Effects of acute estradiol administration on perimenstrual worsening of working memory, verbal fluency, and inhibition in patients with suicidal ideation: A randomized, crossover clinical trial.

Accumulating evidence indicates that most female patients with suicidal ideation (SI) experience a dimensional worsening of depressive symptoms and SI in the perimenstrual phase of the menstrual cycle. Experimental trials demonstrate that acute perimenstrual administration of estradiol (E2; with or without progesterone/P4), can prevent these recurring episodes of increased risk. In this archival sample drawn from one of these clinical trials, we examined whether these beneficial E2 effects extend to specific types of cognition. For a double-blind, placebo-controlled experiment, we recruited transdiagnostic psychiatric outpatients with natural menstrual cycles who experienced past-month SI (N(per-protocol sample)=23; N(intent-to-treat sample)=44). In each of two counterbalanced conditions (perimenstrual administration of 0.1mg/d transdermal E2 vs. placebo), participants completed three cognitive tasks in three menstrual cycle phases (mid-luteal, perimenstrual, mid-follicular). Multilevel models revealed a significant interaction of condition and phase: E2 administration prevented mid-luteal-to-perimenstrual drops in working memory (p=.006) and verbal fluency (p=.005) observed under placebo. No effects were found for inhibitory control. In conclusion, we find perimenstrual declines in working memory and verbal fluency in patients with SI, which can be prevented by administering E2. This study contributes to our understanding of the hormone-brain pathways involved in the cyclical worsening of suicidality.

Bench-Stable 2-Halopyridinium Ketene Hemiaminals as Reagents for the Synthesis of 2-Aminopyridine Derivatives.

2-Chloro-1-(1-ethoxyvinyl)pyridinium triflate and several other bench-stable N-(1-alkoxyvinyl) 2-halopyridinium triflates have been developed as reagents for the synthesis of valuable 2-aminopyridine scaffolds via unusually mild SNAr substitutions with amine nucleophiles. Advantages of this approach include an operationally simple mix-and-stir procedure at room temperature or mild heat and ambient atmosphere and without the need for transition metal catalysts, coupling reagents, or high-boiling solvents. The stable N-(1-ethoxyvinyl) moiety serves as a dual SNAr-activating group and pyridine N-protecting group that can be cleaved under thermal, acidic, or oxidative conditions. Preliminary results of other nucleophilic substitutions using oxygen-, sulfur-, and carbon-based nucleophiles are also demonstrated.

Freshwater Mussel Viromes Increase Rapidly in Diversity and Abundance When Hosts Are Released from Captivity into the Wild.

Freshwater mussels (order: Unionida) are highly imperiled globally and are increasingly the focus of captive propagation efforts to protect and restore wild populations. The Upper Tennessee River Basin (UTRB) in Virginia is a freshwater biodiversity hotspot hosting at least 45 of North America's ~300 species of freshwater mussels, including 21 threatened and endangered species listed under the U.S. Endangered Species Act. Recent studies have documented that viruses and other microbes have contributed to freshwater mussel population declines in the UTRB. We conducted a multi-year longitudinal study of captive-reared hatchery mussels released to restoration sites throughout the UTRB to evaluate their viromes and compare them to captive hatchery environments. We documented 681 viruses from 27 families. The hatchery mussels had significantly less viruses than those deployed to wild sites, with only 20 viruses unique to the hatchery mussels. After the hatchery mussels were released into the wild, their number of viruses initially spiked and then increased steadily over time, with 451 viruses in total unique to the mussels in the wild. We found Clinch densovirus 1 (CDNV-1), a virus previously associated with mass mortality events in the Clinch River, in all samples, but the wild site mussels consistently had significantly higher CDNV-1 levels than those held in the hatchery. Our data document substantial differences between the viruses in the mussels in the hatchery and wild environments and rapid virome shifts after the mussels are released to the wild sites. These findings indicate that mussel release programs might benefit from acclimatization periods or other measures to mitigate the potential negative effects of rapid exposure to infectious agents found in natural environments.

Significant Variability in Postoperative Thromboprophylaxis in Cushing's Disease Patients: A Survey of the North American Skull Base Society and the AANS/CNS Joint Tumor Section.

