Do small effects matter more in vulnerable populations? an investigation using Environmental influences on Child Health Outcomes (ECHO) cohorts.

BACKGROUND: A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. METHODS: Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. RESULTS: When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated. CONCLUSIONS: Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals.

Effects of microplastic interaction with persistent organic pollutants on the activity of the aryl hydrocarbon and estrogen receptors.

Environmental microplastics (MPs) are complex mixtures of plastic polymers and sorbed chemical pollutants with high degrees of heterogeneity, particularly in terms of particle size, morphology and degree of weathering. Currently, limitations exist in sampling sufficient amounts of environmental particles for laboratory studies to assess toxicity endpoints with statistical rigor and to examine chemical pollutant interactions. This study seeks to bridge this gap by investigating environmental plastic particle mimetics and pollutant-polymer interactions by mixing polymer particles with persistent organic pollutants (POPs) at set concentrations over time. Solutions containing combinations of polymers including polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), and polyamide (PA) and POPs including 2,3,7,8 -Tetrachlorodibenzo-p-dioxin (TCDD), bisphenol A (BPA), and atrazine, were stirred for up to 19 weeks and monitored using assays to test for aryl hydrocarbon (AhR) and estrogen receptor (ER) activity which are cell signaling pathways impacted by environmental pollutants. TCDD induced AhR activity decreased over time in the presence of PS in a surface area dependent manner. BPA and atrazine also exhibited AhR antagonist activity in the presence of TCDD. The addition of BPA slowed the loss of activity but atrazine did not, suggesting that polymer chemistry impacts interactions with POPs. We also observed potential differences in TCDD sorption with different plastic polymers and that higher concentrations of PS particles may inhibit BPA-induced estrogen receptor activation. These results emphasize the need for additional understanding of how POPs and polymer chemistry impact their interaction and toxicity.

Designing a Perioperative Mind-Body Intervention for Peripheral Vascular Interventions.

Background: Peripheral vascular interventions (PVIs) performed under procedural sedation and analgesia (PSA) can be associated with anxiety and poor compliance with patient instructions during surgery. Mind-body interventions (MBIs) such as meditation have demonstrated the potential to decrease perioperative anxiety, though this area is understudied, and no tailored interventions have been developed for the vascular surgical patient population. Objectives: We aimed to design a perioperative MBI that specifically targeted vascular surgical patients undergoing PVIs under PSA. We sought to perform this in a scientifically rigorous, multi-disciplinary collaborative manner. Methods: Following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, we designed (Phase 1a) and then refined (Phase 1b) a MBI for patients undergoing PVIs under PSA to decrease perioperative anxiety and sedation and facilitate patient intraoperative compliance. Phase 1a involved a literature review, informal information gathering and synthesis, and drafting a preliminary protocol for a perioperative MBI. Phase 1b involved assembling a multi-disciplinary expert panel of perioperative and mind-body clinicians and researchers to improve the MBI using an iterative, modified Delphi approach. Results: The modified Delphi process was completed, and a consensus was reached after three iterations. The resulting MBI consisted of two seven-minute preoperative guided meditations on the day of surgery, including diaphragmatic breathing, body scans, and guided imagery emphasizing awareness of the ipsilateral leg where the vascular surgery was performed. A document delineating the integration of the MBI into the operating room workflow was produced, including details regarding the intervention's timing, duration, and modality. Conclusion: Using a multi-specialty expert panel, we designed a novel MBI in the form of a guided meditation with elements of mindfulness and guided imagery to decrease anxiety and increase intraoperative compliance for patients undergoing PVIs under PSA. A prospective pilot study is being planned to test the program's feasibility.

Assessing bioactivity of environmental water samples filtered using nanomembrane technology and mammalian cell lines.

This project reports on the use of a novel nanomembrane filtering technology to isolate and analyze the bioactivity of microplastic (MP)-containing debris from Lake Ontario water samples. Environmental MPs are a complex mixture of polymers and sorbed chemicals that are persistent and can exhibit a wide range of toxic effects. Since human exposure to MPs is unavoidable, it is necessary to characterize their bioactivity to assess potential health risks. This work seeks to quantify MP presence in the nearshore waters of Lake Ontario and begin to characterize the bioactivity of the filtrate containing MPs. We utilized silicon nitride (SiN) nanomembrane technology to isolate debris sized between 8 and 20 µm from lake water samples collected at various times and locations. MPs were identified with Nile red staining. Cell-based assays were conducted directly on the filtered debris to test for cell viability, aryl hydrocarbon receptor (AhR) activity, and interleukin 6 (IL-6) levels as a measure of proinflammatory response. All samples contained MPs. None of the isolated debris impacted cell viability. However, AhR activity and IL-6 levels varied over time. Additionally, no associations were observed between the amount of plastic and bioactivity. Observed differences in activity are likely due to variations in the physiochemical properties of debris between samples. Our results highlight the need for increased sampling to fully characterize the bioactivity of MPs in human cells and to elucidate the role that sample physiochemical and spatiotemporal properties play in this activity.

