Experience-dependent modulation of collective behavior in larval zebrafish.

Complex group behavior can emerge from simple inter-individual interactions. Commonly, these interactions are considered static and hardwired and little is known about how experience and learning affect collective group behavior. Young larvae use well described visuomotor transformations to guide interindividual interactions and collective group structure. Here, we use naturalistic and virtual-reality (VR) experiments to impose persistent changes in population density and measure their effects on future visually evoked turning behavior and the resulting changes in group structure. We find that neighbor distances decrease after exposure to higher population densities, and increase after the experience of lower densities. These adaptations develop slowly and gradually, over tens of minutes and remain stable over many hours. Mechanistically, we find that larvae estimate their current group density by tracking the frequency of neighbor-evoked looming events on the retina and couple the strength of their future interactions to that estimate. A time-varying state-space model that modulates agents' social interactions based on their previous visual-social experiences, accurately describes our behavioral observations and predicts novel aspects of behavior. These findings provide concrete evidence that inter-individual interactions are not static, but rather continuously evolve based on past experience and current environmental demands. The underlying neurobiological mechanisms of experience dependent modulation can now be explored in this small and transparent model organism.

Euglena gracilis Extract Protects From Tobacco Smoke Carcinogen-Induced Lung Cancer by Altering Gut Microbiota Metabolome.

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.

Safety and Feasibility Assessment of a Pharmacy-Driven AUC/MIC Vancomycin Dosing Protocol in a Multicenter Hospital System.

Vancomycin is used for Gram-positive infections, including methicillin-resistant Staphylococcus aureus. The 2020 vancomycin guidelines described by M. J. Rybak, J. Le, T. P. Lodise, D. P. Levine, et al. (Am J Health Syst Pharm 77:835-864, 2020, https://doi.org/10.1093/ajhp/zxaa036) provided an update on vancomycin dosing, which recommended an optimal area under the concentration-time curve over 24 h to MIC (AUC/MIC) target of 400 to 600. In 2021, a pharmacy-driven AUC/MIC vancomycin dosing protocol was implemented across 12 Sentara Health System hospitals. The primary objective of this study was to assess if the pharmacy-driven AUC/MIC vancomycin dosing protocol led to fewer acute kidney injury (AKI) events than trough-based dosing. Secondary objectives included vancomycin duration, hospital length of stay, administered vancomycin dose during admission, vancomycin labs drawn during standard lab times, and cost. AKI was assessed in two separate ways: (i) modified AKIN (Acute Kidney Injury Network) criteria and (ii) a modified version from the vancomycin guidelines. Inferential statistics were used to analyze the results of this retrospective study. Per the AKIN definition, the rates of AKI were 13.9% (349/2,507) in the trough-based group and 14.9% (369/2,471) in the AUC/MIC-based group (P = 0.309). Per the definition of the vancomycin guidelines, the rates of AKI were 6.7% (169/2,507) in the trough-based group and 7.6% (187/2,471) in the AUC/MIC-based group (P = 0.258). A total of 52% (2,679/5,151) of vancomycin labs were obtained during standard lab times in the AUC group and 24% (1,144/4,766) in the trough group (P < 0.05). There was no difference in AKI events between AUC and trough dosing. Use of contrast dye may confound these results. AUC/MIC dosing was associated with more lab draws during standard times, a larger number of labs drawn per person, and less total use of vancomycin. IMPORTANCE In this article, we report that there were no differences in rates of acute kidney injury between trough-based vancomycin dosing and AUC/MIC-based vancomycin dosing across 12 hospitals. AUC/MIC dosing resulted in more vancomycin lab draws during standard lab draw times compared to trough dosing, thus making it more convenient for health care personnel. This study includes all uses for vancomycin, including empirical use, and all patient severity levels. Therefore, this research reflects real-world use of vancomycin in hospitals. AUC/MIC dosing is supported by various infectious disease societies. However, the feasibility of incorporating AUC/MIC dosing in hospitals is undetermined. This study is unique in that it includes hospitals of various sizes (small community hospitals and an academic teaching hospital), and it includes a feasibility component. Therefore, this study has broad applicability to other hospitals across the United States. This original research includes the clinical application of vancomycin in a multicenter health system.

Trans-regulatory changes underpin the evolution of the Drosophila immune response.

When an animal is infected, the expression of a large suite of genes is changed, resulting in an immune response that can defend the host. Despite much evidence that the sequence of proteins in the immune system can evolve rapidly, the evolution of gene expression is comparatively poorly understood. We therefore investigated the transcriptional response to parasitoid wasp infection in Drosophila simulans and D. sechellia. Although these species are closely related, there has been a large scale divergence in the expression of immune-responsive genes in their two main immune tissues, the fat body and hemocytes. Many genes, including those encoding molecules that directly kill pathogens, have cis regulatory changes, frequently resulting in large differences in their expression in the two species. However, these changes in cis regulation overwhelmingly affected gene expression in immune-challenged and uninfected animals alike. Divergence in the response to infection was controlled in trans. We argue that altering trans-regulatory factors, such as signalling pathways or immune modulators, may allow natural selection to alter the expression of large numbers of immune-responsive genes in a coordinated fashion.