Introduction Cushing's disease (CD) is associated with hypercoagulability which is associated with an increased risk of venous thromboembolic events (VTEs) perioperatively. This risk persists even after successful transsphenoidal surgery (TSS). However, there are no current guidelines for pharmacologic thromboprophylaxis in this patient population. Objective Characterize existing thromboprophylaxis management practices in patients undergoing TSS for CD. Methods An anonymous RedCap survey comprised of questions about perioperative thromboprophylaxis in CD patients was distributed via the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Tumor Section and the North American Skull Base Society (NASBS) email lists. Results The survey was distributed to 554 members of the AANS/CNS Joint Tumor Section and 1,094 members of NASBS asking that members who surgically treat CD respond. Sixty responses (3.0% response rate) were received. Fifty-two (86.7%) respondents are involved in the postoperative management of CD patients. Thirty-six (69.2%) treat all patients with postoperative VTE chemoprophylaxis, 8 (15.4%) treat some patients, while 8 (15.4%) do not use chemoprophylaxis. Preferred chemoprophylaxis varies as 26 (59.1%) administer low molecular weight heparin, 14 (31.8%) give unfractionated heparin, 1 (2.3%) give direct oral anticoagulants, and 3 (6.8%) give aspirin. Most (28, 53.8%) of the respondents perceive the VTE risk in this patient population to be 0 to 5%, 16 (30.8%) perceive the risk to be 6 to 10%, and 8 (15.4%) perceive it to be 11 to 20%. Conclusion There is great variability in VTE detection and postoperative prevention practice patterns in CD patients. This study highlights the need for prospective studies to clarify optimal pharmacologic chemoprophylaxis strategies and duration in this patient population.

The Elephant in the Room: Clinical Progression and Management of Elephant Ear Plant Toxicity in an Adult.

Elephant ear plants are popular ornamental plants renowned for their large foliage. These plants have been implicated in various inadvertent and deliberate ingestions. The leaves and roots of these plants contain raphides, which are needle-shaped calcium oxalate crystals. Ingestion of these crystals results in a localized inflammatory response, typically manifesting as irritation, edema, hypersalivation, and dysphagia. Herein, we describe a case of an older gentleman who presented to our institution following intentional ingestion of the leaves and roots of an elephant ear plant. This report describes the clinical manifestations secondary to the toxicities related to the ingestion of this plant and displays the successful conservative management approach employed following multiple diagnostic studies.

Novel application of latent class analysis to outcome assessment in traumatic brain injury with multiple injury subtypes or poly-TBI.

OBJECTIVE: The aim of this study was to stratify poly-traumatic brain injury (poly-TBI) patterns into discrete classes and to determine the association of these classes with mortality and withdrawal of life-sustaining treatment (WLST). METHODS: The authors performed a single-center retrospective review of their institutional trauma registry from 2018 to 2020 to identify patients with traumatic brain injury (TBI). Patients were included if they had moderate to severe TBI, defined as Glasgow Coma Scale score ≤ 12 and Abbreviated Injury Scale (AIS) head score ≥ 3, and the presence of more than one TBI subtype. TBI subtypes were defined as subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and epidural hemorrhage (EDH). Latent class analysis was used to identify patient classes based on TBI subtypes and Rotterdam CT (RCT) scores. The authors then evaluated class membership in relation to categorical outcomes of in-hospital mortality and WLST by using Lanza et al.'s method. RESULTS: A total of 125 patients met inclusion criteria for poly-TBI. Latent class analysis yielded 3 poly-TBI classes: class 1-mixed; class 2-SDH/SAH; and class 3-EDH/SAH. Class 1-mixed had a higher likelihood of SDH, SAH, and ICH, and a lower likelihood of EDH. Class 2-SDH/SAH had a higher likelihood of only SDH and SAH. Class 3-EDH/SAH had a higher likelihood of EDH and SAH, and a lower likelihood of SDH and ICH. Class 1-mixed was relatively more likely to have an RCT score of 2. Class 2-SDH/SAH was relatively more likely to have an RCT score of 2, 3, and 4. Class 3-EDH/SAH had a higher likelihood of an RCT score of 3, 4, and 5. Class 1-mixed had significantly lower mortality (χ2 = 7.968; p = 0.005) and less WLST (χ2 = 4.618; p = 0.032) than Class 2-SDH/SAH. Class 2-SDH/SAH had the highest probability of death (0.612), followed by class 3-EDH/SAH (0.385) and class 1-mixed (0.277). Similarly, class 2-SDH/SAH had the highest WLST probability (0.498), followed by class 3-EDH/SAH (0.615) and class 1-mixed (0.238). CONCLUSIONS: Distinct poly-TBI classes were associated with increased in-hospital mortality and WLST. Further research with larger datasets will allow for more comprehensive poly-TBI class definitions and outcomes analysis.

