Venous blood gas and lactate values in adult giraffe trained for voluntary jugular phlebotomy.

Blood gas analyses have previously been performed for giraffe under anesthesia and with physical restraint in a chute; however, reference values for giraffe that are trained to participate in venipuncture without chemical or physical restraint have not previously been described. Using a point-of-care blood gas and lactate analyzer and 20 giraffe trained for voluntary phlebotomy, values were determined for venous blood gasses and plasma lactate concentration. Ninety-five percent confidence in the mean values for venous pH (7.34-7.46), partial pressure of carbon dioxide (PCO2; 28.5-37.8 mmHg), partial pressure of oxygen (PO2; 56-102 mmHg), bicarbonate (HCO3 -; 18.9-21.0 mmol/L), base excess (BE; -6.0 to -3.6 mmol/L), total carbon dioxide (TCO2; 19.9-22.0 mmol/L), and lactate (0.32-0.56 mmol/L) were calculated. This is the first report on venous blood gas analysis values for giraffe without chemical or physical restraint. These data will provide a reference for clinical interpretation of venous blood gas and lactate values in giraffe and demonstrate some of the potential diagnostic benefits to training giraffe and other zoo species for voluntary medical procedures.

Current Practices in the Evaluation of Global Developmental Delay/Intellectual Disability: A Nationwide Survey of Child Neurologists.

Background and Objectives: Global developmental delay/intellectual disability (GDD/ID) are among the most common neurologic conditions evaluated by child neurologists in the United States. No recent neurology-specific guidelines for GDD/ID diagnostic evaluation exist, which could lead to practice variability. We assessed current practices in GDD/ID diagnostic evaluation among US child neurologists, including drivers of exome sequencing (ES). Methods: A 19-item online anonymous survey was distributed between April 2021 and September 2021 to 953 eligible child neurologists by email and/or online platforms through the American Academy of Neurology and Child Neurology Society. Multinomial logistic regression was used to determine the predictors of sending ES as a part of GDD/ID diagnostic evaluation. Results: Of 172 unique respondents, 69.2% reported almost always obtaining a chromosomal microarray while 10.5% reported almost always pursuing ES. However, 65.1% identified ES as a first-tier diagnostic test for GDD/ID. Clinical practice demographics independently associated with a higher likelihood of pursuit of ES were more years of experience (p = 0.002) and more people with GDD/ID in one's practice (p < 0.001). Inclusion of brain MRI, EEG, and metabolic laboratory values as part of GDD/ID diagnostic evaluation varied widely. Modalities to screen for treatable disorders (ES or metabolic laboratory values) were reported to be consistently used by only 24.8% of respondents. Respondents identified key barriers to the pursuit of ES including the need for genetics referral/genetic counseling and insurance coverage/out-of-pocket cost. Discussion: Among US child neurologists, there is marked practice variability in GDD/ID diagnostic evaluation across multiple types of testing, raising concern for disparities in care. There is a widespread lack of screening for treatable causes of ID, which may lead to missed diagnoses and avoidable morbidity. Despite most respondents' support for ES as a first-tier diagnostic test for GDD/ID, only a small minority routinely pursue ES as a part of their evaluation. Provider-level factors (years of experience, percent of patients with GDD/ID) and system-level barriers (access to genetics expertise, lack of insurance coverage) were determinants of the frequency of use of ES. These findings suggest the need for updated consensus guidelines and advocacy/education to improve child neurologists' ability to pursue ES for GDD/ID.

Social Determinants of Genetics Referral and Completion Rates Among Child Neurology Patients.

