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Importance: Individuals with psychiatric disorders have been reported to have elevated levels of inflammatory biomarkers, and prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.

Objective: To assess the associations between inflammation biomarkers and subsequent psychiatric disorders risk.

Design, setting, and participants: This was a prospective cohort study including individuals from the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort, with no prior psychiatric diagnoses and having a measurement of at least 1 inflammatory biomarker. Data from the UK Biobank were used for validation. Longitudinal trajectories of studied biomarkers were visualized before diagnosis of psychiatric disorders in the AMORIS cohort via a nested case-control study. In addition, genetic correlation and mendelian randomization (MR) analyses were conducted to determine the genetic overlap and causality of the studied associations using publicly available GWAS summary statistics.

Exposures: Inflammatory biomarkers, eg, leukocytes, haptoglobin, immunoglobulin G (IgG), C-reactive protein (CRP), platelets, or albumin.

Main outcomes and measures: Any psychiatric disorder or specific psychiatric disorder (ie, depression, anxiety, and stress-related disorders) was identified through the International Statistical Classification of Diseases, Eighth, Ninth, and Tenth Revision codes.

Results: Among the 585 279 individuals (mean [SD] age, 45.5 [14.9] years; 306 784 male [52.4%]) in the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11; 95% CI, 1.09-1.14), haptoglobin (HR, 1.13; 95% CI, 1.12-1.14), or CRP (HR, 1.02; 95% CI, 1.00-1.04) had an elevated associated risk of any psychiatric disorders. In contrast, we found an inverse association for IgG level (HR, 0.92; 95% CI, 0.89-0.94). The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank (n = 485 620). Analyses of trajectories revealed that individuals with psychiatric disorders had higher levels of leukocytes and haptoglobin and a lower level of IgG than their controls up to 30 years before the diagnosis. The MR analysis suggested a possible causal relationship between leukocytes and depression.

Conclusions and relevance: In this cohort study, inflammatory biomarkers including leukocytes, haptoglobin, CRP, and IgG were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. The possible causal link between leukocytes and depression supports the crucial role of inflammation in the development of psychiatric disorders.

Plastic waste is a major threat in our industrialized world and is driving research into bioplastics. The success of biobased polyethylene furanoate (PEF) as a viable alternative to polyethylene terephthalate (PET) of fossil origin will depend on designing effective enzymes to break it down, aiding its recycling. Here, a panel of fungal and bacterial cutinases were functionally expressed in a tandem yeast expression system based on Saccharomyces cerevisiae and Pichia pastoris. The activity of the enzyme panel was tested with soluble PEF model scaffolds, observing a correlation with the degradation of real PEF powder. A high-throughput colorimetric screening assay based on the PEF scaffold diethyl furan-2,5-dicarboxylate was developed, establishing the basis for future directed evolution campaigns of PEFases.

Importance: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes.

Objectives: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood.

Design, setting, and participants: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024.

Exposures: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation.

Main outcomes and measures: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score.

Results: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years.

Conclusions and relevance: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Importance: Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm.

Objective: To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice.

Design, setting, and participants: This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024.

Exposure: Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor.

Main outcomes and measures: The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis.

Results: In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders.

Conclusions and relevance: This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.

The use of nucleic acid-based detection tools for microorganisms and fungi has become a gold standard. This is particularly the case for wood-decaying fungi like Serpula lacrymans, which are hard to discriminate based on macroscopic and microscopic observations. This dry rot is important to detect as it is particularly destructive in an infested building, which requires immediate action to prevent spreading and significant damage to structural elements. Through the development and optimization of loop-mediated isothermal amplification against S. lacrymans-specific rDNA internal transcribed spacer region, we demonstrate that it is possible to achieve rapid and specific amplification without nonspecific self-amplification in a similar range as real-time quantitative PCR without any necessary DNA isolation using a colorimetric detection assay. Through a combined set of self-amplification minimization along with hand-held sample homogenization, the LAMP assay was optimized to provide a femtogram-range assay capable of confirming identification in a real field sample either predominantly composed of S. lacrymans or containing the fungus while remaining negative when tested on different types of fungi found in basement-collected samples.

Importance: Cognitive behavioral therapy for insomnia (CBTi) is the standard of care for treating insomnia disorder, but access is limited. Alternative approaches are needed to expand access to the standard of care.

Objective: To examine the effectiveness of a nurse-supported, self-directed behavioral insomnia intervention for decreasing insomnia severity and improving sleep outcomes among veterans, a population with considerable mental health comorbidity.

Design, setting, and participants: This randomized clinical trial included 178 patients with insomnia disorder who were recruited from a Veterans Affairs hospital (Durham VA Healthcare System) from September 2019 to April 2022 and randomized following baseline assessment; follow-ups were conducted at 8 weeks (primary end point) and 6 months. Data analysis was primarily conducted during the summer of 2023 and concluded in May 2024.

Intervention: Six weekly phone calls from a nurse interventionist plus assigned treatment manual readings covering CBTi treatment components. The health education manual focused on health topics but not sleep.

Main outcomes and measures: The primary outcome was the Insomnia Severity Index (score range, 0-28; remission <8; differential improvement of 3 points targeted) score assessed at 8 weeks postrandomization. Secondary outcomes were sleep outcomes, depression, fatigue, treatment response, and remission.

Results: Of 178 study participants, the mean (SD) age was 55.1 (13.2) years, and 128 (71.9%) identified as men. At 8 weeks, Insomnia Severity Index scores decreased by an estimated mean (SE) of 5.7 (0.51) points in the intervention group and 2.0 (0.47) points in the control group, a differential mean improvement of 3.7 points (95% CI, -5.0 to -2.4; P < .001). Differences were sustained at 6 months (mean, -2.8; 95% CI, -4.4 to -1.3; P < .001). The intervention also resulted in greater improvements at 8 weeks postrandomization in diary sleep onset latency, wake after sleep onset, and sleep efficiency and actigraphy sleep efficiency; these differences were sustained at 6 months. At 8 weeks, depression and fatigue were significantly reduced, and the odds of treatment response and remission were greater in the intervention group compared with controls.

Conclusions and relevance: This randomized clinical trial found that despite greater prevalence of mental health conditions and sleep difficulties among veterans, a nurse-supported self-directed CBTi was more effective than health education control for reducing insomnia severity and improving sleep outcomes. Although less effective than therapist-delivered CBTi, findings were comparable with other trials using modified CBTi protocols.

Trial registration: ClinicalTrials.gov Identifier: NCT03727438.

Importance: While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier.

Objective: To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions.

Data sources: Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk.

Study selection: Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy.

Data extraction and synthesis: Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies.

Main outcomes and measures: The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions.

Results: A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal.

Conclusions and relevance: This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.