Closing the gaps in adolescent vaccinations: Rhode Island's Vaccinate Before You Graduate program as a model for other jurisdictions.

Objective: The northeastern state of Rhode Island (RI) has a Vaccinate Before You Graduate (VBYG) program that supplements the traditional primary care infrastructure by providing vaccines to adolescents while they are in school, with no out-of-pocket expenses. We analyzed data from RI's immunization registry to evaluate whether VBYG also reduces disparities in adolescent immunization rates. Methods: We identified adolescent and catch-up vaccines administered in RI to people who were aged 11-18 at any point during the 5-year study period of 2019-2023, and conducted bivariate and multivariate analyses of vaccine administration data by setting (VBYG clinics, community health centers [CHCs], all other primary care practices [oPCPs], other school-based clinics, and other sites) and adolescent demographics (racial and ethnic identity, insurance status, sex, and age at time of vaccine). Results: Of over 387,000 routine vaccines administered during the study period, 3.3 % were administered by a VBYG clinic despite significant declines during school closures associated with the early COVID-19 pandemic. VBYG-administered doses went to slightly older youth, and a higher proportion were catch-up doses (25.7 % versus 14.1 % for CHC doses and 6.5 % for oPCP). Youths received an average of 2.71 vaccines in VBYG clinics compared to 1.77 from oPCPs and 2.08 from CHCs. A higher proportion of vaccines administered by VBYG went to adolescents of color and those without private insurance than those administered by oPCPs. Conclusions: VBYG provides a model to other jurisdictions of a vaccine safety net for adolescents who may not otherwise receive recommended vaccines before exiting the school system.

Associations of luteal phase changes in vagally mediated heart rate variability with premenstrual emotional changes.

BACKGROUND: A recent meta-analysis revealed that vagally mediated heart rate variability (vmHRV; a biomarker of emotion regulation capacity) significantly decreases in the luteal phase of the menstrual cycle. As two follow-up studies suggest, these vmHRV decreases are driven primarily by increased luteal progesterone (P4). However, analyses also revealed significant interindividual differences in vmHRV reactivity to the cycle, which is in line with longstanding evidence for interindividual differences in mood sensitivity to the cycle. The present study begins to investigate whether these interindividual differences in vmHRV cyclicity can explain who is at higher risk of showing premenstrual emotional changes. We expected a greater degree of midluteal vmHRV decrease to be predictive of a greater premenstrual increase in negative affect. METHODS: We conducted an observational study with a naturally cycling community sample (N = 31, M = 26.03 years). Over a span of six weeks, participants completed (a) daily ratings of negative affect and (b) counterbalanced lab visits in their ovulatory, midluteal, and perimenstrual phases. Lab visits were scheduled based on positive ovulation tests and included assessments of baseline vmHRV and salivary ovarian steroid levels. RESULTS: In line with previous research, multilevel models suggest that most of the sample shows ovulatory-to-midluteal vmHRV decreases which, however, were not associated with premenstrual emotional changes. Interestingly, it was only the subgroup with luteal increases in vmHRV whose negative affect markedly worsened premenstrually and improved postmenstrually. CONCLUSION: The present study begins to investigate cyclical changes in vmHRV as a potential biomarker of mood sensitivity to the menstrual cycle. The results demonstrate a higher level of complexity in these associations than initially expected, given that only atypical midluteal increases in vmHRV are associated with greater premenstrual negative affect. Potential underlying mechanisms are discussed, among those the possibility that luteal vmHRV increases index compensatory efforts to regulate emotion in those with greater premenstrual negative affect. However, future studies with larger and clinical samples and more granular vmHRV assessments should build on these findings and further explore associations between vmHRV cyclicity and menstrually related mood changes.

