ≥ 11 for AHI-PSG ≥ 15 and ODI-Ox ≥ 20 for AHI-PSG ≥ 30. Bland-Altman plots and intraclass correlation indicated acceptable agreement for oximetry., Conclusions: The findings suggest that while the SBQ may be unsuitable to detect moderate or severe OSA for older adults with cognitive impairment, oximetry may be a viable screening tool. Given OSA treatment can optimize sleep and may slow cognitive decline, routine screening for OSA should be part of memory clinic assessments., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Sharon Naismith has received consulting fees from Eisai and Roche pharmaceuticals and is an Editorial Board Member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

During the COVID-19 pandemic, studies reported that restricted living conditions were associated with worse subjective sleep quality. This effect might have been caused by reduced light exposure during lockdowns. We investigated light exposure levels, subjective and objective sleep and physical activity levels in older adults during restricted and free-living conditions after the pandemic. Ninety-one participants (62.7 ± 8.4 years) recruited from the community using social media with 44 participants (63.4 ± 8.9 years) completed follow-up during free-living conditions. Participants wore an actigraphy device and completed sleep diaries for 7 days during each condition. Light values were extracted in hourly bins across the 24-h period and objective and subjective sleep were compared between the conditions. There was an increase in mean 24-h light exposure during restricted-living (1103.7 ± 1024.8 lux) compared to free-living (803.0 ± 803.6 lux; p  < 0.001). This was partially related to participants spending 18 min more in bright light conditions (>1,000 lux) during wakefulness in restricted living (2.6 ± 1.9 h) compared to free-living (2.3 ± 2.0 h; p  = 0.036). Despite differences in light exposure, there were no significant differences in objective and subjective sleep parameters between the two conditions. More research is required to better understand behaviours related to light exposure and how this may impact on sleep.

Dryland agriculture in the Inland Pacific Northwest is challenged in part by rising input costs for seed, fertilizer, and agrichemicals; threats to water quality and soil health, including soil erosion, organic matter decline, acidification, compaction, and nutrient imbalances; lack of cropping system diversity; herbicide resistance; and air quality concerns from atmospheric emissions of particulate matter and greenhouse gases. Technological advances such as rapid data acquisition, artificial intelligence, cloud computing, and robotics have helped fuel innovation and discovery but have also further complicated agricultural decision-making and research. Meeting these challenges has promoted interest in (1) supporting long-term research that enables assessment of ecosystem service trade-offs and advances sustainable and regenerative approaches to agriculture, and (2) developing coproduction research approaches that actively engage decision-makers and accelerate innovation. The R. J. Cook Agronomy Farm (CAF) Long-Term Agroecosystem Research (LTAR) site established a cropping systems experiment in 2017 that contrasts prevailing (PRV) and alternative (ALT) practices at field scales over a proposed 30-year time frame. The experimental site is on the Washington State University CAF near Pullman, WA. Cropping practices include a wheat-based cropping system with wheat (Triticum aestivum L.), canola (Brassica napus, variety napus), chickpea (Cicer arietinum), and winter pea (Pisum sativum), with winter wheat produced every third year under the ALT practices of continuous no-tillage and precision applied N, compared to the PRV practice of reduced tillage (RT) and uniformly applied agrichemicals. Biophysical measurements are made at georeferenced locations that capture field-scale spatial variability at temporal intervals that follow approved methods for each agronomic and environmental metric. Research to date is assessing spatial and temporal variations in cropping system performance (e.g., crop yield, soil health, and water and air quality) for ALT versus PRV and associated tradeoffs. Future research will explore a coproduction approach with the intent of advancing discovery, innovation, and impact through collaborative stakeholder-researcher partnerships that direct and implement research priorities., (© 2024 The Author(s). Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). There is a need to understand molecular mediators that drive recovery and progression to CKD. In particular, the regulatory role of miRNAs in AKI is poorly understood. miRNA and mRNA sequencing were performed on biobanked human kidney tissues obtained in the routine care of subjects with a diagnosis of AKI, minimal change disease, or without known kidney disease in nephrectomy tissue. mRNA analysis revealed that nephrectomy tissues exhibited an injury signature similar to that of AKI and not identified in minimal change disease samples. The transcriptomic signature of human AKI was enriched in pathways involved in cell adhesion, epithelial-to-mesenchymal transition, and cell cycle arrest (eg, CDH6, ITGB6, CDKN1A). In AKI, up-regulation of miR-146a, miR-155, miR-142, and miR-122 was associated with pathways involved in immune cell recruitment, inflammation, and epithelial-to-mesenchymal transition. miR-122 and miR-146 were associated with down-regulation of DDR2 and IGFBP6, which are genes involved in the recovery and progression of kidney disease. These data provide integrated miRNA signatures that complement mRNA and other epigenetic data available in kidney atlases., Competing Interests: Disclosure Statement None declared., (Copyright © 2024. Published by Elsevier Inc.)

