Diversity of mutations in the dystrophin gene and details of muscular lesions in porcine dystrophinopathies.

During meat inspections in pigs, dystrophinopathies are among the muscle lesions targeted for disposal. In this study, the authors examined the lesions and the distribution of dystrophin expression in 25 pigs with dystrophinopathy. In addition, complementary deoxyribonucleic acid (cDNA) sequencing and western blotting were performed in 6 of the 25 cases, all of which were characterized by degeneration, necrosis, and fat replacement of muscle fibers. Comparing the results of immunohistochemistry with anti-dystrophin antibodies that recognized at different sites in the protein, the authors noted that the loss of dystrophin expression was most pronounced in the C-terminus-recognizing antibody (19/25 cases). The authors detected 5 missense mutations and 3 types of shortened transcripts generated by the skipping of exons in the cDNA, which were associated with the pathogenesis. One missense mutation had been reported previously, whereas the remaining mutations identified had not been previously documented in pigs. In the cases with shortened transcripts, normal-sized transcripts were detected together with the defective transcripts, suggesting that these mutations were caused by splicing abnormalities. In addition, they were in-frame mutations, all of which have similar pathogeneses of Becker muscular dystrophy in humans. These cases were 6 months of age and exhibited macroscopic discoloration, fatty replacement, and muscle degeneration, suggesting that the effect of these mutations on skeletal muscle was significant.

Cor triatriatum sinister with dextrocardia in association with ostium secundum atrial septal defect, subpulmonary ventricular septal defect and bicuspid pulmonary valve in a pig.

Necropsy of a 52-day-old Camborough pig revealed numerous cardiac malformations. The positional relationship of the atria, ventricles and great vessels was a mirror image type (I, L and L): inverted arrangement of the atria, with a left-sided right atrium and right-sided left atrium (situs inversus); inverted arrangement of the ventricles, with a left-sided morphological right ventricle and right-sided morphological left ventricle (L-loop); and aortic valve to the front left relative to the pulmonary valve (L-malposed). The major malformations included an ostium secundum atrial septal defect, cor triatriatum sinister (CTS), a subpulmonary ventricular septal defect and a bicuspid pulmonary valve. Histological examination revealed myocyte hypertrophy, focal myocardial necrosis and calcification in the left morphological right ventricle of the heart. To the best of our knowledge, this is the first report of CTS in pigs. Although the individual malformations found in the present case are not unique, an unusual combination of these cardiac malformations has not been described in animals.

A mammary fibroadenoma with terminal end buds-like structures in a 7-week-old male SD rat.

We report a case of mammary fibroadenoma in a 7-week-old male SD rat. This case showed rapid growth within one week from the time when the nodule was detected. Histologically, the nodule was a well-circumscribed subcutaneous mass. The tumor consisted of an epithelial component with island-like proliferation (cribriform to tubular patterns) and an abundant mesenchymal component. Alpha-SMA-positive cells were arranged at the periphery of the epithelial component and showed cribriform and tubular patterns. Discontinuous basement membranes and high cell proliferative activities were observed in the cribriform area. These features resembled those of normal terminal end buds (TEBs). Since the mesenchymal component had abundant fine fibers and a mucinous matrix, its stroma was regarded as neoplastic growth of fibroblasts; thus, this tumor was diagnosed as a fibroadenoma. This case is an extremely rare fibroadenoma in that it occurred in a young male SD rat and was composed of an epithelial component showing multifocal proliferation of TEB-like structures and a mucinous mesenchymal component consisting of fibroblasts with fine collagen fibers.

Macroglossia in a pig diagnosed as Becker muscular dystrophy due to dystrophin pseudoexon insertion derived from intron 26.

