Exposure to domoic acid is an ecological driver of cardiac disease in southern sea otters✰.

Harmful algal blooms produce toxins that bioaccumulate in the food web and adversely affect humans, animals, and entire marine ecosystems. Blooms of the diatom Pseudo-nitzschia can produce domoic acid (DA), a toxin that most commonly causes neurological disease in endothermic animals, with cardiovascular effects that were first recognized in southern sea otters. Over the last 20 years, DA toxicosis has caused significant morbidity and mortality in marine mammals and seabirds along the west coast of the USA. Identifying DA exposure has been limited to toxin detection in biological fluids using biochemical assays, yet measurement of systemic toxin levels is an unreliable indicator of exposure dose or timing. Furthermore, there is little information regarding repeated DA exposure in marine wildlife. Here, the association between long-term environmental DA exposure and fatal cardiac disease was investigated in a longitudinal study of 186 free-ranging sea otters in California from 2001 - 2017, highlighting the chronic health effects of a marine toxin. A novel Bayesian spatiotemporal approach was used to characterize environmental DA exposure by combining several DA surveillance datasets and integrating this with life history data from radio-tagged otters in a time-dependent survival model. In this study, a sea otter with high DA exposure had a 1.7-fold increased hazard of fatal cardiomyopathy compared to an otter with low exposure. Otters that consumed a high proportion of crab and clam had a 2.5- and 1.2-times greater hazard of death due to cardiomyopathy than otters that consumed low proportions. Increasing age is a well-established predictor of cardiac disease, but this study is the first to identify that DA exposure affects the risk of cardiomyopathy more substantially in prime-age adults than aged adults. A 4-year-old otter with high DA exposure had 2.3 times greater risk of fatal cardiomyopathy than an otter with low exposure, while a 10-year old otter with high DA exposure had just 1.2 times greater risk. High Toxoplasma gondii titers also increased the hazard of death due to heart disease 2.4-fold. Domoic acid exposure was most detrimental for prime-age adults, whose survival and reproduction are vital for population growth, suggesting that persistent DA exposure will likely impact long-term viability of this threatened species. These results offer insight into the pervasiveness of DA in the food web and raise awareness of under-recognized chronic health effects of DA for wildlife at a time when toxic blooms are on the rise.

Photobiomodulation therapy for androgenetic alopecia: A clinician's guide to home-use devices cleared by the Federal Drug Administration.

The market for home-use photobiomodulation devices to treat androgenetic alopecia has rapidly expanded, and the Food and Drug Administration (FDA) has recently cleared many devices for this purpose. Patients increasingly seek the advice of dermatologists regarding the safety and efficacy of these hair loss treatments. The purpose of this guide was threefold: (1) to identify all home-use photobiomodulation therapy devices with FDA-clearance for treatment of androgenetic alopecia; (2) to review device design, features and existing clinical evidence; and (3) to discuss practical considerations of photobiomodulation therapy, including patient suitability, treatment goals, safety, and device selection. A search of the FDA 510(k) Premarket Notification database was conducted using product code "OAP" to identify all home-use devices that are FDA-cleared to treat androgenetic alopecia. Thirteen commercially available devices were identified and compared. Devices varied in shape, wavelength, light sources, technical features, price, and level of clinical evidence. To date, there are no head-to-head studies comparing the efficacy of these devices. Photobiomodulation therapy devices have an excellent safety profile and mounting evidence supporting their efficacy. However, long-term, high quality studies comparing these devices in diverse populations are lacking. As these devices become increasingly popular, dermatologists should be familiar with this treatment modality to add to their therapeutic armamentarium. ABBREVIATIONS: AGA, androgenetic alopecia; FDA, Food and Drug Administration; IEC, International Electrotechnical Commission; LED, light-emitting diode; PBMT, photobiomodulation therapy.

ISOLATION AND CHARACTERIZATION OF A NOVEL MARINE BRUCELLA FROM A SOUTHERN SEA OTTER (ENHYDRA LUTRIS NEREIS), CALIFORNIA, USA.

