Ecological correlates of species' roles in highly invaded seed dispersal networks.

Ecosystems with a mix of native and introduced species are increasing globally as extinction and introduction rates rise, resulting in novel species interactions. While species interactions are highly vulnerable to disturbance, little is known about the roles that introduced species play in novel interaction networks and what processes underlie such roles. Studying one of the most extreme cases of human-modified ecosystems, the island of O'ahu, Hawaii, we show that introduced species there shape the structure of seed dispersal networks to a greater extent than native species. Although both neutral and niche-based processes influenced network structure, niche-based processes played a larger role, despite theory predicting neutral processes to be predominantly important for islands. In fact, ecological correlates of species' roles (morphology, behavior, abundance) were largely similar to those in native-dominated networks. However, the most important ecological correlates varied with spatial scale and trophic level, highlighting the importance of examining these factors separately to unravel processes determining species contributions to network structure. Although introduced species integrate into interaction networks more deeply than previously thought, by examining the mechanistic basis of species' roles we can use traits to identify species that can be removed from (or added to) a system to improve crucial ecosystem functions, such as seed dispersal.

Mechanisms underlying interaction frequencies and robustness in a novel seed dispersal network: lessons for restoration.

As human-caused extinctions and invasions accumulate across the planet, understanding the processes governing ecological functions mediated by species interactions, and anticipating the effect of species loss on such functions become increasingly urgent. In seed dispersal networks, the mechanisms that influence interaction frequencies may also influence the capacity of a species to switch to alternative partners (rewiring), influencing network robustness. Studying seed dispersal interactions in novel ecosystems on O'ahu island, Hawai'i, we test whether the same mechanisms defining interaction frequencies can regulate rewiring and increase network robustness to simulated species extinctions. We found that spatial and temporal overlaps were the primary mechanisms underlying interaction frequencies, and the loss of the more connected species affected networks to a greater extent. Further, rewiring increased network robustness, and morphological matching and spatial and temporal overlaps between partners were more influential on network robustness than species abundances. We argue that to achieve self-sustaining ecosystems, restoration initiatives can consider optimal morphological matching and spatial and temporal overlaps between consumers and resources to maximize chances of native plant dispersal. Specifically, restoration initiatives may benefit from replacing invasive species with native species possessing characteristics that promote frequent interactions and increase the probability of rewiring (such as long fruiting periods, small seeds and broad distributions).

Call for improvement in medical school training in genetics: results of a national survey.

PURPOSE: To assess, from the student perspective, medical school training in genetics and genomics. METHODS: In 2019, the Undergraduate Training in Genomics (UTRIG) Working Group developed genetics-related survey and knowledge questions for the RISE-FIRST, an exam administered to postgraduate year 1 (PGY1) pathology residents in the United States during their first months of training. Survey questions focused on perceived knowledge in genetics and the structure and quality of training with responses compared with those in control areas. RESULTS: There were 401 PGY1 pathology residents who took the 2019 RISE-FIRST (65% of those in the United States). There was significantly lower perceived understanding of genetics compared with nongenetics topics. Respondents also reported less time spent learning genetics and lower quality training compared with control areas. Only 53% indicated an interaction during medical school with a medical geneticist. Residents also did not perform as well on the UTRIG-developed knowledge questions than those in other areas of pathology. CONCLUSION: The RISE-FIRST is a useful tool in assessing the current state of medical school training in genetics. This needs assessment may serve as a call to action to improve medical school genetics education and promote greater understanding of the role of genetics professionals in patient care.

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1 .

The Conundrum of Diagnosing Cutaneous Composite Lymphoma in the Molecular Age.

INTRODUCTION: Cutaneous composite lymphoma (CCL) is extremely rare. When 2 potentially distinct lymphoid lesions occur at one skin site, distinguishing between one neoplastic clone and a secondary reactionary lymphoid response versus a second neoplasm is difficult. In this study, we describe a unique case of CCL along with a review of reported cases in literature to identify clues and discuss issues that are relevant to the diagnosis of CCL. DESIGN: Review of a CCL case from our institution and a systematic review of reported cases of CCL in the literature. RESULTS: A total of 18 studies describing 22 cases and a case report from our institution are included. The mean age at diagnosis was 68 years. Most cases herein presented with multiple skin lesions (67%) and reported a history of immune suppression (76%). Nineteen cases (83%) had a combination of T-cell and B-cell neoplasms, whereas the remaining cases had 2 distinct B-cell clones. Clonal differentiation was confirmed based on morphology and immunohistochemistry in all cases, and by polymerase chain reaction studies in 19 cases. Complete remission was achieved in only one quarter of reported cases. CONCLUSION: Diagnosing CCL can be challenging because accurate differentiation of 2 or more clonal populations at 1 site is tedious. A stepwise approach and integration of clinical, morphologic, immunohistochemistry, and molecular data along with an understanding of the prognosis of the lymphomas in question is essential for an accurate diagnosis and necessary because of therapeutic and prognostic implications.

