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Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring a 10-nucleotide deletion mutation in ADIPOQ that cosegregates with diabetes and end-stage renal disease. This mutation introduces a frameshift in exon 3, resulting in a premature termination codon that disrupts translation of adiponectin's globular domain. Subjects with the mutation had dramatically reduced circulating adiponectin and increased long-chain ceramides levels. Functional studies suggest that the mutated protein acts as a dominant negative through its interaction with non-mutated adiponectin, decreasing circulating adiponectin levels, and correlating with metabolic disease., (© 2022. The Author(s).)

Background: Domoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy., Observations: Here the authors describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures after the procedure, and clinical measures of well-being, including weight and feeding habits, have stabilized., Lessons: These preliminary results suggest xenotransplantation has improved the quality of life for this animal and holds tremendous therapeutic promise.

The pharmacokinetics of danofloxacin was investigated in rehabilitated California brown pelicans ( Pelecanus occidentalis californicus ) after a single intramuscular injection at a dose of 15 mg/kg body weight. The concentration of the drug in plasma was assayed by high-pressure liquid chromatography. A sparse-sampling design was used to reduce the number of samples (1-4 venipunctures) obtained from 24 brown pelicans. A population pharmacokinetic analysis with nonlinear mixed-effects modeling was used to accommodate the sparse-sampling strategy. The nonlinear mixed-effects modeling approach measured both fixed effects (typical values for the population) and random effects (between-subject variability) for this population. A 1-compartment model best represented the concentration-versus-time data after injection. After injection, the elimination half-life, peak concentration, area under the curve, and volume of distribution were 2.76 hours, 2.5 µg/mL, 13.75 µg/h/mL, and 4.35 L/kg, respectively. Rate of absorption was highly variable among the birds. The intramuscular injection of danofloxacin in pelicans at this dose produced plasma concentrations that meet therapeutic targets for bacteria with a minimum inhibitory concentration of ≤0.25 µg/mL. This dose can be used for future studies to evaluate the efficacy of danofloxacin for treating susceptible bacteria.

Background: A series of sea lion bites in open-water swimmers recently gained the attention of the national and international media. Pinniped (the clade including seals and sea lions) bites historically have been in people who hunt or handle marine mammals. As populations of humans and pinnipeds continue to grow, interactions with animals by those participating in recreational activities are likely to become more frequent., Case Reports: In December of 2017 and January of 2018, four sea lion (Zalophus californianus) bites in humans occurred at a popular open-water recreational swimming area in San Francisco, California. Three swimmers required treatment at a local trauma center and two required surgery. Two of the wounds were potentially life threatening; one swimmer required a field tourniquet to stop bleeding from the antecubital fossa, and the bite in another narrowly missed the femoral artery. The purpose of this report is to offer an in-depth discussion of antimicrobial use and rabies postexposure prophylaxis in patients with severe pinniped bites. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Information from this report can be used in conjunction with input from local experts to develop a thoughtful therapeutic plan for patients with severe pinniped bites. Doxycycline is the first-line antibiotic therapy, but broader coverage may be needed for severe wounds with the potential for contamination. The likelihood of rabies is low, and rabies postexposure prophylaxis should be reserved for cases that involve unusually aggressive animal behavior or other factors suggestive of rabies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.

Objective: Corneal ulcers are commonly encountered in pinnipeds. Prolonged oral antibiotics and topical ophthalmic solutions may not be practical to administer, and novel treatment techniques are desired. Thermodynamic gels are a potential solution because they hold antimicrobials at the site of injection, slowly releasing drug. This study investigated the clinical efficacy of antibiotic-impregnated poloxamer gel in management of corneal ulceration., Animal Studied: Twenty-six California sea lions undergoing rehabilitation at The Marine Mammal Center., Procedures: A poloxamer gel mixed with 2% enrofloxacin was subconjunctivally injected in the treatment group. Control animals received oral doxycycline. Systemic anti-inflammatories and analgesics were administered as needed. Corneal examinations under general anesthesia were repeated weekly, and included sampling for bacterial culture and corneal cytology, collection of high-quality corneal images, and treatment administration until the ulcers were healed., Results: There was no gross or histologic evidence of a localized tissue reaction to the gel administration in the conjunctiva, and no evidence of systemic reaction to therapy in animals that died due to unrelated causes during the study period (n = 17). In animals that experienced a superficial corneal ulcer involving only epithelium or superficial stroma (n = 12), all lesions resolved completely, in both treatment and control groups. Of those animals with deeper or more complex ulcers involving keratomalacia or descemetoceles (n = 15), four demonstrated complete lesion resolution (all four received gel treatment)., Conclusions: This study demonstrates that subconjunctival antibiotic poloxamer gel administration is a safe and effective alternative therapeutic option to traditional treatments for superficial corneal ulceration in pinnipeds., (© 2016 American College of Veterinary Ophthalmologists.)

