Successful implementation of telehealth visits in the paediatric heart failure and heart transplant population.

The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a working group at the beginning of 2020 during the COVID-19 pandemic, with the aim of using telehealth as an alternative medium to provide quality care to a high-acuity paediatric population receiving advanced cardiac therapies. An algorithm was developed to determine appropriateness, educational handouts were developed for both patients and providers, and post-visit surveys were collected. Telehealth was found to be a viable modality for health care delivery in the paediatric heart failure and transplant population and has promising application in the continuity of follow-up, medication titration, and patient education/counselling domains.

Mysterious microsporidians: springtime outbreaks of disease in Daphnia communities in shallow pond ecosystems.

Parasites can play key roles in ecosystems, especially when they infect common hosts that play important ecological roles. Daphnia are critical grazers in many lentic freshwater ecosystems and typically reach peak densities in early spring. Daphnia have also become prominent model host organisms for the field of disease ecology, although most well-studied parasites infect them in summer or fall. Here, we report field patterns of virulent microsporidian parasites that consistently infect Daphnia in springtime, in a set of seven shallow ponds in Georgia, USA, sampled every 3-4 weeks for 18 months. We detected two distinct parasite taxa, closely matching sequences of Pseudoberwaldia daphniae and Conglomerata obtusa, both infecting all three resident species of Daphnia: D. ambigua, D. laevis, and D. parvula. To our knowledge, neither parasite has been previously reported in any of these host species or anywhere in North America. Infection prevalence peaked consistently in February-May, but the severity of these outbreaks differed substantially among ponds. Moreover, host species differed markedly in terms of their maximum infection prevalence (5% [D. parvula] to 72% [D. laevis]), mean reduction of fecundity when infected (70.6% [D. ambigua] to 99.8% [D. laevis]), mean spore yield (62,000 [D. parvula] to 377,000 [D. laevis] per host), and likelihood of being infected by each parasite. The timing and severity of the outbreaks suggests that these parasites could be impactful members of these shallow freshwater ecosystems, and that the strength of their effects is likely to hinge on the composition of ponds' zooplankton communities.

Outcomes after initial heart failure consultation in Fontan patients.

BACKGROUND: Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care. METHODS: This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as "too late" (death or declined for transplant due to being too sick) and/or "care escalation" (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. "Late referral" was defined as those referred too late and/or had care escalation. RESULTS: Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8-21.5, p=0.004). CONCLUSIONS: Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Prevalence of Immunomodulator Use as Combination Therapy With Vedolizumab or Ustekinumab in Inflammatory Bowel Disease.

INTRODUCTION: The benefit of adding an immunomodulator to vedolizumab and ustekinumab remains unclear and may compromise the safety of these biologics. We evaluated the prevalence and predictors of immunomodulator use with vedolizumab or ustekinumab in patients with inflammatory bowel disease in a large longitudinal cohort. METHODS: Clinical information was ascertained from electronic medical records of patients enrolled in TARGET-IBD, a prospective longitudinal observational cohort of patients with inflammatory bowel disease (IBD) at 34 sites. The prevalence of immunomodulator use with vedolizumab, ustekinumab, and antitumor necrosis factor therapies and predictors of immunomodulator use with vedolizumab and ustekinumab were estimated. Rates of combination therapy were additionally stratified by time from drug approval. RESULTS: Four thousand thirty-nine adults with IBD were identified, of whom 18.8% were treated with vedolizumab and 13.0% were treated with ustekinumab. Combination therapy with vedolizumab and ustekinumab exceeded 30% (30.7% and 36.2%, respectively) and was more likely in those with perianal disease or previous biologic exposure. Age and presence of extraintestinal manifestations did not consistently predict the use of an immunomodulator. Combination therapy decreased in the years after drug approval. DISCUSSION: Combination therapy with vedolizumab or ustekinumab was common and was associated with perianal disease and greater exposure to other biologics, although the practice is decreasing with time. Further data are needed to determine the efficacy and safety of combination therapy in patients initiating vedolizumab or ustekinumab for IBD.

