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Investigates whether sequence rearrangements or methylation changes reflect a locally inactive X chromosome. Uses pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus.

Defines the novel isoforms of the fragile X related protein FXR1P during myogenesis. Causes of the fragile X mental retardation syndrome; Amino acid homologies at the C-terminal ends of FXR1P short and long isoforms; Localization of FXR1P in muscle; Differential sedimentation properties of FXR1P.

Objective: Frailty has been extensively studied in end-stage kidney disease (ESKD) and kidney transplant (KT) patients. The identification of frailty is useful to predict adverse outcomes among ESKD and KT patients. The recent concept of intrinsic capacity (IC) appears as a good and easy-to-understand tool to screen for and monitor frailty in older adults with ESKD. This study aims to assess the relationships between frailty and IC in older adults with ESKD awaiting KT., Design: Cross-sectional study SETTING AND PARTICIPANTS: 236 patients from a day-care geriatric unit undergoing pre-KT geriatric assessment between 2017 and 2022 were included in the main sample, and 151 patients in an independent multicentric replication sample., Measurements: Frailty was evaluated using the physical frailty phenotype (PFP) and IC measures using the World Health Organization's screening (step 1) and diagnostic (step 2) tools for five IC domains (vitality, locomotion, audition, cognition, psychology). Multivariate regressions were run to assess relationships between PFP and IC domains, adjusted for age, sex, and comorbidities. Analyses were replicated using another independent multicenter cohort including 151 patients with ESKD to confirm the results., Results: Impairments in the locomotion, psychology, and vitality IC domains according to WHO screening tools were associated with frailty (odds ratio 9.62 [95% CI 4.09-24.99], 3.19 [95% CI 1.11-8.88], and 3.11 [95% CI 1.32-7.29], respectively). When IC were measured linearly with z-scores, all IC domains except hearing were inversely associated with frailty. In the replication cohort, results were overall similar, with a greater association between psychology domain and frailty., Conclusion: This study highlights the relationship between frailty and IC in ESKD patients. We assume that IC may be assessed and monitored in ESKD patients, to predict and prevent future frailty, and post-KT adverse outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives., Materials and Methods: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives., Results: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials., Conclusion: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

The dataset contains Eulerian velocity and pressure fields, and Lagrangian particle trajectories of the wake flow downstream of a smooth cylinder at a Reynolds number equal to 3900. An open source Direct Numerical Simulation (DNS) flow solver named Incompact3d was used to calculate the Eulerian field around the cylinder. The synthetic Lagrangian tracer particles were transported using a fourth-order Runge-Kutta scheme in time and trilinear interpolations in space. Trajectories of roughly 200,000 particles for two 3D sub-domains are available to the public. This dataset can be used as a test case for tracking algorithm assessment, exploring the Lagrangian physics, statistic analyses, machine learning, and data assimilation interests., Competing Interests: 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., (© 2021 The Authors. Published by Elsevier Inc.)

Background: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers., Methods: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI)., Results: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17])., Conclusions: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

