Role of nerve and tension in maturation of posthatching slow-tonic muscle in chicken

The role of motor innervation and muscle tension in the posthatching maturation of the slow-tonic anterior latissimus dorsi (ALD) muscle of the chicken has been investigated. Modification of the muscle tension was obtained either by maintaining ALD in a shortened state or by stretching, after or without denervation. In denervated as well as in innervated ALD, shortening resulted in atrophy and inhibition of developmental change in muscle fiber population. In contrast, stretch causes hypertrophy, transformation of all 3B fibers, increase in SM2 isomyosin expression, and decrease in Ca2+-activated myosin ATPase in innervated or denervated ALD. On the other hand oxidative activity in ALD fibers was strikingly reduced after denervation even in presence of stretch-induced hypertrophy. This study suggests that a passive stretch can be involved in some, but not all, changes in ALD characteristics occurring after denervation and may be also involved in normal posthatching development of the slow-tonic muscle. Possible clinical implications of these results in relation to treatments for preventing muscle atrophy resulting from immobilization or disuse are suggested.     

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function

BackgroundPhase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV₁) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV₁.MethodsTo evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV₁<40 or ppFEV₁≥90 in comparison with those with ppFEV₁ [40–90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers.Results827 patients were classified into 3 subgroups according to ppFEV₁ at treatment initiation (ppFEV₁<40, n = 121; ppFEV₁ [40–90[, n = 609; ppFEV₁≥90, n = 97). Treatment discontinuation rate was higher in ppFEV₁<40 patients (28.9%) than in those with ppFEV₁ [40–90[(16.4%) or ppFEV₁≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV₁ occurred in the ppFEV₁ [40–90[subgroup (+2.9%, P<0.001), and in those ppFEV₁<40 (+0.5%, P = 0.03) but not in those with ppFEV₁≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV₁<40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups.ConclusionPhe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function_, but the characteristics and magnitude of the response vary depending on ppFEV₁ at baseline.     

Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response

Attenuated measles virus (MV) is currently being evaluated as an oncolytic virus in clinical trials and could represent a new therapeutic approach for malignant pleural mesothelioma (MPM). Herein, we screened the sensitivity to MV infection and replication of twenty-two human MPM cell lines and some healthy primary cells. We show that MV replicates in fifteen of the twenty-two MPM cell lines. Despite overexpression of CD46 by a majority of MPM cell lines compared to healthy cells, we found that the sensitivity to MV replication did not correlate with this overexpression. We then evaluated the antiviral type I interferon (IFN) responses of MPM cell lines and healthy cells. We found that healthy cells and the seven insensitive MPM cell lines developed a type I IFN response in presence of the virus, thereby inhibiting replication. In contrast, eleven of the fifteen sensitive MPM cell lines were unable to develop a complete type I IFN response in presence of MV. Finally, we show that addition of type I IFN onto MV sensitive tumor cell lines inhibits replication. These results demonstrate that defects in type I IFN response are frequent in MPM and that MV takes advantage of these defects to exert oncolytic activity.     

Specificity of stroke in the elderly: clinical characteristics and impact on care

Stroke in the elderly differs from stroke in younger adults in several points. It represents the most frequent consequence of atherothrombotic disease associated with hypertension, diabetes and hypercholesterolemia. It is also the main complication of cardiac arrhythmia. From a clinical point of view, epileptic seizure is frequently observed at the onset, and prognosis is darkened by a high risk of dementia occurrence (20%). Management of stroke in acute phase requires intensive care, which has been shown to decrease mortality and handicap by 20% in Stroke Units. Fibrinolysis with rt-PA can be carried out till 80 years. Primary and secondary prevention are still very efficacious in old patients and decrease not only the risk of stroke, but also the risk of dementia. Moreover, influenzae vaccination has been shown to decrease the risk of stroke in the following year in subjects over 65 years.     

Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23–2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12–1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05–1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.