FATAL ACUTE HEMOLYSIS FOLLOWING TRIAZOLE THERAPY IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS).

Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins (Spheniscus demersus) from four institutions. All penguins underwent stressful events (e.g. relocation, induced molt) and were administered commercial liquid itraconazole formulations or compounded voriconazole liquid suspension. Observed clinical signs in affected penguins prior to death included hyporexia, weight loss, lethargy, dyspnea, red-tinged droppings, and obtunded mentation. Intra- and extravascular hemolysis and hemoglobinuric nephrosis were the primary pathologic manifestations on postmortem examination. The concentration-dependent hemolytic potentials of itraconazole, voriconazole, and commercial and compounded vehicle suspensions were evaluated in vitro by exposing chicken whole blood as a surrogate for penguin blood. Hemoglobin content in blood plasma was then measured by spectrophotometry. Neither itraconazole nor voriconazole alone induced hemolysis in vitro. The vehicle ingredients sorbitol and hydromellose induced hemolysis, but not at predicted plasma levels in chicken erythrocytes, suggesting neither the azole antifungals nor their major vehicles alone were likely to contribute to hemolysis in vivo in these penguins. Potential mechanisms of toxicosis include generation of an unmeasured reactive metabolite causing hemolysis, preexisting erythrocyte fragility, or species-specific differences in hemolytic thresholds that were not assessed in the chicken erythrocyte model. More research is needed on the potential for toxicosis of azole antifungal drugs and carrier molecules in this and other avian species.

Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Histologic lesions of cestodiasis in octopuses.

Parasitism of cephalopods is common, including infection with Aggregata spp., Ichthyobodo spp., dicyemids, cestodes of the orders Tetraphyllidea and Trypanorhynchidea, and various crustaceans. Cestodiasis in octopuses is reported, although a full histologic description of lesions has not been previously described. Cestodiasis was identified in 10 octopuses of 4 different species, which included 4 common octopuses (Octopus vulgaris), 3 Caribbean reef octopuses (Octopus briareus), 2 two-spot octopuses (Octopus bimaculoides), and 1 giant Pacific octopus (Enteroctopus dofleini). Larval cestodes were present in the cecum (n = 5), intestines (n = 4), digestive gland (n = 3), chitinous alimentary tract (n = 2), renal appendage (n = 1), and salivary duct (n = 1). In 5 cases, larval cestodes invaded tissue and were associated with hemocytic inflammation and tracts of necrotic tissue in the intestines (n = 3), digestive gland (n = 3), and/or renal appendage (n = 1). When present in the chitinous alimentary tract (esophagus, stomach) or cecum, larval cestodes were in the central lumen and not associated with lesions. One adult cestode was identified in the mantle cavity and was not associated with lesions. Other common concurrent parasitic infections included enteric Aggregata spp. infection, branchial Rickettsia-like organism infection, enteric nematodiasis, and an arthropod-associated branchitis.

Netrins: Evolutionarily Conserved Regulators of Epithelial Fusion and Closure in Development and Wound Healing.

Epithelial remodelling plays a crucial role during development. The ability of epithelial sheets to temporarily lose their integrity as they fuse with other epithelial sheets underpins events such as the closure of the neural tube and palate. During fusion, epithelial cells undergo some degree of epithelial-mesenchymal transition (EMT), whereby cells from opposing sheets dissolve existing cell-cell junctions, degrade the basement membrane, extend motile processes to contact each other, and then re-establish cell-cell junctions as they fuse. Similar events occur when an epithelium is wounded. Cells at the edge of the wound undergo a partial EMT and migrate towards each other to close the gap. In this review, we highlight the emerging role of Netrins in these processes, and provide insights into the possible signalling pathways involved. Netrins are secreted, laminin-like proteins that are evolutionarily conserved throughout the animal kingdom. Although best known as axonal chemotropic guidance molecules, Netrins also regulate epithelial cells. For example, Netrins regulate branching morphogenesis of the lung and mammary gland, and promote EMT during Drosophila wing eversion. Netrins also control epithelial fusion during optic fissure closure and inner ear formation, and are strongly implicated in neural tube closure and secondary palate closure. Netrins are also upregulated in response to organ damage and epithelial wounding, and can protect against ischemia-reperfusion injury and speed wound healing in cornea and skin. Since Netrins also have immunomodulatory properties, and can promote angiogenesis and re-innervation, they hold great promise as potential factors in future wound healing therapies.