We report a case of Becker muscular dystrophy in a 6-month-old, mixed-breed, castrated male pig detected with macroglossia at a meat inspection center. The pig presented a severely enlarged tongue extending outside its mouth. The tongue was firm and pale with discolored muscles. Histologically, there was severe fibrosis, fatty replacement, and myofiber necrosis, degeneration, and regeneration. Immunofluorescence showed focal and severely weak labeling for dystrophin at the sarcolemma of myocytes in the tongue. Analysis of dystrophin mRNA showed a 62 base pair insertion between exons 26 and 27. The insertion was derived from intron 26. Based on these findings, we diagnosed the case as Becker muscular dystrophy-the first known muscular dystrophy case induced by pseudoexon insertion in animals.

The impact of childhood sexual abuse on the mental and physical health, and healthcare utilization of older adults.

BACKGROUND: The aim of this study is to examine the long-term association between childhood sexual abuse (CSA) and mental and physical health, especially with conditions related to hypothalamic-pituitary-adrenal axis dysfunction such as mood disorders, cardiovascular disorders, gastrointestinal disorders, pain disorders, and measures of frailty and functional mobility. In addition, we examined the impact of CSA on self-reported health and healthcare utilization. METHODS: Data from the Irish Longitudinal Study on Ageing were employed (N = 8,178). The effects of CSA on mental health, physical health, and healthcare utilization in old age population were estimated by ordinal least square, logistic regression, and Poisson regression, controlling for demographic factors, childhood adversities, and behavioral health. RESULTS: Six percent of respondents reported CSA with little variation by gender. A significant association was found between CSA and mental health. Those who reported CSA were more likely to have depression, anxiety, worry, loneliness, and low quality of life. Poor self-reported health, lung disease, arthritis, peptic ulcer, chronic pain as well as high levels of total cholesterol and low-density lipoprotein were associated with CSA. Further, those who reported CSA were more likely to report doctor and hospital visits than those without a history of CSA. CONCLUSIONS: Findings from the present study show that CSA has significant long-term mental and physical consequences, whereby early life events are linked to later life health outcomes.

Early-life circumstances and later-life loneliness in Ireland.

PURPOSE OF THE STUDY: This article examines the impact of early- and later-life circumstances on loneliness among people aged 65+ in Ireland. DESIGN AND METHODS: Data are from the first wave of the Irish Longitudinal Study on Ageing, a nationally representative sample of community-dwelling adults aged 50+. The participants (N = 2,645) aged 65+ were included in the analysis. Because of the large number of never married persons in the older Irish population, we first used a multinomial logistic model to examine which childhood circumstances are associated with current marital status. We then estimated multiple regression models for loneliness, in stages conforming to the life course, to examine the extent to which early events are mediated by later events. RESULTS: Poor childhood socioeconomic status (for men and women) and parental substance abuse (for men) have direct effects on loneliness at older ages. IMPLICATIONS: The results indicate the significance of the childhood environment for understanding loneliness in later life. Future research should examine possible pathways not currently measured that may be responsible for the association of early environment and later-life loneliness and explore the links between childhood and other measures of well-being in old age. The relationship of childhood socioeconomic deprivation and parental substance abuse with adult well-being should be an important consideration in social policy planning.

Cognitive function is preserved in older adults with a reported history of childhood sexual abuse.

Childhood sexual abuse (CSA) is associated with mood and cognitive deficits in children and young adults. Evidence suggests that the effects of early-life adversity persist throughout adulthood; however, the impact of CSA on cognition in older adults is largely unknown. This study investigated cognitive function in older adults with a reported history of CSA. Data are from a population-based study (The Irish Longitudinal Study on Ageing) of 6,912 adults aged 50 years and older. Participants answered questions about CSA as part of a stressful life events questionnaire. Global cognition, executive function, memory (both objective and self-rated), attention, and processing speed were measured via a comprehensive battery of tests. Anxiety and depression, other childhood adversity, health behaviours, chronic disease, and medication use were also assessed. Of the total sample, 6.5% reported CSA. These individuals were more likely to have experienced other forms of childhood adversity and to exhibit poor mental health compared to those who reported no history of CSA. Multivariate regression analyses revealed, however, that CSA was associated with better global cognition, memory, executive function, and processing speed, despite poorer psychological health in this group. Future studies should aim to investigate possible reasons for this finding.

