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Recent evidence showing degeneration of the noradrenergic system in the locus coeruleus (LC) in Alzheimer’s disease (AD) has motivated great interest in noradrenaline (NA) as a potential brain hallmark of the disease. Despite the current exploration of blood markers for AD, the deregulation of the plasma NA concentration ([NA] plasma ) in AD is currently not well understood. This retrospective study includes a cohort of 71 patients (32 AD patients, 22 with other dementia and 17 without dementia) who were given consultations for memory complaints in the Cognitive Neurology Center of Lariboisière (Paris) between 2009 and 2014. As previously described in brain tissue, we show for the first time a linear correlation between [NA] plasma and Mini Mental State Examination (MMSE) score in AD patients. We observed that high [NA] plasma in AD patients was associated with higher [Aβ 1–42 ] CSF than in other AD patients with [NA] plasma similar to NC patients. In parallel, we observed a lower (p-Tau/Tau) CSF in AD patients with low [NA] plasma than in non-AD patients with [NA] plasma similar to [NA] plasma in NC patients. Our data suggest that [NA] plasma could be a potential biomarker of disease evolution in the context of AD and could possibly improve early diagnosis.

(1) Background: While inequalities in the prevalence of cancer, access to care, and survival have been well documented, less research has focused on inequalities in the uptake of supportive oncology care. Given its contribution to improving the quality of life of people affected by cancer, access to such care is a major public health issue. The present study focuses on the access and uptake of those supportive oncology care services. (2) Methods: This study is based on qualitative research methodology, using a thematic analysis tree on NVivo© analysis software. First, an exploratory survey was conducted with users of oncology services, and professionals from these services and supportive oncology care. Then, individual interviews were conducted in June 2022 among people who are currently being treated or have been treated for cancer. (3) Results: The experiences of the 33 respondents revealed that significant variations in the uptake of supportive oncology care are underpinned by identifiable disparities in their healthcare pathways: in their assimilation of information, difficulties in accessing oncology care, personal reluctance and motivations, perceived needs and benefits, and use of other medicines. (4) Conclusion: This study aims to gain some insight into disparities in the uptake of supportive care in the Centre-Val de Loire region (France). Thus, it provides a better understanding of the complex ways in which these inequalities in supportive oncology care uptake are constructed.

A Correction to this paper has been published: https://doi.org/10.1038/s41398-020-01102-y

To report on OPTIPUMP, a cohort study, investigating the impact in real-life clinical settings of continuous subcutaneous apomorphine infusion (CSAI) on the quality of life (HRQoL) of patients with Parkinson’s disease. OPTIPUMP was a prospective, open-label, observational cohort study involving 30 investigational sites in France. CSAI was proposed as part of routine clinical care to patients aged ≥18 years, in absence of dementia, with a PD diagnosis and based on the presence of motor fluctuations not controlled by oral treatments. The impact of APO-pump on quality of life was evaluated as the difference in PDQ-39 scores between the initiation treatment and the follow-up visit after 6 months’ treatment. All adverse events were recorded. Hyper- and hypodopaminergic behavioral tolerance was assessed on the Ardouin Scale of Behavior in Parkinson’s Disease. Between September 2011 and January 2013, we enrolled 142 patients: 42 patients were withdrawn due to pump removal (33), death (4), lost of follow-up (4), no available data (1). 100 completed the study. At 6 months, their HRQoL had significantly improved ( p  = 0.011), as had their total UPDRS score ( p  < 0.001). Regarding the safety profile, Ardouin scale scores indicated that their hyperdopaminergic behaviors had not increased. CSAI had a favorable impact on HRQoL, with benefits outweighing risks. The analysis of the withdrawn patients highlights the heterogeneity of the use of the pump having an impact on its efficacy and tolerability.

•Inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for PSP.•We assessed the safety and efficacy of sodium valproate (VPA), a GSK-3 inhibitor, in PSP.•VPA was not effective as a disease-modifying agent in PSP. Results from preclinical studies suggest that inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for tauopathies. The aim of the present study was therefore to determine the effects of sodium valproate (VPA), a GSK-3 inhibitor, on disease progression in progressive supranuclear palsy (PSP). We performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500mg/day) or matching placebo for 24 months. The primary endpoint was the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 12 and 24 months. Secondary endpoints evaluated the effects of VPA on cognitive and behavioral status (MMSE, Mattis Dementia Rating Scale, Wisconsin Card Sorting, Gröber and Buschke and Oral Denomination 80 tests), tolerability of treatment, and patient compliance. There were no baseline differences between active treatment and placebo groups in age and clinical rating scores. PSPRS score at 12 months was significantly higher in the VPA than in the placebo group (60.8±20 versus 46.9±18.6 respectively, p=0.01), but was similar between the two groups at 24 months. No significant differences were observed between VPA and placebo groups for the secondary endpoints. Our results suggest that VPA is not effective as a disease-modifying agent in PSP.