Perceptions Toward Naloxone Among Patients With Cancer Receiving Opioids.

CONTEXT: Naloxone nasal spray is recommended for patients with risk factors for opioid overdose. However, cancer patients' perceptions and beliefs regarding naloxone prescriptions and their self-perceived risks for overdose are understudied. OBJECTIVE: To determine the proportion of cancer patients at risk for overdose who perceived naloxone as beneficial. METHODS: Between July 2020 and April 2022, we surveyed 150 adult patients from the supportive care ambulatory clinic at a tertiary cancer center in the United States who received a co-prescription of naloxone nasal spray. We measured patients' knowledge of overdose risk-factors, attitudes, beliefs, and education received on naloxone. Risk-factors between beneficial vs. nonbeneficial groups were analyzed. The survey was administered on paper or via a telephone interview. RESULTS: Of the 150 patients, 55% were male, 70% were white, and 81% had advanced cancer. The majority of patients believed naloxone was beneficial (100/150, 67%). When compared to the nonbeneficial group, more patients from the beneficial group agreed that the concurrent use of alcohol (100% vs. 90%; P = 0.004) or sedating drugs (96% vs. 85%; P = 0.04) with opioids could result in overdoses and felt safe having naloxone at home (95% vs. 60%; P <0.0001). More patients from the nonbeneficial group associated naloxone prescription with being suspected of misusing opioids (12/50 vs. 8/100; P = 0.01), and fewer had confidence in their caregivers' ability to administer naloxone (69% vs. 95%; P < 0.0001). CONCLUSION: Most patients understood the benefits of naloxone and felt safe having one at home. More research is needed to identify knowledge gaps and develop educational strategies for those who find it nonbeneficial.

Summary of quality of life in the ASCENT phase 3 clinical trial for people with metastatic triple-negative breast cancer.

WHAT IS THIS SUMMARY ABOUT?: A medicine called sacituzumab govitecan (brand name TRODELVY®) has been proven to be an effective treatment for metastatic triple-negative breast cancer (mTNBC for short). Metastatic breast cancer is cancer that has spread to other parts of the body. In mTNBC, the breast cancer cells do not have 3 common proteins on the cell surface, called receptors. mTNBC is more difficult to treat and more likely to come back than other types of breast cancer. The ASCENT study showed that participants with mTNBC treated with sacituzumab govitecan had a higher likelihood of living longer and delayed progression (worsening) of their cancer than those treated with standard chemotherapy. Here, we summarize the quality of life of participants with mTNBC in the ASCENT study. We compared quality of life between 236 participants treated with sacituzumab govitecan and 183 participants treated with standard chemotherapy. All participants previously received 2 or more chemotherapies that no longer controlled their cancer. WHAT ARE THE KEY TAKEAWAYS?: This analysis showed that participants treated with sacituzumab govitecan had better overall quality of life than participants treated with standard chemotherapy. They also had better "physical functioning", which is the ability to walk and do physical activities. Participants treated with sacituzumab govitecan maintained their overall quality of life for a longer time than those treated with standard chemotherapy. Participants treated with sacituzumab govitecan had less pain and were less tired than those treated with standard chemotherapy. On the other hand, participants treated with sacituzumab govitecan had worse diarrhea (loose or watery stools) and were more likely to have nausea/vomiting (feel sick or throw up) than participants treated with standard chemotherapy. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Participants treated with sacituzumab govitecan had a higher likelihood of living longer and delayed progression (worsening) of their cancer. Participants also had a better overall quality of life, which was maintained (did not get worse) for a longer time. However, they experienced worsening of diarrhea and/or nausea/vomiting.Clinical Trial Registration: NCT02574455 (ASCENT) (ClinicalTrials.gov).

Bee The CURE: Increasing Student Science Self-Efficacy, Science Identity, and Predictors of Scientific Civic Engagement in a Community College CURE.

