Long-term physical health conditions (LTPHCs) are associated with poorer psychological well-being, quality of life, and longevity. Additionally, individuals with LTPHCs report uncertainty in terms of ...condition aetiology, course, treatment, and ability to engage in life. An individual's dispositional ability to tolerate uncertainty-or difficulty to endure the unknown-is termed intolerance of uncertainty (IU), and may play a pivotal role in their adjustment to a LTPHC. Consequently, the current review sought to investigate the relationship between IU and health-related outcomes, including physical symptoms, psychological ramifications, self-management, and treatment adherence in individuals with LTPHCs. A systematic search was conducted for papers published from inception until 27 May 2022 using the databases PsycINFO, PubMed (MEDLINE), CINAHL Plus, PsycARTICLES, and Web of Science. Thirty-one studies (N = 6,201) met the inclusion criteria. Results indicated that higher levels of IU were associated with worse psychological well-being outcomes and poorer quality of life, though impacts on self-management were less clear. With the exception of one study (which looked at IU in children), no differences in IU were observed between patients and healthy controls. Although findings highlight the importance of investigating IU related to LTPHCs, the heterogeneity and limitations of the existing literature preclude definite conclusions. Future longitudinal and experimental research is required to investigate how IU interacts with additional psychological constructs and disease variables to predict individuals' adjustment to living with a LTPHC.
Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing ...sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10
) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression.
Viruses are abundant ubiquitous members of microbial communities and in the marine environment affect population structure and nutrient cycling by infecting and lysing primary producers. Antarctic ...lakes are microbially dominated ecosystems supporting truncated food webs in which viruses exert a major influence on the microbial loop. Here we report the discovery of a virophage (relative of the recently described Sputnik virophage) that preys on phycodnaviruses that infect prasinophytes (phototrophic algae). By performing metaproteogenomic analysis on samples from Organic Lake, a hypersaline meromictic lake in Antarctica, complete virophage and near-complete phycodnavirus genomes were obtained. By introducing the virophage as an additional predator of a predator-prey dynamic model we determined that the virophage stimulates secondary production through the microbial loop by reducing overall mortality of the host and increasing the frequency of blooms during polar summer light periods. Virophages remained abundant in the lake 2 y later and were represented by populations with a. high level of major capsid protein sequence variation (25-100% identity). Virophage signatures were also found in neighboring Ace Lake (in abundance) and in two tropical lakes (hypersaline and fresh), an estuary, and an ocean upwelling site. These findings indicate that virophages regulate host-virus interactions, influence overall carbon flux in Organic Lake, and play previously unrecognized roles in diverse aquatic ecosystems.
Insomnia symptoms are widespread in the population and might have effects on many chronic conditions and their risk factors but previous research has focused on select hypothesised ...associations/effects rather than taking a systematic hypothesis-free approach across many health outcomes.
We performed a Mendelian randomisation (MR) phenome-wide association study (PheWAS) in 336,975 unrelated white-British UK Biobank participants. Self-reported insomnia symptoms were instrumented by a genetic risk score (GRS) created from 129 single-nucleotide polymorphisms (SNPs). A total of 11,409 outcomes from UK Biobank were extracted and processed by an automated pipeline (PHESANT) for the MR-PheWAS. Potential causal effects (those passing a Bonferroni-corrected significance threshold) were followed up with two-sample MR in MR-Base, where possible.
Four hundred thirty-seven potential causal effects of insomnia symptoms were observed for a diverse range of outcomes, including anxiety, depression, pain, body composition, respiratory, musculoskeletal and cardiovascular traits. We were able to undertake two-sample MR for 71 of these 437 and found evidence of causal effects (with directionally concordant effect estimates across main and sensitivity analyses) for 30 of these. These included novel findings (by which we mean not extensively explored in conventional observational studies and not previously explored using MR based on a systematic search) of an adverse effect on risk of spondylosis (OR 95%CI = 1.55 1.33, 1.81) and bronchitis (OR 95%CI = 1.12 1.03, 1.22), among others.
