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Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.

This qualitative study explores intersections between U.S. language policies (federal and state-level) and instructional practice in early childhood settings for multilingual learners (MLs). We draw on the theoretical framework of culturally sustaining pedagogy to engage in a critical content analysis of U.S. federal and state-level policy from three states. In the cross-analysis of policy and pedagogy, we also examine data from ML teachers' instructional artifacts, open-ended surveys, and semi-structured interviews. The findings provide insight into how educators draw on culturally sustaining and asset-based approaches to teaching MLs. Additionally, findings demonstrate how ML teachers negotiate policies that prioritize English language and academic achievement and those focused on teaching discrete language skills (i.e., phonological awareness and phonics) by continually centering children's linguistic and cultural repertoires. Participants in this study advocated for linguistic pluralism in their instruction and as leaders in their schools and communities. The study further illustrates how policies mandate specific aspects of instruction and leave linguistically inclusive pedagogies to individual educators. This tension can be beneficial for educators' freedom in interpreting and navigating the policy in their classroom but can also create disparities for young learners and their literacy opportunities. The significance implies a need for revisiting early childhood ML teachers' role in creating policy that fosters linguistic and cultural inclusion in language and literacy teaching.

UNLABELLED: Vibrio cholerae, the causative agent of the diarrheal disease cholera, poses an ongoing health threat due to its wide repertoire of horizontally acquired elements (HAEs) and virulence factors. New clinical isolates of the bacterium with improved fitness abilities, often associated with HAEs, frequently emerge. The appropriate control and expression of such genetic elements is critical for the bacteria to thrive in the different environmental niches they occupy. H-NS, the histone-like nucleoid structuring protein, is the best-studied xenogeneic silencer of HAEs in gamma-proteobacteria. Although H-NS and other highly abundant nucleoid-associated proteins (NAPs) have been shown to play important roles in regulating HAEs and virulence in model bacteria, we still lack a comprehensive understanding of how different NAPs modulate transcription in V. cholerae. By obtaining genome-wide measurements of protein occupancy and active transcription in a clinical isolate of V. cholerae, harboring recently discovered HAEs encoding for phage defense systems, we show that a lack of H-NS causes a robust increase in the expression of genes found in many HAEs. We further found that TsrA, a protein with partial homology to H-NS, regulates virulence genes primarily through modulation of H-NS activity. We also identified few sites that are affected by TsrA independently of H-NS, suggesting TsrA may act with diverse regulatory mechanisms. Our results demonstrate how the combinatorial activity of NAPs is employed by a clinical isolate of an important pathogen to regulate recently discovered HAEs. IMPORTANCE: New strains of the bacterial pathogen Vibrio cholerae, bearing novel horizontally acquired elements (HAEs), frequently emerge. HAEs provide beneficial traits to the bacterium, such as antibiotic resistance and defense against invading bacteriophages. Xenogeneic silencers are proteins that help bacteria harness new HAEs and silence those HAEs until they are needed. H-NS is the best-studied xenogeneic silencer; it is one of the nucleoid-associated proteins (NAPs) in gamma-proteobacteria and is responsible for the proper regulation of HAEs within the bacterial transcriptional network. We studied the effects of H-NS and other NAPs on the HAEs of a clinical isolate of V. cholerae. Importantly, we found that H-NS partners with a small and poorly characterized protein, TsrA, to help domesticate new HAEs involved in bacterial survival and in causing disease. A proper understanding of the regulatory state in emerging isolates of V. cholerae will provide improved therapies against new isolates of the pathogen.

IntroductionEmerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.MethodsWe used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).ResultsEighteen-month female (but not male) hAβ-KI microbiomes were distinct from WT microbiomes, with AD genotype accounting for 18% of the variance by permutational multivariate analysis of variance (PERMANOVA). Metabolomic diversity differences were observed in females, however no individual metabolites were differentially abundant. hAβ-KI mice microbiomes were distinguishable from 3xTg-AD animals (81% accuracy by random forest modeling), with separation primarily driven by Romboutsia ilealis and Turicibacter species. Microbiomes were highly cage specific, with cage assignment accounting for more than 40% of the PERMANOVA variance between the groups.DiscussionThese findings highlight a sex-dependent variation in the microbiomes of hAβ-KI mice and underscore the importance of considering the microbiome when designing studies that use murine models for AD.HighlightsMicrobial diversity and the abundance of several species differed in human amyloid beta knock-in (hAβ-KI) females but not males. Correlations to Alzheimer's disease (AD) genotype were stronger for the microbiome than the metabolome. Microbiomes from hAβ-KI mice were distinct from 3xTg-AD mice. Cage effects accounted for most of the variance in the microbiome and metabolome.