Background: Nutritional impairment is common in cancer patients and is associated with poor outcomes. Only few studies focused on cachexia. We assessed the prevalence of cachexia in older cancer patients, identified associated risk factors, and evaluated its impact on 6 month overall mortality., Methods: A French nationwide cross-sectional survey (performed in 55 geriatric oncology clinics) of older cancer patients aged ≥70 referred for geriatric assessment prior to treatment choice and initiation. Demographic, clinical, and nutritional data were collected. The first outcome was cachexia, defined as loss of more than 5% of bodyweight over the previous 6 months, or a body mass index below 20 kg/m 2 with weight loss of more than 2%, or sarcopenia (an impaired Strength, Assistance with walking, Rise from chair, Climb stairs and Falls score) with weight loss of more than 2%. The second outcome was 6 month overall mortality., Results: Of the 1030 patients included in the analysis [median age (interquartile range): 83 (79-87); males: 48%; metastatic cancer: 42%; main cancer sites: digestive tract (29%) and breast (16%)], 534 [52% (95% confidence interval: 49-55%)] had cachexia. In the multivariate analysis, patients with breast (P < 0.001), gynaecologic (P < 0.001), urinary (P < 0.001), skin (P < 0.001), and haematological cancers (P = 0.006) were less likely to have cachexia than patients with colorectal cancer. Patients with upper gastrointestinal tract cancers (including liver and pancreatic cancers; P = 0.052), with previous surgery for cancer (P = 0.001), with metastases (P = 0.047), poor performance status (≥2; P < 0.001), low food intake (P < 0.001), unfeasible timed up-and-go test (P = 0.002), cognitive disorders (P = 0.03) or risk of depression (P = 0.005), were more likely to have cachexia. At 6 months, 194 (20.5%) deaths were observed. Cachexia was associated with 6 month mortality risk (adjusted hazard ratio = 1.49; 95% confidence interval: 1.05-2.11) independently of age, in/outpatient status, cancer site, metastatic status, cancer treatment, dependency, cognition, and number of daily medications., Conclusions: More than half of older patients with cancer managed in geriatric oncology clinics had cachexia. The factors associated with cachexia were upper gastrointestinal tract cancer, metastases, poor performance status, poor mobility, previous surgery for cancer, cognitive disorders, a risk of depression, and low food intake. Cachexia was independently associated with 6 month mortality., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13)., Patients and Methods: The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate., Results: Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P =  0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P<0.0001). Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival., Conclusion: With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy.

Based on physical laws describing the multiscale structure of turbulent flows, this paper proposes a regularizer for fluid motion estimation from an image sequence. Regularization is achieved by imposing some scale invariance property between histograms of motion increments computed at different scales. By reformulating this problem from a Bayesian perspective, an algorithm is proposed to jointly estimate motion, regularization hyperparameters, and to select the most likely physical prior among a set of models. Hyperparameter and model inference are conducted by posterior maximization, obtained by marginalizing out non--Gaussian motion variables. The Bayesian estimator is assessed on several image sequences depicting synthetic and real turbulent fluid flows. Results obtained with the proposed approach exceed the state-of-the-art results in fluid flow estimation.

Background: Postoperative delirium is common in the elderly and is associated with a significant increase in mortality, complications, length of hospital stay and admission in long care facility. Although several interventions have proved their effectiveness to prevent it, the Cochrane advises an assessment of multifaceted intervention using rigorous methodology based on randomized study design. Our purpose is to present the methodology and expected results of the CONFUCIUS trial, which aims to measure the impact of a multifaceted program on the prevention of postoperative delirium in elderly., Method/design: Study design is a stepped wedge cluster randomized trial within 3 surgical wards of three French university hospitals. All patients aged 75 and older, and admitted for scheduled surgery will be included. The multifaceted program will be conducted by mobile geriatric team, including geriatric preoperative consultation, training of the surgical staff and implementation of the Hospital Elder Life Program, and morbidity and mortality conference related to delirium cases. The primary outcome is based on postoperative delirium rate within 7 days after surgery. This program is planned to be implemented along four successive time periods within all the surgical wards. Each one will be affected successively to the control arm and to the intervention arm of the trial and the order of program introduction within each surgical ward will be randomly assigned. Based on a 20% reduction of postoperative delirium rate (ICC = 0.25, α = 0.05, β = 0.1), three hundred sixty patients will be included i.e. thirty patients per service and per time period. Endpoints comparison between intervention and control arms of the trial will be performed by considering the cluster and time effects., Discussion: Better prevention of delirium is expected from the multifaceted program, including a decrease of postoperative delirium, and its consequences (mortality, morbidity, postoperative complications and length of hospital stay) among elderly patients. This study should allow better diagnosis of delirium and strengthen the collaboration between surgical and mobile geriatric teams. Should the program have a substantial impact on the prevention of postoperative delirium in elderly, it could be extended to other facilities., Trial Registration: ClinicalTrials.gov: NCT01316965.