Objective: To investigate clinical, social, and systems-level determinants predictive of genetics clinic referral and completion of genetics clinic visits among child neurology patients. Methods: Electronic health record data were extracted from patients 0-18 years old who were evaluated in child neurology clinics at a single tertiary care institution between July 2018 to January 2020. Variables aligned with the Health Equity Implementation Framework. Referral and referral completion rates to genetics and cardiology clinics were compared among Black vs White patients using bivariate analysis. Demographic variables associated with genetics clinic referral and visit completion were identified using logistic regressions. Results: In a cohort of 11,371 child neurology patients, 304 genetics clinic referrals and 82 cardiology clinic referrals were placed. In multivariate analysis of patients with Black or White ethnoracial identity (n=10,601), genetics clinic referral rates did not differ by race, but were significantly associated with younger age, rural address, neurodevelopmental disorder diagnosis, number of neurology clinic visits, and provider type. The only predictors of genetics clinic visit completion number of neurology clinic visits and race/ethnicity, with White patients being twice as likely as Black patients to complete the visit. Cardiology clinic referrals and visit completion did not differ by race/ethnicity. Interpretation: Although race/ethnicity was not associated with differences in genetics clinic referral rates, White patients were twice as likely as Black patients to complete a genetics clinic visit after referral. Further work is needed to determine whether this is due to systemic/structural racism, differences in attitudes toward genetic testing, or other factors.

Ionic liquids on oxide surfaces.

Ionic liquids (ILs) supported on oxide surfaces are being investigated for numerous applications including catalysis, batteries, capacitors, transistors, lubricants, solar cells, corrosion inhibitors, nanoparticle synthesis and biomedical applications. The study of ILs with oxide surfaces presents challenges both experimentally and computationally. The interaction between ILs and oxide surfaces can be rather complex, with defects in the oxide surface playing a key role in the adsorption behaviour and resulting electronic properties. The choice of the cation/anion pair is also important and can influence molecular ordering and electronic properties at the interface. These controllable interfacial behaviours make ionic liquid/oxide systems desirable for a number of different technological applications as well as being utilised for nanoparticle synthesis. This topical review aims to bring together recent experimental and theoretical work on the interaction of ILs with oxide surfaces, including TiO2, ZnO, Al2O3, SnO2and transition metal oxides. It focusses on the behaviour of ILs at model single crystal surfaces, the interaction between ILs and nanoparticulate oxides, and their performance in prototype devices.

Teaching scripts via smartphone app facilitate resident-led teaching of medical students.

BACKGROUND: Previous studies have suggested that resident physicians are the most meaningful teachers during the clinical clerkships of third-year medical students (MS3s). Unfortunately, residents often feel unprepared for this crucial role. The pediatrics clerkship at our institution identified a paucity in the frequency of resident-led teaching with MS3s. Lack of confidence, suboptimal teaching space, and insufficient time were cited as the most significant barriers. To enhance resident-led teaching of MS3s, we created teaching scripts of general pediatrics topics accessible via a smartphone application (app). METHODS: Prior to the implementation of the app, MS3s and pediatric residents were surveyed on clerkship teaching practices. From May 2017 through July 2018, pediatric residents working with MS3s were introduced to the app, with both groups queried on resident teaching habits afterward. We compared pre-intervention and post-intervention data of time spent teaching, teaching frequency, and a ranking of pediatric resident teaching performance compared to residents of other MS3 core clerkships. RESULTS: 44 out of 90 residents (49%) responded to a pre-intervention survey on baseline teaching habits. 49 out of 61 residents (80%) completed our post-intervention survey. Pre-intervention, 75% (33/44) of residents reported spending less than 5 min per teaching session on average. Post-intervention, 67% (33/49) reported spending more than 5 min (p < 0.01). 25% (11/44) of residents reported teaching at least once per day pre-intervention, versus 55% (27/49, p = 0.12) post-intervention. Post-intervention data demonstrated a statistically significant correlation between app use and increased frequency of teaching (p < 0.01). The MS3 average ranking of pediatric resident teaching increased from 2.4 to 3.4 out of 6 (p < 0.05) after this intervention. CONCLUSIONS: Residency programs looking to reform resident-led teaching, particularly of residents early in their training, should consider our novel approach. In addition to addressing barriers to teaching and creating a platform for near-peer teaching, it is adaptable to any specialty or learner level. Future direction includes developing objective measures for teaching performance and content proficiency to better assess our intervention as an educational curriculum, as well as further investigation of the intervention as a controlled trial.