Effects of cetacean morbillivirus (CeMV) on dolphins vary from causing epidemics to subclinical infections. The former have been documented in the North Atlantic Ocean and Mediterranean Sea but not in the North Pacific Ocean, and the reasons for this are unknown. To explore the distribution of this virus in areas that have not experienced epidemics, we reviewed evidence for morbilliviral infection in odontocetes stranded along the California coast, US from 2000-15. Nine of 212 animals examined histologically had lesions compatible with morbilliviral infection, and 11 were tested for CeMV via reverse transcriptase-PCR. One striped dolphin ( Stenella coeruleoalba ) was PCR positive, and the sequenced product was most closely related to sequences in two strains found in cetaceans in Hawaii. This study suggests that CeMV may be a cause of morbidity and a rare contributor to mortality in cetaceans stranding along the California coast. Additional work is needed to understand CeMV distribution and host species susceptibility in this region.

People who use drugs are at increased risk for HIV acquisition, poor engagement in health care, and late screening for HIV with advanced HIV at diagnosis and increased HIV-related morbidity, mortality, and health care costs. This systematic review evaluates current evidence about the effectiveness and feasibility of implementing HIV testing in U.S. substance use treatment programs. The literature search identified 535 articles. Full text review was limited to articles that explicitly addressed strategies to implement HIV testing in substance use programs: 17 met criteria and were included in the review; nine used quantitative, qualitative, or mixed-method designs to describe or quantify HIV testing rates, acceptance by clients and staff, and cost-effectiveness; eight organization surveys described barriers and facilitators to testing implementation. The evidence supported the effectiveness and feasibility of rapid, routine, and streamlined HIV testing in substance use treatment programs. Primary challenges included organizational support and sustainable funding., (Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.)

Objective: To review cases of bites and contact abrasions in open-water swimmers from California sea lions (Zalophus californianus) and harbor seals (Phoca vitulina richardii)., Methods: Open-water swimmers from a San Francisco swimming club were questioned about encounters with pinnipeds (seals and sea lions) that resulted in bites or contact abrasions. When possible, wounds were documented with photographs. Medical follow-up and treatment complications were also reviewed., Results: From October 2011 to December 2014, 11 swimmers reported bites by a sea lion (n = 1), harbor seal (n = 7), or unidentified pinniped (n = 3). Ten of the encounters occurred in San Francisco Bay; 1 occurred in the Eld Inlet, in Puget Sound, near Olympia, WA. None of the swimmers were wearing wetsuits. All bites involved the lower extremities; skin was broken in 4 of 11 bites and antibiotics were prescribed in 3 cases. One swimmer, who was bitten by a harbor seal, also had claw scratches. A treatment failure occurred with amoxicillin/clavulanate in another swimmer who was bitten by an unidentified pinniped; the wound healed subsequently with doxycycline, suggesting an infection with Mycoplasma spp. There were no long-lasting consequences from any of the bites. The majority of cases occurred at low tide, and bumping of the swimmer by the animal before or after a bite was common, but no clear tide or attack pattern was identified., Conclusions: Bites and contact abrasions from sea lions and harbor seals are reported infrequently in open-water swimmers and typically involve the lower extremities. Because of the risk of Mycoplasma infection, treatment with a tetracycline is recommended in pinniped bites with signs of infection or serious trauma. Attempting to touch or pet sea lions or seals is inadvisable and prohibited by the Marine Mammal Protection Act. Swimmers should leave the water as soon as possible after a bite or encounter., (Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Marine mammals are often cited as "sentinels of ocean health" yet accessible, synthesized data on their health changes that could effectively warn of ocean health changes are rare. The objectives of this study were to 1) perform a systematic review of published cases of marine mammal disease to determine spatial and temporal trends in disease from 1972-2012, including changes in regions and taxa affected and specific causes; and 2) compare numbers of published cases of neoplasia with known, hospital-based neoplasia records to explore the causes of discrepancy between numbers of published cases and true disease trends. Peer-reviewed literature was compiled, and data were collected from The Marine Mammal Center database in Sausalito, California for comparison of numbers of neoplasia cases. Toxicoses from harmful algal blooms appear to be increasing. Viral epidemics are most common along the Atlantic U.S. coastline, while bacterial epidemics, especially leptospirosis, are most common along the Pacific coast. Certain protozoal and fungal zoonoses appear to be emerging, such as Toxoplasma gondii in southern sea otters in California, and Cryptococcus gattii in cetaceans in the Pacific Northwest. Disease reports were most common from California where pinniped populations are large, but increased effort also occurs. Anthropogenic trauma remains a large threat to marine mammal health, through direct mortality and indirect chronic disease. Neoplasia cases were under-reported from 2003-2012 when compared to true number of cases, and over-reported in several years due to case duplication. Peer-reviewed literature greatly underestimates the true magnitude of disease in marine mammals as it focuses on novel findings, fails to reflect etiology of multifactorial diseases, rarely reports prevalence rather than simple numbers of cases, and is typically presented years after a disease first occurs. Thus literature cannot guide management actions adequately, nor inform indices of ocean health. A real-time, nationally centralized system for reporting marine mammal disease data is needed to be able to understand how marine mammal diseases are changing with ecosystem changes, and before these animals can truly be considered 'sentinels of ocean health'.

