Is Greenness Associated with Dementia? A Systematic Review and Dose–Response Meta-analysis

Purpose of review: We assessed the relation between environmental greenness and risk of dementia and cognitive impairment, based on a systematic review and meta-analysis up to March 30, 2022, characterizing whenever possible the shape of the association using dose-response meta-analysis. Recent findings: Twelve studies were included in this review, either using normalized difference vegetation index (NDVI) or land use/cover (LU/LC) methodology to assess greenness. Comparing the highest versus lowest exposure categories of greenness assessed using the NDVI (6 studies) or LU/LC (6 studies), we found no association with dementia. Dose-response meta-analysis of the association between greenness measured by LU/LC and dementia, based on only 3 studies, indicated a U-shaped association, but estimates were imprecise. Our systematic review and meta-analysis provided some evidence of a slight inverse association between greenness and dementia at intermediate exposure levels, but not at high levels. Potential methodological limitations, such as exposure misclassification and unmeasured confounding, may have affected the results

Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP)

International audienceSummaryBackground High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. Methods We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18–55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. Findings Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days (SD 3·6) and 7·4 days (3·9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment difference 0·5%, 90% CI −9·5 to 10·4). Rates of adverse events were similar, but insomnia was more frequently reported in the oral group (77 [77%]) than in the intravenous group (63 [64%]). Interpretation Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile. This finding could have implications for access to treatment, patient comfort, and cost, but indication should always be properly considered by clinicians. Funding French Health Ministry, Ligue Française contre la SEP, Tev

Combinatorial CRISPR screen identifies fitness effects of gene paralogues.

Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells

Arch Neurol

BACKGROUND: Friedreich ataxia (FA) is the most frequent type of autosomal recessive cerebellar ataxia, occurring at a mean age of 16 years. Nearly 98% of patients with FA present with homozygous GAA expansions in the FXN gene. The remaining patients are compound heterozygous for an expansion and a point mutation. Patients who are compound heterozygous for an exonic deletion and an expansion are exquisitely rare. OBJECTIVES: To describe 6 patients affected with FA due to an exonic deletion mutation (FAexdel) and to compare these 6 patients with FAexdel with 46 patients consecutively diagnosed with typical FA due to homozygous GAA expansion and whose small expansions were within the same range as that of the expansions of the patients with FAexdel. DESIGN: Description of a series. SETTING: Academic research. PATIENTS: Six patients with FAexdel and 46 patients with typical FA. INTERVENTION: FXN gene analysis, including assessments of GAA expansion and exon sequencing and determination of exonic copy numbers using multiplex ligation-dependent probe amplification. RESULTS: We identified 6 patients with FA who presented with the combination of 1 GAA expansion and 1 FXN exonic deletion. The mean (SD) age at onset of the disease was earlier for patients with FAexdel (7 [4] years [range, 3-12 years]) than for patients with typical FA (15 [5] years [range, 6-30 years]) (P = .001), and the median time to confinement to wheelchair was shorter for patients with FAexdel (20 years) than for patients with typical FA (28 years) (P = .002). There was no difference between the mean (SD) size of the expansion for the patients with FAexdel (780 [256] GAA triplet repeat sequences [range, 340-1070 GAA triplet repeat sequences]) and the mean (SD) size of the short expansion for the patients with typical FA (634 [163] GAA triplet repeat sequences [range, 367-1000 GAA triplet repeat sequences]) (P = .10). The mean disease duration before becoming wheelchair bound was shorter for patients with FAexdel (9 years) than for patients with typical FA (13 years), and the incidence of cardiomyopathy was higher for patients with FAexdel (84%) than for patients with typical FA (68%). However, these differences were not significant, probably owing to the small size of the FAexdel group. The other extraneurological signs, such as scoliosis or diabetes mellitus, were particularly frequently observed in the FAexdel group. One patient presented at 9 years of age with severe angina and marked cardiomyopathy that confined her to a wheelchair. Three patients had disabling autonomic disturbances. It appears that exonic deletion significantly contributes to the clinical picture of patients with FA. CONCLUSIONS: Friedreich ataxia due to an exonic deletion mutation corresponds to an early onset and severe variant of FA. FXN should be investigated for exonic deletion in patients with early-onset FA in which only 1 GAA expansion without a point mutation is found. Patients with FAexdel have to be carefully observed using cardiological, orthopaedic, endocrinological, gastroenterological, and ophthalmological data. Friedreich ataxia due to an exonic deletion mutation should be suspected in young patients presenting with severe scoliosis