The ultrametric backbone is the union of all minimum spanning forests.

Minimum spanning trees and forests are powerful sparsification techniques that remove cycles from weighted graphs to minimize total edge weight while preserving node reachability, with applications in computer science, network science, and graph theory. Despite their utility and ubiquity, they have several limitations, including that they are only defined for undirected networks, they significantly alter dynamics on networks, and they do not generally preserve important network features such as shortest distances, shortest path distribution, and community structure. In contrast, distance backbones, which are subgraphs formed by all edges that obey a generalized triangle inequality, are well defined in directed and undirected graphs and preserve those and other important network features. The backbone of a graph is defined with respect to a specified path-length operator that aggregates weights along a path to define its length, thereby associating a cost to indirect connections. The backbone is the union of all shortest paths between each pair of nodes according to the specified operator. One such operator, the max function, computes the length of a path as the largest weight of the edges that compose it (a weakest link criterion). It is the only operator that yields an algebraic structure for computing shortest paths that is consistent with De Morgan's laws. Applying this operator yields the ultrametric backbone of a graph in that (semi-triangular) edges whose weights are larger than the length of an indirect path connecting the same nodes (i.e. those that break the generalized triangle inequality based on max as a path-length operator) are removed. We show that the ultrametric backbone is the union of minimum spanning forests in undirected graphs and provides a new generalization of minimum spanning trees to directed graphs that, unlike minimum equivalent graphs and minimum spanning arborescences, preserves all max - min shortest paths and De Morgan's law consistency.

Adherence to adult clinical practice guidelines for Down syndrome.

Adults with Down syndrome (DS) have unique health care needs with evidence-based care guidelines to address these. Yet, the 2020 adult guidelines were unstudied; we aimed to assess adherence to these guidelines. We reviewed clinical and demographic data from medical charts of 327 adults with DS who were seen in the MGH DSP. We calculated adherence to care guidelines and analyzed correlations between both demographic traits and clinical results. Mean adherence rate to each of the nine adult guidelines was 67.3%. Adherence rates that were below our mean adherence rate included colonoscopy (42.9%), iron (41.9%), audiology specialist (35.8%), and audiogram (35.2%). We found four significant correlations: assigned females at birth had a significantly higher body mass index (BMI) than assigned males at birth (p < 0.001), Hispanic patients had a significantly higher BMI than other patients (p = 0.015), Hispanic patients had a significantly higher rate of diabetes than other patients (p = 0.036), and Black patients had a significantly lower rate of hypothyroidism than other patients (p = 0.004). We assessed the adherence rates to adult DS guidelines and highlighted disparities in healthcare for patients with DS to inform clinicians on how to improve care for patients with DS.

Proton-coupled electron transfer at a mis-metalated zinc site detected with protein charge ladders.

Distinguishing proton-coupled electron transfer (PCET) from uncoupled electron transfer (ET) in proteins can be challenging. A recent investigation [J. C. Koone, M. Simmang, D. L. Saenger, M. L. Hunsicker-Wang and B. F. Shaw, J. Am. Chem. Soc., 145, 16488-16497] reported that protein charge ladders and capillary electrophoresis can distinguish between single ET, PCET, and two-proton coupled ET (2PCET) by directly measuring the change in protein net charge upon reduction/oxidation (ΔZET). The current study used similar methods to assess PCET in zinc-free, "double copper" superoxide dismutase-1 (4Cu-SOD1), where one copper is bound at the copper site of each monomer and one copper is bound at the bridging zinc site, resulting in a quasi-type III Cu center. At pH 7.4, the net charge (Z) of the 4Cu-SOD1 dimer was unaffected by reduction of all four Cu2+ ions, i.e., ΔZ4ET = -0.09 ± 0.05 per dimer (-0.02 ± 0.01 per copper atom). These values suggest that PCET is taking place at all four Cu atoms of the homodimer. Molecular dynamics and Poisson-Boltzmann calculations suggest that a metal-coordinating histidine at the zinc site (His71) is the proton acceptor. These data show how ligands of a naturally occurring zinc site can help facilitate PCET when the right redox metal is bound.

Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation.

RATIONALE: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD. AIMS: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers. METHODS: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1ß were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity. RESULTS: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1ß, nor TNF-α (p's>0.05). CONCLUSION: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.

Estimation of maximum body size in fossil species: A case study using Tyrannosaurus rex.

Among extant species, the ability to sample the extremes of body size-one of the most useful predictors of an individual's ecology-is highly unlikely. This improbability is further exaggerated when sampling the already incomplete fossil record. We quantify the likelihood of sampling the uppermost limits of body size in the fossil record using Tyrannosaurus rex Osborn, 1905 as a model, selected for its comparatively well-understood life history parameters. We computationally generate a population of 140 million T. rex (based on prior estimates), modelling variation about the growth curve both with and without sexual dimorphism (the former modelled after Alligator mississippiensis), and building in sampling limitations related to species survivorship and taphonomic bias, derived from fossil data. The 99th percentile of body mass in T. rex has likely already been sampled, but it will probably be millennia before much larger giants (99.99th percentile) are sampled at present collecting rates. Biomechanical and ecological limitations notwithstanding, we estimate that the absolute largest T. rex may have been 70% more massive than the currently largest known specimen (~15,000 vs. ~8800 kg). Body size comparisons of fossil species should be based on ontogenetically controlled statistical parameters, rather than simply comparing the largest known individuals whose recovery is highly subject to sampling intensity.

The Impact of Culture Negativity on the Outcomes of Revision Total Knee Arthroplasty for Chronic PJI.

Culture-positive (CP) and culture-negative (CN) periprosthetic joint infections (PJI) remain a crucial area of research; however, current studies comparing these infections rely on unstandardized outcome reporting tools. Our study aimed to compare the outcomes of two-stage revision of CP and CN PJI using the standardized Musculoskeletal Infection Society (MSIS) outcome reporting tool. We retrospectively reviewed 138 patients who were diagnosed with PJI and indicated for two-stage revision total knee arthroplasty (rTKA). The majority of patients in both CP and CN cohorts achieved infection control without the need for reoperation (54.1% and 62.5%, respectively). There was a significant difference in the overall distribution of MSIS outcomes (p = 0.043), with a significantly greater rate of CN patients falling into Tier 1 (infection control without the use of suppressive antibiotics) (52.5% versus 29.6%, p = 0.011). There was also a significant difference in the distribution of septic versus aseptic reoperations after 2nd stage (p = 0.013), with more CP reoperations being septic and more CN reoperations being aseptic. The duration from first to second stage was significantly shorter in the CN cohort (p = 0.002). While overall infection control was similar between cohorts, these data suggest that the outcomes of two-stage rTKA are favorable in cases of CN PJI.

Viruses of free-roaming and hunting dogs in Uganda show elevated prevalence, richness and abundance across a gradient of contact with wildlife.