TRANSTHORACIC ECHOCARDIOGRAPHIC EVALUATION AND SERUM CARDIAC TROPONIN VALUES IN ANESTHETIZED HEALTHY FEMALE SOUTHERN SEA OTTERS (ENHYDRA LUTRIS NEREIS).

Information about antemortem cardiac evaluation in sea otters (Enhydra lutris) is limited, despite well-established clinical care and rehabilitation procedures and a reported elevated risk of cardiac disease for this species. Serum cardiac troponin I (cTnI) concentration and echocardiographic assessment are two ways of screening for and diagnosing cardiac disease. However, no baseline data or reference intervals for either evaluation are published for sea otters. The objectives of this prospective study were to establish serum cTnI concentrations and echocardiographic technique and quantitative measurements in anesthetized healthy female southern sea otters (Enhydra lutris nereis) (n=15). Serum cTnI values were assessed by a high-sensitivity assay. Serum cTnI concentration ranged from <0.006 to 0.038 ng/ml. A complete echocardiogram, including two-dimensional and M-mode modalities, was performed. Echocardiographic measurements for left atrial size, aorta size, left ventricular structure, and left ventricular function were reported. The median left atrial size to aorta ratio was 1.22 (range 0.80-1.59) in short-axis and 1.70 (range 1.39-2.15) in long-axis. The median left ventricular internal dimension was 3.53 cm (range 2.87-4.92 cm) when assessed in two dimensions and 3.58 cm (range 2.80-4.48 cm) by M-mode. Serum concentrations of cTnI and transthoracic echocardiography may represent valuable tools for the antemortem diagnosis of cardiac disease in sea otters.

Aquatic Adaptation and Depleted Diversity: A Deep Dive into the Genomes of the Sea Otter and Giant Otter.

Despite its recent invasion into the marine realm, the sea otter (Enhydra lutris) has evolved a suite of adaptations for life in cold coastal waters, including limb modifications and dense insulating fur. This uniquely dense coat led to the near-extinction of sea otters during the 18th-20th century fur trade and an extreme population bottleneck. We used the de novo genome of the southern sea otter (E. l. nereis) to reconstruct its evolutionary history, identify genes influencing aquatic adaptation, and detect signals of population bottlenecks. We compared the genome of the southern sea otter with the tropical freshwater-living giant otter (Pteronura brasiliensis) to assess common and divergent genomic trends between otter species, and with the closely related northern sea otter (E. l. kenyoni) to uncover population-level trends. We found signals of positive selection in genes related to aquatic adaptations, particularly limb development and polygenic selection on genes related to hair follicle development. We found extensive pseudogenization of olfactory receptor genes in both the sea otter and giant otter lineages, consistent with patterns of sensory gene loss in other aquatic mammals. At the population level, the southern sea otter and the northern sea otter showed extremely low genomic diversity, signals of recent inbreeding, and demographic histories marked by population declines. These declines may predate the fur trade and appear to have resulted in an increase in putatively deleterious variants that could impact the future recovery of the sea otter.

Adaptations for amphibious vision in sea otters (Enhydra lutris): structural and functional observations.