Giant Axonal Neuropathy (GAN) is a neurodegenerative disease caused by loss-of-function mutations in the KLHL16 gene, encoding the cytoskeleton regulator gigaxonin. In the absence of functional gigaxonin, intermediate filament (IF) proteins accumulate in neurons and other cell types due to impaired turnover and transport. GAN neurons exhibit distended, swollen axons and distal axonal degeneration, but the mechanisms behind this selective neuronal vulnerability are unknown. Our objective was to identify novel gigaxonin interactors pertinent to GAN neurons. Unbiased proteomics revealed a statistically significant predominance of RNA-binding proteins (RBPs) within the soluble gigaxonin interactome and among differentially-expressed proteins in iPSC-neuron progenitors from a patient with classic GAN. Among the identified RBPs was TAR DNA-binding protein 43 (TDP-43), which associated with the gigaxonin protein and its mRNA transcript. TDP-43 co-localized within large axonal neurofilament IFs aggregates in iPSC-motor neurons derived from a GAN patient with the 'axonal CMT-plus' disease phenotype. Our results implicate RBP dysfunction as a potential underappreciated contributor to GAN-related neurodegeneration.

Venetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty-seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy. The R/R cohort had high-risk cytomolecular genetic alterations and prior extensive treatments, with 50% (n = 9) of relapse patients (n = 18) having undergone haematopoietic stem cell transplantation (HSCT). Venetoclax treatment using the 400 mg adult exposure-equivelant dosing (AED) had a median duration of 21 days (range 7-30 days). Grade 3-4 toxicities included neutropenia (90%), anaemia (64%), thrombocytopenia (64%) and febrile neutropenia (44%). The overall complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 73% (77% minimal residual disease [MRD] negativity <0.1%), with 60% undergoing HSCT. Among newly diagnosed patients (n = 9), 89% achieved CR/CRi (78% MRD negativity) and 78% proceeded to HSCT. The R/R cohort (n = 21) showed a 67% CR/CRi rate (71% MRD negativity), with 52% undergoing HSCT. These findings support the safety and efficacy of HMA + VEN in paediatric/AYA AML, indicating it as a viable option for patients unfit for intensive chemotherapy. Further studies are necessary to determine optimal venetoclax dosing, chemotherapy combinations and pharmacokinetics in this population., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Study Objectives: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population., Methods: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + β) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup., Results: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI., Conclusions: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Qualitative alterations in type I collagen due to pathogenic variants in the COL1A1 or COL1A2 genes, result in moderate and severe Osteogenesis Imperfecta (OI), a rare disease characterized by bone fragility. The TGF-β signaling pathway is overactive in OI patients and certain OI mouse models, and inhibition of TGF-β through anti-TGF-β monoclonal antibody therapy in phase I clinical trials in OI adults is rendering encouraging results. However, the impact of TGF-β inhibition on osteogenic differentiation of mesenchymal stem cells from OI patients (OI-MSCs) is unknown. The following study demonstrates that pediatric skeletal OI-MSCs have imbalanced osteogenesis favoring the osteogenic commitment. Galunisertib, a small molecule inhibitor (SMI) that targets the TGF-β receptor I (TβRI), favored the final osteogenic maturation of OI-MSCs. Mechanistically, galunisertib downregulated type I collagen expression in OI-MSCs, with greater impact on mutant type I collagen, and concomitantly, modulated the expression of unfolded protein response (UPR) and autophagy markers. In vivo, galunisertib improved trabecular bone parameters only in female oim/oim mice. These results further suggest that type I collagen is a tunable target within the bone ECM that deserves investigation and that the SMI, galunisertib, is a promising new candidate for the anti-TGF-β targeting for the treatment of OI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Obstructive sleep apnea is a common comorbidity that occurs in individuals with obesity. It classically manifests with excessive daytime sleepiness, resulting in reduced quality of life, workplace productivity, and an increased risk of motor vehicle accidents. Weight gain plays an important role in its pathogenesis through worsening upper airway collapsibility, and current treatment options are targeted towards mechanically overcoming upper airway obstruction and weight loss. Continuous positive airway pressure therapy remains the most widely prescribed treatment for obstructive sleep apnea but poor tolerance is a common barrier to effective treatment. Sustainable weight loss is an important treatment option but can be difficult to achieve without bariatric surgery. The recent advances in incretin-based pharmacotherapies represent a promising avenue not only in achieving long-term weight loss but also in treating obstructive sleep apnoea and alleviating the burden of its symptoms and comorbidities., (© 2024 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background and Aims: This study assessed whether the addition of continuous positive airway pressure (CPAP) during weight loss would enhance cardiometabolic health improvements in patients with obesity and Obstructive Sleep Apnoea (OSA)., Methods and Results: Patients with overweight or obesity, pre-diabetes and moderatesevere OSA were randomised to receive CPAP therapy with a weight loss programme (CPAP+WL) or a weight loss programme alone (WL alone)., Primary Outcome: 2-hour glucose assessed by an oral glucose tolerance test., Secondary Outcomes: 24 hr blood pressure, body composition (DEXA) and fasting blood markers. 17 patients completed 3-month follow-up assessments (8 CPAP+WL and 9 WL alone). Overall, participants in both groups lost ∼12 kg which reduced polysomnography determined OSA severity by ∼45 %. In the CPAP+WL group, CPAP use (compliance 5.29 hrs/night) did not improve any outcome above WL alone. There was no improvement in 2-hour glucose in either group. However, in the pooled (n = 17) analysis there were overall improvements in most outcomes including insulin sensitivity (.000965 units, p = .008), sleep systolic BP (- 16.2 mmHg, p = .0003), sleep diastolic BP (-9.8 mmHg, p = 0.02), wake diastolic BP (- 4.3 mmHg, p = .03) and sleepiness (Epworth Sleepiness Score -3.2, p = .0003). In addition, there were reductions in glucose area under the curve (-230 units, p = .009), total (-0.86 mmol/L, p = 0.006) and LDL cholesterol (-0.58 mmol/L, p = 0.007), triglycerides (-0.75 mmol/L, p = 0.004), fat mass (-7.6 kg, p < .0001) and abdominal fat (-310 cm3, p < .0001)., Conclusion: Weight loss reduced OSA and improved sleepiness and cardiometabolic health. These improvements were not further enhanced by using CPAP. Results suggest weight loss should be the primary focus of treatment for patients with OSA and obesity., Competing Interests: Declaration of Competing Interest S. Postnova reports grants unrelated to the manuscript from NHMRC and ARC. T. Markovich reports grants unrelated to the manuscript from NHMRC and advisory board participation with Nestle Health Science and Eli Lilly. S. Twigg reports advisory board participation with Abbott Diabetes care and Nevro Inc and payments from Nevro Inc and Astra Zeneca Inc for presentations. R. Grunstein reports advisory board participation and payments from Eli Lilly for SURMOUNT OSA weight loss trial. All other authors have no conflict of interest to declare., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Quantum dots are promising candidates for telecom single photon sources due to their tunable emission across the different low-loss telecommunications bands, making them compatible with existing fiber networks. Their suitability for integration into photonic structures allows for enhanced brightness through the Purcell effect, supporting efficient quantum communication technologies. Our work focuses on InAs/InP QDs created via droplet epitaxy MOVPE to operate within the telecoms C-band. We observe a short radiative lifetime of 340 ps, arising from a Purcell factor of 5, owing to integration of the QD within a low-mode-volume photonic crystal cavity. Through in-situ control of the sample temperature, we show both temperature tuning of the QD's emission wavelength and a preserved single photon emission purity at temperatures up to 25K. These findings suggest the viability of QD-based, cryogen-free C-band single photon sources, supporting applicability in quantum communication technologies., (© 2024. The Author(s).)