Herbivory and nutrients shape grassland soil seed banks.

Anthropogenic nutrient enrichment and shifts in herbivory can lead to dramatic changes in the composition and diversity of aboveground plant communities. In turn, this can alter seed banks in the soil, which are cryptic reservoirs of plant diversity. Here, we use data from seven Nutrient Network grassland sites on four continents, encompassing a range of climatic and environmental conditions, to test the joint effects of fertilization and aboveground mammalian herbivory on seed banks and on the similarity between aboveground plant communities and seed banks. We find that fertilization decreases plant species richness and diversity in seed banks, and homogenizes composition between aboveground and seed bank communities. Fertilization increases seed bank abundance especially in the presence of herbivores, while this effect is smaller in the absence of herbivores. Our findings highlight that nutrient enrichment can weaken a diversity maintaining mechanism in grasslands, and that herbivory needs to be considered when assessing nutrient enrichment effects on seed bank abundance.

Administrative Databases: Friend or Foe in Paediatric Cardiomyopathy.

Background: Cardiomyopathy (CM) is a rare childhood disease associated with morbidity and mortality. Limited data exist on paediatric CM in Canada. Given the rare nature, single-centre studies are not sufficiently powered to address important questions. Therefore, administrative health data may serve as a resource for the study of childhood CM. The goal of this study was to validate the accuracy of International Classification of Diseases (ICD)-based algorithms to identify paediatric CM in health databases using a clinical registry as the gold standard. Methods: The clinical registry was compiled from outpatient and inpatient records at the Stollery Children's Hospital (January 1, 2013, to December 31, 2021). Patients were categorized as having CM or screened without CM. Data were linked to administrative health databases using the patient's Unique Lifetime Identifier. Algorithms based on the presence of ICD, 10th Revision, codes for CM were then evaluated, and cross-tabulations against the clinical registry were generated. Accuracy, positive predictive value, negative predictive value, sensitivity, and specificity were calculated. Results: The clinical registry had 90 patients with CM and 249 screened without CM. The algorithms ruled out CM (high negative predictive value) but had variability in the ability to diagnose CM positive predictive value. The algorithm that performed the best was based on a diagnosis of CM in a hospitalization or 2 ambulatory visits. Conclusions: A combination of inpatient and outpatient databases can be used, with acceptable accuracy, to identify paediatric patients with CM. This finding allows for the use of the identified algorithm for the comprehensive study of paediatric CM in Canada.

Contexte: La cardiomyopathie (CM) est une maladie rare de l'enfance associée à des taux élevés de morbidité et de mortalité et sur laquelle les données sont limitées en contexte canadien. En raison de la rareté de cette maladie, les études monocentriques ne peuvent atteindre la puissance statistique nécessaire pour répondre à certaines questions importantes. Les données administratives sur la santé peuvent donc constituer une ressource intéressante pour examiner la CM chez les enfants. La présente étude visait à valider l'exactitude d'algorithmes fondés sur la Classification internationale des maladies (CIM) pour repérer les cas de CM pédiatrique dans des bases de données sur la santé, en utilisant un registre clinique comme référence. Méthodologie: Un registre clinique a été élaboré à partir des dossiers de clinique interne et externe du Stollery Children's Hospital (du 1er janvier 2013 au 31 décembre 2021). Les patients ont été classés en deux catégories : atteints de CM ou dépistés sans CM. Les données ont été liées aux bases de données administratives sur la santé en utilisant le numéro d'identification unique des patients (Unique Lifetime Identifier). Des algorithmes fondés sur les codes de la CIM-10 ont été évalués et des analyses croisées avec le registre clinique ont été réalisées. L'exactitude, la valeur prédictive positive (VPP), la valeur prédictive négative (VPN), la sensibilité et la spécificité des algorithmes ont été calculées. Résultats: Le registre clinique comprenait 90 patients atteints de CM et 249 patients dépistés sans CM. Les algorithmes permettaient d'exclure correctement la CM (VPN élevée), mais leur capacité à établir le diagnostic de CM variait (VPP). L'algorithme le plus performant était fondé sur l'attribution d'un code diagnostique de CM lors d'une hospitalisation ou de deux visites ambulatoires. Conclusions: La combinaison de bases de données sur les hospitalisations et sur les soins externes peut être utilisée pour identifier les enfants atteints de CM avec une exactitude acceptable. Cette observation corrobore l'utilisation de l'algorithme ciblé pour réaliser une étude exhaustive de la CM chez l'enfant au Canada.

