Self care programs and multiple sclerosis: Physical therapeutics treatment - literature review

AbstractObjectiveTo clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy.MethodA non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: “multiple sclerosis”, “self-care”, “self-management” and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed.ResultsCounseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms’ diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms’ impact and to improve treatment access are the aims of educational therapy.ConclusionTherapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary

Epigenetic Chromatin Silencing: Bistability and Front Propagation

The role of post-translational modification of histones in eukaryotic gene regulation is well recognized. Epigenetic silencing of genes via heritable chromatin modifications plays a major role in cell fate specification in higher organisms. We formulate a coarse-grained model of chromatin silencing in yeast and study the conditions under which the system becomes bistable, allowing for different epigenetic states. We also study the dynamics of the boundary between the two locally stable states of chromatin: silenced and unsilenced. The model could be of use in guiding the discussion on chromatin silencing in general. In the context of silencing in budding yeast, it helps us understand the phenotype of various mutants, some of which may be non-trivial to see without the help of a mathematical model. One such example is a mutation that reduces the rate of background acetylation of particular histone side-chains that competes with the deacetylation by Sir2p. The resulting negative feedback due to a Sir protein depletion effect gives rise to interesting counter-intuitive consequences. Our mathematical analysis brings forth the different dynamical behaviors possible within the same molecular model and guides the formulation of more refined hypotheses that could be addressed experimentally.Comment: 19 pages, 5 figure

Determinants of smoking and cessation in older women

BACKGROUND: although the benefits of quitting smoking even at an advanced age have been proved, few campaigns target the older population. The goals of this study were to analyse the characteristics of older women smokers help and support those wanting to quit. METHODS: we assessed the determinants of smoking cessation in a prospective cohort study performed in 7,609 older women. A questionnaire about smoking habits was sent to the 486 eligible smokers. Smoking dependence and smokers' readiness to quit was assessed. Participants who had quit smoking during follow-up were asked about their previous reasons for quitting and the methods used to quit. RESULTS: 372 women of the 424 (88%) responded to our questionnaire and were included. The most common reasons for smoking were relaxation, pleasure, and habit. Major obstacles to quitting smoking were 'no benefit to quitting at an advanced age', 'smoking few or "light" cigarettes yields no negative health consequences', and 'smoking does not increase osteoporotic risk'. During the 3-year follow-up period, 57 of the 372 (15%) women successfully quit smoking. Being an occasional smoker (OR=2.4) and reporting 'quitting is not difficult' (OR=3.7) were positively associated with having recently quit smoking. Only 11% of successful cessations were reported to have received physician advice. CONCLUSIONS: these data illustrate the specific smoking behaviour of older women, suggesting that cessation interventions ought to be tailored to these characteristics. Willingness to quit was associated with a low education level. The most frequent obstacles to quitting were all based on incorrect information

Comparison of 6 Mortality Risk Scores for Prediction of 1-Year Mortality Risk in Older Adults with Multimorbidity