Depressive symptoms among older adults: the impact of early and later life circumstances and marital status.

OBJECTIVE: This article contributes to the literature on depression and the life course by examining the impact of both early and later life circumstances on depressive symptoms among men and women aged 65 and over in Ireland. METHOD: Data are from the first wave of The Irish Longitudinal Study on Ageing, a nationally representative sample of 8504 community-dwelling adults aged 50 years and older. About 3507 respondents aged 65 years and over were included in the analysis. Multinomial logistic regression was used to examine the childhood and early adult life circumstances associated with marital status. A series of nested models were estimated to evaluate which childhood and adulthood circumstances are associated with depressive symptoms. Models were estimated separately for men and women. RESULTS: Ill health in childhood and in later life has a strong and direct effect on depression in later life for both men and women. Other early stressors are mediated by later circumstances. Marital status is a significant independent predictor of depression in later life. Later life circumstances mediate between some marital statuses and depressive symptoms. When later life circumstances are included, widowhood and, for men, divorce, are directly associated with depression, but singlehood is not. Income in later life is strongly associated with depressive symptoms for women. CONCLUSION: Both early and later life circumstances affect late-life depressive symptoms. Our findings indicate that previous studies which did not consider both may have underestimated or overestimated the effect of marital status, education, current health and education on depressive symptoms.

Comparison of centre and home-based health assessments: early experience from the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: some cohort studies of ageing and health supplement questionnaire-based surveys with in-home measurements of biological parameters and others have required respondents to attend assessment centres. Centre-based assessments facilitate detailed measurements and novel technologies, but may differentially influence participation. The aim of this paper is to compare the characteristics of participants who attended a centre with those who chose a home assessment and those who did not have a health assessment. METHODS: trained field workers administered a computer-assisted personal interview (CAPI) to a random sample of community-dwelling people aged 50 and over in the participants' homes. All questionnaire respondents were invited to attend an assessment centre for a comprehensive physical assessment. Participants who refused or were unable to attend a centre were offered a home assessment. RESULTS: of the 291 participants who completed the CAPI, 176 had a health assessment: 138 in an assessment centre and 38 in their own home. The centre, home and no visit respondents differed in demographic characteristics, behavioural factors, physical functioning and health. Lower socio-economic status, physical inactivity and current smoking were the most robust predictors of non-participation in the health assessment. Home respondents had the highest levels of physical disability and were much weaker (grip strength) and slower (walking speed) than centre respondents. CONCLUSION: home and centre physical assessments are required to avoid systematically over-representing healthier and wealthier respondents.

The differential impact of subjective and objective aspects of social engagement on cardiovascular risk factors.

BACKGROUND: This article provides new insights into the impact of social engagement on CVD risk factors in older adults. We hypothesized that objective (social participation, social ties and marital status) and subjective (emotional support) aspects of social engagement are independently associated with objective measures of cardiovascular risk. METHODS: Data from the English Longitudinal Study on Ageing (ELSA) were analyzed. The effects of social participation, social ties, marital status, and emotional support on hypertension, obesity, high sensitivity C-reactive protein, and fibrinogen were estimated by logistic regression controlling for age, sex, education, physical function, depression, cardiovascular disease, other chronic diseases, physical activity, and smoking. RESULTS: Social participation is a consistent predictor of low risk for four risk factors, even after controlling for a wide range of covariates. Being married is associated with lower risk for hypertension. Social ties and emotional support are not significantly associated with any of the cardiovascular risk factors. CONCLUSION: Our analysis suggests that participation in social activities has a stronger association with CV risk factors than marital status, social ties or emotional support. Different forms of social engagement may therefore have different implications for the biological risk factors involved.