Realistic rates of nitrogen addition increase carbon flux rates but do not change soil carbon stocks in a temperate grassland.

Changes in the biosphere carbon (C) sink are of utmost importance given rising atmospheric CO2 levels. Concurrent global changes, such as increasing nitrogen (N) deposition, are affecting how much C can be stored in terrestrial ecosystems. Understanding the extent of these impacts will help in predicting the fate of the biosphere C sink. However, most N addition experiments add N in rates that greatly exceed ambient rates of N deposition, making inference from current knowledge difficult. Here, we leveraged data from a 13-year N addition gradient experiment with addition rates spanning realistic rates of N deposition (0, 1, 5, and 10 g N m-2  year-1 ) to assess the rates of N addition at which C uptake and storage were stimulated in a temperate grassland. Very low rates of N addition stimulated gross primary productivity and plant biomass, but also stimulated ecosystem respiration such that there was no net change in C uptake or storage. Furthermore, we found consistent, nonlinear relationships between N addition rate and plant responses such that intermediate rates of N addition induced the greatest ecosystem responses. Soil pH and microbial biomass and respiration all declined with increasing N addition indicating that negative consequences of N addition have direct effects on belowground processes, which could then affect whole ecosystem C uptake and storage. Our work demonstrates that experiments that add large amounts of N may be underestimating the effect of low to intermediate rates of N deposition on grassland C cycling. Furthermore, we show that plant biomass does not reliably indicate rates of C uptake or soil C storage, and that measuring rates of C loss (i.e., ecosystem and soil respiration) in conjunction with rates of C uptake and C pools are crucial for accurately understanding grassland C storage.

Drooping After Scoping: A Rare Case of Peripheral Facial Nerve Palsy After RoutineEsophagogastroduodenoscopy.

Peripheral facial nerve palsy is a prevalent type of mononeuropathy that can have a variety of etiologies. Facial nerve damage because of esophagogastroduodenoscopy, however, is exceedingly rare and has only been reported in 1 patient. We report the first case in the United States of a patient who developed left-sided facial nerve palsy after a routine esophagogastroduodenoscopy, with little meaningful recovery of nerve function. We hope to bring awareness to gastroenterologists of this rare complication with potential long-term detrimental effects that can be avoided with the adjustment of equipment and patient position before the procedure.

Adult-like neural representation of species-specific songs in the auditory forebrain of zebra finch nestlings.

Encoding of conspecific signals during development can reinforce species barriers as well as set the stage for learning and production of species-typical vocalizations. In altricial songbirds, the development of the auditory system is not complete at hatching, so it is unknown the degree to which recently hatched young can process auditory signals like birdsong. We measured in vivo extracellular responses to song stimuli in a zebra finch (Taeniopygia guttata) secondary auditory forebrain region, the caudomedial nidopallium (NCM). We recorded from three age groups between 13 days post-hatch and adult to identify possible shifts in stimulus encoding that occur before the opening of the sensitive period of song motor learning. We did not find differences in putative cell type composition, firing rate, response strength, and selectivity across ages. Across ages narrow-spiking units had higher firing rates, response strength, accuracy, and trial-by-trial reliability along with lower selectivity than broad-spiking units. In addition, we showed that stimulus-specific adaptation, a characteristic of adult NCM, was also present in nestlings and fledglings. These results indicate that most features of secondary auditory processing are already adult-like shortly after hatching. Furthermore, we showed that selectivity for species-specific stimuli is similar across all ages, with the greatest fidelity in temporal coding in response to conspecific song and domesticated Bengalese finch song, and reduced fidelity in response to owl finch song, a more ecologically relevant heterospecific, and white noise. Our study provides the first evidence that the electrophysiological properties of higher-order auditory neurons are already mature in nestling songbirds.

Cervical Cancer Screening in Inflammatory Bowel Disease: Who Should Be Screening?

BACKGROUND: Immunosuppressed women with inflammatory bowel disease (IBD) are at elevated risk of cervical cancer yet have lower screening rates. The objective of this study was to assess the familiarity with cervical cancer screening recommendations, and the perceived responsibility for implementing screening among three physician groups involved in the clinical care of women with IBD: primary care physicians (PCP), gastroenterologists (GI) and gynecologists (GYN). METHODS: We anonymously surveyed a sample of 117 PCP, 52 GYN and 35 GI physicians affiliated with Saint Louis University, Saint Louis, MO, USA, from April 2018 to January 2019. The physicians completed a questionnaire adressing essential aspects of cervical cancer screening such as screening age, screening frequency, human papillomavirus (HPV) vaccination, comfort level in performing Papanicolaou (Pap) smears, perception of physician responsibility in terms of which physicians should perform Pap smears. RESULTS: A total of 2.6% of PCPs, 37% of GIs and 29% of GYNs reported familiarity with cervical cancer screening recommendations. In addition, PCP and GI had no definite opinions regarding which physicians should be in charge of cervical cancer screening and performing Pap smears. However, 94% of GYNs felt that they should be in charge of cervical cancer screening and performing Pap smears. CONCLUSIONS: An apparent lack of familiarity exists among all three physician groups regarding cervical cancer screening recommendations in immunosuppressed patients with IBD. Similarly, there is no consensus regarding which specialty should be responsible for cervical cancer screening in this patient population.

Fungal Bioremediation of Selenium-Contaminated Industrial and Municipal Wastewaters.

Selenium (Se) is an essential element for most organisms yet can cause severe negative biological consequences at elevated levels. The oxidized forms of Se, selenate [Se(VI)] and selenite [Se(IV)], are more mobile, toxic, and bioavailable than the reduced forms of Se such as volatile or solid phases. Thus, selenate and selenite pose a greater threat to ecosystems and human health. As current Se remediation technologies have varying efficiencies and costs, novel strategies to remove elevated Se levels from environments impacted by anthropogenic activities are desirable. Some common soil fungi quickly remove Se (IV and VI) from solution by aerobic reduction to solid or volatile forms. Here, we perform bench-scale culture experiments of two Se-reducing Ascomycota to determine their Se removal capacity in growth media conditions containing either Se(IV) or Se(VI) as well as in Se-containing municipal (∼25 µg/L Se) and industrial (∼2000 µg/L Se) wastewaters. Dissolved Se was measured throughout the experiments to assess Se concentration and removal rates. Additionally, solid-associated Se was quantified at the end of each experiment to determine the amount of Se removed to solid phases (e.g., Se(0) nanoparticles, biomass-adsorbed Se, or internal organic selenoproteins). Results show that under optimal conditions, fungi more efficiently remove Se(IV) from solution compared to Se(VI). Additionally, both fungi remove a higher percentage of Se from the filtered municipal wastewater compared to the industrial wastewater, though cultures in industrial wastewater retained a greater amount of solid-associated Se. Additional wastewater experiments were conducted with supplemental carbohydrate- or glycerin-based carbon products and additional nitrogen- and phosphorous-containing nutrients in some cases to enhance fungal growth. Relative to unamended wastewater experiments, supplemental carbohydrates promote Se removal from municipal wastewater but minimally impact industrial wastewater removal. This demonstrates that carbon availability and source impacts fungal Se reduction and removal from solution. Calculations to assess the leaching potential of solid-associated Se from fungal biomass show that wastewater Se release will not exceed regulatory limits. This study highlights the considerable potential for the mycoremediation of Se-contaminated wastewaters.

