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Multiple lines of evidence have linked oxidative stress, tau pathology and neuronal cell cycle re-activation to Alzheimer's disease (AD). While a prevailing idea is that oxidative stress-induced neuronal cell cycle reactivation acts as an upstream trigger for pathological tau phosphorylation, others have identified tau as an inducer of cell cycle abnormalities in both mitotic and postmitotic conditions. In addition, nuclear hypophosphorylated tau has been identified as a key player in the DNA damage response to oxidative stress. Whether and to what extent these observations are causally linked remains unclear. Using immunofluorescence, fluorescence-activated nucleus sorting and single-nucleus sequencing, we report an oxidative stress-associated accumulation of nuclear hypophosphorylated tau in a subpopulation of cycling neurons confined in S phase in AD brains, near amyloid plaques. Tau downregulation in murine neurons revealed an essential role for tau to promote cell cycle progression to S phase and prevent apoptosis in response to oxidative stress. Our results suggest that tau holds oxidative stress-associated cycling neurons in S phase to escape cell death. Together, this study proposes a tau-dependent protective effect of neuronal cell cycle reactivation in AD brains and challenges the current view that the neuronal cell cycle is an early mediator of tau pathology., Competing Interests: Declaration of Competing Interests The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective. Tau ablation has a protective effect in epilepsy due to inhibition of the hyperexcitability/hypersynchrony. Protection may also occur in transgenic models of Alzheimer's disease by reducing the epileptic activity and normalizing the excitation/inhibition imbalance. However, it is difficult to determine the exact functions of tau, because tau knockout ( tau KO ) brain networks exhibit elusive phenotypes. In this study, we aimed to further explore the physiological role of tau using brain network remodeling. Approach. The effect of tau ablation was investigated in hippocampal-entorhinal slice co-cultures during network remodeling. We recorded the spontaneous extracellular neuronal activity over 2 weeks in single-slice cultures and co-cultures from control and tau KO mice. We compared the burst activity and applied concepts and analytical tools intended for the analysis of the network synchrony and connectivity. Main results. Comparison of the control and tau KO co-cultures revealed that tau ablation had an anti-synchrony effect on the hippocampal-entorhinal two-slice networks at late stages of culture, in line with the literature. Differences were also found between the single-slice and co-culture conditions, which indicated that tau ablation had differential effects at the sub-network scale. For instance, tau ablation was found to have an anti-synchrony effect on the co-cultured hippocampal slices throughout the culture, possibly due to a reduction in the excitation/inhibition ratio. Conversely, tau ablation led to increased synchrony in the entorhinal slices at early stages of the co-culture, possibly due to homogenization of the connectivity distribution. Significance. The new methodology presented here proved useful for investigating the role of tau in the remodeling of complex brain-derived neural networks. The results confirm previous findings and hypotheses concerning the effects of tau ablation on neural networks. Moreover, the results suggest, for the first time, that tau has multifaceted roles that vary in different brain sub-networks., (© 2022 IOP Publishing Ltd.)

This French study aimed to evaluate oncologists' and patients' perception of physical activity, particularly adapted physical activity, in order to identify the obstacles and levers to its practice in patients with metastatic cancer., Method: Between October 2019 and March 2020, 60 medical oncologists and 305 patients with metastatic cancer were asked to fill in a self-completed questionnaire., Results: The benefits of physical activity are recognised by most oncologists and patients. These benefits were perceived more by oncologists in prevention (78%) or in the early stage (72%) of the disease than in the metastatic stage (55%) (P=0.01). Patient's physical condition (45%) and age (37%) but also the lack of time during the consultation to explain supportive care (35%) are the main obstacles identified by the oncologist to the integration of physical activity into patient care. Furthermore, lack of knowledge of adapted programmes is the main reason given by the physicians who have never prescribed physical activity (51%). On the patient side, while 88% of them had heard of the benefits of physical activity, only 11% had received a prescription. Most oncologists and patients were very interested in receiving information on where and what types of activities to practice, as well as what to avoid., Conclusion: Efforts in terms of information for both oncologists and patients seem necessary to increase the level of physical activity prescription and practice for patients followed for metastatic cancer., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer's disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Human, material, and financial resources being limited, the organization of the care system must allow an efficient allocation of resources. The management of cancers leads to specific and repetitive care for which the reimbursement of transport costs represents a high cost. We carried out an analysis of the additional transport costs, linked to the care of patients in Île-de-France, in a center other than the radiotherapy center closest to their home., Materials and Methods: Using data from the Île-de-France Regional Health Agency, we have created a model evaluating the additional cost linked to