(1) Background: While inequalities in the prevalence of cancer, access to care, and survival have been well documented, less research has focused on inequalities in the uptake of supportive oncology care. Given its contribution to improving the quality of life of people affected by cancer, access to such care is a major public health issue. The present study focuses on the access and uptake of those supportive oncology care services. (2) Methods: This study is based on qualitative research methodology, using a thematic analysis tree on NVivo© analysis software. First, an exploratory survey was conducted with users of oncology services, and professionals from these services and supportive oncology care. Then, individual interviews were conducted in June 2022 among people who are currently being treated or have been treated for cancer. (3) Results: The experiences of the 33 respondents revealed that significant variations in the uptake of supportive oncology care are underpinned by identifiable disparities in their healthcare pathways: in their assimilation of information, difficulties in accessing oncology care, personal reluctance and motivations, perceived needs and benefits, and use of other medicines. (4) Conclusion: This study aims to gain some insight into disparities in the uptake of supportive care in the Centre-Val de Loire region (France). Thus, it provides a better understanding of the complex ways in which these inequalities in supportive oncology care uptake are constructed.

In the high-stakes realm of critical care, where daily decisions are crucial and clear communication is paramount, comprehending the rationale behind Artificial Intelligence (AI)-driven decisions appears essential. While AI has the potential to improve decision-making, its complexity can hinder comprehension and adherence to its recommendations. “Explainable AI” (XAI) aims to bridge this gap, enhancing confidence among patients and doctors. It also helps to meet regulatory transparency requirements, offers actionable insights, and promotes fairness and safety. Yet, defining explainability and standardising assessments are ongoing challenges and balancing performance and explainability can be needed, even if XAI is a growing field.

Purpose of the Review Obesity and type 2 diabetes (T2D) are considered chronic inflammatory diseases. While early publications have reported the implication of innate immune cells such as macrophages to promote systemic inflammation and metabolic dysfunctions, recent publications underline the alterations of the T cell compartment in human obesity and type 2 diabetes. These recent findings are the focus of this review. Recent Findings In humans, obesity and T2D induce the expansion of proinflammatory T cells such as CD4 Th1, Th17, and CD8 populations, whereas innate T cells such as MAIT and iNKT cells are decreased. These alterations reflect a loss of total T cell homeostasis that may contribute to tissue and systemic inflammation. Summary Whether these changes are adaptive to nutritional variations and/or contribute to the progression of metabolic diseases remains to be clarified. T cell phenotyping may improve obese and/or T2D patient stratification with therapeutic and prognostic implications.

The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the different stages of the T2DM disease progression in humans: an early prediabetic phase characterized by an hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia, hepatic fibrosis and pancreatic β-cell failure. Histopathological analyses combined to [ 18 F]-FDG PET imaging further demonstrated the presence of several end-organ long-term complications, including reduction in myocardial glucose utilization, renal dysfunction as well as microvascular neuropathy and retinopathy. We also provide for the first time a comprehensive µ-PET whole brain imaging of the changes in glucose metabolic activity within discrete cerebral regions in HF/HF/Stz diabetic rats. Altogether, we developed and characterized a unique non-genetic preclinical model of T2DM adapted to the current diet and lifestyle that recapitulates the major metabolic features of the disease progression, from insulin resistance to pancreatic β-cell dysfunction, and closely mimicking the target-organ damage occurring in type 2 diabetic patients at advanced stages.

Abstract The objective was to evaluate the effects of a specific strain of live yeast (LY) on growth performance, fermentation parameters, feed efficiency, and bacterial communities in the rumen of growing cattle fed low-quality hay. In experiment (exp.) 1, 12 Droughtmaster bull calves (270 ± 7.6 kg initial body weight [BW]) were blocked by BW into two groups, allocated individually in pens, and fed ad libitum Rhodes grass hay (8.4% of crude protein [CP]) and 300 g/bull of supplement (52% CP) without (Control) or with LY (8 × 109 colony-forming unit [CFU]/d Saccharomyces cerevisiae CNCM I-1077; Lallemand Inc., Montreal, Canada) for 28 d, followed by 7 d in metabolism crates. Blood and rumen fluid were collected before feeding and 4 h after feeding. In exp. 2, for assessment of growth performance, 48 Charbray steers (329 ± 20.2 kg initial BW) were separated into two blocks by initial BW and randomly allocated into 12 pens. The steers were fed Rhodes grass hay (7.3% CP) and 220 g/steer of supplement (60% CP) without or with LY (8 × 109 CFU/d) for 42 d, after a 2-wk adaptation period. In exp. 1, fiber digestibility was calculated from total fecal collection, and, in exp 2, indigestible neutral detergent fiber (NDF) was used as a marker. Inclusion of LY increased (P = 0.03) NDF intake by 8.3% in exp. 1, without affecting total tract digestibility. No changes were observed in microbial yield or in the efficiency of microbial production. There was a Treatment × Time interaction (P < 0.01) for the molar proportion of short-chain fatty acids, with LY increasing propionate before feeding. Inclusion of LY decreased rumen ammonia 4 h after feeding (P = 0.03). The addition of LY reduced rumen bacterial diversity and the intraday variation in bacterial populations. Relative populations of Firmicutes and Verrucomicrobia varied over time (P < 0.05) only within the Control group. At the genus level, the relative abundance of an unclassified bacterial genus within the order Clostridiales, a group of cellulolytic bacteria, was reduced from 0 to 4 h after feeding in the Control group (P = 0.02) but not in the LY group (P = 1.00). During exp. 2, LY tended to increase average daily gain (ADG) (P = 0.08) and feed efficiency (P = 0.10), with no effect on NDF intake or digestibility. In conclusion, S. cerevisiae CNCM I-1077 reduced the intraday variation of rumen bacteria and increased the amount of NDF digested per day. These observations could be associated with the tendency of increased ADG and feed efficiency in growing cattle fed a low-quality forage.