Domestic dogs (Canis lupus familiaris) live with humans, frequently contact other animals and may serve as intermediary hosts for the transmission of viruses. Free-roaming dogs, which account for over 70% of the world's domestic dog population, may pose a particularly high risk in this regard. We conducted an epidemiological study of dog viromes in three locations in Uganda, representing low, medium and high rates of contact with wildlife, ranging from dogs owned specifically for traditional hunting in a biodiversity and disease 'hotspot' to pets in an affluent suburb. We quantified rates of contact between dogs and wildlife through owner interviews and conducted canine veterinary health assessments. We then applied broad-spectrum viral metagenomics to blood plasma samples, from which we identified 46 viruses, 44 of which were previously undescribed, in three viral families, Sedoreoviridae, Parvoviridae and Anelloviridae. All 46 viruses (100 %) occurred in the high-contact population of dogs compared to 63 % and 39 % in the medium- and low-contact populations, respectively. Viral prevalence ranged from 2.1 % to 92.0 % among viruses and was highest, on average, in the high-contact population (22.3 %), followed by the medium-contact (12.3 %) and low-contact (4.8 %) populations. Viral richness (number of viruses per dog) ranged from 0 to 27 and was markedly higher, on average, in the high-contact population (10.2) than in the medium-contact (5.7) or low-contact (2.3) populations. Viral richness was strongly positively correlated with the number of times per year that a dog was fed wildlife and negatively correlated with the body condition score, body temperature and packed cell volume. Viral abundance (cumulative normalized metagenomic read density) varied 124-fold among dogs and was, on average, 4.1-fold higher and 2.4-fold higher in the high-contact population of dogs than in the low-contact or medium-contact populations, respectively. Viral abundance was also strongly positively correlated with the number of times per year that a dog was fed wildlife, negatively correlated with packed cell volume and positively correlated with white blood cell count. These trends were driven by nine viruses in the family Anelloviridae, genus Thetatorquevirus, and by one novel virus in the family Sedoreoviridae, genus Orbivirus. The genus Orbivirus contains zoonotic viruses and viruses that dogs can acquire through ingestion of infected meat. Overall, our findings show that viral prevalence, richness and abundance increased across a gradient of contact between dogs and wildlife and that the health status of the dog modified viral infection. Other ecological, geographic and social factors may also have contributed to these trends. Our finding of a novel orbivirus in dogs with high wildlife contact supports the idea that free-roaming dogs may serve as intermediary hosts for viruses of medical importance to humans and other animals.

Alcaligenes faecalis corrects aberrant matrix metalloproteinase expression to promote reepithelialization of diabetic wounds.

Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here, we focused on Alcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis treatment promotes reepithelialization of diabetic keratinocytes, a process that is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that A. faecalis treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.

Perspectives on the Impact of the COVID-19 Pandemic on Research: A Cross-Sectional Survey of Pediatric Otolaryngologists.

OBJECTIVE: To investigate the perspectives of pediatric otolaryngologists on the impact of the coronavirus disease 2019 (COVID-19) pandemic on their research. METHODS: Two surveys were sent to members of the American Society of Pediatric Otolaryngology (ASPO) in 2019 and 2021 to assess research perspectives before and during the COVID-19 pandemic. The surveys contained questions about research engagement, barriers, time allocation, and shifts in research focus. RESULTS: The COVID-19 pandemic reshaped research within pediatric otolaryngology, with a mixed impact on the amount of time allocated to research endeavors. Almost half of respondents reported a change in research focus to COVID-19-related studies. Protected time and funding were significant pre-pandemic barriers, whereas reduced staff, collaboration opportunities, and enrollment limitations emerged as key pandemic-related obstacles. A personal commitment to research was most strongly correlated with time spent on this endeavor. During the pandemic, women were less likely to report an increase in research activity when compared to men, possibly due to a disproportionate burden of caregiving on women during school closures and stay-at-home orders. CONCLUSION: Overall, the pandemic prompted both increases and decreases in research time allocation, depending on individual circumstances and priorities. Despite new challenges, pediatric otolaryngologists remain committed to research and have continued to remain productive.

Future Directions for Community-Engaged Research in Clinical Psychological Science with Youth.

Despite advances in clinical science, the burden of mental health problems among youth is not improving. To tackle this burden, clinical science with youth needs methods that include youth and family perspectives on context and public health. In this paper, we illustrate how community-engaged research (CEnR) methods center these perspectives. Although CEnR methods are well-established in other disciplines (e.g. social work, community psychology), they are underutilized in clinical science with youth. This is due in part to misperceptions of CEnR as resource-intensive, overly contextualized, incompatible with experimentally controlled modes of inquiry, or irrelevant to understanding youth mental health. By contrast, CEnR methods can provide real-world impact, contextualized clinical solutions, and sustainable outcomes. A key advantage of CEnR strategies is their flexibility-they fall across a continuum that centers community engagement as a core principle, and thus can be infused in a variety of research efforts, even those that center experimental control (e.g. randomized controlled trials). This paper provides a brief overview of this continuum of strategies and its application to youth-focused clinical science. We then discuss future directions of CEnR in clinical science with youth, as well as structural changes needed to advance this work. The goals of this paper are to help demystify CEnR and encourage clinical scientists to consider adopting methods that better consider context and intentionally engage the communities that our work seeks to serve.