There is accumulating evidence that has linked OSA with increased risk of cognitive decline and dementia. Here we present the protocol for an Australian, multi-site randomised controlled, parallel open-label trial which will evaluate the feasibility for a full-scale trial investigating the effects of treating OSA on cognitive decline in older adults at risk of dementia within memory clinic settings. We will randomise 180 older adults to either the treatment intervention group or control group for 2 years. Inclusion criteria include: 50-85 years; mild-severe OSA (defined average ODI ≥ 10 with 3% oxygen desaturation determined by wrist oximetry over two nights); and subjective cognitive complaints or mild cognitive impairment. The treatment intervention arm aims to achieve an optimal treatment response based on reducing hypoxic burden with either CPAP, mandibular advancement splint, positional therapy, or oxygen therapy. Furthermore, participants will receive up to 8 sessions which involve motivational interviewing, collaborative goal setting, and behavioural sleep management. The control arm will not receive OSA treatment as part of this trial, however there will be no OSA treatment restrictions, and any treatment will be documented. Primary outcomes are 1) acceptability based upon willingness of participants to be randomised; 2) alleviating hypoxic burden by reducing OSA severity; 3) tolerability of the trial burden based upon collection of outcomes over the 2-year follow-up. Secondary outcomes include safety and cognitive function. Outcomes will be collected at 0, 6 and 24-months. This feasibility study aims to will provide the basis for a larger longer-term trial of dementia prevention., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RRG: has received consulting fees from Lilly as a member of an advisory board and lecture fees from Praxhub., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with AKI or CKD. We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient's histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive periglomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation, and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques used by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy., (Copyright © 2023 by the American Society of Nephrology.)

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks., (© 2024. The Author(s).)