Sea otters (Enhydra lutris) are amphibious mammals that maintain equal in-air and underwater visual acuity. However, their lens-based underwater accommodative mechanism presumably requires a small pupil that may limit sensitivity across light levels. In this study, we consider adaptations for amphibious living by assessing the tapetum lucidum, retina, and pupil dynamics in sea otters. The sea otter tapetum lucidum resembles that of terrestrial carnivores in thickness and fundic coverage. A heavily rod-dominated retina appears qualitatively similar to the ferret and domestic cat, and a thick outer nuclear layer relative to a thinner inner nuclear layer is consistent with nocturnal vertebrates and other amphibious carnivores. Pupil size range in two living sea otters is smaller relative to other amphibious marine carnivores (pinnipeds) when accounting for test conditions. The pupillary light response seems slower than other aquatic and terrestrial species tested in comparable brightness, although direct comparisons require further assessment. Our results suggest that sea otters have retained features for low-light vision but rapid adjustments and acute underwater vision may be constrained across varying light levels by a combination of pupil shape, absolute eye size, and the presumed coupling between anterior lens curvature and pupil size during accommodation.

The Role of Netrins and Their Receptors in Epithelial Mesenchymal Plasticity during Development.

Transitions between mesenchymal and epithelial cells are underpinned by changes in motility, adhesion, and polarity. Netrins and their receptors can control each of these cellular properties, and are emerging as important regulators of epithelial mesenchymal plasticity (EMP). Netrins were first identified in the worm Caenorhabditis elegans as secreted chemoattractants/repellents that could guide migrating mesodermal cells and axonal growth cones. Orthologues were subsequently found to play conserved roles in vertebrates and in the vinegar fly Drosophila. In the years that have followed it has become clear that, in addition to chemotaxis, netrin pathways have a number of other biological roles, many of which are directly relevant to the processes of EMP. Netrins and their receptors regulate morphogenesis of epithelial branched structures in the lung, mammary gland, pancreas, and vasculature, and can also promote the loss of epithelial structure. More recently they have been shown to drive apicobasal cell polarization events in vertebrates, flies, and worms. Given these many and varied roles in regulating epithelial morphogenetic events, together with their well-established roles in cell motility, netrins are likely to remain an important future avenue for EMP research.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

OBJECTIVE: To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. RESULTS: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Dual congenital transmission of Toxoplasma gondii and Sarcocystis neurona in a late-term aborted pup from a chronically infected southern sea otter (Enhydra lutris nereis).

Toxoplasma gondii and Sarcocystis neurona are protozoan parasites with terrestrial definitive hosts, and both pathogens can cause fatal disease in a wide range of marine animals. Close monitoring of threatened southern sea otters (Enhydra lutris nereis) in California allowed for the diagnosis of dual transplacental transmission of T. gondii and S. neurona in a wild female otter that was chronically infected with both parasites. Congenital infection resulted in late-term abortion due to disseminated toxoplasmosis. Toxoplasma gondii and S. neurona DNA was amplified from placental tissue culture, as well as from fetal lung tissue. Molecular characterization of T. gondii revealed a Type X genotype in isolates derived from placenta and fetal brain, as well as in all tested fetal organs (brain, lung, spleen, liver and thymus). This report provides the first evidence for transplacental transmission of T. gondii in a chronically infected wild sea otter, and the first molecular and immunohistochemical confirmation of concurrent transplacental transmission of T. gondii and S. neurona in any species. Repeated fetal and/or neonatal losses in the sea otter dam also suggested that T. gondii has the potential to reduce fecundity in chronically infected marine mammals through parasite recrudescence and repeated fetal infection.

Ebola Virus Disease: A Review of Its Past and Present.

Ebola virus, the virus responsible for Ebola virus disease, has spawned several epidemics during the past 38 years. In 2014, an Ebola epidemic spread from Africa to other continents, becoming a pandemic. The virus's relatively unique structure, its infectivity and lethality, the difficulty in stopping its spread, and the lack of an effective treatment captured the world's attention. This article provides a brief review of the known history of Ebola virus disease, its etiology, epidemiology, and pathophysiology and a review of the limited information on managing patients with Ebola virus disease.

Examining the Role of Nutrition in Cancer Survivorship and Female Fertility: A Narrative Review.