Protective Actions of Epithelial 5-Hydroxytryptamine 4 Receptors in Normal and Inflamed Colon.

BACKGROUND & AIMS: The 5-hydroxytryptamine receptor 4 (5-HT4R or HTR4) is expressed in the colonic epithelium but little is known about its functions there. We examined whether activation of colonic epithelial 5-HT4R protects colons of mice from inflammation. METHODS: The 5-HT4R agonist tegaserod (1 mg/kg), the 5-HT4R antagonist GR113808 (1 mg/kg), or vehicle (control) were delivered by enema to wild-type or 5-HT4R knockout mice at the onset of, or during, active colitis, induced by administration of dextran sodium sulfate or trinitrobenzene sulfonic acid. Inflammation was measured using the colitis disease activity index and by histologic analysis of intestinal tissues. Epithelial proliferation, wound healing, and resistance to oxidative stress-induced apoptosis were assessed, as was colonic motility. RESULTS: Rectal administration of tegaserod reduced the severity of colitis compared with mice given vehicle, and accelerated recovery from active colitis. Rectal tegaserod did not improve colitis in 5-HT4R knockout mice, and intraperitoneally administered tegaserod did not protect wild-type mice from colitis. Tegaserod increased proliferation of crypt epithelial cells. Stimulation of 5-HT4R increased Caco-2 cell migration and reduced oxidative stress-induced apoptosis; these actions were blocked by co-administration of the 5-HT4R antagonist GR113808. In noninflamed colons of wild-type mice not receiving tegaserod, inhibition of 5-HT4Rs resulted in signs of colitis within 3 days. In these mice, epithelial proliferation decreased and bacterial translocation to the liver and spleen was detected. Daily administration of tegaserod increased motility in inflamed colons of guinea pigs and mice, whereas administration of GR113808 disrupted motility in animals without colitis. CONCLUSIONS: 5-HT4R activation maintains motility in healthy colons of mice and guinea pigs, and reduces inflammation in colons of mice with colitis. Agonists might be developed as treatments for patients with inflammatory bowel diseases.

Natural History of Patients Presenting with Autoimmune Hepatitis and Coincident Nonalcoholic Fatty Liver Disease.

BACKGROUND: Given the increase of nonalcoholic fatty liver disease (NAFLD) in the general population, a similar rise might be expected in autoimmune hepatitis (AIH) patients. AIMS: We sought to determine the clinical outcome of patients with coincident AIH and NAFLD. METHODS: We identified all intradepartmental AIH cases, and those meeting study criteria were placed into one of three cohorts: AIH only, AIH and simple steatosis (SS), and AIH and nonalcoholic steatohepatitis (NASH). The following outcome and clinical data were analyzed: incidence of all-cause mortality, incidence of liver-related mortality, incidence of liver-related adverse outcomes, and prevalence of cirrhosis at index biopsy. RESULTS: Out of a total 73 study patients, 14 % classified as AIH with SS and 16 % as AIH and NASH. Fifty percent of AIH and NASH patients had cirrhosis at index biopsy as compared to 18 % of AIH-only patients (p = 0.032). Patients with AIH and NASH had a relative risk of 7.65 (95 % CI 1.43-40.8) for liver-related mortality and 2.55 (95 % CI 0.92-7.09) for liver-related adverse outcomes, as compared to the AIH-only cohort. No significant difference in outcome measures existed in comparing (AIH only) with (AIH and SS) cohorts. DISCUSSION: Patients with coincident AIH and NASH were more likely to present with cirrhosis and more likely to develop adverse clinical outcome with decreased survival as compared to AIH-only patients. These findings suggest that simultaneous exposure confers a clinically significant increased risk, which may warrant closer follow-up and surveillance.

Affinity for natal environments by dispersers impacts reproduction and explains geographical structure of a highly mobile bird.