Importance: The most appropriate therapy for older adults with multimorbidity may depend on life expectancy (ie, mortality risk), and several scores have been developed to predict 1-year mortality risk. However, often, these mortality risk scores have not been externally validated in large sample sizes, and a head-to-head comparison in a prospective contemporary cohort is lacking. Objective: To prospectively compare the performance of 6 scores in predicting the 1-year mortality risk in hospitalized older adults with multimorbidity. Design, Setting, and Participants: This prognostic study analyzed data of participants in the OPERAM (Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People) trial, which was conducted between December 1, 2016, and October 31, 2018, in surgical and nonsurgical departments of 4 university-based hospitals in Louvain, Belgium; Utrecht, the Netherlands; Cork, Republic of Ireland; and Bern, Switzerland. Eligible participants in the OPERAM trial had multimorbidity (≥3 coexisting chronic diseases), were aged 70 years or older, had polypharmacy (≥5 long-term medications), and were admitted to a participating ward. Data were analyzed from April 1 to September 30, 2020. Main Outcomes and Measures: The outcome of interest was any-cause death occurring in the first year of inclusion in the OPERAM trial. Overall performance, discrimination, and calibration of the following 6 scores were assessed: Burden of Illness Score for Elderly Persons, CARING (Cancer, Admissions ≥2, Residence in a nursing home, Intensive care unit admit with multiorgan failure, ≥2 Noncancer hospice guidelines) Criteria, Charlson Comorbidity Index, Gagné Index, Levine Index, and Walter Index. These scores were assessed using the following measures: Brier score (0 indicates perfect overall performance and 0.25 indicates a noninformative model); C-statistic and 95% CI; Hosmer-Lemeshow goodness-of-fit test and calibration plots; and sensitivity, specificity, and positive and negative predictive values. Results: The 1879 patients in the study had a median (IQR) age of 79 (74-84) years and 835 were women (44.4%). The median (IQR) number of chronic diseases was 11 (8-16). Within 1 year, 375 participants (20.0%) died. Brier scores ranged from 0.16 (Gagné Index) to 0.24 (Burden of Illness Score for Elderly Persons). C-statistic values ranged from 0.62 (95% CI, 0.59-0.65) for Charlson Comorbidity Index to 0.69 (95% CI, 0.66-0.72) for the Walter Index. Calibration was good for the Gagné Index and moderate for other mortality risk scores. Conclusions and Relevance: Results of this prognostic study suggest that all 6 of the 1-year mortality risk scores examined had moderate prognostic performance, discriminatory power, and calibration in a large cohort of hospitalized older adults with multimorbidity. Overall, none of these mortality risk scores outperformed the others, and thus none could be recommended for use in daily clinical practice.

Novel Clinical Criteria Allow Detection of Short Stature Homeobox-Containing Gene Haploinsufficiency Caused by Either Gene or Enhancer Region Defects

Introduction: Short stature homeobox-containing gene (SHOX) haploinsufficiency is associated with short stature, Madelung deformity and mesomelia. Current clinical screening tools are based on patients with intragenic variants or deletions. However, recent discoveries showed that deletions of the enhancer elements are quite common. The majority of these patients show less body disproportion and respond better to recombinant human growth hormone treatment. We redefined clinical criteria for genetic analysis to facilitate detection of the full spectrum of SHOX haploinsufficiency. Methods: We analyzed 51 children with SHOX variants or deletions and 25 children with a deletion in its enhancer region. Data were compared to 277 children referred for suspicion of growth failure without endocrine or genetic pathology. Results: Only half of the patients with an enhancer region deletion fulfilled any of the current screening criteria. We propose new clinical criteria based on sitting height to height ratio >1 SDS or arm span ≥3 cm below height, with a sensitivity of 99%. When these criteria are combined with obligatory short stature, the sensitivity to detect SHOX haploinsufficiency is 68.1%, the specificity 80.6%, and the number needed to screen 21 patients. Conclusion: Novel clinical criteria for screening for SHOX haploinsufficiency allow the detection of patients within the full genetic spectrum, that is, intragenic variants and enhancer region deletions

Novel bleeding risk score for patients with atrial fibrillation on oral anticoagulants, including direct oral anticoagulants

Objective: Balancing bleeding risk and stroke risk in patients with atrial fibrillation (AF) is a common challenge. Though several bleeding risk scores exist, most have not included patients on direct oral anticoagulants (DOACs). We aimed at developing a novel bleeding risk score for patients with AF on oral anticoagulants (OAC) including both vitamin K antagonists (VKA) and DOACs. Methods: We included patients with AF on OACs from a prospective multicenter cohort study in Switzerland (SWISS-AF). The outcome was time to first bleeding. Bleeding events were defined as major or clinically relevant non-major bleeding. We used backward elimination to identify bleeding risk variables. We derived the score using a point score system based on the β-coefficients from the multivariable model. We used the Brier score for model calibration (<0.25 indicating good calibration), and Harrel's c-statistics for model discrimination. Results: We included 2147 patients with AF on OAC (72.5% male, mean age 73.4 ± 8.2 years), of whom 1209 (56.3%) took DOACs. After a follow-up of 4.4 years, a total of 255 (11.9%) bleeding events occurred. After backward elimination, age > 75 years, history of cancer, prior major hemorrhage, and arterial hypertension remained in the final prediction model. The Brier score was 0.23 (95% confidence interval [CI] 0.19–0.27), the c-statistic at 12 months was 0.71 (95% CI 0.63–0.80). Conclusion: In this prospective cohort study of AF patients and predominantly DOAC users, we successfully derived a bleeding risk prediction model with good calibration and discrimination