Chordoma of the sacrum of an adult naked mole-rat.

The naked mole-rat (NMR; Heterocephalus glaber)-a small, eusocial, subterranean rodent native to East Africa-is distinguished by its capability to live long and resist changes associated with the aging process. Notably, a growing amount of research has been dedicated to NMRs' multifactorial capacity to resist cancer. Since 2016, however, zoos have begun to document various neoplasms in a handful of individuals. We present herein radiographic, gross anatomic, and histopathologic features of a case of a sacral chordoma in a geriatric female. Chordomas originate in notochordal remnants. These spinal tumors are most commonly seen in ferrets; chordomas are rare in humans, can be difficult to treat, and need wide surgical margins.

Acute Disseminated Encephalomyelitis in Children: An Updated Review Based on Current Diagnostic Criteria.

Acute disseminated encephalomyelitis is an inflammatory disorder of the central nervous system. Uniform diagnostic criteria for acute disseminated encephalomyelitis did not exist until publication of expert-defined consensus definitions by the International Pediatric Multiple Sclerosis Society Group in 2007, with updates in 2013. In the expanding field of pediatric neuroimmunology, consistent diagnostic criteria are essential to correctly categorize patients as increasing information regarding prognosis and management becomes available. Scientific literature is relatively lacking in review articles on International Pediatric Multiple Sclerosis Society Group-defined acute disseminated encephalomyelitis. This review focuses primarily on references applying the International Pediatric Multiple Sclerosis Society Group criteria for acute disseminated encephalomyelitis presenting specific, up-to-date, and translatable information regarding the epidemiology, pathophysiology, clinical features, diagnosis, management, and prognosis of acute disseminated encephalomyelitis in the pediatric population.

MicroRNA-29b mediates altered innate immune development in acute leukemia.

Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients. This absence was not due to elimination by cell death or selective reduction in proliferation, but rather to the result of a block in NK cell differentiation. Indeed, NK cells from leukemic mice and humans with AML showed lower levels of TBET and EOMES, transcription factors that are critical for terminal NK cell differentiation. Further, the microRNA miR-29b, a regulator of T-bet and EOMES, was elevated in leukemic NK cells. Finally, deletion of miR-29b in NK cells reversed the depletion of this NK cell subset in leukemic mice. These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer.

PTEN is a negative regulator of NK cell cytolytic function.

Human NK cells are characterized by their ability to initiate an immediate and direct cytolytic response to virally infected or malignantly transformed cells. Within human peripheral blood, the more mature CD56(dim) NK cell efficiently kills malignant targets at rest, whereas the less mature CD56(bright) NK cells cannot. In this study, we show that resting CD56(bright) NK cells express significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein when compared with CD56(dim) NK cells. Consistent with this, forced overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and loss of PTEN in CD56(bright) NK cells resulted in elevated cytolytic activity. Comparable studies in mice showed PTEN overexpression did not alter NK cell development or NK cell-activating and inhibitory receptor expression yet, as in humans, did decrease expression of downstream NK activation targets MAPK and AKT during early cytolysis of tumor target cells. Confocal microscopy revealed that PTEN overexpression disrupts the NK cell's ability to organize immunological synapse components including decreases in actin accumulation, polarization of the microtubule organizing center, and the convergence of cytolytic granules. In summary, our data suggest that PTEN normally works to limit the NK cell's PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic mediators toward the target cell and suggest that PTEN is among the active regulatory components prior to human NK cells transitioning from the noncytolytic CD56(bright) NK cell to the cytolytic CD56(dim) NK cells.

The transcription Factor AHR prevents the differentiation of a stage 3 innate lymphoid cell subset to natural killer cells.

Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called "stage 3" developmental intermediate minimally characterized by a CD34(-)CD117(+)CD94(-) immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that include interleukin-1 receptor (IL-1R1)-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1(hi) human ILC3s to CD56(bright)CD94(+) interferon (IFN)-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1(hi) ILC3s from differentiating into NK cells.