Water conservation and appliance efficiency standards programs in the United States encounter challenges in assessing their economic impacts due to the limited availability of representative water and wastewater price data. In this report, we review water and sewage price and price trend data from two established sources: the Water and Sewerage Consumer Price Index from the U.S. Bureau of Labor Statistics and water and wastewater rate survey data from Raftelis/American Water Works Association (AWWA). By leveraging historical Raftelis/AWWA data, we develop an empirical approach to (1) interpolate the data by establishing regional trends that capture the pace of price increases as transparently and consistently as possible, and (2) extrapolate prices for future years for the purpose of quantifying water cost savings resulting from policy decisions. Additionally, our prediction models offer a means to verify data consistency when new rate survey data from Raftelis/AWWA become available.

One teacher preparation program worked toward improving teacher preparation by strengthening the network of support among teacher candidates, mentor teachers, and teacher educators. Drawing on third-generation cultural historical activity theory, we modeled activity systems framing the experiences of teacher candidates and contradictions within and between activity systems. Using cycles of learning over one year, we learned 1) how direct and indirect activity systems interact and 2) how meaningful and influential contradictions erupt between two systems. Contradictions included the theory-practice divide alongside the implementation of equity supports, the teacher candidates' navigation of their role, and shifting rules during the transition to distance learning across contexts during COVID-19. This study has implications for enacting dynamic, program-wide change in teacher education programs.

This paper explores teacher enjoyment and the notion of the intentional teacher in early childhood education. The research is part of a wider interrogation challenging existing discourses associated with the intentional teacher. A mixed-method research design was used to gather perspectives from early childhood teachers in relation to their experiences of enjoyment in their teaching practices and the connection with being an intentional teacher. Findings from participant responses highlight important aspects associated with early childhood teacher enjoyment and intentionality. The connection between enjoyment and intentional teaching was reflected in reports of ways of doing or acting, as well as in ways of being associated with teacher identity. Connection was made between experiences of enjoyment and intentional teaching through contributing, adding value, and personal impact. Association was also made with promoting social justice. Whilst small in scale, the research highlights the importance of challenging existing and potentially limiting discourses of the intentional teacher by giving attention to how intentional teaching is generated, as an internal encounter associated with ways of being and becoming and the role that enjoyment plays within this process.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.

The nation faces tremendous costs required to maintain and improve its water and wastewater infrastructure. Effective management of water delivery and treatment systems would benefit from a regular national water demand data collection effort that captures consumption by economic sector as well as by end use. A water demand survey would provide the data necessary to better understand water demand trends, and ultimately to assess implications for water infrastructure needs and the U.S. economy. This report summarizes current publicly available water demand information and recommends data parameters for a national water demand survey.

A 4-year-old male neutered Boston Terrier was presented with status epilepticus. He was diagnosed with idiopathic epilepsy and hospitalized with supportive care. During hospitalization, the patient developed both supraventricular and ventricular arrhythmias as well as focal left ventricular dyskinesis. Cardiac troponin I was significantly increased, which was supportive of myocardial damage. Neurogenic stunned myocardium was suspected, and the patient was treated and responded to esmolol. Follow-up echocardiography demonstrated the resolution of the ventricular dyskinesia. This report describes the clinical presentation, diagnostic findings, treatment, management, and outcome of the first reported case of naturally occurring neurogenic stunned myocardium in a dog. Electrocardiogram monitoring, cardiac troponin I, and echocardiography should be considered in patients presenting with seizure activity, especially when exhibiting cluster seizures or in status epilepticus.

Disparate impact rules are formally neutral but indirectly discriminate against protected groups (i.e., by targeting a characteristic that is more prevalent in a given group). Because these rules are not obviously malicious, they have been widely enacted to circumvent policies against explicit discrimination. In a series of four experiments, we show that adults and children are sensitive to the moral implications of disparate impact rules. However, we also find that they are more accepting of these rules when strong justification is provided, compared to rules with no justification. Crucially, demographic differences also impact people's judgments of disparate impact rules and their creators. We find that conservatives and those from groups not directly affected by the rule tend to be more accepting of it. By studying people's reasoning about disparate impact rules, this work aims to identify the mechanisms by which these rules may evade detection. Finally, we discuss how these insights may inform the development of interventions that highlight the problematic effects of indirectly discriminatory policies.

