Lower Limb Radiology of Distal Myopathy due to the S60F Myotilin Mutation

Distal myopathies are a clinically and genetically heterogenous group of disorders in which the distal limb musculature is selectively or disproportionately affected. Precisely defining specific categories is a challenge because of overlapping clinical phenotypes, making it difficult to decide which of the many known causative genes to screen in individual cases. In this study we define the distinguishing magnetic resonance imaging findings in myotilin myopathy by studying 8 genealogically unrelated cases due to the same point mutation in TTID. Proximally, the vastii, biceps femoris and semimembranosus were involved with sparing of gracilis and sartorius. Distally, soleus, gastrocnemius, tibialis anterior, extensor hallicus and extensor digitorum were involved. This pattern contrasts with other distal myopathies and provides further support for the role of imaging in the clinical investigation of muscle disease. Copyright (C) 2009 S. Karger AG, Base

The Indirect Effect of Smoking Level in the Association Between Urban Stress and Readiness to Quit Smoking among Adults Experiencing Homelessness

Over 70% of adults experiencing homelessness are cigarette smokers, a fivefold greater rate than in the general U.S. population. Consequently, tobacco-related conditions are the leading causes of disease and death for this group. Adults experiencing homelessness tend to seek shelter in urban areas. Thus, they not only experience the daily stressors of being homeless, but they may additionally experience unique or additive urban stressors (e.g., stress related to using public services, crime and violence, and/or cultural conflicts with others). For some smokers, stress is known to increase smoking rates and decrease readiness to quit smoking. Likewise, increased smoking rates alone may lead to a lower likelihood of making a quit attempt. The current study examined the potential mediating role of smoking level in the association of urban stress and quit readiness among adults experiencing homelessness (N = 411). Two multinomial logistic regression analyses revealed that urban stress was positively associated with smoking level (p = 0.02). The odds ratio for one-unit increase in stress was 1.047 (CI.95:1.014, 1.082) for being a heavy vs. non-daily smoker. Furthermore, analyses revealed smoking level mediated the effect of stress on quit readiness (ab = -0.005, CI.95:-0.010, -0.002]). Homeless smokers who report high levels of stress might smoke at higher levels, which could attenuate quit readiness

Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas

Abstract Background Gene expression is widely used for the characterisation of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilisation due to sample X-ray and of diagnostic core cutting. Methods Twenty-six paired core-cuts were taken immediately after tumour excision and up to 90 minutes delay due to sample X-ray; 57 paired core-cuts were taken at diagnosis and 2 weeks later at surgical excision. Whole genome expression analysis was conducted on extracted RNA. Correlations and differences were assessed between the expression of individual genes, gene sets/signatures and intrinsic subtypes. Results Twenty-three and 56 sample pairs, respectively, were suitable for analysis. The range of correlations for both sample sets were similar with the majority being >0.97 in both. Correlations between pairs for 18 commonly studied genes were also similar between the studies and mainly with Pearson correlation coefficients >0.6 except for a small number of genes, which had a narrow-dynamic range (e.g. MKI67, SNAI2). There was no systematic difference in intrinsic subtyping between the first and second sample of either set but there was c.15 % discordance between the subtype assignments between the pairs, mainly where the subtyping of individual samples was less certain. Increases in the expression of several stress/early-response genes (e.g. FOS, FOSB, JUN) were found in both studies and confirmed findings in earlier smaller studies. Increased expression of IL6, IGFBP2 and MYC (by 17 %, 14 % and 44 %, respectively) occurred between the samples taken 2 weeks apart and again confirmed findings from an earlier study. Conclusions There is generally good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes. Substantial changes in expression of early-response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy. Trial registration Trial number CRUK/07/015 . Study start date September 2008

