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A diterpenoid biosynthetic gene cluster (BGC) has been identified in a few species in the Lamiaceae (mint) family, but its origin and evolution remain unclear. Here, the authors report assembly of genomes of three species within the family and reveal the dynamic evolutionary trajectory of the BGC.

Multitiered systems of support (MTSS) are composed of tiered prevention and intervention in multiple domains. MTSS is often referred to as an umbrella framework that includes both a multi-tiered approach to proactive school-wide behavior (e.g., Schoolwide Positive Behavior Interventions and Supports) and academic supports in reading, writing, and/or mathematics (e.g., Response to Intervention). Integrating behavior and academic support systems can become complex, requiring significant coordination and implementation efforts within schools. However, efforts to measure implementation and study how such implementation across behavioral and academic domains relates are limited. In the current study, we used MTSS implementation data from 225 schools in a U.S. Midwestern state to examine a factor structure of schoolwide MTSS implementation measures in behavioral and academic domains (reading and mathematics). Results suggest (a) a hierarchical factor model for behavioral and academic MTSS measures fits well, indicating that integrated behavioral and academic supports are driven by an overall implementation factor, and (b) the overall factor had no relation to school-level achievement. Implications for practice and future directions for research are discussed.

School context can shape relative intervention response in myriad ways due to factors, such as instructional quality, resource allocation, peer effects, and correlations between the school context and characteristics of enrolled students (e.g., higher-poverty students attending higher-poverty schools). In the current study, we used data from 16,000 U.S. Grade 3 students in a community-based supplemental reading intervention program to investigate the degree to which school context factors (percentage eligible for free/reduced-price lunch [FRPL], school-level achievement) relate to the differences in triannual reading fluency growth rates between students actively receiving supplemental intervention (active recipients) and those that formerly received intervention (and therefore only received general class instruction at this time; former recipients). Using Bayesian multilevel modeling, our findings indicate that school-level FRPL eligibility played a more prominent factor in growth rate differences between these two groups than school-level reading achievement. However, school-level reading achievement was much more strongly related to reading fluency differences between active and former intervention recipients at the beginning of the school year (when controlling for FRPL). Implications for investigating school-level heterogeneity in intervention response and sustainability are discussed.

Microplastics are ubiquitous environmental contaminants for which there are documented human exposures, but there is a paucity of research evaluating their impacts on human health. We conducted a rapid systematic review using the Navigation Guide systematic review method. We searched four databases in July 2022 and April 2024 with no restriction on the date. We included studies using predefined eligibility criteria that quantitatively examined the association of microplastic exposure with any health outcomes. We amended the eligibility criteria after screening studies and prioritized digestive, reproductive, and respiratory outcomes for further evaluation. We included three human observational studies examining reproductive (n = 2) and respiratory (n = 1) outcomes and 28 animal studies examining reproductive (n = 11), respiratory (n = 7), and digestive (n = 10) outcomes. For reproductive outcomes (sperm quality) and digestive outcomes (immunosuppresion) we rated overall body evidence as high quality and concluded microplastic exposure is suspected to adversely impact them. For reproductive outcomes (female follicles and reproductive hormones), digestive outcomes (gross or microanatomic colon/small intestine effects, alters cell proliferation and cell death, and chronic inflammation), and respiratory outcomes (pulmonary function, lung injury, chronic inflammation, and oxidative stress) we rated the overall body of evidence as moderate quality and concluded microplastic exposure is suspected to adversely impact them. We concluded that exposure to microplastics is unclassifiable for birth outcomes and gestational age in humans on the basis of the low and very low quality of the evidence. We concluded that microplastics are suspected to harm human reproductive, digestive, and respiratory health, with a suggested link to colon and lung cancer. Future research on microplastics should investigate additional health outcomes impacted by microplastic exposure and identify strategies to reduce exposure.

