Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects the skin and the nervous system. The condition is completely penetrant with extreme clinical variability, resulting in ...unpredictable manifestations in affected offspring, complicating reproductive decision-making. One of the reproductive options to prevent the birth of affected offspring is preimplantation genetic testing (PGT). We performed a retrospective review of the medical files of all couples (n = 140) referred to the Dutch PGT expert center with the indication NF1 between January 1997 and January 2020. Of the couples considering PGT, 43 opted out and 15 were not eligible because of failure to identify the underlying genetic defect or unmet criteria for in vitro fertilization (IVF) treatment. The remaining 82 couples proceeded with PGT. Fertility assessment prior to IVF treatment showed a higher percentage of male infertility in males affected with NF1 compared to the partners of affected females. Cardiac evaluations in women with NF1 showed no contraindications for IVF treatment or pregnancy. For 67 couples, 143 PGT cycles were performed. Complications of IVF treatment were not more prevalent in affected females compared to partners of affected males. The transfer of 174 (out of 295) unaffected embryos led to 42 ongoing pregnancies with a pregnancy rate of 24.1% per embryo transfer. There are no documented cases of misdiagnosis following PGT in this cohort. With these results, we aim to provide an overview of PGT for NF1 with regard to success rate and safety, to optimize reproductive counseling and PGT treatment for NF1 patients.
Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also ...exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology. Furthermore, the role of membrane-bound and sTREM-1 in polygenic infections is currently unknown. In a mouse co-infection model where preceding viral infection greatly enhances bacteria co-infection, we now determine a mechanisms for the striking increase in sTREM-1 and the loss of TREM-1 on surface of neutrophils. We identified a matrix metalloproteinase (MMP)-9 cleavage site in TREM-1 and that the increase of MMP-9 in bronchoalveolar lavage fluid mirrors sTREM-1 release. In vitro studies with neutrophils and MMP-9 and the reduction of sTREM-1 in vivo after MMP-9 inhibition verifies that this enzyme cleaves TREM-1. Intriguingly, MMP-9 inhibition significantly reduces bacterial load and ensuing immunopathology in a co-infection model. This highlights MMP-9 inhibition as a potential therapeutic via blocking cleavage of TREM-1.
Mental illness within Christian communities may be subject to stigmatization, with some attributing it to demonic possession, lack of faith, personal sin, or other negative spiritual influences. ...Contrasting research, however, suggests a potentially supportive role, in that Christian faith and community may aid recovery from mental illness and/or act as a buffer against onset or relapse. The aim of this qualitative review was to systematically collate and characterize published qualitative evidence that explores the experiences of adult Christians with mental illness in relation to their faith and community. An electronic search of 15 databases was conducted, alongside the manual review of notable journals in the area and expert consultation. Twenty-two studies were included from 12,607 reviewed articles. A thematic synthesis identified four higher level themes: positive experiences of Christian communities (subthemes: congregational support; faith leaders and pastoral care), positive coping through Christian meaning systems (subthemes: religious meaning- making; positive coping through relationship with God), negative experiences of Christian communities (subthemes: imposed spiritualization of mental illness; stigma, exclusion, and marginalization), difficulties navigating faith amid suffering (subthemes: dissonance: mental illness and faith; negative affect). This qualitative systematic review provides support to the vital importance of Christian faith and community for Christians who experience mental illness. It categorizes the idiographic and often diverse ways in which Christians living with mental illness may experience their faith and church community and explores how Christian religious systems and communities may function to support or hinder experiences of mental illness. (PsycInfo Database Record (c) 2023 APA, all rights reserved) (Source: journal abstract)
The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological ...knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology.
Demonic etiologies of mental illness (e.g., demonic attack, oppression, or possession) promoted by some evangelical Christians groups may lead to the isolation and stigmatization of those ...experiencing mental ill-health. Yet belief in demonic etiologies can also serve psychological functions, helping people to construct meaning in response to adversity and suffering. This research seeks to explore the factors associated with a demonic etiology of mental illness that are considered both helpful and unhelpful to evangelicals experiencing mental ill-health. A convenience sample of 50 evangelical Christians completed a qualitative survey regarding the relationship between the supernatural and mental health. A contextualist thematic analysis identified three main themes: (1) conceptualizations of mental illness, (2) demonic conceptualizations of mental illness as helpful, and (3) demonic conceptualizations of mental illness as unhelpful. Findings suggest that while spiritual etiologies of mental illness are widespread, these may frequently also coalesce with a nuanced recognition and appreciation for biopsychosocial factors. Demonic etiologies of mental illness may be experienced as helpful by affording individuals meaning in their suffering and enabling positive spiritual coping. Conversely, demonic etiologies may be experienced as unhelpful when they discourage access to secular mental health support and lead to stigmatization and isolation. These findings underline the complexities of studying etiological accounts of mental illness in religious communities and confirm the limitations of a dichotomized approach to psychological illness in evangelical Christian communities whereby spiritual accounts are rendered as pathological or unhelpful. (PsycInfo Database Record (c) 2023 APA, all rights reserved) (Source: journal abstract)
Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most. This study aimed to summarize ...the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most.
Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search. Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models.
Fourteen trials representing 3,282 patients were included. Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval CI 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality. Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026). In none of these subgroups, a consistent effect was shown on all relevant outcomes.
Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice. Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended.
The addition of cattle slurry to agricultural land is a widespread practise, but if not correctly managed it can pose a contamination risk to aquatic ecosystems. The transport of inorganic and ...organic components of cattle slurry to watercourses is a major concern, yet little is known about the physical transport mechanisms and associated fluxes and timings of contamination threats. Therefore, the aim of the study was to ascertain the importance of flow pathway partitioning in the transport (fluxes and timing) of dissolved and particulate slurry-derived compounds with implications for off-site contamination. A series of rainfall–runoff and erosion experiments were carried out using the TRACE (Test Rig for Advancing Connectivity Experiments) experimental hillslope facility. The experiments allowed the quantification of the impact of changing slope gradient and rainfall intensity on nutrient transport from cattle slurry applied to the hillslope, via surface, subsurface, and vertical percolated flow pathways, as well as particulate transport from erosion. The dissolved components were traced using a combination of ammonium (NH4+) and fluorescence analysis, while the particulate fraction was traced using organic biomarkers, 5β-stanols. Results showed that rainfall events which produced flashy hydrological responses, resulting in large quantities of surface runoff, were likely to move sediment and also flush dissolved components of slurry-derived material from the slope, increasing the contamination risk. Rainfall events which produced slower hydrological responses were dominated by vertical percolated flows removing less sediment-associated material, but produced leachate which could contaminate deeper soil layers, and potentially groundwater, over a more prolonged period. Overall, this research provides new insights into the partitioning of slurry-derived material when applied to an unvegetated slope and the transport mechanisms by which contamination risks are created.
Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. ...The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.
It has been hypothesized that as soil fertility increases, the amount of carbon allocated to below-ground production (fine roots) should decrease. To evaluate this hypothesis, we measured the ...standing crop fine root mass and the production of fine roots (<2 mm) by two methods: (1) ingrowth cores and, (2) sequential soil coring, during 2.2 years in two lowland forests growing on different soils types in the Colombian Amazon. Differences of soil resources were defined by the type and physical and chemical properties of soil: a forest on clay loam soil (Endostagnic Plinthosol) at the Amacayacu National Natural Park and, the other on white sand (Ortseinc Podzol) at the Zafire Biological Station, located in the Forest Reservation of the Calderón River. We found that the standing crop fine root mass and the production was significantly different between soil depths (0–10 and 10–20 cm) and also between forests. The loamy sand forest allocated more carbon to fine roots than the clay loam forest with the production in loamy sand forest twice (mean±standard error=2.98±0.36 and 3.33±0.69 Mg C ha−1 yr−1, method 1 and 2, respectively) as much as for the more fertile loamy soil forest (1.51±0.14, method 1, and from 1.03±0.31 to 1.36±0.23 Mg C ha−1 yr−1, method 2). Similarly, the average of standing crop fine root mass was higher in the white-sands forest (10.94±0.33 Mg C ha−1) as compared to the forest on the more fertile soil (from 3.04±0.15 to 3.64±0.18 Mg C ha−1). The standing crop fine root mass also showed a temporal pattern related to rainfall, with the production of fine roots decreasing substantially in the dry period of the year 2005. These results suggest that soil resources may play an important role in patterns of carbon allocation to the production of fine roots in these forests as the proportion of carbon allocated to above- and below-ground organs is different between forest types. Thus, a trade-off between above- and below-ground growth seems to exist with our results also suggesting that there are no differences in total net primary productivity between these two forests, but with higher below-ground production and lower above-ground production for the forest on the nutrient poor soil.
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