Birth NI: a survey of women’s experience of maternity care in NI

The Survey of Women’s Experiences of Maternity Care in Northern Ireland (Birth NI) is the first survey of its kind in Northern Ireland. Birth NI used a similar format to that employed by the National Perinatal Epidemiology Unit (NPEU) in their maternity care surveys and is based on their most recent 2014 survey and ‘Safely Delivered” report. The questionnaire was divided into sections on experiences during pregnancy, labour and birth and after birth. There were also sections on health and well-being and on partner’s involvement. A total of 2722 women completed and returned questionnaires. A response rate of 47%, with a useable response rate of 45%, was achieved, which is comparable with other recent population-based maternity surveys. In addition to presenting data on all women, findings are presented by parity throughout to highlight the impact of previous pregnancy and childbirth on experiences of care. In the final sections of this report, we have conducted further analyses to explore the key aspects of maternity care experience for women living in the most deprived areas and those currently not living with a partner to identify areas of potential unmet need

Identifying postnatal anxiety: comparison of self-identified and self-reported anxiety using the Edinburgh Postnatal Depression Scale

BACKGROUND: Identifying women with perinatal anxiety is important in order to provide timely support and prevent adverse outcomes. Self-report instruments are commonly used in maternity settings. An alternative is to ask women directly whether they self-identify as having anxiety. We examine the agreement between self-reported and self-identified anxiety at 3 months postpartum and compare the characteristics of women with self-reported and self-identified anxiety. METHODS: A secondary analysis of national maternity surveys conducted in 2014 in England and Northern Ireland was conducted. Self-reported anxiety was assessed using the Edinburgh Postnatal Depression Scale anxiety subscale (EPDS-3A). Agreement between self-reported and self-identified anxiety was measured using Cohen’s kappa. Logistic regression was used to identify characteristics of women in each group. RESULTS: In our sample of 6752 women, 14.2% had self-reported anxiety, 5.9% had self-identified anxiety and 3.5% were positive on both measures. Among those with self-identified anxiety, 58.1% also had self-reported anxiety. Of those with self-reported anxiety, 24.4% also had self-identified anxiety. Statistical agreement between the two measures was minimal with Cohen’s kappa 0.283 at an EPDS-3A threshold of ≥6. Among both self-identified and self-reported anxiety groups, psychological factors were the strongest associated factors. Women with self-reported anxiety had higher odds of being from Northern Ireland (OR 1.81); having a mixed or unhappy reaction to the pregnancy (OR 1.65); living without a partner (aOR 1.37); and antenatal depression (aOR 1.32). Women with self-identified anxiety had higher odds of physical problems (OR 1.84); and being of Black or minority ethnicity (OR 0.39). CONCLUSIONS: Asking postnatal women directly whether they self-identify as having anxiety identifies a different group of women from those who score highly on self-report measures. Women with self-identified anxiety may benefit from further follow-up and support

FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging

The transcription factor foxo is a known regulator of lifespan extension and tissue homeostasis. It has been linked to the maintenance of neuronal processes across many species and has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and synaptic plasticity at the neuromuscular junction (NMJ). However, the role of foxo in aging neuromuscular junction function has yet to be determined. We profiled adult Drosophila foxo- null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and shorter terminal branches. We also observed changes to the axonal cytoskeleton and an accumulation of late endosomes in foxo null mutants and motor neuron-specific foxo knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of foxo can delay age-dependent changes to NMJ morphology, suggesting foxo is responsible for maintaining NMJ integrity during aging. Through genetic screening, we identify several downstream factors mediated through foxo-regulated NMJ homeostasis, including genes involved in the MAPK pathway. Interestingly, the phosphorylation of p38 was increased in the motor neuron-specific foxo knockdown flies, suggesting foxo acts as a suppressor of p38/MAPK activation. Our work reveals that foxo is a key regulator for NMJ homeostasis, and it may maintain NMJ integrity by repressing MAPK signaling.This article is published as Birnbaum A, Sodders M, Bouska M, Chang K, Kang P, McNeill E and Bai H (2021) FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging. Front. Aging Neurosci. 12:567861. doi: 10.3389/fnagi.2020.567861. Posted with permission. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Identifying postnatal depression: Comparison of a self-reported depression item with Edinburgh Postnatal Depression Scale scores at three months postpartum