We used triannual reading curriculum-based measurement of oral reading fluency data from 11,834 U.S. students in Grades 2 and 3 enrolled in an evidence-based Tier 2 reading intervention program (Reading Corps) to investigate the extent to which family involvement in the intervention might buffer against a negative effect of lower intervention dosage. The relation between family involvement in Reading Corps and growth in oral reading fluency was stronger when students spent fewer hours in tutoring, suggesting that family involvement in tiered reading intervention can compensate for receiving less intervention dosage. There was noticeable variation in this effect across tutors, suggestive of tutor-level heterogeneity of this relation. The relation between sending family engagement materials to families and the materials that are returned to tutors also substantially varied across tutors. We discuss findings in terms practical significance for school-based academic intervention systems. We highlight limitations and opportunities for future directions as well.

BACKGROUND: Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. METHODS: Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. DISCUSSION: This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

The University of California San Diego (UCSD) School of Medicine (SOM) is transitioning its third-year primary care curriculum from a year-long longitudinal primary care course to a three-week clerkship in Family Medicine (FM). Additionally, there is a lack of FM physicians in the US, and limited information on what factors affect students’ decisions to enter FM. The aim of this pilot study is to analyze the effects of introducing sub-specialty tracks within an FM clerkship on student attitudes towards FM. A limiting factor for students within FM clerkships is that often they are not exposed to the full spectrum of FM. The aim of the tracks is to demonstrate that there are many FM clinicians practicing what may be considered more specialized aspects of primary care, including sports, sexual and reproductive health, and lifestyle and integrative medicine. There is a pre-existing family medicine clerkship for fourth-year medical students (FPM 426), which will serve as the pilot program. Three subspecialty tracks (sports medicine, sexual and reproductive health, and lifestyle and integrative medicine) will be introduced. Students will be assigned a track based on interest. A student will not be assigned a track if they did not express interest or if there was insufficient space to accommodate. Students not assigned a track will serve as the control group for this study. At the end of the clerkship, students will be emailed an anonymous survey to complete, and time will be provided during the course to complete the survey. The post-clerkship survey will collect data on students’ experience of the clerkship and perceptions of FM. We hypothesize that students placed in the subspecialty tracks will report a better experience during their clerkship and an expanded understanding of the scope of practice of family physicians. Comparisons will be made between students within tracks and those not in a track, who will serve as the control.

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates which support the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the approximately 200 structurally diverse HMOs at scale has proved difficult. Here we produce a diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high-value and complex HMOs, such as lacto-N-fucopentaose I. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement with potential applications in adult and infant health. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the low-cost and sustainable production of HMOs.

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.

Hippocampal pyramidal cells possess elaborate dendritic arbors with distinct domains that are targeted with input-specific synaptic sites. This synaptic arrangement is facilitated by synaptic cell-adhesion molecules that act as recognition elements to connect presynaptic and postsynaptic neurons. In this study, we investigate the organization of the synaptic recognition molecule latrophilin-2 at the surface of pyramidal neurons classified by spatial positioning and action potential firing patterns. Surveying two hippocampal neurons that highly express latrophilin-2, late-bursting CA1 pyramidal cells and early-bursting subiculum pyramidal cells, we found the molecule to be differentially positioned on their respective dendritic compartments. Investigating this latrophilin-2 positioning at the synaptic level, we found that the molecule is not present within either the pre- or postsynaptic terminal but rather is tightly coupled to synapses at a perisynaptic location. Together these findings indicate that hippocampal latrophilin-2 distribution patterning is cell-type specific, and requires multiple postsynaptic neurons for its synaptic localization.

Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.

OBJECTIVE: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS). METHODS: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines. The following subjects will be tested: 1) neurotypical controls; 2) patients with symptomatology suggestive for early ALS but not meeting probable or definite ALS by Awaji Criteria; 3) patients with a known ALS mimic. The recruitment period is between 3/31/2021 and 12/31/2025. Written consent will be sought from the subject or the subjects legally authorized representative during enrollment. RESULTS: The endpoints of this study include: 1) whether adding IMC to the Awaji ALS criteria improve its sensitivity in early ALS and can allow for diagnosis earlier; 2) constructing a database of IMC across different ages, genders, and ethnicities. SIGNIFICANCE: This study may validate a new inexpensive, painless, and widely available tool for the diagnosis of ALS.

Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.

