Persistent insomnia, although very common in general practice, often proves problematic to manage. This study investigates the clinical effectiveness and the feasibility of applying cognitive ...behavior therapy (CBT) methods for insomnia in primary care.
Pragmatic randomized controlled trial of CBT versus treatment as usual.
General medical practice.
Two hundred one adults (mean age, 54 years) randomly assigned to receive CBT (n = 107; 72 women) or treatment as usual (n = 94; 65 women).
CBT comprised 5 sessions delivered in small groups by primary care nurses. Treatment as usual comprised usual care from general practitioners.
Assessments were completed at baseline, after treatment, and at 6-month follow-up visits. Sleep outcomes were appraised by sleep diary, actigraphy, and clinical endpoint. CBT was associated with improvements in self-reported sleep latency, wakefulness after sleep onset, and sleep efficiency. Improvements were partly sustained at follow-up. Effect sizes were moderate for the index variable of sleep efficiency. Participants receiving treatment as usual did not improve. Actigraphically estimated sleep improved modestly after CBT, relative to no change in treatment as usual. CBT was also associated with significant positive changes in mental health and energy/vitality. Comorbid physical and mental health difficulties did not impair sleep improvement following CBT.
This study suggests that trained and supervised nurses can effectively deliver CBT for insomnia in routine general medical practice. Treatment response to small-group service delivery was encouraging, although effect sizes were smaller than those obtained in efficacy studies. Further research is required to consider the possibility that CBT could become the treatment of first choice for persistent insomnia in primary healthcare.
Soybean cyst nematode (SCN), Heterodera glycines, HG type 1.2.5.7 is the most virulent and widespread SCN biotype in the southern states of the USA, but its effect on soybean (Glycine max L. Merr.) ...nitrogen fixation (NF) activity and growth is not well documented. The objectives of this study were to: (1) measure the impact of HG type 1.2.5.7 on NF activity during the early vegetative stage of three soybean genotypes and (2) compare the impact on soybean leaf and root development, and plant growth. The NF activity of two susceptible (S) genotypes ("Ellis" and "Williams 82") and one resistant (R) genotype (PI 88,788), subjected to a 10,000-egg treatment, was measured using an in-situ flow-through acetylene reduction assay. The average NF activity of the soybean genotypes was decreased by SCN activity. Time points assessment showed that the NF activity was differently impacted among the genotypes. Based on the measured values, the NF activity was decreased by 30% in SCN infected plants of Williams 82 but that of PI 88,788 and Ellis was affected. Likewise, soybean leaf color and leaf area were affected by SCN infection, but there was no impact on root length and root area. These results showed that SCN HG type 1.2.5.7 can exhibit varying negative impact on NF and shoot growth of S soybean genotypes, while R genotypes may be unaffected. Thus, indicating genetic resistance continues to be a critical tool for the management of the SCN.
Objective. For pharmacy students to successfully meet competencies related to Accreditation Council for Pharmacy Education Standards 3 and 4, it is essential for pharmacy programs to assess student ...progression in the affective domain. The purpose of this study was to develop and assess the validity of a situational judgment test (SJT) for evaluating student mastery of Standards 3 and 4.
Methods. A multi-institutional faculty team developed an 18-item SJT that consisted of scenarios asking the respondent to rank the effectiveness of four response options mapped to Standards 3 and 4. The research team systematically reviewed the literature, created items, and deliberated until consensus was achieved. Subject matter experts (SMEs) reviewed and provided feedback on the instrument. Students from two institutions were recruited to participate in cognitive interviews about the finalized instrument. Cognitive interview data were analyzed to identify themes.
Results. After edits were made to the instrument based on SME feedback, students (n=18) in the cognitive interviews identified item length as a concern and commented on item/response clarity and comprehensiveness. Data from the cognitive interviews were used to modify the SJT to reduce the length and clarify items. The result was two shorter versions of the instrument, both with similar mapping to all elements in Standards 3 and 4.
Conclusion. Early steps in validating the SJT suggested that the instrument may be a promising tool to assess student progression in the affective domain. The SJT instrument is intended to provide evidence of student pharmacist development that occurs in the didactic, experiential, and co-curricular portions of pharmacy education. The instrument can serve as one part of a comprehensive assessment plan.
Offspring of parents with bipolar disorder (BD-I/II) are at increased risk to develop the disorder. Previous work indicates that bipolar spectrum disorder (BPSD) is often preceded by mood/anxiety ...symptoms. In school-age offspring of parents with BD, we previously built a risk calculator to predict BPSD onset, which generates person-level risk scores. Here, we test whether preschool symptoms predict school-age BPSD risk.
We assessed 113 offspring of parents with BD 1-3 times during preschool years (2-5 years old) and then approximately every 2 years for a mean of 10.6 years. We used penalized (lasso) regression with linear mixed models to assess relationships between preschool mood, anxiety, and behavioral symptoms (parent-reported) and school-age predictors of BPSD onset (i.e., risk score, subthreshold manic symptoms, and mood lability), adjusting for demographics and parental symptomatology. Finally, we conducted survival analyses to assess associations between preschool symptoms and school-age onset of BPSD and mood disorder.