Understanding dispersal and habitat selection behaviours is central to many problems in ecology, evolution and conservation. One factor often hypothesized to influence habitat selection by dispersers is the natal environment experienced by juveniles. Nonetheless, evidence for the effect of natal environment on dispersing, wild vertebrates remains limited. Using 18 years of nesting and mark-resight data across an entire North American geographical range of an endangered bird, the snail kite (Rostrhamus sociabilis), we tested for natal effects on breeding-site selection by dispersers and its consequences for reproductive success and population structure. Dispersing snail kites were more likely to nest in wetlands of the same habitat type (lacustrine or palustrine) as their natal wetland, independent of dispersal distance, but this preference declined with age and if individuals were born during droughts. Importantly, dispersing kites that bred in natal-like habitats had lower nest success and productivity than kites that did not. These behaviours help explain recently described population connectivity and spatial structure across their geographical range and reveal that assortative breeding is occurring, where birds are more likely to breed with individuals born in the same wetland type as their natal habitat. Natal environments can thus have long-term and large-scale effects on populations in nature, even in highly mobile animals.

Antisecretory medication is associated with decreased Helicobacter pylori detection in gastric marginal zone lymphoma.

Helicobacter pylori status influences the prognosis and management of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), so accurate determination of H pylori status is of clinical importance. The low rate of histologic H pylori positivity among gastric MALT lymphoma cases at our institution prompted investigation for possible causes. A case series of 24 patients as having gastric MALT lymphoma (with no diffuse large B-cell component) in a tertiary care setting between 1997 and 2010 was identified, and clinical records were reviewed. Immunohistochemical staining for H pylori and BCL10 was performed. This study received institutional review board approval (protocol number M13-033). Thirty-nine percent of cases (9/23) were H pylori positive by histology, and 4 additional patients had positive serologic results; overall, 57% of cases (13/23) were positive for H pylori. Treatment with antisecretory medications was associated with a lower likelihood of histologic positivity (13% among treated patients vs 75% among untreated; P = .04). Nuclear localization of BCL10 was seen in 2 cases and was not associated with H pylori status. Antisecretory medications decrease the likelihood of histologic detection of H pylori in gastric MALT lymphoma cases. Incorporation of results of serologic or other testing is needed to ensure correct classification with respect to H pylori status.

Impact of Schwartz enhanced visualization solution on staging colorectal cancer and clinicopathological features associated with lymph node count.

BACKGROUND: Stage-specific survival for colon cancer improves when more lymph nodes are reported in the surgical specimen. This has led to a minimum standard of identifying 12 lymph nodes as a quality indicator. OBJECTIVE: The aim of this study was to determine whether the addition of Schwartz solution increases node yield and impacts pathologic staging. DESIGN: This is a prospective cohort study. SETTING: The study was conducted in an academic medical center. PATIENTS: Included were 104 consecutive patients with colorectal cancer. MAIN OUTCOME MEASURES: Lymph node counts before and after specimen treatment with Schwartz solution and incidence of upstaging were measured. RESULTS: An additional 20 minutes (interquartile range, 15-40 minutes) was spent searching for lymph nodes, increasing the median number of nodes from 22.5 to 29.0 nodes. However, only 1 patient was upstaged. Schwartz solution decreased the number of specimens with less than 12 lymph nodes from 15 to 6. The following factors were associated with Schwartz solution leading to the detection of additional nodes: number of nodes detected initially with formalin only (p < 0.000), mesenteric fat volume (p < 0.000), mesenteric fat weight (p < 0.000), length of specimen (p < 0.016), tumor greatest dimension (p < 0.016), patient body surface area (p < 0.034), and patient age (p < 0.003). LIMITATIONS: Clinical data for this study were obtained retrospectively and were not available for all of the patients. CONCLUSIONS: Although Schwartz solution increased the number of nodes detected in 95% of patients and improved compliance with the 12-node standard for colon resection, there was minimal impact on cancer staging. Upstaging is unlikely to explain the increase in overall survival in patients with higher lymph node counts, casting doubt on the validity of this process measure as a meaningful quality indicator. Rather, the lymph node count may be a reflection of inherent tumor biology or host-related factors.

Equity, community, and accountability: Leveraging a department-level climate survey as a tool for action.