Do stakeholders matter in strategic decision making of a sports organization?

This study aims to identify and prioritize the stakeholders involved in making decisions in a sports organization. A multiple linear regression analysis was used to assess the influence of the attributes of power, legitimacy and urgency on the salience of the various stakeholders. The results showed a convergence of external and internal decision makers’ perceptions, concerning the three main stakeholder groups: top management, sponsors and member association. Pearson correlations identified four types of stakeholder: definitive, dangerous, demanding and non-stakeholders. A generalized differentiation was also found in stakeholder classification, regarding evaluation of attributes, between external and internal decision makers. In addition, the study suggests the success of organizations’ management will depend on correct identification of stakeholders and consequent assessment of their relevance, in order to highlight who should get priority, and how, in strategic decision making

Integrated irrigation water policies: Economic and Environmental impact in the "Renana" Reclamation and irrigation board, Italy

This study was laid out in the \u201cRenana\u201d reclamation and irrigation board, in the Italian region of Emilia Romagna (northern Italy). Its objective was to evaluate the current and future possible policies adopted or to be adopted in order to spur a rational planning and decision making in water management and to give valid scientific answers to the local decision makers. A mathematical stochastic model was designed and implemented using data collected from farms in the area and other local sources. These policies are mainly based on modifying water quantity, the irrigable area, and the flat water tariffs. Finally all these changes are also analyzed in the presence of a volumetric water tariff designed by the European Water Framework Directive (WFD). Results have shown how fundamental it is to improve distribution efficiency of the channel system in order to increase irrigated land, for the positive socio-economic and environmental impacts on the territory. However, the introduction of a volumetric tariff could be an effective tool to control water demand expected to augment due to such policy measures, depending on yearly water availability; it could be very profitable to the RIB which will increase returns.Cette \ue9tude a \ue9t\ue9 r\ue9alis\ue9e aupr\ue8s de l\u2019Office de mise en valeur et de l\u2019irrigation \u201cRenana\u201d, dans la r\ue9gion italienne Emilie Romagne (dans le nord de l\u2019Italie). L\u2019objectif \ue9tait d\u2019\ue9valuer les politiques actuelles et les politiques futures qui pourraient \ueatre adopt\ue9es afin d\u2019encourager une planification et une prise de d\ue9cisions raisonn\ue9es en mati\ue8re d\u2019am\ue9nagement de l\u2019eau et de proposer des solutions scientifiques appropri\ue9es aux d\ue9cideurs locaux. A cette fin, un mod\ue8le math\ue9matique stochastique a \ue9t\ue9 mis au point et appliqu\ue9 en s\u2019appuyant sur des donn\ue9es collect\ue9es au niveau des exploitations de la r\ue9gion ou \ue0 partir d\u2019autres sources locales. Ces politiques reposent essentiellement sur la modification de la quantit\ue9 d\u2019eau, de la surface irrigable et des taux forfaitaires. Ces modifications sont successivement analys\ue9es en prenant en compte la tarification volum\ue9trique de l\u2019eau \ue9labor\ue9e dans le cadre de la Directive Cadre sur l\u2019Eau (DCE) de l\u2019Union Europ\ue9enne. Les r\ue9sultats ont confirm\ue9 l\u2019importance d\u2019am\ue9liorer l\u2019efficience de distribution du syst\ue8me de canalisation pour accroitre la surface irrigu\ue9e, vu les effets socio-\ue9conomiques et environnementaux positifs g\ue9n\ue9r\ue9s sur le territoire. Toutefois, l\u2019introduction d\u2019un tarif volum\ue9trique pourrait repr\ue9senter un outil efficace pour contr\uf4ler la demande d\u2019eau qui est cens\ue9e pouvoir augmenter, suite \ue0 l\u2019adoption de ces mesures, selon la disponibilit\ue9 annuelle d\u2019eau. Ceci pourrait repr\ue9senter un avantage tr\ue8s significatif en terme de rentabilit\ue9 pour l\u2019Office de mise en valeur et de l\u2019irrigation \uab Renana \ubb qui r\ue9ussirait ainsi \ue0 accro\ueetre ses recettes