The ability to predict and understand other people's actions is critical for real-world social behavior. Here we hypothesized that representations of social roles (e.g., cashier, mechanic, doctor) enable people to build rapid expectations about what others know and how they might act. Using a self-paced reading paradigm and a variety of everyday roles, we show that the mere mention of a role (e.g., “mechanic”) supports real time expectations about what the person will do (e.g., in the mechanic case, take your car keys but not your cellphone) and the knowledge they might possess (e.g., in the mechanic case, having private information about your car). Moreover, people reported more surprisal when the events deviated from role expectations, and they were more likely to misremember what happened. Our results suggest that roles are a powerful route for social understanding that has been previously understudied in social cognition.

OBJECTIVE: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. DATA SOURCES: Publicly available FDA data on drugs and devices approved in 2022. REVIEW METHODS: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgerys (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. CONCLUSION: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. IMPLICATIONS FOR PRACTICE: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.

Abstract Background Rates of cocaine use disorder (CUD) among men who have sex with men (MSM) are high and rising. Among MSM, cocaine use is associated with negative socioeconomic, medical, and psychological outcomes. There are no FDA-approved pharmacotherapy options to treat CUD, and psychosocial interventions demonstrate limited efficacy. While there have been numerous trials evaluating possible medications for CUD, there is a scarcity of qualitative data on the barriers and facilitators of medication-assisted treatment. Methods Semi-structured interviews were conducted with 16 participants enrolled in a phase II randomized control trial evaluating extended-release lorcaserin among MSM with CUD. Participants were asked about their motivations for enrolling in the study, attitudes towards taking a medication for CUD, barriers and facilitators of study pill adherence, and their general study experience. Interviews were analyzed using an inductive and exploratory approach to thematic analysis. Results Participants were highly motivated to reduce cocaine use and viewed pharmacotherapy as a viable and desirable treatment option. Pharmacotherapy was seen as having fewer access and adherence structural barriers compared to existing psychosocial therapies. Medication reminders facilitated pill taking, while side effects, travel, and active substance use presented barriers to study pill adherence. Disclosure of study participation within social networks was variable pointing to anticipated substance use and treatment stigma. Conclusions Our study highlights important factors affecting the acceptability and uptake of medication-assisted treatment for CUD among a diverse sample of MSM. These findings can help guide the development and implementation of future pharmacotherapy options for CUD and other substance use disorders in this key population.

Methodologies for identifying atmospheric oxidized mercury (HgII) compounds, including particulate-bound HgII (HgII(p)) and gaseous oxidized mercury (HgII(g)), by mass spectrometry are currently under development. This method requires preconcentration of HgII for analysis due to high instrument detection limits relative to ambient HgII concentrations. The objective of this work was to identify and test materials for quantitative capture of HgII from the gas phase and to suggest potential surfaces onto which HgII can be collected, thermally desorbed, and characterized using mass spectrometry methods. From the literature, several compounds were identified as potential sorbent materials and tested in the laboratory for uptake of gaseous elemental mercury (Hg0) and HgII(g) (permeated from a HgBr2 salt source). Chitosan, α-Al2O3, and γ-Al2O3 demonstrated HgII(g) capture in ambient air laboratory tests, without sorbing Hg0 under the same conditions. When compared to cation exchange membranes (CEMs), chitosan captured a comparable quantity of HgII(g), while ≤90 % of loaded HgII(g) was recovered from α-Al2O3 and γ-Al2O3. When deployed in the field, the capture efficiency of chitosan decreased compared to CEMs, indicating that environmental conditions impacted the sorption efficiency of this material. The poor recovery of HgII from the tested materials compared to CEMs in the field indicates that further identification and exploration of alternative sorbent materials are required to advance atmospheric mercury chemistry analysis by mass spectrometry methods.