Organizational climate is a key determinant of diverse aspects of success in work settings, including in academia. Power dynamics in higher education can result in inequitable experiences of workplace climate, potentially harming the well-being and productivity of employees. Quantifying experiences of climate across employment categories can help identify changes necessary to create a more equitable workplace for all. We developed and administered a climate survey within our academic workplace-the Department of Zoology and Physiology at the University of Wyoming-to evaluate experiences of climate across three employment categories: faculty, graduate students, and staff. Our survey included a combination of closed-response (e.g., Likert-scale) and open-ended questions. Most department members (82%) completed the survey, which was administered in fall 2021. Faculty generally reported more positive experiences than staff. Graduate students often fell between these two groups, though in some survey sections (e.g., mental health and well-being) students reported the most negative experiences of departmental climate. Three common themes emerged from the analysis of open-ended responses: equity, community, and accountability. We discuss how these themes correspond to concrete action items for improving our departmental climate, some of which have been implemented already, while others constitute future initiatives and/or require a collective push towards systemic change in academia. Finally, service work of this type often falls outside of job descriptions, requiring individuals to either work more or trade-off productivity in other areas that are formally evaluated. With the goal of minimizing this burden for others, we detail our process and provide the materials and framework necessary to streamline this process for other departments aiming to evaluate workplace climate as a key first step in building a positive work environment for all employees.

The role of connexin-36 gap junctions in alcohol intoxication and consumption.

Ventral tegmental area (VTA) GABA neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in alcohol reward. The aim of this study was to examine the role of midbrain connexin-36 (Cx36) gap junctions (GJs) in ethanol intoxication and consumption. Using behavioral, molecular, and electrophysiological methods, we compared the effects of ethanol in mature Cx36 knockout (KO) mice and age-matched wild-type (WT) controls. Compared to WT mice, Cx36 KO mice exhibited significantly more ethanol-induced motor impairment in the open field test, but less disruption in motor coordination in the rotarod paradigm. Cx36 KO mice, and WT mice treated with the Cx36 antagonist mefloquine (MFQ), consumed significantly less ethanol than their WT controls in the drink-in-the-dark procedure. The firing rate of VTA GABA neurons in WT mice was inhibited by ethanol with an IC50 of 0.25 g/kg, while VTA GABA neurons in KO mice were significantly less sensitive to ethanol. Dopamine neuron GABA-mediated sIPSC frequency was reduced by ethanol (30 mM) in WT mice, but not affected in KO mice. Cx36 KO mice evinced a significant up-regulation in DAT and D2 receptors in the VTA, as assessed by quantitative RT-PCR. These findings demonstrate the behavioral relevance of Cx36 GJ-mediated electrical coupling between GABA neurons in mature animals, and suggest that loss of coupling between VTA GABA neurons results in disinhibition of DA neurons, a hyper-DAergic state and lowered hedonic valence for ethanol consumption.

Mefloquine effects on ventral tegmental area dopamine and GABA neuron inhibition: a physiologic role for connexin-36 GAP junctions.

Connexin-36 (Cx36) gap junctions (GJs) appear to be involved in the synchronization of GABA interneurons in many brain areas. We have previously identified a population of Cx36-connected ventral tegmental area (VTA) GABA neurons that may regulate mesolimbic dopamine (DA) neurotransmission, a system implicated in reward from both natural behaviors and drugs of abuse. The aim of this study was to determine the effect mefloquine (MFQ) has on midbrain DA and GABA neuron inhibition, and the role Cx36 GJs play in regulating midbrain VTA DA neuron activity in mice. In brain slices from adolescent wild-type (WT) mice the Cx36-selective GJ blocker mefloquine (MFQ, 25 µM) increased VTA DA neuron sIPSC frequency sixfold, and mIPSC frequency threefold. However, in Cx36 KO mice, MFQ only increased sIPSC and mIPSC frequency threefold. The nonselective GJ blocker carbenoxolone (CBX, 100 µM) increased DA neuron sIPSC frequency twofold in WT mice, did not affect Cx36 KO mouse sIPSCs, and did not affect mIPSCs in WT or Cx36 KO mice. Interestingly, MFQ had no effect on VTA GABA neuron sIPSC frequency. We also examined MFQ effects on VTA DA neuron firing rate and current-evoked spiking in WT and Cx36 KO mice, and found that MFQ decreased WT DA neuron firing rate and current-evoked spiking, but did not alter these measures in Cx36 KO mice. Taken together these findings suggest that blocking Cx36 GJs increases VTA DA neuron inhibition, and that GJs play in key role in regulating inhibition of VTA DA neurons. Synapse, 2011. © 2011 Wiley-Liss, Inc.

Engage in Exploration: Pathology Gross Laboratory in the COVID-Era.

