Aetiology of MDS: With a Focus on Hereditary Predisposition

Myelodysplastic syndromes affect an older age group with a median age at onset in the eighth decade of life. As such, there is a relationship between the pathogenesis of MDS and age-related processes affecting haematopoietic stem/progenitor cells and/or the bone marrow microenvironment. MDS with an onset in younger people may be associated with recognised hereditary myeloid malignancy syndromes, and ‘forme fruste’ presentations of inherited syndromes in later life are now increasingly recognised such as germline mutations in DDX41. The considerable clinical and research interest in hereditary disorders is reflected in the relative emphasis within our manuscript. Prior chemo/radiotherapy is a clear cause of MDS but the predisposition factors for therapy-related MDS remain unclear. Clonal haematopoiesis is common in older people and may evolve to MDS, although once again, the biological factors driving this evolution are largely unknown. Finally, environmental exposure to genotoxic agents is likely to play only a minor role in the contemporary occupational/recreational setting.

Aggiornamenti su Bartolomeo Varnucci

This article outlines the figure of the Florentine Bartolomeo Varnucci, an illuminator who for decades had his workshop in the Badia Fiorentina, where he was assisted by his brothers Giovanni and Chimenti. They where all cartolai, craftsmen able to take care of the production of manuscripts as a whole, from the preparation of the parchment to the binding. Active from the third to the eighth decade of the fifteenth century, Bartolomeo was able to interpret the rise of humanistic book production, with its typical decoration of white vine stems, but also to move through the vast requests of the devotional world, more inclined to conservative artistic solutions. This contribution gives a complete survey of the artist’s milieu and work, adding several new works to his catalogue.

Prevalence and Outcomes of p.Val142Ile TTR Amyloidosis Cardiomyopathy: A Systematic Review

Background: The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly develop a cardiomyopathy (variant transthyretin amyloidosis cardiomyopathy) phenotype. Yet, there are conflicting data on the prevalence and outcomes of p.Val142Ile variant carriers. Methods: We performed a systematic review of the prevalence and outcomes of p.Val142Ile variant transthyretin amyloidosis cardiomyopathy among subjects of African descent. We found 62 relevant articles after searching the MEDLINE databases from 1980 to 2020 that reported data for ≈150 000 subjects. Results: The reported worldwide prevalence of the p.Val142Ile variant is 0.3% to 1.6% in the general population. Among people of African descent, the reported prevalence from all studies ranges from 1.1% to 9.8%, but for studies with >1000 subjects, it is 3% to 3.5%. The prevalence of the p.Val142Ile variant in a region is dependent on the reported percentage of subjects who are of African descent in that region. p.Val142Ile variant transthyretin amyloidosis cardiomyopathy typically presents in the seventh to eighth decade of life and the majority of cases reported were male, with 25% to 38% diagnosed with atrial fibrillation. It was associated with a longitudinally worse quality of life and a lower adjusted survival compared with other types of transthyretin amyloidosis cardiomyopathy. Conclusion: The p.Val142Ile variant is the most common variant of the transthyretin gene with most carriers being of African descent. The true penetrance is unknown but the p.Val142Ile variant is associated with increased rates of incident heart failure and portends a lower overall survival. Increased awareness could lead to earlier diagnosis and improved heart failure outcomes among those of African descent, which is of increasing importance given the advent of novel therapeutics for this disease.

The Human Female Paradox: Biological Disadvantage Preimplantation, Biological Advantage, Thereafter

The vital statistics show that human females outlive males at every biological stage. Once the embryo arrives in the uterus, more males die at every stage, at least until the eighth decade when the majority of survivors are female. Unexpectedly, the same statistics also show that more boys are born than girls, which is difficult to explain, because the sperm that determine the sex of the fetus, are not skewed toward males. Recently, new data reveal the reason for the increased number of male births; they imply the significant loss of females before the fetus arrives in the womb. Thereafter, there is an excessive loss of males – not only in utero but throughout their lives. One likely reason for the sex differences in fetal survival is the way that humans compensate for the sex difference in number of X chromosomes.

Three major dimensions of human brain cortical ageing in relation to cognitive decline across the eighth decade of life

Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.

Blood pressure and cognitive function across the eighth decade: a prospective study of the Lothian Birth Cohort of 1936

ObjectivesWe investigated the associations among blood pressure and cognitive functions across the eighth decade, while accounting for antihypertensive medication and lifetime stability in cognitive function.DesignProspective cohort study.SettingThis study used data from the Lothian Birth Cohort 1936 (LBC1936) study, which recruited participants living in the Lothian region of Scotland when aged 70 years, most of whom had completed an intelligence test at age 11 years.Participants1091 members of the LBC1936 with assessments of cognitive ability in childhood and older adulthood, and blood pressure measurements in older adulthood.Primary and secondary outcome measuresParticipants were followed up at ages 70, 73, 76 and 79, and latent growth curve models and linear mixed models were used to analyse both cognitive functions and blood pressure as primary outcomes.ResultsBlood pressure followed a quadratic trajectory in the eighth decade: on average blood pressure rose in the first waves and subsequently fell. Intercepts and trajectories were not associated between blood pressure and cognitive functions. Women with higher early-life cognitive function generally had lower blood pressure during the eighth decade. Being prescribed antihypertensive medication was associated with lower blood pressure, but not with better cognitive function.ConclusionsOur findings indicate that women with higher early-life cognitive function had lower later-life blood pressure. However, we did not find support for the hypothesis that rises in blood pressure and worse cognitive decline are associated with one another in the eighth decade.