Orthodontic and oral health literacy in adults.

OBJECTIVE: The primary aim of the study was to determine levels of literacy in both oral health and orthodontics in an adult population. The secondary study aim was to investigate differences in literacy between males and females. METHODS: Participants included individuals 18 years or older seeking dental treatment at the East Carolina University (ECU) School of Dental Medicine. To determine levels of oral health literacy (OHL) and orthodontic literacy (OrthoL), validated instruments were administered, including the Rapid Estimate of Adult Literacy in Medicine and Dentistry, the Oral Health Literacy Instrument and its separate scales, and a questionnaire on orthodontic literacy. Summary statistics were computed, and statistical significance was set at 0.05. RESULTS: One hundred seventy-two individuals participated in the study and had a mean age of 55.03 (range:18-88). Greater than 70% of the sampled population exhibited inadequate or marginal oral health knowledge. Additionally, greater than 70% of the sample possessed no more than an 8th grade reading level, with regard to basic medical and dental terms. Higher education was weakly associated with higher OrthoL and OHL. Higher age was also weakly associated with lower OrthoL and OHL. Males on average exhibited significantly higher OHL (p < .05) but there were no OrthoL differences between males and females. Dental visit frequency was not associated with OrthoL or OHL. CONCLUSION: Low levels of OrthoL and OHL were observed in the study. While males demonstrated a higher level of OHL than females, neither age nor the occurrence of dental appointments significantly influenced levels of literacy.

A Water Extract from Chlorella sorokiniana Cell Walls Stimulates Growth of Bone Marrow Cells and Splenocytes.

A water extract derived from the isolated cell walls of Chlorella sorokiniana (C. sorokiniana, Chlorella water extract, CWE) was analyzed for the presence of lipopolysaccharide (LPS)-related material via the Limulus amebocyte lysate (LAL) assay and evaluated for its growth stimulation effect on the bone marrow cells and splenocytes in vitro cell cultures. The extract contained low levels of LPS-related material, and a mass spectrum suggested that the extract contained many components, including a low level of a lipid A precursor, a compound known as lipid X, which is known to elicit a positive response in the LAL assay. Treatment with the CWE dose- and time-dependently stimulated the growth of mouse bone marrow cells (BMCs) and splenocytes (SPLs). Treatment with the CWE also increased specific BMC subpopulations, including antigen-presenting cells (CD19+ B cells, 33D1+ dendritic cells and CD68+ macrophages), and CD4+ and CD8+ T cells, but decreased the number of LY6G+ granulocytes. Treatment with the CWE also increased cytokine mRNA associated with T cell activation, including TNFα, IFNγ, and granzyme B in human lymphoblasts. The present study indicates that the cell wall fraction of C.sorokiniana contains an LPS-like material and suggests a candidate source for the bioactivity that stimulates growth of both innate and adaptive immune cells.

Surface-Atmosphere Coupling Scale, the Fate of Water, and Ecophysiological Function in a Brazilian Forest.

Tropical South America plays a central role in global climate. Bowen ratio teleconnects to circulation and precipitation processes far afield, and the global CO2 growth rate is strongly influenced by carbon cycle processes in South America. However, quantification of basin-wide seasonality of flux partitioning between latent and sensible heat, the response to anomalies around climatic norms, and understanding of the processes and mechanisms that control the carbon cycle remains elusive. Here, we investigate simulated surface-atmosphere interaction at a single site in Brazil, using models with different representations of precipitation and cloud processes, as well as differences in scale of coupling between the surface and atmosphere. We find that the model with parameterized clouds/precipitation has a tendency toward unrealistic perpetual light precipitation, while models with explicit treatment of clouds produce more intense and less frequent rain. Models that couple the surface to the atmosphere on the scale of kilometers, as opposed to tens or hundreds of kilometers, produce even more realistic distributions of rainfall. Rainfall intensity has direct consequences for the "fate of water," or the pathway that a hydrometeor follows once it interacts with the surface. We find that the model with explicit treatment of cloud processes, coupled to the surface at small scales, is the most realistic when compared to observations. These results have implications for simulations of global climate, as the use of models with explicit (as opposed to parameterized) cloud representations becomes more widespread.

Evaluating an Indigenous health curriculum for diabetes prevention: engaging the community through talking circles and knowledge translation of results.