The outbreak of Covid-19 has changed education, including the mechanism of delivery of gross pathology laboratories. Herein, we describe how we revised our preclinical gross pathology lab to a flipped model to fit with COVID-19 regulations. A series of short, session objective-driven videos are made available online. Students are expected to watch the videos before coming to the hands-on lab. Groups of 2 students enter the gross lab on a timed basis and rotate through a series of stations. At each station, students examine gross pathology specimens while answering questions designed to apply the clinical correlation of pathophysiology and heighten observational skills. One or 2 pathologists are available throughout the lab session to address the questions from the students. The design of this laboratory exercise maintains appropriate distancing and hygiene in the time of COVID-19. The laboratory rooms are mapped to set up an appropriate number of timed stations. Flow-through of the rooms is unidirectional. Comparing with the traditional show-and-tell of teaching gross pathology, the renovated flipped model is genuinely student-centered and focuses on active learning. Holding the specimen in their hands, students learn from discovery as they are completely engaged by exploring the specimen and deriving answers themselves. The flipped learning gross pathology method has been very well received and evaluated highly by both faculty and students.

Choosing Wisely in Pre-clinical Medical Education: a Direct Comparison of Active Learning Methods for Teaching Metabolic Liver Disease.

BACKGROUND: With the movement away from lectures and towards active learning sessions, medical school faculty must choose a format that fits the learning objectives and is achievable with available resources. Small groups bring organizational challenges including additional faculty and classrooms. Large groups are an opportunity to conduct case-based active learning exercises with fewer faculty. Our study compares the learning effectiveness of an active learning session on metabolic liver disease conducted in both the small group and large group formats. METHODS: All MS1 students at University of Vermont Larner College of Medicine (LCOM) (n = 120) were randomized to participate in either the small or large group session. The same pre-learning videos and computer-based active learning module were used for all students in both session types. A post-session questionnaire was administered, and student exam performance was analyzed to evaluate each session type on the following criteria: (1) student preparedness for the session, (2) student perceptions of the session's learning effectiveness, (3) learner knowledge upon completion of the session, and (4) knowledge retention at 10 days. RESULTS: No statistically significant differences were found between the large and small group cohorts on student perceptions of learning effectiveness or knowledge assessment, both immediate and delayed. Students assigned to the large group did choose their collaborators differently than those in the small group, tending more often to work with their friends. CONCLUSION: When organized well, a large group active learning format may be used in place of a small group without diminishing the learning effectiveness of the activity.

Design and Implementation of a Pathology-Specific Handoff Tool for Residents.

Miscommunication is a source of clinical errors. Tools to decrease the risk of miscommunication (ie, patient handoff tools) are routinely used in clinical specialties that see patients but not routinely used in pathology residency programs. Our primary goal was to develop a structured handoff tool for pathology residents useful for both patient-specific communication and information about general laboratory operation with a secondary goal to increase resident confidence in on-call situations. The CATCH tool was developed and implemented in a pathology residency program with a pre- and postimplementation survey given to residents. The structured handoff tool for pathology residents provided consistent and timely communication between residents and attending physicians. Resident confidence with pathology on-call issues was more likely related to progression through the residency training program rather than implementation of a structured handoff tool.

Teaching Genomic Pathology: Translating Team-Based Learning to a Virtual Environment Using Computer-Based Simulation.

CONTEXT.­: Developing skills related to use of computer-based tools is critical for practicing genomic pathology. However, given the relative novelty of genomics education, residency programs may lack faculty members with adequate expertise and/or time to implement training. A virtual team-based learning (TBL) environment would make genomic pathology education available to more trainees. OBJECTIVE.­: To translate an extensively implemented in-person TBL genomic pathology workshop into a virtual environment and to evaluate both knowledge and skill acquisition. DESIGN.­: Using a novel interactive simulation approach, online modules were developed translating aspects of the TBL experience into the virtual environment with a goal of acquisition of necessary computer-related skills. The modules were evaluated at 10 postgraduate pathology training programs using a pre-post test design with participants deidentified. A postmodule anonymous survey obtained participant feedback on module quality and efficacy. RESULTS.­: There were 147 trainees who received an email request to voluntarily participate in the study. Of these, 43 trainees completed the pretest and 15 (35%) subsequently completed the posttest. Mean overall scores were 45% on the pretest compared with 70% on the posttest ( P < .001; effect size = 1.4). Posttest improvement of results was similar for questions testing acquisition of knowledge versus skills. Regarding the 19 participants who took the survey, 18 (95%) would recommend the modules to others and believed they met the stated objectives. CONCLUSIONS.­: A simulation-based approach allows motivated pathology trainees to acquire computer-related skills for practicing genomic pathology. Future work can explore efficacy in a nonvoluntary setting and adaptation to different specialties, learners, and computer tools.