"Bee the CURE" is a Power-of-Place course-based undergraduate research experience (PoP-CUREs; Jaeger et al., 2024) that combines place-based education (Demarest, 2014; Gruenewald, 2014) with CUREs, emphasizing student scientific civic engagement where research is relevant to the community where the research is taking place. PoP-CUREs have potential to build students' knowledge, skills, value, and self-efficacy when engaging with the public using science skills (i.e., scientific civic engagement). A mixed-methods sequential explanatory design utilizing surveys and semistructured interviews was used for this study (Warfa, 2016). Students made gains in science self-efficacy over the course of the semester and showed a trend of increasing science identity in both Fall 2021 and Spring 2022 semesters. Students' scientific civic knowledge, or a student's sense of how to use or apply knowledge and skills to help a community, increased significantly, while other predictors of scientific civic engagement started high and remained high throughout the course. Bee the CURE demonstrates psychosocial outcomes that are similar to previously studied CUREs and expands our understanding of how PoP-CUREs might influence outcomes with evidence that an important predictor of future scientific civic engagement increases. Implications for PoP-CURE instruction at Hispanic serving community colleges are discussed.

Pinning Down Small Populations of Photoinduced Intermediates Using Transient Absorption Spectroscopy and Time-Dependent Density Functional Theory Difference Spectra to Provide Mechanistic Insight into Controlling Pyridine Azo Dynamics with Protons.

In this work, the impact of protonation on the photoisomerization (trans → cis) and reversion (cis → trans) of three pyridine-based azo dyes (PyrN) is investigated by using a combination of transient absorption spectroscopy and time-dependent density functional theory computed difference spectra. The photophysical behaviors of the PyrN dyes are altered by the addition of one or two protons. Protonation of basic pyridine nitrogens results in an ultrafast accelerated reversion mechanism after photoisomerization, while protonation of azo bond nitrogens restricts cis isomer formation entirely. Computed difference spectra provide spectral signatures that are critical for the assignment of low-population long-lived states, providing direct evidence of the accelerated reversion mechanism. Thus, the addition of organic acids can selectively control the photophysics of azo dyes for a wide range of applications, including materials design and pharmaceuticals.

Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial.

For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

Ancient developmental genes underlie evolutionary novelties in walking fish.

A critical question in biology is how new traits evolve, but studying this in wild animals remains challenging. Here, we probe the genetic basis of trait gain in sea robin fish, which have evolved specialized leg-like appendages for locomotion and digging along the ocean floor. We use genome sequencing, transcriptional profiling, and interspecific hybrid analysis to explore the molecular and developmental basis of leg formation. We identified the ancient, conserved transcription factor tbx3a as a major determinant of sensory leg development. Genome editing confirms that tbx3a is required for normal leg formation in sea robins, and for formation of enlarged central nervous system lobes, sensory papillae, and adult digging behavior. Our study establishes sea robins as a model organism for studying the evolution of major trait gain and illustrates how ancient developmental control genes can underlie novel organ formation.

Surface engineering enhances the therapeutic potential of systemically delivered extracellular vesicles following acute myocardial infarction.

The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere-derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery. We hypothesized that engineering the surface of EVs to target cardiomyocytes would enhance their therapeutic efficacy following systemic delivery in a model of acute MI. CDC-derived EVs were engineered to express a CM-specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent both intramyocardial and intravenous delivery of EVs, CMP-EVs and placebo in a double-blind study. LVEF was assessed by echo at 2- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. CMP-EVs demonstrated superior cardiac targeting and retention when compared with unmodified EVs 24 h post-MI. Mice treated with IV delivered CMP-EVs demonstrated a significant improvement in LVEF and a significant reduction in remote zone cardiomyocyte apoptosis when compared with IV delivered non-targeted EVs at 28-day post-MI. Systemic administration of CMP-EVs improved cardiac function and reduced remote zone cardiomyocyte apoptosis compared with IV-administered unmodified EVs, demonstrating a strategy to optimize therapeutic EV delivery post-MI.

Bias intervention messaging in student evaluations of teaching: The role of gendered perceptions of bias.