Background: Kahnawà:ke is a Kanien'kehá:ka (Mohawk) community in Quebec, Canada. In 1997, the community-controlled Kateri Memorial Hospital Centre in partnership with the Kahnawake Education Center, and the Kahnawake Schools Diabetes Prevention Project (KSDPP) developed an elementary school diabetes prevention health education program, aimed to increase knowledge of Type 2 diabetes, healthy eating and active lifestyles. Long-term goals for KSDPP community and school interventions are to decrease obesity and diabetes. Objectives: To evaluate the Kateri Memorial Hospital Centre Health Education Program for Diabetes Prevention (HEP) and use key principles of knowledge translation to promote understanding of results to upgrade HEP content and improve delivery. Methods: A KSDPP community-based participatory research team used mixed methods for evaluation, combining a cross-sectional survey for 23 teachers with interviews of two elementary school principals and three culturally appropriate Indigenous talking circles with HEP authors, teachers and parents. Questionnaire results were presented as descriptive statistics. The thematic textual analysis identified emerging themes from talking circles and interviews. Results: Facilitators of HEP delivery were an acknowledgement of its importance; appreciation of prepared lesson plans for teachers; and KSDPP's strong community presence. Barriers included reduced administrative support and instructional time due to competing academic demands; the need for increased Kanien'kehá:ka cultural content; and outdated resource materials. Recommendations included increasing teacher training, Kanien'kehá:ka cultural content and administrative support. Conclusion: Community researchers undertook detailed knowledge translation activities of facilitators, barriers and recommendations with hospital and education centre administrators and Kahnawà:ke community to maximize uptake of findings before external dissemination of results.

Snails from heavy-metal polluted environments have reduced sensitivity to carbon dioxide-induced acidity.

Anthropogenic atmospheric CO2 reacts with water to form carbonic acid (H2CO3) which increases water acidity. While marine acidification has received recent consideration, less attention has been paid to the effects of atmospheric carbon dioxide on freshwater systems-systems that often have low buffering potential. Since many aquatic systems are already impacted by pollutants such as heavy metals, we wondered about the added effect of rising atmospheric CO2 on freshwater organisms. We studied aquatic pulmonate snails (Physella columbiana) from both a heavy-metal polluted watershed and snails from a reference watershed that has not experienced mining pollution. We used gaseous CO2 to increase water acidity and we then measured changes in antipredatory behavior and also survival. We predicted a simple negative additive effect of low pH. We hypothesized that snails from metal-polluted environments would be physiologically stressed and impaired due to defense responses against heavy metals. Instead, snails from populations that acclimated or evolved in the presence of heavy metal mining pollution were more robust to acidic conditions than were snails from reference habitats. Snails from mining polluted sites seemed to be preadapted to a low pH environment. Their short-term survival in acidic conditions was better than snails from reference sites that lacked metal pollution. In fact, the 48 h survival of snails from polluted sites was so high that it did not significantly differ from the 24 h survival of snails from control sites. This suggests that the response of organisms to a world with rising anthropogenic carbon dioxide levels may be complex and difficult to predict. Snails had a weaker behavioral response to stressful stimuli if kept for 1 month at a pH that differed from their lake of origin. We found that snails raised at a pH of 5.5 had a weaker response (less of a decrease in activity) to concentrated heavy metals than did snails raised at their natal pH of 6.5. Furthermore, snails raised a pH of 5.5, 6.0, and 7.0 all had a weaker antipredatory response to an extract of crushed snail cells than did the pH 6.5 treatment snails.

Rethinking resilience from indigenous perspectives.

The notions of resilience that have emerged in developmental psychology and psychiatry in recent years require systematic rethinking to address the distinctive cultures, geographic and social settings, and histories of adversity of indigenous peoples. In Canada, the overriding social realities of indigenous peoples include their historical rootedness to a specific place (with traditional lands, communities, and transactions with the environment) and the profound displacements caused by colonization and subsequent loss of autonomy, political oppression, and bureaucratic control. We report observations from an ongoing collaborative project on resilience in Inuit, Métis, Mi'kmaq, and Mohawk communities that suggests the value of incorporating indigenous constructs in resilience research. These constructs are expressed through specific stories and metaphors grounded in local culture and language; however, they can be framed more generally in terms of processes that include: regulating emotion and supporting adaptation through relational, ecocentric, and cosmocentric concepts of self and personhood; revisioning collective history in ways that valorize collective identity; revitalizing language and culture as resources for narrative self-fashioning, social positioning, and healing; and renewing individual and collective agency through political activism, empowerment, and reconciliation. Each of these sources of resilience can be understood in dynamic terms as emerging from interactions between individuals, their communities, and the larger regional, national, and global systems that locate and sustain indigenous agency and identity. This social-ecological view of resilience has important implications for mental health promotion, policy, and clinical practice.