Abstract Background Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD ...and account for 65%-70% of cases in western countries. Objective To understand the clinical manifestations associated with the X-linked CGD carrier state. Methods We undertook a comprehensive retrospective study of 162 affected females. We examined dihydrorhodamine oxidation (DHR) data for percent (%) X chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ levels over time. Results Clinical data were available for 93 females: The %DHR+ was 46% (mean) and 47% (median)(SD=24). Using %DHR+ as the criterion for X inactivation, 78% of patients had levels of inactivation 20-80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ of 8% (n=14, range 0.06-48 %); those with only autoimmune or inflammatory manifestations (AIM) had median %DHR+ of 39% (n=31, range 7.4-74%). Those with both infections and autoimmunity had low %DHR+ (n=6, range=3-14%). A %DHR+ <10 % was strongly associated with infections (OR:99). Strong association persisted when the %DHR+ was <20% (OR=12) Autoimmunity was not associated with %DHR+. In two sets of identical twins the %DHR+ populations tracked closely over time. While the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated. Conclusions A low %DHR+ strongly predicts infection risk in X-linked CGD carriers, while the carrier state itself is associated with autoimmunity.
The survival effect in memory refers to the memory enhancement for materials encoded in reference to a survival scenario compared to those encoded in reference to a control scenario or with other ...encoding strategies. The current study examined whether this effect is well maintained in old age by testing young (ages 18-29) and older adults (ages 65-87) on the survival effect in memory for words encoded in ancestral and/or non-ancestral modern survival scenarios relative to a non-survival control scenario. A pilot study was conducted to select the best matched comparison scenarios based on potential confounding variables, such as valence and arousal. Experiment 1 assessed the survival effect with a well-matched negative control scenario in both young and older adults. The results showed an age-equivalent survival effect across an ancestral and a non-ancestral modern survival scenario. Experiment 2 replicated the survival effect in both age groups with a positive control scenario. Taken together, the data suggest a robust survival effect that is well preserved in old age across ancestral and non-ancestral survival scenarios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Older adults with early forms of neurodegenerative disease are at risk for functional disability, which is often defined by the loss of independence in instrumental activities of daily living ...(IADLs). The current study investigated the influence of mild changes in everyday functional abilities (referred to as functional limitations) on risk for development of incident functional disability. A total of 407 participants, who were considered cognitively normal or diagnosed with mild cognitive impairment (MCI) at baseline, were followed longitudinally over an average 4.1 years (range=0.8-9.2 years). Informant-based ratings from the Everyday Cognition (ECog; Farias et al., 2008) and the Instrumental Activities of Daily Living (Lawton & Brody, 1969) scales assessed the degree of functional limitations and incident IADL disability, respectively. Cox proportional hazards models revealed that more severe functional limitations (as measured by the Total ECog score) at baseline were associated with approximately a four-fold increased risk of developing IADL disability a few years later. Among the ECog domains, functional limitations in Everyday Planning, Everyday Memory, and Everyday Visuospatial domains were associated with the greatest risk of incident functional disability. These results remained robust even after controlling for participants' neuropsychological functioning on tests of executive functions and episodic memory. Current findings indicate that early functional limitations have prognostic value in identifying older adults at risk for developing functional disability. Findings highlight the importance of developing interventions to support everyday abilities related to memory, executive function, and visuospatial skills in an effort to delay loss of independence in IADLs.
Abstract It is recognized that individuals with mild cognitive impairment (MCI) already demonstrate difficulty in aspects of daily functioning, which predicts disease progression. This study examined ...the relationship between self- versus informant-report of functional ability, and how those reports relate to objective disease measures across the disease spectrum (i.e. cognitively normal, MCI, Alzheimer's disease). A total of 1080 subjects with self- and/or informant-rated Everyday Cognition questionnaires were included. Objective measures included cognitive functioning, structural brain atrophy, cerebrospinal fluid abnormalities, and a marker of amyloid deposition using positron emission tomography with 18 FAV45 (florbetapir). Overall, informant-report was consistently more associated with objective markers of disease than self-report although self-reported functional status may still have some utility in early disease.
Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish (Oryzias melastigma) exposed to hypoxia show reproductive impairments (retarded ...gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans.
Aim
Recruiting young women to weight management research programs is difficult. The purpose of this study was to gain insights into the barriers and motivators that influence participation and to ...explore effective methods of recruitment from the perspective of young women with obesity living in both urban and regional areas.
Methods
Semi‐structured interviews were used to elicit information from focus groups. The interviews were transcribed, coded and analysed qualitatively. Eight focus groups, which included a total of 27 women, were conducted. Participants had a mean age of 29.1 (±5.1) years and a mean body mass index of 35.8 (±2.9) kg/m2.
Results
The barriers to participation were multifaceted and largely similar across urban and regional participants. Fear of judgement and uncertainty about the process were major psychosocial barriers. A lack of tailoring of program content was an important program‐related barrier. Physical barriers such as time commitment, cost and access were discussed extensively, particularly in urban groups. The provision of incentives and the use of positive language that focusses on the benefits of the intervention were viewed positively. Physical and virtual methods of recruitment were identified as potentially effective provided they were presented in media that this group is likely to use and can access in a private location.
Conclusions
The results of this study provide a greater understanding of the challenges faced by young women in relation to participation in weight management programs and some of the potential methods that could be utilised to facilitate participation.
•A new in vitro test for EDC using fish primary pituitary, testis and ovary cells.•Deciphering the target sites and mechanisms of EDCs.•mRNA expression of some genes upon exposure to NP, PBDE, E2 and ...hypoxia was tested.•Result of the in vitro test was comparable to other in vivo and in vitro studies.
While endocrine disrupting chemicals (EDCs) pose a significant threat to wildlife worldwide, their diverse chemical structures present a major challenge to their detection, particularly since they are present at very low concentrations in the environment. We here report the development of an in vitro system for rapid screening of EDCs, using primary cell cultures (pituitary, ovarian follicular and testicular cells) of the marine medaka (Oryzias melastigma). Pituitary, testis and ovary cell cultures were developed and challenged by environmentally relevant concentrations of three well known EDCs (viz. estradiol, 2,2′,4,4′-tetrabromodiphenyl ether, and 4-n-nonylphenol) as well as hypoxia (which has been shown to be a potent endocrine disruptor). In general, the mRNA expression levels of gonadotropins, their receptors and steroidogenic enzymes exhibited dose response relationships to the four endocrine disruptors in different tissues. The sensitivity and responses were also comparable to in vivo responses of whole fish and in vitro responses of the H295R human adrenocortical cell line. Our results suggest that the use of marine medaka primary cultured cells can serve as a cost effective tool for rapid screening of EDCs in the marine environment, and at the same time, sheds light on the underlying mechanisms of EDCs by deciphering their specific target sites along the hypothalamus-pituitary-gonad axis of vertebrates.
The marine medaka (Oryzias melastigma) has been increasingly used as a fish model for detecting environmental stresses and chemical contaminants in the marine environment. Recent mammalian studies ...have shown that environmental stresses can alter the expression profiles of microRNAs (miRNAs), leading to transgenerational effects. Here, we use high-throughput Illumina RNA sequencing (RNA-Seq) for miRNA transcriptome analysis of brain, liver, and gonads from sexually mature male and female marine medaka. A total of 128,883,806 filtered sequence reads were generated from six small RNA libraries, identifying a total of 2,125,663 non-redundant sequences. These sequences were aligned and annotated to known animal miRNAs (miRBase) using the BLAST method. A total of 223 distinct miRNA types were identified, with the greatest number expressed in brain tissue. Our data suggested that 55 miRNA types from 34 families are common to all tested tissues, while some of the miRNAs are tissue-enriched or sex-enriched. Quantitative real-time PCR analysis further demonstrated that let-7a, miR-122, and miR-9-3p were downregulated in hypoxic female medaka, while miR-2184 was specifically upregulated in the testis of hypoxic male fish. This is the first study to identify miRNAs in O. melastigma using small RNA deep sequencing technology. Because miRNA expression is highly conserved between marine medaka and other vertebrates, marine medaka may serve as a good model for studies on the functional roles of miRNAs in hypoxia stress response and signaling in marine fish.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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