Insomnia symptoms potentially cause a wide range of adverse health-related outcomes and behaviours. This has implications for developing interventions to prevent and treat a number of diseases in order to reduce multimorbidity and associated polypharmacy.
In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. ...Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine, marine-derived, meromictic (stratified) lake (Ace Lake) in Antarctica. Nine million open reading frames were analyzed, representing microbial samples taken from six depths of the lake size fractionated on sequential 3.0, 0.8 and 0.1 μm filters, and including metaproteome data from matching 0.1 μm filters. We determine how the interactions of members of this highly structured and moderately complex community define the biogeochemical fluxes throughout the entire lake. Our view is that the health of this delicate ecosystem is dictated by the effects of the polar light cycle on the dominant role of green sulfur bacteria in primary production and nutrient cycling, and the influence of viruses/phage and phage resistance on the cooperation between members of the microbial community right throughout the lake. To test our assertions, and develop a framework applicable to other microbially driven ecosystems, we developed a mathematical model that describes how cooperation within a microbial system is impacted by periodic fluctuations in environmental parameters on key populations of microorganisms. Our study reveals a mutualistic structure within the microbial community throughout the lake that has arisen as the result of mechanistic interactions between the physico-chemical parameters and the selection of individual members of the community. By exhaustively describing and modelling interactions in Ace Lake, we have developed an approach that may be applicable to learning how environmental perturbations affect the microbial dynamics in more complex aquatic systems.
Antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) is recommended to prevent infective endocarditis (IE) in those at high IE risk, but there are sparse data supporting a link ...between IDPs and IE or AP efficacy in IE prevention.
The purpose of this study was to investigate any association between IDPs and IE, and the effectiveness of AP in reducing this.
We performed a case-crossover analysis and cohort study of the association between IDPs and IE, and AP efficacy, in 7,951,972 U.S. subjects with employer-provided Commercial/Medicare-Supplemental coverage.
Time course studies showed that IE was most likely to occur within 4 weeks of an IDP. For those at high IE risk, case-crossover analysis demonstrated a significant temporal association between IE and IDPs in the preceding 4 weeks (OR: 2.00; 95% CI: 1.59-2.52; P = 0.002). This relationship was strongest for dental extractions (OR: 11.08; 95% CI: 7.34-16.74; P < 0.0001) and oral-surgical procedures (OR: 50.77; 95% CI: 20.79-123.98; P < 0.0001). AP was associated with a significant reduction in IE incidence following IDP (OR: 0.49; 95% CI: 0.29-0.85; P = 0.01). The cohort study confirmed the associations between IE and extractions or oral surgical procedures in those at high IE risk and the effect of AP in reducing these associations (extractions: OR: 0.13; 95% CI: 0.03-0.34; P < 0.0001; oral surgical procedures: OR: 0.09; 95% CI: 0.01-0.35; P = 0.002).
We demonstrated a significant temporal association between IDPs (particularly extractions and oral-surgical procedures) and subsequent IE in high–IE-risk individuals, and a significant association between AP use and reduced IE incidence following these procedures. These data support the American Heart Association, and other, recommendations that those at high IE risk should receive AP before IDP.
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We study the effect of sanitary and phytosanitary (SPS) measures on Chinese agricultural exports and the role of trade intermediaries in this process following China's accession to the World Trade ...Organization. While both agricultural exports and SPS regulations have grown, the use of trade intermediaries has declined sharply. We develop a model of heterogeneous producer-level decisions about choice of export mode that is consistent with this trend. In our econometric analysis, we analyse the effects of SPS measures and trade intermediaries on Chinese fruit and vegetable exports using transaction-level customs data. In contrast to much of the literature, we find some evidence of positive relationships among SPS measures, trade intermediaries and exports.
Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly ...individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.
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