transport generated by the care of a radiotherapy patient far from his home. In order to take into account the uncertainties linked to the hypotheses made in the development of the model, we carried out deterministic and probabilistic sensitivity analyzes., Results: In the base case, the additional annual cost related to transport was 841,176 euros in Île-de-France. The probabilistic sensitivity analysis reports a total annual additional cost of 2,817,481 euros., Conclusion: Our results are similar to a report from the General Inspectorate of Social Affairs published in July 2011, which then pointed to an additional cost of between 4 and 6 million euros annually. The long-term care of cancer patients from their homes contributes to a deterioration in the quality of life linked to travel times, a delay in the care of potential treatment complications, and the spread of infectious diseases, such as COVID-19, and bacteria resistant to antibiotics., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background & Aims: To assess the prevalence of sarcopenia before cancer treatment and its predictive value during the treatment., Methods: We searched MEDLINE via PubMed for articles published from 2008 to 2016 that reported prospective observational or interventional studies of the prevalence of pre-therapeutic sarcopenia and its consequences in adults with cancer who were 18 years or older. Two independent reviewers selected articles based on titles and/or abstracts before a complete review. Sarcopenia had to be measured before cancer treatment. Methods recommended by consensuses (CT scan, MRI, dual X-ray absorptiometry or bio-impedancemetry) to assess sarcopenia were considered. Characteristics of the studies included the prevalence of pre-therapeutic sarcopenia and the prognostic value for outcomes during the cancer treatment., Results: We selected 35 articles involving 6894 participants (in/out patients, clinical trials). The mean age ranged from 53 to 69.6 years. Pre-therapeutic sarcopenia was found in 38.6% of patients [95% CI 37.4-39.8]. Oesophageal and small-cell lung cancers showed the highest prevalence of pre-therapeutic sarcopenia. Pre-therapeutic sarcopenia was significantly and independently associated with post-operative complications, chemotherapy-induced toxicity and poor survival in cancer patients., Conclusions: Pre-therapeutic sarcopenia is highly prevalent in cancer patients and has severe consequences for outcomes of cancer patients., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Cancer-related fatigue is serious and complex, as well as one of the most common symptoms experienced by patients with colorectal cancer, with the potential to compromise quality of life, activities of daily living, and ultimately survival. There is a lack of consensus about the definition of cancer-related fatigue; however, definitions have been put forward by the European Association for Palliative Care (EAPC) and the National Comprehensive Cancer Network (NCCN). Numerous cancer- and treatment-related factors can contribute to fatigue, including disease progression, comorbidities, medical complications such as anemia, side effects of other medications, and a number of physical and psychologic factors. This underlines the importance of tackling factors that may contribute to fatigue before reducing the dose of treatment. NCCN guidelines and the EAPC have proposed approaches to managing fatigue in cancer patients; however, relatively few therapeutic agents have been demonstrated to reduce fatigue in randomized controlled trials. It is recognized that physical activity produces many beneficial physiologic modifications to markers of physical performance that can help to counteract various causes of fatigue. In appropriately managed and monitored patients with colorectal cancer, emerging evidence indicates that exercise programs may have a favorable influence on cancer-related fatigue, quality of life, and clinical outcomes, and therefore may help patients tolerate chemotherapy. This review assesses fatigue in patients with colorectal cancer and proposes updates to a treatment algorithm that may help clinicians manage this common problem., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial. Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords "colorectal cancer, physical activity, and survival" in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, "high" PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44-0.86). The corresponding HR OS was 0.62 (0.54-0.71). HR CSS for prediagnosis PA was 0.75 (0.62-0.91). The corresponding HR OS was 0.74 (0.62-0.89). Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk).

Background: The kidneys are dose-limiting organs when total body irradiation or irradiation of the digestive tract is planned. The incidence of radiation-induced toxicity is probably underestimated due to its latency and confounding factors like chemotherapy., Material and Methods: A search of the literature for radiation induced renal toxicity was performed., Results: Most toxicities occur around 18 months. Renal mobility is significant in terms of dosimetric consequences, in particular in the young child. In case of total body irradiation, the dose responsible for a 5% risk of toxicities is around 16 Gy in 2 Gy fractions over 2 weeks. For partial renal irradiation, the volume receiving 20 Gy should be below 32% of the total renal volume. Compensatory mechanisms remain possible in areas receiving 12 Gy or less in 1 Gy fractions. When nephrotoxic chemotherapy, these tolerance doses must be lowered. Treatment of radiation-induced nephropathy may include ACE inhibitors., Discussion/conclusion: Prospective assessment of dose-volume histograms and consideration of renal mobility in treatment plans along with improving radiation techniques should help to improve treatment plans including the kidneys.