Many studies have documented discrepancies in student evaluation of teaching ratings between male and female instructors and between ethnic majority and minority instructors. Given the importance of such ratings to academic careers and the likelihood of potential intergroup bias, it is crucial that institutions consider approaches to mitigate such biases. Several recent studies have found that simple bias mitigation messaging can be effective in reducing gender and other biases. In the present research, students enrolled in several large Faculty of Science undergraduate courses at an Australian university were recruited on a volunteer basis via the course learning management system. Half of the participants were randomly assigned an intervention message highlighting potential biases relating to gender and language background. Data from 185 respondents were analysed using Bayesian ordinal regression models assessing the impact of message exposure on evaluation scores. Reading a bias intervention message caused students to significantly adjust their scores, with the nature of that change dependent on student and instructor characteristics. Among male students, the bias intervention message significantly increased scores for all except male instructors with English speaking backgrounds, for whom there was no significant impact of the message. In contrast, among female students, the bias intervention message significantly decreased scores for male instructors with English speaking backgrounds only. The sample showed an overall decrease in scores in the intervention group relative to the control group. This is the first study to detect a negative impact of bias intervention messaging on SET scores. Our results suggest students may not acknowledge their own potential bias towards instructors with whom they share similar demographic backgrounds. In conclusion, bias intervention messaging may be a simple method of mitigating bias, but it may lead to consequences in which one or more groups receive lower ratings as a result of the correction.

Dose de-intensified 3-day photon, proton, or brachytherapy: a nonrandomized controlled partial breast irradiation trial.

BACKGROUND: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS: A multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. RESULTS: Between June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. CONCLUSIONS: De-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02453737.

Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations.

Florfenicol is a broad-spectrum and bacteriostatic antibiotic with a time-dependent killing action. It is commonly used to treat respiratory diseases in goats in an extra-label manner. This study aimed to determine the plasma pharmacokinetics and milk residue depletion profiles and calculate the milk withdrawal interval (WDI) of florfenicol and its main metabolite florfenicol amine in lactating goats. Five healthy lactating goats were administered with 40 mg/kg florfenicol by subcutaneous injection, twice, 96 h apart. Plasma and milk samples were collected up to 864 h post the first injection. Non-compartmental analysis was used to estimate the plasma pharmacokinetic parameters. Milk WDIs were calculated using the U.S. Food and Drug Administration (FDA) method and European Medicines Agency (EMA) method. A Monte Carlo simulation was performed to generate simulated data for five virtual animals to meet the data requirement of the FDA method. The calculated milk WDIs based on florfenicol, florfenicol amine, and the combined (the sum of florfenicol and florfenicol amine) were 720.28, 690.45, and 872.69 h after the last injection using the FDA method. In conclusion, this study improves our understanding on the plasma pharmacokinetics and milk residue depletion kinetics of florfenicol and florfenicol amine in lactating ruminants after subcutaneous injections.

Validation of different automated segmentation models for target volume contouring in postoperative radiotherapy for breast cancer and regional nodal irradiation.

Introduction: Target volume delineation is routinely performed in postoperative radiotherapy (RT) for breast cancer patients, but it is a time-consuming process. The aim of the present study was to validate the quality, clinical usability and institutional-specific implementation of different auto-segmentation tools into clinical routine. Methods: Three different commercially available, artificial intelligence-, ESTRO-guideline-based segmentation models (M1-3) were applied to fifty consecutive reference patients who received postoperative local RT including regional nodal irradiation for breast cancer for the delineation of clinical target volumes: the residual breast, implant or chestwall, axilla levels 1 and 2, the infra- and supraclavicular regions, the interpectoral and internal mammary nodes. Objective evaluation metrics of the created structures were conducted with the Dice similarity index (DICE) and the Hausdorff distance, and a manual evaluation of usability. Results: The resulting geometries of the segmentation models were compared to the reference volumes for each patient and required no or only minor corrections in 72 % (M1), 64 % (M2) and 78 % (M3) of the cases. The median DICE and Hausdorff values for the resulting planning target volumes were 0.87-0.88 and 2.96-3.55, respectively. Clinical usability was significantly correlated with the DICE index, with calculated cut-off values used to define no or minor adjustments of 0.82-0.86. Right or left sided target and breathing method (deep inspiration breath hold vs. free breathing) did not impact the quality of the resulting structures. Conclusion: Artificial intelligence-based auto-segmentation programs showed high-quality accuracy and provided standardization and efficient support for guideline-based target volume contouring as a precondition for fully automated workflows in radiotherapy treatment planning.

Conceptual masking disrupts change-detection performance.