Purpose: To describe the patterns of care of elderly cancer patients (ECPs) (>70 years old) and the factors affecting the referral by general practitioners (GPs) of patients to cancer specialists (SPs), in Alsace France., Methods: A postal mail questionnaire was sent to a total of 2818 physicians including primary care physicians and specialists. The factors possibly responsible for a poor referral rate of ECPs and the factors affecting treatment implementation by specialists were explored. We also searched for unmet needs such as the incorporation of geriatric assessment into routine practice and continuous medical education (CME) programs., Results: A total of 1217 questionnaires were returned (46.9%) from 1053 GPs and 214 SPs. Patients' age did not negatively impact referral to SPs as opposed to patients' performance status, wishes, and co-morbidities. Conversely, a significant decrease in patients' file presentation by SPs to tumor boards was observed for patients over 80 years old. Neither reimbursement nor SPs' waiting lists were an issue. The need for CME programs in geriatric oncology was emphasized by both GPs and SPs., Conclusions: Age was not the governing variable that impacted patient referral. The need for CME in geriatrics was highlighted for both GPs and SPs., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: A number of studies have shown that elderly cancer patients were denied optimal anticancer treatment because of age. Colorectal cancer is among the most frequent cancers in Western countries, and adjuvant chemotherapy has proven efficacy and tolerance in this condition. This study was undertaken to explore the current approaches to adjuvant chemotherapy in elderly cancer patients in a single institution., Patients and Methods: We retrospectively analyzed all patients' files that were discussed in the gastro-intestinal tumor board of the Hôpitaux Universitaires de Strasbourg during 3 years (2004-2006). The recorded variables included sex, age, tumor stage, cancer location colon vs rectum, number of comorbidities, occurrence of an oncogeriatric assessment, type and tolerance of chemotherapy. We investigated the reason to not administer adjuvant therapy in patients whom should have received this treatment if guidelines had to be applied., Results: A total of 193 consecutive patients' files were extracted from colorectal cancer patients that had been discussed in the gastro-intestinal tumor board. Among these, we isolated patients over 70 years old who were proposed with either adjuvant chemotherapy (group A, n=65) or follow up (group B, n=128). The median age in group A was 75.3 years old. Tumor board recommendations were in accordance with guidelines in 91% of cases. Chemotherapy was delivered in 44 pts (76%) and completed in 42 (95%). The median age in group B was 78.6 years old, and in this group tumor board proposal met the guidelines in 83% of cases. In the logistic regression model, disease stage was the major variable leading to adjuvant treatment recommendation, age and comorbidities being of lesser importance., Conclusions: In our series, elderly colorectal cancer patients are not undertreated. Efforts should be maintained to educate physicians with regard to feasibility of adjuvant chemotherapy in elderly patients., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: The preservation of autonomy and the ability of elderly to carry out the basic activities of daily living, beyond the therapeutic care of any pathologies, appears as one of the main objectives of care during hospitalization., Objectives: To identify early clinical markers associated with the loss of independence in elderly people in short stay hospitals., Methods: Among the 1,306 subjects making up the prospective and multicenter SAFEs cohort study (Sujet Agé Fragile: Evolution et suivi-Frail elderly subjects, evaluation and follow-up), 619 medical inpatients, not disabled at baseline and hospitalized through an emergency department were considered. Data used in a multinomial logistic regression were obtained through a comprehensive geriatric assessment (CGA) conducted in the first week of hospitalization. Dependency levels were assessed at baseline, at inclusion and at 30 days using Katz's ADL index. Baseline was defined as the dependence level before occurrence of the event motivating hospitalization. To limit the influence of rehabilitation on the level of dependence, only stays shorter than 30 days were considered., Results: About 514 patients were eligible, 15 died and 90 were still hospitalized at end point (n = 619). Two-thirds of subjects were women, with a mean age of 83. At day 30 162 patients (31%) were not disabled; 61 (12%) were moderately disabled and 291 severely disabled (57%). No socio-demographic variables seemed to influence the day 30 dependence level. Lack of autonomy (odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2-3.6), walking difficulties (OR = 2.7, 95% CI = 1.3-5.6), fall risk (OR = 2.1, 95% CI = 1.3-6.8) and malnutrition risk (OR = 2.2, 95% CI = 1.5-7.6) were found in multifactorial analysis to be clinical markers for loss of independence., Conclusions: Beyond considerations on the designing of preventive policies targeting the populations at risk that have been identified here, the identification of functional factors (lack of autonomy, walking difficulties, risk of falling) suggests above all that consideration needs to be given to the organization per se of the French geriatric hospital care system, and in particular to the relevance of maintaining sector-type segregation between wards for care of acute care and those involved in rehabilitation.