BACKGROUND: Early identification of postnatal depression is important in order to minimize adverse outcomes. The Edinburgh Postnatal Depression Scale (EPDS) is commonly used as a screening tool but a single, direct question on depression may offer an alternative means of identifying women in need of support. This study examines the agreement between these methods and characteristics of women who self-identify as depressed and those with EPDSand#160;and#8805;and#160;13. METHODS: Secondary analysis of two national maternity surveys conducted in England and Northern Ireland. Agreement between the direct question and EPDS scores was assessed using Cohen's kappa. Logistic regression was used to identify characteristics of women in each group. RESULTS: 6752 women were included. At three months postpartum, 6.1% of women self-identified as having depression, 9.1% scored EPDSand#160;and#8805;and#160;13, 2.8% were positive on both. Agreement between the two methods was minimal (Cohen's kappaand#160;andlt;and#160;0.3). Women who self-identified as having depression had higher odds of being agedand#160;andgt;and#160;40 years (OR 1.8; 95% CI 1.2-2.8). EPDSand#160;and#8805;and#160;13 was associated withand#160;andlt;and#160;16 years of education (OR 1.4; 95% CI 1.1-1.8), minority ethnicity (OR 1.4; 95% CI 1.1-1.9), living without a partner (OR 1.7; 95% CI 1.3-2.2), and a less than happy reaction to the pregnancy (OR 1.7; 95% CI 1.4-2.1). LIMITATIONS: Low survey response limits the representativeness of findings. The absence of a diagnostic interview limits conclusions on accuracy or internal validity of the measures. CONCLUSIONS:A direct question about postnatal depression may offer a valuable addition to screening tools to identify women in need of support.</p

Australia (in XVII New Literatures)

This chapter has seven sections: 1. Africa; 2. Australia; 3. Canada; 4. The Caribbean; 5. South Asia: The Indian Subcontinent and Sri Lanka; 6. New Zealand; 7. Southeast Asia. Section 1 is by Margaret Daymond and Tony Simoes Da Silva; section 2 is by Marguerite Nolan; section 3 is by Sally Carpentier, Paul Sharrad, and Ian Whitehouse; section 4 is by Giselle Rampaul and Geraldine Skeete; section 5 is by Mridula Nath Chakraborty and Ira Raja; section 6 is by Dougal McNeill; section 7 is by Philip Holden

Complete Genome Sequence of Rickettsia typhi and Comparison with Sequences of Other Rickettsiae

Rickettsia typhi, the causative agent of murine typhus, is an obligate intracellular bacterium with a life cycle involving both vertebrate and invertebrate hosts. Here we present the complete genome sequence of R. typhi (1,111,496 bp) and compare it to the two published rickettsial genome sequences: R. prowazekii and R. conorii. We identified 877 genes in R. typhi encoding 3 rRNAs, 33 tRNAs, 3 noncoding RNAs, and 838 proteins, 3 of which are frameshifts. In addition, we discovered more than 40 pseudogenes, including the entire cytochrome c oxidase system. The three rickettsial genomes share 775 genes: 23 are found only in R. prowazekii and R. typhi, 15 are found only in R. conorii and R. typhi, and 24 are unique to R. typhi. Although most of the genes are colinear, there is a 35-kb inversion in gene order, which is close to the replication terminus, in R. typhi, compared to R. prowazekii and R. conorii. In addition, we found a 124-kb R. typhi-specific inversion, starting 19 kb from the origin of replication, compared to R. prowazekii and R. conorii. Inversions in this region are also seen in the unpublished genome sequences of R. sibirica and R. rickettsii, indicating that this region is a hot spot for rearrangements. Genome comparisons also revealed a 12-kb insertion in the R. prowazekii genome, relative to R. typhi and R. conorii, which appears to have occurred after the typhus (R. prowazekii and R. typhi) and spotted fever (R. conorii) groups diverged. The three-way comparison allowed further in silico analysis of the SpoT split genes, leading us to propose that the stringent response system is still functional in these rickettsiae