The present study investigated the effects of long-term knowledge on backward masking interference in visual working memory (VWM) by varying the similarity of mask stimuli along categorical dimensions. To-be-remembered items and masks were taken from categories controlled for perceptual distinctiveness and distinctiveness in kinds (e.g., there are many kinds of cars and few kinds of coffee mugs). Participants completed a change-detection task in which the memory array consisted of exemplars from either a similar or distinctive category, followed by a mask array of items from the same category (conceptually similar versus conceptually distinct categories), a different category, or no mask. The results over two experiments showed greater interference from conceptually similar masks as compared with the other conditions across stimulus onset asynchrony (SOA) conditions, suggesting masking with conceptually similar categories leads to more interference even when masks are shown well after the stimulus. These results have important implications for both the nature and time course of long-term conceptual knowledge influencing VWM, particularly when using complex real-world objects.

Prospective cohort study to evaluate narrow diameter implants for the restoration of a missing maxillary lateral incisor in patients with a cleft palate: Five-year results.

STATEMENT OF PROBLEM: The maxillary lateral incisor is often congenitally missing in patients with a cleft palate. The congenital cleft presents the practitioner with challenges including quantity and quality of bone, a surgically managed cleft correction, and limited clinical space. PURPOSE: The purpose of this investigation was to calculate the 5-year success and survival rate of narrow-diameter implants used to restore a missing lateral incisor in patients with a cleft palate. MATERIAL AND METHODS: Fourteen study participants with a cleft palate and a missing maxillary lateral incisor were enrolled based on established criteria. Seventeen narrow-diameter implants (AstraTech OsseoSpeed 3.0S and OsseoSpeed TX 3.5 mm) were placed using a 2-stage protocol and restored with a custom titanium abutment and a cement-retained crown. Clinical and radiographic examinations were performed annually for 5 years. Four probe depth measurements were measured and evaluated using an analysis of covariance (ANCOVA) with Tukey-Kramer multiple comparisons tests. Radiographic marginal bone loss was measured annually using a digital subtraction technique and evaluated with ANCOVA, and the least square mean was derived. The restoration was evaluated using Pink (PES) and White (WES) Esthetic scores. RESULTS: Regarding probing depth measurements, a significant variance was found between the 4 locations (P<.001), and a linear effect of year was also found (P=.005). The multiple comparisons tests showed the mean buccal probe depth was lower compared with the mean at each of the other 3 locations (P≤.039) from baseline to 5-year follow-up. The least square mean ±standard deviation of the marginal bone loss over the 5-year entire study was 0.55 ±0.088 mm. Regarding prosthesis evaluation, the mean score for PES was 6.15 and 6.63 for the WES with a maximum score of 10. The level for clinical acceptance was set at a total score of 6. To meet the criteria for success over the 5-year period, no more than 2.3 mm of total bone loss was acceptable. The number of implants that met the criteria for success at 5 years was 92%. Regarding survival, the number of implants still in place, functional, and asymptomatic at 5 years was 100%. CONCLUSIONS: Based on the findings, the peri-implant soft tissue probe depths exhibited significant change during the 5-year investigation. Regarding esthetic outcomes, single tooth NDI for replacing a lateral incisor in the cleft patient is a clinically acceptable treatment. Narrow-diameter implants may be a reliable treatment for replacing a missing lateral incisor in patients with a cleft at 5-year follow-up with an implant survival rate of 100% and a success rate of 92%.

Eosinophils respond to, but are not essential for control of an acute Salmonella enterica serovar Typhimurium infection in mice.

Eosinophils are a highly abundant cell type in the gastrointestinal tract during homeostatic conditions, where they have recently been reported to take on an activated phenotype following colonization by the bacterial microbiota. To date, there have been few studies investigating whether eosinophils respond to infection with enteric bacterial pathogens and/or investigating the requirements for eosinophils for effective bacterial pathogen control. In this study, we investigated the response of eosinophils to an acute enteric infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium. We also assessed whether eosinophil deficiency impacted Salmonella burdens in the intestinal tract or impacted the systemic dissemination of Salmonella following an oral infection of littermate wild-type BALB/cJ and eosinophil-deficient ΔdblGATA BALB/cJ mice. We found comparable Salmonella burdens in the intestinal tract of wild-type and eosinophil-deficient mice and no significant differences in the levels of Salmonella disseminating to systemic organs within 3 days of infection. Despite our evidence suggesting that eosinophils are not an essential cell type for controlling bacterial burdens in this acute infection setting, we found higher levels of eosinophils in gut-draining lymph nodes following infection, indicating that eosinophils do respond to Salmonella infection. Our data contribute to the growing evidence that eosinophils are responsive to bacterial stimuli, yet the influence of and requirements for eosinophils during bacterial infection appear to be highly context-dependent.