Differential display-polymerase chain reaction (DD-PCR) was used to evaluate changes in mRNA expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) treated human neutrophils to better understand how this cytokine affects the functions of neutrophils at the molecular level. Although a variety of cDNA fragments were identified as modulated by GM-CSF with the use of DD-PCR, one fragment in particular, NGS-17 (neutrophil GM-CSF-stimulated fragment #17), was characterized. The NGS-17 fragment hybridized to a 3.8-kh mRNA that encodes for a protein of a predicted molecular mass of 47.6 kDa. After cloning and sequencing, this gene was found to code for the recently sequenced tapasin or TAP-A protein. Immunoprecipitation and immunoblotting studies using anti-tapasin antibodies showed that tapasin is expressed in neutrophils and is associated with the MHC class I-TAP complex. Moreover, tapasin expression was found to be induced by dimethyl sulfoxide and by retinoic acid in HL-60 cells. This is the first report on the expression of tapasin in human neutrophils. It provides novel information, at the molecular level, on how GM-CSF enhances the functions of these cells.

We report the results of a 14-center collaborative study of genotype-phenotype correlations in 318 fragile X families; these families comprised 2,253 individuals, 1,344 of whom carried a fragile X mutation and 693 of whom had a typical full fragile X mutation. This study demonstrates that direct DNA diagnosis establishes the genotype at the FRAXA-FMR-1 locus. There was a significantly higher prevalence of "mosaic" cases among males who carry a full mutation (12%) than among females who carry a full mutation (6%); the mosaic males had a larger expansion than did the mosaic females. Mental status of premutated individuals did not differ from that of those with a normal genotype. Both the abnormal methylation of the FMR-1-EagI site and the size of the expansion were highly correlated with cytogenetics, facial dysmorphism, macroorchidism, and mental retardation (MR). Among female carriers of a full mutation, those with MR had significantly larger expansion than did those without MR. Among 164 independent couples, 3 unrelated husbands carried a premutation that suggests that the prevalence of fragile X premutations in the general population is approximately 0.9% of the X chromosomes. Our data validate the use of direct DNA testing for fragile X diagnosis as well as for carrier identification and support and complete the established relationships among the DNA results and the cytogenetic, physical, and psychological aspects of the disease.

Fragile-X syndrome, the most common inherited form of mental retardation, has a very unusual mode of inheritance. The disease is caused by a multistep expansion, in successive generations, of a polymorphic CGG repeat localized in a 5' exon of FMR-1, a gene of unknown function. Two main mutation types have been categorized. Premutations are moderate expansions of the repeat and do not cause mental retardation. Full mutations are found in affected individuals and involve larger expansions of the repeat, with abnormal methylation of the neighboring CpG island. The full mutations demonstrate striking somatic instability and extinguish expression of FMR-1. Premutations are changed to full mutation only when transmitted by a female with a frequency that increases up to 100% as a function of the initial size of the premutation. Direct detection of the mutations provides an accurate test for pre- and postnatal diagnosis of the disease, and for carrier detection. A similar unstable expansion of a trinucleotide repeat occurs in myotonic dystrophy.

To identify the sequences involved in the expression of the fragile X and to characterize the molecular basis of the genetic lesion, we have constructed yeast artificial chromosomes (YACs) containing human DNA and have screened them with cloned DNA probes which map close to the fragile site at Xq27.3. We have isolated and partly characterized a YAC containing approximately 270 kb of human DNA from an X chromosome which expresses the fragile X. This sequence in a yeast artificial ring chromosome, XTY26, hybridizes to the two closest DNA markers, VK16 and Do33, which flank the fragile site. The human DNA sequence in XTY26 also spans the fragile site on chromosome in situ hybridization. When a restriction map of XTY26, derived by using infrequently cutting restriction enzymes, is compared with similar YAC maps derived from non-fragile-X patients, no large-scale differences are observed. This YAC, XTY26, may enable (a) the fragile site to be fully characterized at the molecular level and (b) the pathogenetic basis of the fragile-X syndrome to be determined.

We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.