Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis.

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

Assessing the Determinants of the Wish to Die among the Elderly Population in Ghana.

BACKGROUND: A wish to die is common in elderly people. Concerns about death wishes among the elderly have risen in Ghana, where the ageing transition is comparable to other low-and middle-income countries. However, nationally representative research on death wishes in the elderly in the country is not readily available. Our study aimed to assess the determinants of the wish to die among the elderly in Ghana. METHODS: We analysed data from the World Health Organisation Global Ageing and Adult Health Survey, Wave 1 (2007-2008) for Ghana. Data on the wish to die, socio-demographic profiles, health factors and substance abuse were retrieved from 2147 respondents aged 65 and above. Ages of respondents were categorised as 65-74 years; 75-84 years; 85+ to reflect the main stages of ageing. Logistic regression models were fitted to assess the association between these factors and the wish to die. RESULTS: Age, sex, place of residence, education, body mass index, hypertension, stroke, alcohol consumption, tobacco use, income, diabetes, visual impairment, hopelessness and depression had statistically significant associations with a wish to die. Older age cohorts (75-84 and 85+) were more likely to have the wish to die (AOR = 1.05, CI = 1.02-1.16; AOR = 1.48, CI = 1.22-1.94), compared to younger age cohorts (65-74 years). Persons who felt hopeless had higher odds (AOR = 2.15, CI = 2.11-2.20) of experiencing the wish to die as compared to those who were hopeful. CONCLUSIONS: In view of the relationship between socio-demographic (i.e., age, sex, education and employment), hopelessness, anthropometric (body mass index), other health factors and the wish to die among the elderly in Ghana, specific biopsychosocial health promotion programmes, including timely identification of persons at risk, for appropriate intervention (e.g., psychotherapy, interpersonal support, alcohol-tobacco cessation therapy, clinical help) to promote their wish for a longer life is needed.

Looking for an explanation for the excessive male mortality in England and Wales since the end of the 19th century.

Several papers have primarily considered a female disadvantage in mortality as something to explain, considering a male disadvantage to be a "natural condition". Even if, due to biological reasons, shorter life expectancy among males has been demonstrated, other factors need to be involved to explain firstly the increasing, and then the decreasing, of the male relative disadvantage over the past century. The principal aim of this paper is to provide a clearer picture of the major age-class and cause-of-death contributions to male excess mortality in England and Wales from 1881 to 2011. Results indicate a clear shift in contributions to the male disadvantage from differences occurring during the first year of life to those occurring in ageing people, and from tuberculosis, respiratory diseases, external causes and perinatal and congenital conditions to neoplasms and circulatory diseases. In contrast, the narrowing of the gap since 1981 seems to be most closely related to the decrease in the male disadvantage in respiratory diseases and to the simultaneous increasing in the female disadvantage in old-age diseases. The most important novelty of this research relates to the method: instead of using ratios to investigate gender differences in health, we use decomposition methods.