Acute graft-versus-host disease and steroid treatment impair CD11c+ and CD123+ dendritic cell reconstitution after allogeneic peripheral blood stem cell transplantation

Human dendritic cells (DC) comprise 2 subsets-plasmacytoid CD123+ and myeloid CD11c+ DC-that may have distinct roles in the regulation of immunity after allogeneic hematopoietic stem cell transplantation. In this study, we analyzed the kinetics of CD123+ DC and CD11c+ DC reconstitution in 31 patients who underwent transplantation with allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells from HLA-identical sibling donors after myeloablative conditioning. Lineage marker-negative HLA-DR+ CD11c+ CD11c+ DC and lineage marker-negative HLA-DR+ CD123+ CD123+ DC, as well as monocytes and lymphoid subsets, were enumerated in donor grafts and in the PB of patients at various time points after transplantation. Reconstitution of both CD11c+ DC and CD123+ DC to normal levels occurred within 6 to 12 months and was not affected by the diagnosis, preparatory regimen, or graft composition. However, PB CD11c+ DC and CD123+ DC counts were significantly reduced in patients with acute GVHD grade II to IV (at 1 and 3 months) and grade I (at 1 month). Patients with chronic GVHD instead showed reduced CD123+ DC counts only 6 months after transplantation. Moreover, treatment with steroids (>0.1 mg/kg) was significantly associated with reduced PB CD11c+ DC and CD123+ DC counts at all time points after transplantation. In multivariate analysis, only acute GVHD affected DC reconstitution early after transplantation. These results will prompt new studies addressing whether DC reconstitution correlates with immunity against infectious agents or with graft-versus-tumor reactions after PB stem cell allotransplantation. © 2004 American Society for Blood and Marrow Transplantatio

High completeness of the brest stroke registry evidenced by analysis of sources and capture-recapture method.

International audienceBACKGROUND: Population-based stroke registries are necessary to evaluate the precise burden of stroke. The methodology used in the Brest Stroke Registry and an estimation of its completeness are described. METHODS: 'Hot pursuit' as well as 'cold pursuit' were used, and five sources of identification were included: emergency wards, brain imaging, practitioners, death certificates and hospital-based electronic research. Ascertainment for each case was certified by a neurologist. Inclusion criteria were: (1) age >15 years; (2) a stroke defined by WHO criteria or all neurological deficits lasting at least 1 h. Completeness was estimated using capture-recapture method. RESULTS: For 2008, 2009 and 2010, 851, 898, 823 patients were collected, respectively. The number of sources of identification per patient was as follows: one source: 30.8, 24.1 and 18.7%; two sources: 54.5, 42.9 and 31.0%; three sources: 13.4, 30.1 and 46%; four sources: 1.3, 3.0 and 3.8%. Capture-recapture analysis showed data completeness over 90%. Standardized cumulative first-ever stroke incidence using a world standard population was 87 in 2008, 87 in 2009 and 84 in 2010. CONCLUSIONS: Case ascertainment by a neurologist, numerous sources, as well as 'hot' and 'cold' pursuit can provide a reliably large data set suitable for further epidemiological studies