Of 113 preschool offspring, 33 developed new-onset mood disorder, including 19 with new-onset BPSD. Preschool irritability, sleep problems, and parental factors were lasso-selected predictors of school-age risk scores. After accounting for demographic and parental factors, preschool symptoms were no longer significant. Lasso regressions to predict mood lability and subthreshold manic symptoms yielded similar predictors (irritability, sleep problems, and parental affective lability), but preschool symptoms remained predictive even after adjusting for parental factors (ps < .005). Exploratory analyses indicated that preschool irritability univariately predicted new-onset BPSD (p = .02) and mood disorder (p = .02).
These results provide initial prospective evidence that, as early as preschool, youth who will develop elevated risk scores, mood lability, and subthreshold manic symptoms are already showing symptomatology; these preschool symptoms also predict new-onset BPSD. While replication of findings in larger samples is warranted, results point to the need for earlier assessment of risk and development of early interventions.
Angiotensin Converting Enzyme 2 (ACE2) is the primary cell entry receptor for SARS-CoV and SARS-CoV-2 viruses. A disintegrin and metalloproteinase 17 (ADAM17) is a protease that cleaves ectodomains ...of transmembrane proteins, including that of ACE2 and the proinflammatory cytokine TNF-α, from cell surfaces upon cellular activation. We hypothesized that blockade of ADAM17 activity would alter COVID-19 pathogenesis. To assess this pathway, we blocked the function of ADAM17 using the monoclonal antibody MEDI3622 in the K18-hACE2 transgenic mouse model of COVID-19. Antibody-treated mice were healthier, less moribund, and had significantly lower lung pathology than saline-treated mice. However, the viral burden in the lungs of MEDI3622-treated mice was significantly increased. Thus, ADAM17 appears to have a critical anti-viral role, but also may promote inflammatory damage. Since the inflammatory cascade is ultimately the reason for adverse outcomes in COVID-19 patients, there may be a therapeutic application for the MEDI3622 antibody.
Individuals who identify as lesbian, gay, bisexual, transgender, queer, and otherwise nonstraight and/or non-cisgender (LGBTQ+) have often not felt welcome or represented in the biology community. ...Additionally, biology can present unique challenges for LGBTQ+ students because of the relationship between certain biology topics and their LGBTQ+ identities. Currently, there is no centralized set of guidelines to make biology learning environments more inclusive for LGBTQ+ individuals. Rooted in prior literature and the collective expertise of the authors who identify as members and allies of the LGBTQ+ community, we present a set of actionable recommendations to help biologists, biology educators, and biology education researchers be more inclusive of individuals with LGBTQ+ identities. These recommendations are intended to increase awareness of LGBTQ+ identities and spark conversations about transforming biology learning spaces and the broader academic biology community to become more inclusive of LGBTQ+ individuals.
Experimental studies were conducted to examine the oxidation of carbamazepine, an anticonvulsant drug widely detected in surface waters and sewage treatment effluent, by potassium salts of ...permanganate (Mn(VII); KMnO4) and ferrate (Fe(VI); K2FeO4). Results show that both Mn(VII) and Fe(VI) rapidly oxidize carbamazepine by electrophilic attack at an olefinic group in the central heterocyclic ring, leading to ring-opening and a series of organic oxidation products. Reaction kinetics follow a generalized second-order rate law, with apparent rate constants at pH 7.0 and 25 °C of 3.0(±0.3) × 102 M−1 s−1 for Mn(VII) and 70(±3) M−1 s−1 for Fe(VI). Mn(VII) reaction rates exhibit no pH dependence, whereas Fe(VI) reaction rates increase dramatically with decreasing pH, due to changing acid−base speciation of Fe(VI). Further studies with Mn(VII) show that most common nontarget water constituents, including natural organic matter, have no significant effect on rates of carbamazepine oxidation; reduced metals and (bi)sulfide exert a stoichiometric Mn(VII) demand that can be incorporated into the kinetic model. The removal of carbamazepine in two utility source waters treated with KMnO4 agrees closely with predictions from the kinetic model that was parametrized using experiments conducted in deionized water at much higher reagent concentrations.
The mitogen-activated protein kinase (MAPK) pathway is a crucial regulator of cell proliferation, survival, and resistance to apoptosis. MEK inhibitors are being explored as a treatment option for ...patients with KRAS-mutant colorectal cancer who are not candidates for EGFR-directed therapies. Initial clinical results of MEK inhibitors have yielded limited single-agent activity in colorectal cancer, indicating that rational combination strategies are needed.
In this study, we conducted unbiased gene set enrichment analysis and synthetic lethality screens with selumetinib, which identified the noncanonical Wnt/Ca++ signaling pathway as a potential mediator of resistance to the MEK1/2 inhibitor selumetinib. To test this, we used shRNA constructs against relevant WNT receptors and ligands resulting in increased responsiveness to selumetinib in colorectal cancer cell lines. Further, we evaluated the rational combination of selumetinib and WNT pathway modulators and showed synergistic antiproliferative effects in in vitro and in vivo models of colorectal cancer.
Importantly, this combination not only showed tumor growth inhibition but also tumor regression in the more clinically relevant patient-derived tumor explant (PDTX) models of colorectal cancer. In mechanistic studies, we observed a trend toward increased markers of apoptosis in response to the combination of MEK and WntCa(++) inhibitors, which may explain the observed synergistic antitumor effects.
These results strengthen the hypothesis that targeting both the MEK and Wnt pathways may be a clinically effective rational combination strategy for patients with metastatic colorectal cancer.
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