An RNA Polymerase III-Dependent Heterochromatin Barrier at Fission Yeast Centromere 1

Heterochromatin formation involves the nucleation and spreading of structural and epigenetic features along the chromatin fiber. Chromatin barriers and associated proteins counteract the spreading of heterochromatin, thereby restricting it to specific regions of the genome. We have performed gene expression studies and chromatin immunoprecipitation on strains in which native centromere sequences have been mutated to study the mechanism by which a tRNAAlanine gene barrier (cen1 tDNAAla) blocks the spread of pericentromeric heterochromatin at the centromere of chromosome 1 (cen1) in the fission yeast, Schizosaccharomyces pombe. Within the centromere, barrier activity is a general property of tDNAs and, unlike previously characterized barriers, requires the association of both transcription factor IIIC and RNA Polymerase III. Although the cen1 tDNAAla gene is actively transcribed, barrier activity is independent of transcriptional orientation. These findings provide experimental evidence for the involvement of a fully assembled RNA polymerase III transcription complex in defining independent structural and functional domains at a eukaryotic centromere

Excursion Ardèche (13-15 mai 1977)

International audienceLes massifs hercyniens ont été longuement érodés pendant le Permien. Des sédiments gréseux et dolomitiques du Trias se sont ensuite déposés sur une plate-forme uniformisée et peu profonde. Toutefois la monotonie de l'ensemble n'excluait pas l'influence de reliefs sous-marins d'origine hercynienne. Les termes liasiques montrent à la fois une épaisseur réduite et des variations de faciès dues à une plate-forme sous-marine instable. Les influences obéissent d'une part à la direction cévenole (NE-SW) et d'autre part à une direction qui lui est orthogonale. A partir du Callovien les conditions deviennent homogènes dans l'ensemble de la région et paraissent le rester jusque dans le Jurassique terminal

A Single Heterochromatin Boundary Element Imposes Position-Independent Antisilencing Activity in Saccharomyces cerevisiae Minichromosomes

Chromatin boundary elements serve as cis-acting regulatory DNA signals required to protect genes from the effects of the neighboring heterochromatin. In the yeast genome, boundary elements act by establishing barriers for heterochromatin spreading and are sufficient to protect a reporter gene from transcriptional silencing when inserted between the silencer and the reporter gene. Here we dissected functional topography of silencers and boundary elements within circular minichromosomes in Saccharomyces cerevisiae. We found that both HML-E and HML-I silencers can efficiently repress the URA3 reporter on a multi-copy yeast minichromosome and we further showed that two distinct heterochromatin boundary elements STAR and TEF2-UASrpg are able to limit the heterochromatin spreading in circular minichromosomes. In surprising contrast to what had been observed in the yeast genome, we found that in minichromosomes the heterochromatin boundary elements inhibit silencing of the reporter gene even when just one boundary element is positioned at the distal end of the URA3 reporter or upstream of the silencer elements. Thus the STAR and TEF2-UASrpg boundary elements inhibit chromatin silencing through an antisilencing activity independently of their position or orientation in S. cerevisiae minichromosomes rather than by creating a position-specific barrier as seen in the genome. We propose that the circular DNA topology facilitates interactions between the boundary and silencing elements in the minichromosomes

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis: Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods: We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. Results: In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation: This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia