Search

Study objectiveMost long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms.MethodsThis study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID illness were measured. Prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms were also assessed.ResultsOf 1,618 eligible patients, 1455 (89.9%) agreed to participate, including 33.4% African Americans and 30.9% Latino/a. Of the patients, 17.1% lacked primary care. In total, 33.2% had persistent COVID-19 symptoms lasting >1 month, and 20.3% had symptoms >3 months. Moreover, 49.8% with long COVID symptoms missed work/school because of symptoms; 30.3% of all participants and 33.5% of participants who had long COVID symptoms had prior awareness and self-declared understanding of long COVID. Characteristics associated with poor understanding of long COVID were African American race (adjusted odds ratio [aOR] 3.68, 95% confidence interval [CI] 2.66 to 5.09) and Latino/a ethnicity (aOR 3.16, 95% CI 2.15 to 4.64). Participants lacking primary care were less likely to have received long COVID care (24.6% versus 51.2%; difference 26.6%; 95% CI 13.7% to 36.9%).ConclusionsDespite high prevalence and impact on school/work attendance of long COVID symptoms, most of this ED population had limited awareness and self-declared understanding of long COVID, and many had not received care. EDs should consider the development of protocols for diagnosis, education, and treatment of long COVID illness.

At-risk urban youth benefit from mentored activities. The Champion Academy (CA) is a youth mentoring program for high risk urban youth. We used a community based participatory research (CBPR) approach to explore: 1) youth perspectives on health and wellness, EH and EJ; and 2) community perspectives on the intersection of structural racism, health equity, and youth health and wellness. We surveyed CA participants to assess health and wellness and conducted youth and adult interviews and focus groups to understand what environmental factors impact their daily lives. In 45 youth surveys, 64% reported enjoying time outdoors; 45% had concerns about pollution. The five youth focus groups (N = 49) and individual interviews (N = 10) identified 3 themes: (1) pervasive community violence; (2) systemic racism, and (3) limited power to make change. The two adult focus groups (N = 7) and individual interviews (N = 5) identified: 1) normalization of environmental problems and violence; 2) youth prioritize survival over health and wellness; 3) CA education should emphasize relevance to youth; 4) access to healthy foods is limited; and 5) mindsets need to change. In sum, youth's real-life environmental concerns must be addressed as part of more typical EH concerns.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

Abstract Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit active inference and reinforcement learning computational models to a novel two-armed bandit reversal learning task capable of capturing engagement behaviour in rats. The model revealed that after receiving psilocybin, rats achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.

Abstract Background Despite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19. Results Here we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na+/K+-ATPase α3 isoform is critical for OLN suppression of GRP78 stress induction. OLN, in nanomolar range, enhances apoptosis, sensitizes colorectal cancer cells to chemotherapeutic agents, and reduces the viability of patient-derived colon cancer organoids. Likewise, OLN, suppresses GRP78 expression and impedes tumor growth in an orthotopic breast cancer xenograft model. Furthermore, OLN blocks infection by SARS-CoV-2 and its variants and enhances existing anti-viral therapies. Notably, GRP78 overexpression mitigates OLN-mediated cancer cell apoptotic onset and suppression of virus release. Conclusion Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

Despite widespread commitment to inclusive education as government policy, global progress in the last two decades has been slow and uneven. This article explores the relationship between policy and its enactment to examine what conditions make inclusion available as a course of action within education systems. Focusing on learners with additional learning needs, evidence from the Welsh context is presented in relation to two policy turns in the last decade, the most recent of which is a turn towards a Fourth Way "professional capital approach" that appears to signal movement towards more inclusive education. It is noted that, at the level of practice and practitioner beliefs about learners with additional learning needs, these policy movements appear to have had remarkably little impact. Drawing on a hybrid model of analysis, we argue that the collective agency needed for inclusion requires an account of the belief systems of a range of policy actors, particularly in education systems where hierarchies of learners are fundamentally upheld. Using evidence from educational reform in Wales, we describe how conditions for collective agency for inclusion may be experienced as unavailable within education systems.

BackgroundIn 2020, the Veterans' Affairs (VA) healthcare system deployed a heart failure (HF) dashboard for use nationally. The initial version was notably imprecise and unreliable for the identification of HF subtypes. We describe the development and subsequent optimization of the VA national HF dashboard.Materials and methodsThis study describes the stepwise process for improving the accuracy of the VA national HF dashboard, including defining the initial dashboard, improvement of case definitions, utilization of natural language processing for patient identification, and incorporation of an imaging quality hierarchy model. Optimization further included evaluating whether to require concurrent ICD-codes for inclusion in the dashboard and assessing various imaging modalities for patient characterization.ResultsThrough multiple rounds of optimization, the dashboard accuracy (defined as the proportion of true results to the total population) was improved from 54.1% to 89.2% for the identification of HF with reduced ejection fraction (HFrEF) and from 53.9% to 88.0% for the identification of HF with preserved ejection fraction (HFpEF). To align with current guidelines, HF with mildly reduced ejection fraction (HFmrEF) was added to the dashboard output with 88.0% accuracy.ConclusionsThe inclusion of an imaging quality hierarchy model and natural language processing algorithm improved the accuracy of the VA national HF dashboard. The revised dashboard informatics algorithm has higher utilization rates and improved reliability for population health management.

It has become conventional wisdom to say that rural America is (and rural Americans are) in “crisis,” and this has generated a cottage industry of commentary from journalists, academics, politicians, policy makers, and others. Sometimes the story of crisis is economic: jobs harder and harder to find in the rural pockets of the nation. Sometimes it is social: rural isolation and desperation that lead to drug addiction and suicide. Whatever its cause, the result has been that rural America has been “left behind,” to borrow from the title of sociologist Robert Wuthnow's recent book on the topic. And the sub-title of his book encapsulates the politics this crisis has generated: decline and rage. This article interrogates the narrative of crisis and decline by historicizing it more deeply, by examining how enduring rural mythologies continue to shape our discourse about rural places, and to argue that far from being “left behind” in the national parade, rural America has often been leading it.

PURPOSE: Prior studies have identified a significant relationship between internalized transphobia and poor mental health among transgender and gender-diverse (TGD) adults; however, this relationship has not been extensively examined among youth. Further, little research has sought to explore protective factors, such as identity pride, and their influence on this relationship. We examined the association between internalized transphobia and depression and anxiety symptoms among TGD youth and explored the moderating role of gender identity pride on these associations. METHODS: Participants were 315 TGD youth ages 12-20 years (mean = 16; standard deviation = 1.89) seeking gender-affirming hormone treatment at one of four major pediatric hospitals across the United States. At the time of enrollment, participants were naïve to gender-affirming hormone treatment. Participants self-reported mental health, internalized transphobia, and identity pride. Multiple regression models were used with depression and anxiety symptoms as outcomes and age, designated sex at birth, and perceived parental support included as covariates. RESULTS: Greater internalized transphobia was associated with greater depressive symptoms, and gender identity pride moderated this relationship, such that greater gender identity pride was associated with fewer depressive symptoms. Greater internalized transphobia was significantly associated with greater anxiety symptoms; no moderation effect was observed for this relationship. DISCUSSION: Gender identity pride influenced mental health symptoms for youth experiencing internalized transphobia and represents a potential key protective factor. These results support efforts to further develop, test, and implement clinical inventions to bolster identity pride for TGD youth.

Ice-associated seals rely on sea ice for a variety of activities, including pupping, breeding, molting, and resting. In the Arctic, many of these activities occur in spring (April through June) as sea ice begins to melt and retreat northward. Rapid acceleration of climate change in Arctic ecosystems is therefore of concern as the quantity and quality of suitable habitat is forecast to decrease. Robust estimates of seal population abundance are needed to properly monitor the impacts of these changes over time. Aerial surveys of seals on ice are an efficient method for counting seals but must be paired with estimates of the proportion of seals out of the water to derive population abundance. In this paper, we use hourly percent-dry data from satellite-linked bio-loggers deployed between 2005 and 2021 to quantify the proportion of seals hauled out on ice. This information is needed to accurately estimate abundance from aerial survey counts of ice-associated seals (i.e., to correct for the proportion of animals that are in the water, and so are not counted, while surveys are conducted). In addition to providing essential data for survey ‘availability’ calculations, our analysis also provides insights into the seasonal timing and environmental factors affecting haul-out behavior by ice-associated seals. We specifically focused on bearded (Erignathus barbatus), ribbon (Histriophoca fasciata), and spotted seals (Phoca largha) in the Bering and Chukchi seas. Because ringed seals (Phoca (pusa) hispida) can be out of the water but hidden from view in snow lairs analysis of their ‘availability’ to surveys requires special consideration; therefore, they were not included in this analysis. Using generalized linear mixed pseudo-models to properly account for temporal autocorrelation, we fit models with covariates of interest (e.g., day-of-year, solar hour, age and sex class, wind speed, barometric pressure, temperature, precipitation) to examine their ability to explain variation in haul-out probability. We found evidence for strong diel and within-season patterns in haul-out behavior, as well as strong weather effects (particularly wind and temperature). In general, seals were more likely to haul out on ice in the middle of the day and when wind speed was low and temperatures were higher. Haul-out probability increased through March and April, peaking in May and early June before declining again. The timing and frequency of haul-out events also varied based on species and age-sex class. For ribbon and spotted seals, models with year effects were highly supported, indicating that the timing and magnitude of haul-out behavior varied among years. However, we did not find broad evidence that haul-out timing was linked to annual sea-ice extent. Our analysis emphasizes the importance of accounting for seasonal and temporal variation in haul-out behavior, as well as associated environmental covariates, when interpreting the number of seals counted in aerial surveys.

Antimicrobial resistance (AMR) poses a global health crisis demanding innovative solutions. Traditional antibiotics, though pivotal over the past century in combating bacterial infections, face diminished efficacy against evolving bacterial defense mechanisms, especially in Gram‐negative strains. This study explores self‐assembled ionizable lipid nanoparticles (LNPs) with the incorporation of two ionizable lipid components (one cationic, one anionic) in nanocarriers for advanced antimicrobial drug delivery of the broad‐spectrum antibiotic Piperacillin (Pip). Incorporating cationic ionizable lipid ALC‐0315, recognized as a functional lipid in the Pfizer‐BioNTech mRNA‐based SARS‐CoV‐2 vaccine, into LNPs allowed mesophase transition, pH responsiveness, and ionization behavior in acidic environments found in sites of bacterial infections, to be studied using synchrotron small angle X‐ray scattering, dynamic light scattering, and a 2‐(p‐toluidino)‐6‐naphthalene sulfonic acid assay. Incorporating another anionic ionizable lipid, oleic acid not only modulates the LNPs’ physicochemical properties, such as size, internal phase nanostructure, and surface charge but also synergistically enhances the antimicrobial potency together with ALC‐0315 with a benefit enhancing permeability and fusion with bacterial membranes. This study introduces a strategy for tailoring ionizable lipid compositions in LNPs, providing a new approach to antimicrobial treatment contributing to the fight against AMR.

Objective:. The objective of this study was to measure potential associations between surgeon sex and number of days alive and at home (DAH). Background:. Patients treated by female surgeons appear to have lower rates of mortality, complications, readmissions, and healthcare costs when compared with male surgeons. DAH is a validated measure, shown to better capture the patient experience of postoperative recovery. Methods:. We conducted a retrospective study of adults (≥18 years of age) undergoing common surgeries between January 01, 2007 and December 31, 2019 in Ontario, Canada. The outcome measures were the number of DAH within 30-, 90-, and 365-days. The data was summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results:. During the study period, 1,165,711 individuals were included, of which 61.9% (N = 721,575) were female. Those managed by a female surgeon experienced a higher mean number of DAH when compared with male surgeons at 365 days (351.7 vs. 342.1 days; P < 0.001) and at each earlier time point. This remained consistent following adjustment for covariates, with patients of female surgeons experiencing a higher number of DAH at all time points, including at 365 days (343.2 [339.5–347.1] vs. 339.4 [335.9–343.0] days). Multivariable regression modeling revealed that patients of male surgeons had a significantly lower number of DAH versus female surgeons. Conclusions:. Patients of female surgeons experienced a higher number of DAH when compared with those treated by male surgeons at all time points. More time spent at home after surgery may in turn lower costs of care, resource utilization, and potentially improve quality of life. Further studies are needed to examine these findings across other care contexts.

Commercially-available location-based services (LBS) data derived primarily from mobile devices may provide an alternative to surveys for monitoring physically-active transportation. Using Spearman correlation, we compared county-level metrics of walking and bicycling from StreetLight with metrics of physically-active commuting among U.S. workers from the American Community Survey. Our strongest pair of metrics ranked counties (n = 298) similarly for walking (rho = 0.53 [95% CI: 0.44-0.61]) and bicycling (rho = 0.61 [0.53-0.67]). Correlations were higher for denser and more urban counties. LBS data may offer public health and transportation professionals timely information on walking and bicycling behavior at finer geographic scales than some existing surveys.

Purpose: Culturally responsive teaching (CRT) is a recurring topic in preservice teacher and special education personnel training, especially as academic institutions work to implement anti-racist and anti-oppressive teaching pedagogies. These methods of instruction, specifically in the areas of language and literacy, can be implemented by programs that understand the needs of the Indigenous students that their trainees or students will eventually serve. Academic institutions must transform their teaching and mentoring approach to better prepare educators and clinicians who engage with Indigenous communities. Method: This tutorial includes a critical review and will focus on the Diné traditional perspectives of Sa'ah Naagháí Bik'eh Hózhóón (SNBH), as it applies to the educational experiences of Diné students. The principle, which represents the process of lifelong learning and reflection, will be used as a model for how Indigenous epistemologies can be used within a decolonized educational philosophy, Red Pedagogy, to improve language and literacy instruction for young Indigenous children. Results: American Indian (AIs; Indigenous) students start school with unique heritages and diverse learning experiences that influence their learning styles. Often, the formal Western education experience beginning in early childhood and elementary program provides a cultural shock to young AI students, whose learning experiences are centered on oral storytelling, experiential and collective learning, and land-based experiences. As methods of CRT evolve and more AI professionals lead educational research, the Indigenization of teaching pedagogies is amplified. More importantly, the prioritization of Indigenous knowledge systems, including methods of teaching, is being centered as strategies toward decolonization of learning spaces. Discussion: The SNBH principle, which represents the process of lifelong learning and reflection, is a model for how Indigenous epistemologies can be used within a decolonized educational philosophy, Red Pedagogy, to improve language and literacy instruction for young Indigenous children.

Abstract Background Deforestation is an important driver of malaria dynamics, with a relevant impact on mosquito ecology, including larval habitat availability, blood-feeding behaviour, and peak biting time. The latter is one of several entomological metrics to evaluate vectorial capacity and effectiveness of disease control. This study aimed to test the effect of forest cover percentage on the peak biting time of Plasmodium-uninfected and infected Nyssorhynchus darlingi females. Methods Mosquitoes were captured utilizing human landing catch (HLC) in the peridomestic habitat in field collections carried out in the wet, wet-dry transition, and dry seasons from 2014 to 2017 in areas with active malaria transmission in Amazonian Brazil. The study locations were in rural settlements in areas with the mean annual malaria parasite incidence (Annual Parasite Incidence, API ≥ 30). All Ny. darlingi females were tested for Plasmodium spp. infection using real time PCR technique. Forest cover percentage was calculated for each collection site using QGIS v. 2.8 and was categorized in three distinct deforestation scenarios: (1) degraded, 70% forest cover. Results The highest number of uninfected female Ny. darlingi was found in degraded landscape-sites with forest cover 70% forest cover, a peak biting at 19:00–20:00, and in sites with 30–70% forest cover at 22:00–23:00. Conclusions Results of this study show empirically that degraded landscapes favour uninfected Ny. darlingi with a peak biting time at dusk (18:00–19:00), whereas partially degraded landscapes affect the behaviour of Plasmodium-infected Ny. darlingi by shifting its peak biting time towards hours after dark (21:00–23:00). In preserved sites, Plasmodium-infected Ny. darling i bite around dusk (18:00–19:00) and shortly after (19:00–20:00).

Abstract Background While a core aim of early intervention psychosis services (EIPS) is to prevent hospitalisation, many with a first episode of psychosis (FEP) will require inpatient care. We explored young people’s (YP) and their carers’ hospitalisation experiences prior to and during EIPS engagement and how factors across these services influenced these experiences. Methods Using purposive sampling, we recruited twenty-seven YP, all of whom had been involved with the hospital system at some stage, and twelve support persons (parents and partners of YP) from state and federally funded EIPS in Australia with different models of care and integration with secondary mental health care. Audio-recorded interviews were conducted face-to-face or via phone. A diverse research team (including lived experience, clinician, and academic researchers) used an inductive thematic analysis process. Results Four key themes were identified as influential in shaping participant’s hospital experiences and provide ideas for an approach to care that is improved by the effective coordination of that care, and includes this care being delivered in a trauma informed manner: (1) A two-way street: EIPS affected how participants experienced hospitalisation, and vice versa; (2) It’s about people: the quality and continuity of relationships participants had with staff, in hospital and at their EIPS, was central to their experience; (3) A gradual feeling of agency: participants viewed EIPS as both reducing involuntary care and supporting their self-management; and (4) Care coordination as navigation for the healthcare system: great when it works; frustrating when it breaks down. Conclusions Hospitalisation was viewed as a stressful and frequently traumatic event, but a approach to care founded on trust, transparency, and collaboration that is trauma-informed ameliorated this negative experience. Consistent EIPS care coordination was reported as essential in assisting YP and carers navigate the hospital system; conversely, discontinuity in EIPS staff and lack of integration of EIPS with hospital care undermined the positive impact of the EIPS care coordinator during hospitalisation. Care coordinator involvement as a facilitator, information provider, and collaborator in inpatient treatment decisions may improve the usefulness and meaningfulness of hospital interventions.

Abstract Background In malaria endemic regions of the Peruvian Amazon, rainfall together with river level and breeding site availability drive fluctuating vector mosquito abundance and human malaria cases, leading to temporal heterogeneity. The main variables influencing spatial transmission include location of communities, mosquito behaviour, land use/land cover, and human ecology/behaviour. The main objective was to evaluate seasonal and microgeographic biting behaviour of the malaria vector Nyssorhynchus (or Anopheles) darlingi in Amazonian Peru and to investigate effects of seasonality on malaria transmission. Methods We captured mosquitoes from 18:00 to 06:00 h using Human Landing Catch in two riverine (Lupuna, Santa Emilia) and two highway (El Triunfo, Nuevo Horizonte) communities indoors and outdoors from 8 houses per community, during the dry and rainy seasons from February 2016 to January 2017. We then estimated parity rate, daily survival and age of a portion of each collection of Ny. darlingi. All collected specimens of Ny. darlingi were tested for the presence of Plasmodium vivax or Plasmodium falciparum sporozoites using real-time PCR targeting the small subunit of the 18S rRNA. Results Abundance of Ny. darlingi varied across village, season, and biting behaviour (indoor vs outdoor), and was highly significant between rainy and dry seasons (p

ObjectiveThe purpose of this study was to characterize similarities and differences in HPV vaccine misinformation narratives present in the comment sections of top-performing initial creator posts across three social media platforms.MethodsA qualitative multi-method design was used to analyze comments collected from social media posts. A sample of 2996 comments were used for thematic analysis (identifying similar themes) and content analysis (identifying differences in comment type, opinion, and misinformation status).ResultsMisinformation was pervasive in comment sections. Cross-cutting misinformation themes included adverse reactions, unnecessary vaccine, conspiracy theories, and mistrust of authority. The proportion of comments related to these themes varied by platform. Initial creator posts crafted to be perceived as educational or with an anti-vaccine opinion had a higher proportion of misinformation in the comment sections. Facebook had the highest proportion of misinformation comments.ConclusionDifferences in the proportion of cross-cutting themes in the comment sections across platforms suggests the need for targeted communication strategies to counter misinformation narratives and support vaccine uptake.InnovationThis study is innovative due to its characterization of misinformation themes across three social media platforms using multiple qualitative methods to assess similarities and differences and focusing on conversations occurring within the comment sections.

The gut microbial ecosystem communicates bidirectionally with the brain in what is known as the gut-microbiome-brain axis. Bidirectional signaling occurs through several pathways including signaling via the vagus nerve, circulation of microbial metabolites, and immune activation. Alterations in the gut microbiota are implicated in Alzheimer’s disease (AD), a progressive neurodegenerative disease. Perturbations in gut microbial communities may affect pathways within the gut-microbiome-brain axis through altered production of microbial metabolites including ɣ-aminobutyric acid (GABA), the primary inhibitory mammalian neurotransmitter. GABA has been shown to act on gut integrity through modulation of gut mucins and tight junction proteins and may be involved in vagus nerve signal inhibition. The GABAergic signaling pathway has been shown to be dysregulated in AD, and may be responsive to interventions. Gut microbial production of GABA is of recent interest in neurological disorders, including AD. Bacteroides and Lactic Acid Bacteria (LAB), including Lactobacillus, are predominant producers of GABA. This review highlights how temporal alterations in gut microbial communities associated with AD may affect the GABAergic signaling pathway, intestinal barrier integrity, and AD-associated inflammation.

ABSTRACT The metabolic intimacy of symbiosis often demands the work of specialists. Natural products and defensive secondary metabolites can drive specificity by ensuring infection and propagation across host generations. But in contrast to bacteria, little is known about the diversity and distribution of natural product biosynthetic pathways among fungi and how they evolve to facilitate symbiosis and adaptation to their host environment. In this study, we define the secondary metabolism of Escovopsis and closely related genera, symbionts in the gardens of fungus-farming ants. We ask how the gain and loss of various biosynthetic pathways correspond to divergent lifestyles. Long-read sequencing allowed us to define the chromosomal features of representative Escovopsis strains, revealing highly reduced genomes composed of seven to eight chromosomes. The genomes are highly syntenic with macrosynteny decreasing with increasing phylogenetic distance, while maintaining a high degree of mesosynteny. An ancestral state reconstruction analysis of biosynthetic pathways revealed that, while many secondary metabolites are shared with non-ant-associated Sordariomycetes, 56 pathways are unique to the symbiotic genera. Reflecting adaptation to diverging ant agricultural systems, we observe that the stepwise acquisition of these pathways mirrors the ecological radiations of attine ants and the dynamic recruitment and replacement of their fungal cultivars. As different clades encode characteristic combinations of biosynthetic gene clusters, these delineating profiles provide important insights into the possible mechanisms underlying specificity between these symbionts and their fungal hosts. Collectively, our findings shed light on the evolutionary dynamic nature of secondary metabolism in Escovopsis and its allies, reflecting adaptation of the symbionts to an ancient agricultural system.IMPORTANCEMicrobial symbionts interact with their hosts and competitors through a remarkable array of secondary metabolites and natural products. Here, we highlight the highly streamlined genomic features of attine-associated fungal symbionts. The genomes of Escovopsis species, as well as species from other symbiont genera, many of which are common with the gardens of fungus-growing ants, are defined by seven chromosomes. Despite a high degree of metabolic conservation, we observe some variation in the symbionts’ potential to produce secondary metabolites. As the phylogenetic distribution of the encoding biosynthetic gene clusters coincides with attine transitions in agricultural systems, we highlight the likely role of these metabolites in mediating adaptation by a group of highly specialized symbionts.

Cationic lipids are crucial in medical and biotechnological applications including cellular transfection and gene delivery. Ionizable cationic lipids are critical components of the mRNA‐based COVID vaccines while permanently charged cationic lipids have shown promise in cancer treatment. Despite significant research progress over the past few decades in designing improved, biocompatible cationic lipids, their transfection efficiency remains lower than that of viral vectors. Cationic lipids with additional functionalities like fusogenicity, stimuli‐responsiveness, targeting capabilities, and therapeutic activity have been engineered to improve their performance. This review highlights the importance of molecular hybridization toward the design of biocompatible cationic lipids having fusogenic, stimuli‐responsive, targeting, or therapeutic properties. This review mainly focuses on cationic lipids, having a permanent positive charge in the headgroup region, as these are typically employed to both increase cellular interactions and for improved loading, particularly for anionic nucleic acid‐based therapeutics and vaccines. Structure–activity relationships between the lipid chemical structure (headgroup, spacer, hydrocarbon chain) and, to a lesser extent, the self‐assembled nanostructure and the intrinsic biological activity of the multi‐functional cationic lipids are described. Finally, the challenges involved in developing smart lipids without affecting their inherent capacity to self‐assemble into structured nano‐carriers are discussed.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism’s suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

D2O, an isotope of H2O, is commonly used as a solvent in neutron scattering; the large difference in scattering length density between H and D can provide better contrast between the sample and the solvent. However, this is of concern for studies using enzymes as the use of D2O can influence protein interactions (due to differences in hydrogen bonding) and is therefore expected to affect the function, activity and solubility of enzymes. Neutron-based in vitro digestion assays on proteins, including those found in food or as oral protein and peptide drugs, often involve different solvents or pH conditions where the activity of the digestive enzyme may not be optimal. Herein, we investigate the structure and activity of the main gastric protease, porcine pepsin, in both H2O and D2O at pH values in the range 1 – 8. We showed that the activity of pepsin was lower in D2O, although the relative change in activity with pH was similar for both solvents. We demonstrated using a combination of SAXS and CD that this relative change in activity was not related to any structural change within the protein but was, rather, linked to relative changes in solubility of the protein.

The emergence of virtual reality (VR) humanitarian filmmaking as a genre over the past ten years has generated a large body of critical debate around the efficacy and ethics of VR as a tool for generating empathy towards marginalised communities. Whilst numerous studies have indicated the potential for VR to impact empathy levels of end users, there have been recurrent critiques of the power dynamics of VR production, as well as the value of empathy as a means of producing social change. Lacking in these discussions has been a detailed consideration of VR aesthetics and the extent to which stylistic strategies impact audience positioning. Through the example of the animated VR experience The Key (Celine Tricart, 2019), this article will explore experience design in the context of ethical debates around humanitarian VR. As an interactive, narrative experience that addresses themes of loss and displacement, The Key can be productively analysed in relation to both VR ethics and wider cultural understandings of home and belonging. Responding to ethical debates around proximity within immersive experiences, the article will examine aesthetic strategies within The Key for ensuring what Roger Silverstone has labelled “proper distance” between the user and the virtually represented space. Through its use of visual abstraction and simplification, as well as the limited physical interaction it affords with its virtual world, the virtual home of The Key will be understood as a site of resistance to universalising narratives of home, one which invites critical reflection on the factors that determine our access to shelter.

Abstract Background Dentists serve a crucial role in managing treatment complications for patients with head and neck cancer, including post-radiation caries and oral infection. To date, dental services for head and neck cancer patients in Ontario, Canada have not been well characterized and considerable disparities in allocation, availability, and funding are thought to exist. The current study aims to describe and assess the provision of dental services for head and neck cancer patients in Ontario. Methods A mixed methods scoping assessment was conducted. A purposive sample of dentist-in-chiefs at each of Ontario’s 9 designated head and neck cancer centres (tertiary centres which meet provincially-set quality and safety standards) was invited to participate. Participants completed a 36-item online survey and 60-minute semi-structured interview which explored perceptions of dental services for head and neck cancer patients at their respective centres, including strengths, gaps, and inequities. If a centre did not have a dentist-in-chief, an alternative stakeholder who was knowledgeable on that centre’s dental services participated instead. Thematic analysis of the interview data was completed using a mixed deductive-inductive approach. Results Survey questionnaires were completed at 7 of 9 designated centres. A publicly funded dental clinic was present at 5 centres, but only 2 centres provided automatic dental assessment for all patients. Survey data from 2 centres were not captured due to these centres’ lack of active dental services. Qualitative interviews were conducted at 9 of 9 designated centres and elicited 3 themes: (1) lack of financial resources; (2) heterogeneity in dentistry care provision; and (3) gaps in the continuity of care. Participants noted concerning under-resourcing and limitations/restrictions in funding for dental services across Ontario, resulting in worse health outcomes for vulnerable patients. Extensive advocacy efforts by champions of dental services who have sought to mitigate current disparities in dentistry care were also described. Conclusions Inequities exist in the provision of dental services for head and neck cancer patients in Ontario. Data from the current study will broaden the foundation for evidence-based decision-making on the allocation and funding of dental services by government health care agencies.

This workshop aimed at summarising knowledge and key issues in psychiatric prescribing and psychological testing in children and adults with Duchenne muscular dystrophy (DMD). It comprised clinicians and patient representatives from the UK and the Netherlands. The following topics were discussed: a model for capturing the range of non-motor problems in the domains of cognition, learning, emotion and behaviour; psychosocial screening tools for use with children and adults; assessing neurocognitive functioning in children and adults; parent and teacher perspectives on psychosocial needs; and psychopharmacological treatment for affective disorders, anxiety disorders, obsessive compulsive disorder, attention deficit hyperactivity disorder (ADHD) and insomnia. Some key considerations included: the need for tools used to assess behavioural and psychosocial functioning to consider motor aspects in DMD; to understand more about working memory performance; the need for early interventions for automatisation problems, which affect reading and arithmetic; appropriate selection of tests for neuropsychology assessments; in schools, acknowledging the range of psychosocial risks and gathering evidence of psychosocial needs; the suitability of selective serotonin reuptake inhibitors for mood and anxiety disorders; the use of stimulant medications for ADHD; melatonin use for insomnia; the cautious use of benzodiazepines; and the need for improving pathways for psychosocial care.