Health Maintenance and Vaccination of Patients With Inflammatory Bowel Disease: Practice and Perception of Responsibility of Gastroenterologists vs Primary Care Providers.

Background: Although it is well established that patients with inflammatory bowel disease (IBD) are at increased risk of complicating diseases and vaccination-preventable infections, whether gastroenterologists (GIs) or primary care providers (PCPs) assume responsibility for these patients' health maintenance is not clear. Methods: We anonymously surveyed a convenience sample of 94 PCPs and 61 GIs at Saint Louis University School of Medicine in St. Louis, MO, about their practice and perception of the health maintenance and vaccination of patients with IBD. Results: Response rates were 82% and 93% for GIs and PCPs, respectively. GIs were as likely as PCPs to screen for smoking (88% vs 89%) and were significantly less likely to screen for depression/anxiety (24% vs 54%) or to provide pertussis (14% vs 44%) or diphtheria (20% vs 48%) vaccines. GIs were significantly more likely than PCPs to assess for colonoscopy need (94% vs 80%); to screen for nonmelanoma skin cancer (62% vs 14%), melanoma (56% vs 7%), osteoporosis (72% vs 51%), or tuberculosis (94% vs 44%); to prescribe calcium/vitamin D (74% vs 53%); to perform nutritional assessment (78% vs 33%); or to provide hepatitis A (60% vs 39%) or hepatitis B (86% vs 56%) vaccines. GIs were as likely as PCPs (64% vs 75%) to perceive that PCPs should order vaccinations and significantly more likely to perceive that GIs should track vaccinations (58% vs 16%) and other health maintenance issues (90% vs 49%). We found positive associations between performing the various health maintenance and vaccination tasks and the perception of responsibility. Conclusion: Several health maintenance aspects are inadequately addressed by GIs and PCPs, in part because of conflicting perceptions of responsibility. Clear guidelines and better GI/PCP communication are required to ensure effective health maintenance for patients with IBD.

The variability of song variability in zebra finch (Taeniopygia guttata) populations.

Birdsong is a classic example of a learned social behaviour. Song behaviour is also influenced by genetic factors, and understanding the relative contributions of genetic and environmental influences remains a major goal. In this study, we take advantage of captive zebra finch populations to examine variation in a population-level song trait: song variability. Song variability is of particular interest in the context of individual recognition and in terms of the neuro-developmental mechanisms that generate song novelty. We find that the Australian zebra finch Taeniopygia guttata castanotis (TGC) maintains higher song diversity than the Timor zebra finch T. g. guttata (TGG) even after experimentally controlling for early life song exposure, suggesting a genetic basis to this trait. Although wild-derived TGC were intermediate in song variability between domesticated TGC populations and TGG, the difference between domesticated and wild TGC was not statistically significant. The observed variation in song behaviour among zebra finch populations represents a largely untapped opportunity for exploring the mechanisms of social behaviour.

Quantitative acoustic differentiation of cryptic species illustrated with King and Clapper rails.

Reliable species identification is vital for survey and monitoring programs. Recently, the development of digital technology for recording and analyzing vocalizations has assisted in acoustic surveying for cryptic, rare, or elusive species. However, the quantitative tools that exist for species differentiation are still being refined. Using vocalizations recorded in the course of ecological studies of a King Rail (Rallus elegans) and a Clapper Rail (Rallus crepitans) population, we assessed the accuracy and effectiveness of three parametric (logistic regression, discriminant function analysis, quadratic discriminant function analysis) and six nonparametric (support vector machine, CART, Random Forest, k-nearest neighbor, weighted k-nearest neighbor, and neural networks) statistical classification methods for differentiating these species by their kek mating call. We identified 480 kek notes of each species and quantitatively characterized them with five standardized acoustic parameters. Overall, nonparametric classification methods outperformed parametric classification methods for species differentiation (nonparametric tools were between 57% and 81% accurate, parametric tools were between 57% and 60% accurate). Of the nine classification methods, Random Forest was the most accurate and precise, resulting in 81.1% correct classification of kek notes to species. This suggests that the mating calls of these sister species are likely difficult for human observers to tell apart. However, it also implies that appropriate statistical tools may allow reasonable species-level classification accuracy of recorded calls and provide an alternative to species classification where other capture- or genotype-based survey techniques are not possible.