Purpose: There is an urgent need for teacher preparation programs to equip teachers to teach in innovative and transformative ways, meeting the needs of diverse learners. Coaching is an instrumental tool for supporting change and development, especially in contexts with decentralized teacher preparation guidelines. Design/methodology/approach: This multicase study examines cross-institutional programmatic innovations for coaching teacher candidates (TCs) and centering equity using improvement science and equity coaching. The authors explore the networked improvement community's (NIC's) examination of problems of practice through plan-do-study-act cycles in three coaching contexts within and across seven institutions. Findings: Qualitative methods revealed that adapting coaching protocols can center equity and build equity-focused practices. This work highlights revisions to coaching within and across teacher preparation programs (TPPs), which the authors hope inspires extending equity-centered coaching and improvement science to new contexts. This cross-case analysis revealed program innovations for coaches, digital technologies and alignment. Practical implications: This study addresses ongoing challenges faced by TPPs in the United States, including TCs' understandings of equity in teaching and decentralized teacher preparation that results in varied and incongruent understandings about quality teaching. This study builds on previous scholarship that examines shifts in coaching practices by disrupting silos in TPPs as examined innovations. Originality/value: The paper offers a unique view of cross-institutional collaboration in coaching to improve transformative teaching experiences in teacher preparation field experiences.

Early differences in sensory responsiveness may contribute to difficulties with communication among autistic children; however, this theory has not been longitudinally assessed in infants at increased familial versus general population-level likelihood for autism (Sibs-autism vs. Sibs-NA) using a comprehensive battery of sensory responsiveness and communication. In a sample of 40 infants (20 Sibs-autism, of whom six were later diagnosed with autism; 20 Sibs-NA), we tested (a) associations between sensory responsiveness at 12-18 months and communication 9 months later and (b) evaluated whether such associations were moderated by sibling group, autism diagnosis, or age. We found negative zero-order correlations between sensory responsiveness (i.e., caregiver reported hyperresponsiveness and hyporesponsiveness; an observational measure of hyperresponsiveness) and later communication. Additionally, caregiver reported sensory seeking was negatively associated with later expressive communication only in Sibs-NA. Limitations include our relatively small sample size of infants diagnosed with autism. Implications for future research are discussed.

Across three pre-registered studies (n = 221 4-9-year olds, 51% female; 218 parents, 80% female; working- and middle-class backgrounds; data collected during 2019-2021) conducted in the United States (Studies 1-2; 74% White) and China (Study 3; 100% Asian), we document the emergence of a preference for "strivers." Beginning at age 7, strivers (who work really hard) were favored over naturals (who are really smart) in both cultures (R[superscript 2] ranging 0.03-0.11). We explored several lay beliefs surrounding this preference. Beliefs about outcomes and the controllability of effort predicted the striver preference: Children who expected strivers to be more successful than naturals and believed effort was more controllable than talent preferred strivers more. Implications of the striver preference in education and beyond are discussed.

This article examines a culturally sustaining approach to learning about and enacting multimodal literacy instruction that was developed during a field-based reading methods course for elementary preservice teachers. Despite a large body of work exploring preservice teachers' learning about multimodal literacies, few studies have explored their experiences incorporating multimodal literacies from an explicitly culturally sustaining lens, nor examined learning about multimodal instruction in field-based settings. In this qualitative case study, we explore the ways in which one preservice teacher's experiences in a field-based reading methods course impacted her conception of multimodal literacies and her understanding of the cultural and semiotic resources of diverse students. The findings detail the culturally sustaining, multimodal literacy instruction that emerged from a mentoring dyad of the focal preservice teacher and a second-grade multilingual student, the preservice teacher's developing conceptions of multimodal literacy, and the conditions of learning that facilitated her teaching and learning.

Across two preregistered studies with children (3-12-year-olds; N = 356) and adults (N = 262) from the United States, we find robust expectations for intergroup empathic biases. Participants predicted that people would feel better about ingroup fortunes than outgroup fortunes and worse about ingroup misfortunes than outgroup misfortunes. Expectations of empathic bias were stronger when there was animosity and weaker when there was fondness between groups. The largest developmental differences emerged in participants' expectations about how others feel about outgroup misfortunes, particularly when there was intergroup animosity. Whereas young children (3-5-year-olds) generally expected people to feel empathy for the outgroup (regardless of the relationship between the groups), older children (9-12-year-olds) and adults expected Schadenfreude (feeling good when an outgroup experiences a misfortune) when the groups disliked one another. Overall, expectations of empathic biases emerge early but may be weaker when there are positive intergroup relationships. (PsycInfo Database Record (c) 2023 APA, all rights reserved).