Female cancer survivors have a higher chance of experiencing infertility than females without a history of cancer diagnosis. This risk remains high despite advances in fertility treatments. There is a need to augment fertility treatments with cost-effective methods such as nutritional guidance to improve fertility chances. The aim of this review article is to connect the current literature on cancer survivorship nutrition and fertility nutrition, focusing on the importance of integrating nutritional guidance into fertility counseling, assessment, and treatment for female cancer survivors. Consuming a healthful diet comprising whole grains, soy, fruits, vegetables, seafood, and unsaturated fats has improved both female fertility and cancer survivorship. Similarly, maintaining a healthy body weight also improves female fertility and cancer survivorship. Therefore, dietary interventions to support female cancer survivors with fertility challenges are of immense importance. The period of follow-up fertility counseling and assessment after cancer treatment may provide a unique opportunity for implementing nutritional guidance for female cancer survivors. Dietary interventions are a promising strategy to improve pregnancy chances and overall quality of life among female cancer survivors; thus, researchers should investigate perceptions regarding fertility, barriers, and challenges to changing nutrition-related behaviors, and preferences for nutritional guidance to support fertility treatments in this population.

Regulation of Drosophila mesoderm migration by phosphoinositides and the PH domain of the Rho GTP exchange factor Pebble.

The Drosophila RhoGEF Pebble (Pbl) is required for cytokinesis and migration of mesodermal cells. In a screen for genes that could suppress migration defects in pbl mutants we identified the phosphatidylinositol phosphate (PtdInsP) regulator pi5k59B. Genetic interaction tests with other PtdInsP regulators suggested that PtdIns(4,5)P2 levels are important for mesoderm migration when Pbl is depleted. Consistent with this, the leading front of migrating mesodermal cells was enriched for PtdIns(4,5)P2. Given that Pbl contains a Pleckstrin Homology (PH) domain, a known PtdInsP-binding motif, we examined PtdInsP-binding of Pbl and the importance of the PH domain for Pbl function. In vitro lipid blot assays showed that Pbl binds promiscuously to PtdInsPs, with binding strength associated with the degree of phosphorylation. Pbl was also able to bind lipid vesicles containing PtdIns(4,5)P2 but binding was strongly reduced upon deletion of the PH domain. Similarly, in vivo, loss of the PH domain prevented localisation of Pbl to the cell cortex and severely affected several aspects of early mesoderm development, including flattening of the invaginated tube onto the ectoderm, extension of protrusions, and dorsal migration to form a monolayer. Pbl lacking the PH domain could still localise to the cytokinetic furrow, however, and cytokinesis failure was reduced in pbl(ΔPH) mutants. Taken together, our results support a model in which interaction of the PH-domain of Pbl with PtdIns(4,5)P2 helps localise it to the plasma membrane which is important for mesoderm migration.

Psychotropic Medication Use in Children and Youth with Autism Enrolled in Medicaid.

Children with autism frequently present with complex mental health diagnoses and psychotropic medications are often a component of comprehensive biopsychosocial treatment plans for these conditions. The purpose of this study is to provide rates and patterns of psychotropic medication use, and predictors thereof, in children and youth with autism enrolled in Medicaid across the US. This study examined national Medicaid claims from 2008 to 2016 of all children and youth with autism ages 0-21 years enrolled in Medicaid. Psychotropic medication use was examined across several child and youth characteristics, including age, co-occurring mental health conditions, sex, and race and ethnicity. About half of children and youth with autism enrolled in Medicaid had at least one psychotropic prescription in a year, a number that decreased slightly across the study period due to decreases in the prescription of antipsychotics. As new medications for autism or co-occurring conditions are developed and deployed, and as the understanding of the characteristics of the population of children with autism evolves, studying rates of medication usage helps to understand utilization patterns and differences in access to quality care.

Pathology, microbiology, and genetic diversity associated with Erysipelothrix rhusiopathiae and novel Erysipelothrix spp. infections in southern sea otters (Enhydra lutris nereis).

Erysipelothrix spp., including E. rhusiopathiae, are zoonotic bacterial pathogens that can cause morbidity and mortality in mammals, fish, reptiles, birds, and humans. The southern sea otter (SSO; Enhydra lutris nereis) is a federally-listed threatened species for which infectious disease is a major cause of mortality. We estimated the frequency of detection of these opportunistic pathogens in dead SSOs, described pathology associated with Erysipelothrix infections in SSOs, characterized the genetic diversity and antimicrobial susceptibility of SSO isolates, and evaluated the virulence of two novel Erysipelothrix isolates from SSOs using an in vivo fish model. From 1998 to 2021 Erysipelothrix spp. were isolated from six of >500 necropsied SSOs. Erysipelothrix spp. were isolated in pure culture from three cases, while the other three were mixed cultures. Bacterial septicemia was a primary or contributing cause of death in five of the six cases. Other pathology observed included suppurative lymphadenopathy, fibrinosuppurative arteritis with thrombosis and infarction, bilateral uveitis and endophthalmitis, hypopyon, petechia and ecchymoses, mucosal infarction, and suppurative meningoencephalitis and ventriculitis. Short to long slender Gram-positive or Gram-variable bacterial rods were identified within lesions, alone or with other opportunistic bacteria. All six SSO isolates had the spaA genotype-four isolates clustered with spaA E. rhusiopathiae strains from various terrestrial and marine animal hosts. Two isolates did not cluster with any known Erysipelothrix spp.; whole genome sequencing revealed a novel Erysipelothrix species and a novel E. rhusiopathiae subspecies. We propose the names Erysipelothrix enhydrae sp. nov. and Erysipelothrix rhusiopathiae ohloneorum ssp. nov. respectively. The type strains are E. enhydrae UCD-4322-04 and E. rhusiopathiae ohloneorum UCD-4724-06, respectively. Experimental injection of tiger barbs (Puntigrus tetrazona) resulted in infection and mortality from the two novel Erysipelothrix spp. Antimicrobial susceptibility testing of Erysipelothrix isolates from SSOs shows similar susceptibility profiles to isolates from other terrestrial and aquatic animals. This is the first description of the pathology, microbial characteristics, and genetic diversity of Erysipelothrix isolates recovered from diseased SSOs. Methods presented here can facilitate case recognition, aid characterization of Erysipelothrix isolates, and illustrate assessment of virulence using fish models.

Snail-dependent repression of the RhoGEF pebble is required for gastrulation consistency in Drosophila melanogaster.

The Rho GTP exchange factor, Pebble (Pbl), long recognised as an essential activator of Rho during cytokinesis, also regulates mesoderm migration at gastrulation. Like other cell cycle components, pbl expression patterns broadly correlate with proliferative tissue. Surprisingly, in spite of its role in the early mesoderm, pbl is downregulated in the presumptive mesoderm before ventral furrow formation. Here, we show that this mesoderm-specific repression of pbl is dependent on the transcriptional repressor Snail (Sna). pbl repression was lost in sna mutants but was unaffected when Sna was ectopically expressed, showing that Sna is necessary, but not sufficient, for pbl repression. Using DamID, the first intron of pbl was identified as a Sna-binding region. Nine sites with the Sna-binding consensus motif CAGGT[GA] were identified in this intron. Mutating these to TAGGC[GA] abolished the ventral repression of pbl. Surprisingly, Sna-dependent repression of pbl was not essential for viability or fertility. Loss of repression did, however, increase the frequency of low-penetrance gastrulation defects. Consistent with this, expression of a pbl-GFP transgene in the presumptive mesoderm generated similar gastrulation defects. Finally, we show that a cluster of Snail-binding sites in the middle of the first intron of pbl orthologues is a conserved feature in the other 11 sequenced Drosophila species. We conclude that pbl levels are precisely regulated to ensure that there is enough protein available for its role in early mesoderm development but not so much as to inhibit the orderly progression of gastrulation.

COVID-19 Pandemic and Impact on Patients with Autism Spectrum Disorder.

The COVID-19 infectious disease pandemic has caused significant fear and uncertainty around the world and had significant adverse psychological impact. Children, adolescents and adults with autism spectrum disorder (ASD) are a particularly vulnerable population, impacted by stay-at-home orders, closures at nonessential services, and social distancing standards. This commentary describes various challenges faced by individuals with ASD in the United States including disruptions caused by educational and vocational changes, challenges to home and leisure routines, limited access to behavioral health services and changes in health services delivery due to the pandemic. We highlight the need for ongoing skills development for individuals and development within systems to better respond to needs of the ASD population in future emergencies.

Anatomy of the sense of touch in sea otters: Cutaneous mechanoreceptors and structural features of glabrous skin.

Sea otters (Enhydra lutris) demonstrate rapid, accurate tactile abilities using their paws and facial vibrissae. Anatomical investigations of neural organization in the vibrissal bed and somatosensory cortex coincide with measured sensitivity, but no studies describe sensory receptors in the paws or other regions of glabrous (i.e., hairless) skin. In this study, we use histology to assess the presence, density, and distribution of mechanoreceptors in the glabrous skin of sea otters: paws, rhinarium, lips, and flipper digits, and we use scanning electron microscopy to describe skin-surface texture and its potential effect on the transduction of mechanical stimuli. Our results confirm the presence of Merkel cells and Pacinian corpuscles, but not Meissner corpuscles, in all sea otter glabrous skin. The paws showed the highest density of Merkel cells and Pacinian corpuscles. Within the paw, relative densities of mechanoreceptor types were highest in the distal metacarpal pad and digits, which suggests that the distal paw is a tactile fovea for sea otters. In addition to the highest receptor density, the paw displayed the thickest epidermis. Rete ridges (epidermal projections into the dermis) and dermal papillae (dermal projections into the epidermis) were developed across all glabrous skin. These quantitative and qualitative descriptions of neural organization and physical features, combined with previous behavioral results, contribute to our understanding of how structure relates to function in the tactile modality. Our findings coincide with behavioral observations of sea otters, which use touch to maintain thermoregulatory integrity of their fur, explore objects, and capture visually cryptic prey.

Preliminary Investigation into Developing the Use of Swabs for Skin Cortisol Analysis for the Ocean Sunfish (Mola mola).

The ocean sunfish (mola; Mola mola) is the heaviest bony fish in the world. This slow-moving fish often is injured by fishing boats that use drift gillnets attributing to its listing as Vulnerable by the IUCN. The Monterey Bay Aquarium (Monterey, CA, USA) has a program that brings in smaller molas from the ocean and acclimates them for an exhibit. When they grow too large for the million-gallon Open Seas exhibit, they are returned to Monterey Bay through a "reverse" acclimatization. Our overall goal was to use skin swabs to evaluate mola stress physiology to better understand the effects of this program. Our objectives were to validate this non-invasive method by taking opportunistic swabs throughout acclimatization and during stressful events. We swabbed each individual (n = 12) in three different body locations. Swabs were analyzed using a cortisol enzyme immunoassay. We averaged the three swabs and examined the absolute change of cortisol from the first taken upon handling to during treatments and the different acclimation stages. We considered elevated cortisol concentrations to be ≥1.5-fold higher than the first sample. Overall, mean (±SEM) cortisol varied among individuals (564.2 ± 191.5 pg/mL swab (range, 18.3-7012.0 pg/mL swab). The majority (four of six) of molas swabbed within the first week or month had elevated skin cortisol compared to their first sample. All seven molas that were being treated for an injury or illness had elevated skin cortisol (range, 1.7- to 127.6-fold higher) compared to their post-acclimation sample. This is the first step in validating the use of non-invasive skin swabs for glucocorticoid analysis in the mola. Further biochemical analysis is needed to determine the specific steroids that are being measured.