Primary Gastric ALK-negative EBV-negative Anaplastic Large Cell Lymphoma Presenting with Iron Deficiency Anemia.

Anaplastic large cell lymphoma (ALCL) is a rare subtype of non-Hodgkin lymphoma (NHL). Primary gastric anaplastic lymphoma kinase (ALK) negative ALCL is extremely rare. Diagnosis of primary gastric ALK-negative ALCL is difficult to establish and prognosis is worse than ALK-positive ALCL. Here, we report a case of an 82-year-old man with a history of cerebrovascular disease presented with weakness and iron deficiency anemia. He denied any abdominal discomforts. The esophagogastroduodenoscopy revealed a large ulcerated, friable mass in the gastric body which encompassed about 80% of entire stomach. Biopsy showed a high grade malignant tumor composed of undifferentiated epithelioid atypical cells, making it difficult to determine the cell of origin. Immunostains for lymphoma, carcinoma, and sarcoma were performed. The tumor cells were positive for CD30, CD4, and CD43, negative for CD20, CD3, ALK-1 and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) in situ hybridization, establishing the diagnosis of primary gastric ALK-negative ALCL. The patient is currently undergoing chemotherapy with clinical improvement. To the best of our knowledge, this is the first reported case of primary gastric ALK-negative and EBV-negative anaplastic large T-cell lymphoma that presented without gastroenterological symptoms.

Eluxadoline-Associated Pancreatitis in a Post-Cholecystectomy Patient: A Case Report.

Eluxadoline has emerged as an effective treatment option for patients with diarrhea- predominant irritable bowel syndrome (IBS-D). It was approved by the Food and Drug Administration (FDA) in May 2015 for treatment of IBS-D. It is a p-opioid receptor agonist and 6-receptor antagonist that acts locally in the gastrointestinal (GI) tract. In recently published phase IlIl IBS-3001 and IBS- 3002 trials, eight patients experienced abdominal pain due to sphincter of Oddi dysfunction (SOD), and one patient had acute pancreatitis, thought to be related to eluxadoline. Here, we describe a patient with eluxadoline- induced pancreatitis, the first case we know of to be reported outside of phase Ill clinical trials. Interestingly, only patients with prior cholecystectomy developed SOD and acute pancreatitis in the IBS 3001/3002 trials which also stands true with our patient. The enthusiasm with the efficacy of this drug should not have clinicians disregard the potential adverse effects, particularly serious ones, such as acute pancreatitis. We expect more cases of eluxadoline-induced pancreatitis and SOD to be reported, and future studies should focus on better understanding this association so as to guide treatment recommendations.

Synchronous Ileal Neuroendocrine Tumor and Ovarian Steroid Cell Tumor Present in a Female With Hyperandrogenism.

Well-differentiated neuroendocrine tumors (NET) of the ileum are generally slow-growing tumors with metastatic potential that may cause systemic symptoms from the secretion of serotonin, cortisol, and other biologically active substances. Likewise, steroid cell tumors of the ovary are slow-growing tumors that cause systemic symptoms from the functional production of androgens, estrogens, and other hormones. To the best of our knowledge, synchronous ileal NET and ovarian steroid cell tumors have not been previously reported in the English literature. We present a case of a 59-yr-old woman with 2 primary tumors that were found incidentally: a Stage III (T2N1M0) 1.6 cm well-differentiated NET (NET G2) of the terminal ileum with metastasis to a mesenteric lymph node and a 2.4 cm steroid cell tumor of the left ovary. The patient had suffered from hyperandrogenism for several years before diagnosis of an ovarian steroid cell tumor, but had no symptoms attributable to the NET. From review of the literature, this is the first case description of these 2 primaries arising in the same individual.