A female harbor seal pup rescued along the coast of San Diego on 13 June 2012 was diagnosed with bilateral mature cataracts, apparently congenital, in association with vitreal herniation in the anterior chamber of each eye. The cataracts were surgically removed on 1 August 2012 with single-port aphakic phacoemulsification and automated anterior vitrectomy. Postoperative monitoring during the next several weeks indicated that vision had been functionally repaired and that she could visually orient to and capture live fish in three different environments and in the presence of other animals. Consequently, we equipped the seal with a satellite-linked radio transmitter and returned her to the Pacific Ocean on 21 November 2012, and then monitored her movements until radio contact ended on 2 March 2013. She remained along the San Diego coast from 21 November until 5 December 2012 when she relocated to the Coronado Islands and remained there until 26 December. She then traveled directly to San Clemente Island and remained foraging in the near-shore kelp beds there through 2 March 2013, when radio contact ended. To our knowledge, this is the first published report of cataract treatment in a marine mammal using high-frequency ultrasound to emulsify the lenses followed by suction removal of the emulsified microfragments (i.e., phacoemulsification). Moreover, the rapid postoperative recovery of the seal and its quick acclimation, orientation, navigation, and foraging in marine habitats after return to the Pacific Ocean indicates that these surgical procedures can be safe and effective treatments for cataracts in seals, with substantially reduced postsurgical complications relative to other types of lens fragmentation and removal procedures.

Histopathologic diagnosis of thyroid neoplasia in teleosts is complicated, because thyroid tissue is unencapsulated, and normal tissue can have wide ectopic extensions. Assessment of thyroid hormone concentrations in conjunction with histologic evaluation of thyroid carcinoma has not been reported in teleosts, even though routinely performed in other species. A yellowbar angelfish (Pomacanthus maculosus) presented with a mass that extended beyond the gill arches. Partial surgical resection was performed, and a histologic diagnosis of thyroid carcinoma was made. Plasma from the affected fish and two control Pomacanthus were used to assess thyroid hormone concentrations using a domestic mammalian assay. Thyroid-stimulating hormone and throxine were undetectable in two of three fish. Triiodothyronine was lower in the affected fish than in controls. The tumor did not appear to be actively secreting hormone. This is the first characterization of thyroid tumors and corresponding thyroid hormones in teleosts, which may assist in diagnosis of this disease.

The objective of this study was to investigate the pharmacokinetics of meloxicam in bottlenose dolphins (Tursiops truncatus). Ten adult bottlenose dolphins were used for the study. Each animal received a single oral dose of meloxicam at 0.1 mg/kg. Two to seven serial blood samples were collected per animal, at one of fourteen time points between T = 0 and T = 240 hr. Complete blood count and serum chemistry analysis were performed prior to drug administration, as well as at the final time point for each individual. Plasma drug concentrations were determined by high-pressure liquid chromatography. No adverse hematological, biochemical or clinical changes were noted during the study period. After oral administration, a peak plasma concentration of 1.03 microg/mL was achieved at approximately 11 hr. This suggests that a single oral dose of 0.1 mg/kg provides a peak plasma level similar to what is considered therapeutic in other species. However, the elimination of meloxicam in cetaceans was slower than in other species, with an elimination half-life of almost 70 hr, and detectable drug concentrations up to 7 days. A single oral dose of 0.1 mg/kg appears safe for use in this species, but caution in repeated dosing must be used, due to the prolonged elimination, until multi-dose pharmacokinetic studies are determined.