Association of cerebral small vessel disease burden with brain structure and cognitive and vascular risk trajectories in mid-to-late life

We characterize the associations of total cerebral small vessel disease (SVD) burden with brain structure, trajectories of vascular risk factors, and cognitive functions in mid-to-late life. Participants were 623 community-dwelling adults from the Whitehall II Imaging Sub-study with multi-modal MRI (mean age 69.96, SD = 5.18, 79% men). We used linear mixed-effects models to investigate associations of SVD burden with up to 25-year retrospective trajectories of vascular risk and cognitive performance. General linear modelling was used to investigate concurrent associations with grey matter (GM) density and white matter (WM) microstructure, and whether these associations were modified by cognitive status (Montreal Cognitive Asessment [MoCA] scores of < 26 vs. ≥ 26). Severe SVD burden in older age was associated with higher mean arterial pressure throughout midlife (β = 3.36, 95% CI [0.42-6.30]), and faster cognitive decline in letter fluency (β = −0.07, 95% CI [−0.13–−0.01]), and verbal reasoning (β = −0.05, 95% CI [−0.11–−0.001]). Moreover, SVD burden was related to lower GM volumes in 9.7% of total GM, and widespread WM microstructural decline (FWE-corrected p < 0.05). The latter association was most pronounced in individuals who demonstrated cognitive impairments on MoCA (MoCA < 26; F_3,608 = 2.14, p = 0.007). These findings highlight the importance of managing midlife vascular health to preserve brain structure and cognitive function in old age.     

Measuring Physical Activity and Sedentary Behaviors in Women with Young Children: A Systematic Review

Current evidence indicates that women with young children are less active than women without children. In this review the authors investigated the methods of measuring physical activity employed in studies of women with young children (aged 1–5 years) and the associated challenges in measurement. Articles from databases (MEDLINE, OVID, CINAHL, Google Scholar) and manual searches were limited to English peer-reviewed journals published from 1990 to 2010. Studies that included measurement of physical activity in samples of women with young children were selected. Measurement properties were extracted, and original reliability and validity articles were reviewed for physical activity measurement tools used by 15 samples. The evidence base was dominated by self-report measurement tools, many of which assessed leisure-time physical activity only. Use of motion sensors to assess physical activity in this population was limited. It is likely that much of the habitual physical activity performed by women with young children has not been captured by self-report measures. Further investigation should be undertaken using tools that capture adequately all health-enhancing physical activity among women with young children.     

Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma

Aims: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non‐obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER‐2 overexpression (triple‐negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC‐NST). Methods and results: We report on a case comprising MGA, AMGA and a high‐grade IDC‐NST. The three components were separately microdissected and subjected to genetic analysis with high‐resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple‐negative phenotype and variable positivity for basal markers. Conclusions: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non‐obligate precursor of a subgroup of high‐grade triple‐negative and basal‐like breast carcinomas.     

Microsatellite markers for the freshwater shrimp Paratya australiensis (Atyidae)

Paratya australiensis is a common freshwater shrimp found in most catchments in south-eastern Australia. Microsatellite loci were isolated from a partial genomic library created using 454 sequencing. Of the 25 tested, 13 were found to be polymorphic, however, for pooling purposes only 12 were used for genotyping. The number of alleles per locus varied from 2 to 14 in a population from Wakefield River, South Australia, and the mean (range) observed and expected heterozygosity were 0.512 (0.136–0.909) and 0.590 (0.165–0.788), respectively across all alleles. These microsatellites will be used to study the genetic structure of populations in two catchments in South Australia.     

Paediatric stroke: The need for interdisciplinary models of care

Abstract:   Stroke is an important cause of mortality and long-term morbidity in children. The aetiology of stroke in childhood differs from that of adults, with vasculopathies and congenital heart disease being the most commonly identified risk factors. Recognition and diagnosis are often delayed, limiting access to acute medical interventions such as thrombolysis. Optimal management of stroke in children is still not known and existing guidelines are at the level of expert consensus. Interdisciplinary childhood stroke programmes are required to meet the needs of this population and to contribute to the development of evidence-based therapies.     

Case report of very late gastric cancer recurrence

Very late recurrence of gastric cancer is rare. Here, we report a dramatic recurrence of gastric cancer, with isolated skeletal metastasis and bone marrow carcinomatosis, 22 years after the patient’s initial presentation. Gastric cancer recurrence involving bone or bone marrow is also uncommon and associated with poor prognosis. Pathology from a bone marrow biopsy showed signet ring cell morphology. The patient in this case demonstrated a surprising response—lasting 11 months—to palliative chemotherapy with cisplatin and capecitabine. This case report and literature review describes the characteristics of late gastric cancer recurrence and an approach to the diagnosis and management of patients with bone metastasis or bone marrow carcinomatosis.     

Physiological concentration of calcium inhibits elastase-induced cleavage of a functional recombinant fragment of surfactant protein D

Surfactant protein D (SP-D) plays an important role in lung host defence. SP-D levels have been shown to be depleted in cystic fibrosis (CF) patients. A recombinant fragment of the human SP-D (rfhSP-D) which consist of a hydrophobic neck and a CRD has been shown to be active in vivo and partially reverses the symptoms of the SP-D deficiency in the lungs when administered to SP-D knock-out mice. In this paper we studied the in vitro effect of different proteolytic enzymes commonly found in CF patients lungs, such as neutrophil elastase, cathepsin G and protease 3 as well as Pseudomonas elastase, on rfhSP-D. It was also shown that cleavage was inhibited by physiological concentration of calcium. When Western blot was compared with ELISA, we show that an anti-SP-D ELISA is a not a reliable assay of functional SP-D levels since non-functional fragments of SP-D are also detected. Thus, ELISA cannot be used as a reliable “diagnostic” tool for SP-D deficiency. Finally, we observe that SP-D is not cleaved in control patients but is degraded in about half the samples from cystic fibrosis patients, indicating that degradation of endogenous SP-D, by enzymes present in CF bronchioalveolar lavage fluid (BALF), may lead to deficiency of the protein as seen in CF and therefore rfhSP-D may be a useful future therapy.     

Induction of autoimmune cholangitis in non‐obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC‐E2) leads to an anti‐mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non‐obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2‐octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti‐mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA‐BSA, but not with BSA alone, develop high titre anti‐mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8⁺ cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.     

An integrated model to predict the atmospheric spread of foot-and-mouth disease virus

The application of a computer model called Rimpuff for simulating the airborne spread of foot-and-mouth disease (FMD) is described. Rimpuff is more sophisticated and accurate than other FMD simulation models previously described. It can be run on a desktop computer and performs analyses very quickly. It can be linked to a geographical information system and so the information generated can be integrated with geographical and demographical data for display in a format that can be easily assimilated and transmitted electronically. The system was validated using historical data from outbreaks of FMD in France and the UK in 1981, and from Denmark and the former German Democratic Republic (GDR) in 1982. A very good fit was obtained between the direction of the plumes of virus simulated by the model and the spread of disease from France to the UK in 1981. Although cattle in the UK were infected during the episode, the concentrations of airborne virus in the plumes simulated by the model were beneath the infectivity threshold for cattle. It was concluded from the analysis that the number of pigs infected in France, and therefore the source concentration of airborne virus, was probably much higher than was recorded at the time of the outbreaks. Analysis of the Denmark/GDR episode pointed to the possibility that the source of virus for the 1982 epidemic in Denmark could have been one or more unreported outbreaks involving pigs in the former GDR.