Sleep in Frontotemporal Dementia is Equally or Possibly More Disrupted, and at an Earlier Stage, When Compared to Sleep in Alzheimer's Disease

Background: Conversely to other neurodegenerative diseases (i.e., Alzheimer's disease, AD), sleep in frontotemporal dementia (FTD) has not been studied adequately. Although some evidence exists that sleep-wake disturbances occur in FTD, very little is known regarding sleep macrostructure and/or primary sleep disorders. Objective: To investigate these issues in this population and compare them to similar issues in AD and in healthy elderly (HE). Methods: Twelve drug-naïve behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 ± 8.6 years were compared to seventeen drug-naïve AD patients (9 men/8 women) of mean age 69.0 ± 9.9 years and twenty drug-naïve HE (12 men/8 women) of mean age 70.2 ± 12.5 years. All participants were fully assessed clinically, through a sleep questionnaire, an interview, and video-polysomnography recordings. Results: The two patient groups were comparably cognitively impaired. However, compared to FTD patients, the AD patients had a statistically significant longer disease duration. Overall, the sleep profile was better preserved in HE. Sleep complaints did not differ considerably between the two patient groups. Sleep parameters and sleep macrostructure were better preserved in AD compared to FTD patients, regardless of primary sleep disorders, which occurred equally in the two groups. Conclusions: With respect to AD, FTD patients had several sleep parameters similarly or even more affected by neurodegeneration, but in a much shorter time span. The findings probably indicate a centrally originating sleep deregulation. Since in FTD patients sleep disturbances may be obvious from an early stage of their disease, and possibly earlier than in AD patients, physicians and caregivers should be alert for the early detection and treatment of these symptoms

Mutation in the xpsD gene of Xanthomonas axonopodis pv. citri affects cellulose degradation and virulence

The Gram-negative bacterium Xanthomonas axonopodis pv. citri, the causal agent of citrus canker, is a major threat to the citrus industry worldwide. Although this is a leaf spot pathogen, it bears genes highly related to degradation of plant cell walls, which are typically found in plant pathogens that cause symptoms of tissue maceration. Little is known on Xac capacity to cause disease and hydrolyze cellulose. We investigated the contribution of various open reading frames on degradation of a cellulose compound by means of a global mutational assay to selectively screen for a defect in carboxymethyl cellulase (CMCase) secretion in X. axonopodis pv. citri. Screening on CMC agar revealed one mutant clone defective in extracellular glycanase activity, out of nearly 3,000 clones. The insertion was located in the xpsD gene, a component of the type II secretion system (T2SS) showing an influence in the ability of Xac to colonize tissues and hydrolyze cellulose. In summary, these data show for the first time, that X. axonopodis pv. citri is capable of hydrolyzing cellulose in a T2SS-dependent process. Furthermore, it was demonstrated that the ability to degrade cellulose contributes to the infection process as a whole

Co- and post-translational translocation through the protein-conducting channel:analogous mechanisms at work?

Many proteins are translocated across, or integrated into, membranes. Both functions are fulfilled by the 'translocon/translocase', which contains a membrane-embedded proteinconducting channel (PCC) and associated soluble factors that drive translocation and insertion reactions using nucleotide triphosphates as fuel. This perspective focuses on reinterpreting existing experimental data in light of a recently proposed PCC model comprising a front-to-front dimer of SecY or Sec61 heterotrimeric complexes. In this new framework, we propose (i) a revised model for SRP-SR-mediated docking of the ribosome-nascent polypeptide to the PCC; (ii) that the dynamic interplay between protein substrate, soluble factors and PCC controls the opening and closing of a transmembrane channel across, and/or a lateral gate into, the membrane; and (iii) that co-and post-translational translocation, involving the ribosome and SecA, respectively, not only converge at the PCC but also use analogous mechanisms for coordinating protein translocation

Respir Res

Background: Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD). However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice. The aim of this study is to evaluate the impact of COPD on patient’s sexuality and the explanatory variables of sexual dissatisfaction. Methods: Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website. Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected. Results: Seven hundred and fifty one subjects were included and were characterized as follows: women—51%, mean age—61 years, in a couple—62% and 70%—retired. Every grade of COPD was represented. Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity. From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position). Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs). ASEX questionnaire confirmed patients’ dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue. Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8). Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation. Conclusion: Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected. Sexual guidance should be a part of patient’s consultations improve quality of sexual life. © 2020, The Author(s)

Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease

We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn’s disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols

Health related quality of life at various stages of disability in multiple sclerosis

The relationship between increasing disability and QoL scores was shown to be linear only in ambulatory subjects, then it loses linearity, above all for subscores assessing mental well-being, suggesting that differences in perceived health status are not fully explained by disease progressio

Retless leg syndrome in pregnancy: preliminary epidemiolgical results in 130 women.

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Disruption Of Sleep-Wake Continuum In Dementia And Mild Cognitive Impairment: Macrostructural And Microstructural Findings

The relationship between sleep and cognitive performance (mainly all types of memory) has been supported by recent theories on sleep-related neuronal plasticity (i.e. the hippocampal-neocortical theory and the synaptic downscaling theory). Recent findings suggest that altered sleep/wake activity relates strongly to cognitive impairment and symptoms of dementia. Daytime sleepiness and primary sleep disorders (e.g. insomnia) not only correlate with disturbed cognitive performance (e.g., attention, memory), but they can also be risk factors for cognitive decline and dementia. Concerning, mild cognitive impairment (MCI), which is an intermediate state between normal ageing and dementia, epidemiological data suggest equally disturbed sleep in these patients when compared to patients with dementia, while studies performed with the use of objective tools suggest moderate differences. More specifically, although no major differences in sleep parameters are shown between MCI and demented patients, disturbed sleep in MCI correlates to impaired memory consolidation. Sleep microstructure (e.g. arousals and CAP) in MCI is also compromised. Finally, sleep parameters (e.g., increased napping, decreased slow wave sleep, a more altered sleep microstructure) seem to correlate with a higher risk of MCI progression to dementia, indicating the importance of specific sleep variables as possible biomarkers of disease evolution

Sleep and sleep disorders durino late pregnancy.

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