OBJECTIVE: Patient memory for treatment is emerging as an important transdiagnostic mechanism of treatment outcomes. However, patient memory for treatment is limited. The Memory Support Intervention was developed to improve patient memory for treatment and thereby strengthen treatment outcomes. In this secondary analysis, the primary, preregistered aim was to test the 12-month follow-up outcomes of the Memory Support Intervention when used with cognitive therapy (CT + MS) for major depressive disorder, relative to CT-as-usual. The secondary, exploratory aim was to investigate opportunities to improve efficacy of the Memory Support Intervention. METHOD: Adults (N = 178) with major depressive disorder were randomized to CT-as-usual or CT + MS. Therapist use of memory support and patient memory for treatment, depression symptoms, and overall functioning were measured in blind assessments. RESULTS: Findings did not support differences between treatment conditions at 12-month follow-up. Therapists used memory support strategies with a narrow subset of treatment contents, and similarly, patients recalled a narrow subset of treatment contents. CONCLUSIONS: The findings highlight ways to strengthen the efficacy of the Memory Support Intervention, such as applying memory support strategies across a wider variety of treatment contents, which in turn, may boost patient recall and outcomes.

Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic Bacteroidaceae species. Animals were fed a Western diet supplemented with pea fiber. After community assembly, an inducible CRISPR-based system was used to selectively and temporarily reduce the absolute abundance of Bacteroides thetaiotaomicron or B. cellulosilyticus by 10- to 60-fold. Each knockdown resulted in specific, reproducible increases in the abundances of other Bacteroidaceae and dynamic alterations in their expression of genes involved in glycan utilization. Emergence of these alternate consumers was associated with preservation of community saccharolytic activity. Using an inducible system for CRISPR base editing in vitro, we disrupted translation of transporters critical for utilizing dietary polysaccharides in Phocaeicola vulgatus, a B. cellulosilyticus knockdown-responsive taxon. In vitro and in vivo tests of the resulting P. vulgatus mutants allowed us to further characterize mechanisms associated with its increased fitness after knockdown. In principle, the approach described can be applied to study utilization of a range of nutrients and to preclinical efforts designed to develop therapeutic strategies for precision manipulation of microbial communities.

Open science practices such as posting data or code and pre-registering analyses are increasingly prescribed and debated in the applied sciences, but the actual popularity and lifetime usage of these practices remain unknown. This study provides an assessment of attitudes toward, use of, and perceived norms regarding open science practices from a sample of authors published in top-10 (most-cited) journals and PhD students in top-20 ranked North American departments from four major social science disciplines: economics, political science, psychology, and sociology. We observe largely favorable private attitudes toward widespread lifetime usage (meaning that a researcher has used a particular practice at least once) of open science practices. As of 2020, nearly 90% of scholars had ever used at least one such practice. Support for posting data or code online is higher (88% overall support and nearly at the ceiling in some fields) than support for pre-registration (58% overall). With respect to norms, there is evidence that the scholars in our sample appear to underestimate the use of open science practices in their field. We also document that the reported lifetime prevalence of open science practices increased from 49% in 2010 to 87% a decade later.

OBJECTIVES: Mental health care clinicians training in treating sleep problems was investigated. We examined clinicians (1) prior training in providing treatment for sleep problems, (2) interest in receiving training in treatment for sleep problems, and (3) perceptions of the importance of treating sleep problems and interest in incorporating sleep treatments into their practices. METHODS: An online survey was completed by 137 clinicians. RESULTS: The majority of clinicians (61.31%) reported receiving prior training in treating sleep problems, most commonly in the form of a workshop and after receiving a graduate degree. Most clinicians reported interest in receiving further training in treating sleep problems. Clinicians reported that the majority (66.67%) of their clients experience sleep problems, yet reported that they address sleep with fewer than half of clients. Addressing sleep in treatment was rated as somewhat to very important and most clinicians indicated further interest in receiving training in treating sleep. CONCLUSIONS: Mental health care clinicians receive limited training in treating sleep problems. As clinicians are interested in gaining further training to address sleep concerns within their clinical practice, training programs and continuing education programs should consider increasing the amount of programming in sleep treatment and assessment.