We characterize Brucella infection in a wild southern sea otter ( Enhydra lutris nereis) with osteolytic lesions similar to those reported in other marine mammals and humans. This otter stranded twice along the central California coast, US over a 1-yr period and was handled extensively at two wildlife rehabilitation facilities, undergoing multiple surgeries and months of postsurgical care. Ultimately the otter was euthanized due to severe, progressive neurologic disease. Necropsy and postmortem radiographs revealed chronic, severe osteoarthritis spanning the proximal interphalangeal joint of the left hind fifth digit. Numerous coccobacilli within the joint were strongly positive on Brucella immunohistochemical labelling, and Brucella sp. was isolated in pure culture from this lesion. Sparse Brucella-immunopositive bacteria were also observed in the cytoplasm of a pulmonary vascular monocyte, and multifocal granulomas were observed in the spinal cord and liver on histopathology. Findings from biochemical characterization, 16S ribosomal DNA, and bp26 gene sequencing of the bacterial isolate were identical to those from marine-origin brucellae isolated from cetaceans and phocids. Although omp2a gene sequencing revealed 100% homology with marine Brucella spp. infecting pinnipeds, whales, and humans, omp2b gene sequences were identical only to pinniped-origin isolates. Multilocus sequence typing classified the sea otter isolate as ST26, a sequence type previously associated only with cetaceans. Our data suggest that the sea otter Brucella strain represents a novel marine lineage that is distinct from both Brucella pinnipedialis and Brucella ceti. Prior reports document the zoonotic potential of the marine brucellae. Isolation of Brucella sp. from a stranded sea otter highlights the importance of wearing personal protective equipment when handling sea otters and other marine mammals as part of wildlife conservation and rehabilitation efforts.

Among patients with left bundle branch block, T-wave peak to T-wave end time is prolonged in the presence of acute coronary occlusion.

BACKGROUND: Assessing the effect of myocardial ischemia on ventricular repolarization in the setting of left bundle branch block (LBBB) poses a challenge due to secondary prolongation of the QT interval inherent in LBBB. The T-wave peak to T-wave end (TpTe) interval has been noted to prolong during myocardial ischemia and correct after reperfusion in patients with normal conduction. Here we compare the TpTe intervals of patients with LBBB both with and without complete acute coronary occlusion (ACO). METHODS: Retrospectively, emergency department patients with LBBB and symptoms of myocardial ischemia were identified both with angiographically-proven ACO and with No-ACO. The longest QT, JT, and TpTe intervals were analyzed. RESULTS: The ACO and No-ACO groups consisted of 33 and 129 patients, respectively. The mean TpTe was longer in ACO (103.6ms [95%CI 98.5-108.7]) compared to No-ACO patients (88.6ms [95%CI 85.3-91.9]) (P<0.0001) and this held true after correction for heart rate. In ACO versus No-ACO, the TpTe also more frequently exceeded prolongation cutoffs of 85ms (30 [90%] versus 69 [54%]) and 100ms (25 [76%] versus 42 [33%]) (P<0.0001 for all). The mean QT, JT, QTc, and JTc intervals were not significantly different between the groups for either the Bazett's or Rautaharju's correction formulas. CONCLUSIONS: In patients with LBBB on the ECG, the TpTe is longer and more frequently prolonged in patients with ACO compared to patients without ACO. Future studies of ventricular repolarization in patients with LBBB should include analyses of the TpTe interval.

THE HIGH COST OF MOTHERHOOD: END-LACTATION SYNDROME IN SOUTHERN SEA OTTERS (ENHYDRA LUTRIS NEREIS) ON THE CENTRAL CALIFORNIA COAST, USA.

Sea otters ( Enhydra lutris ) have exceptionally high energetic requirements, which nearly double during lactation and pup care. Thus, females are extremely vulnerable to caloric insufficiency. Despite a number of compensatory strategies, the metabolic challenge of reproduction culminates in numerous maternal deaths annually. Massive depletion of energy reserves results in a case presentation that we define as end-lactation syndrome (ELS), characterized by moderate to severe emaciation not attributable to a concurrent, independent disease process in females dying during late pup care or postweaning. We compiled detailed data for 108 adult female southern sea otters ( Enhydra lutris nereis) examined postmortem that stranded in California, US, 2005-12, and assessed pathology, reproductive status, and the location and timing of stranding. We introduce simple, grossly apparent, standardized physical criteria to assess reproductive stage for female sea otters. We also describe ELS, examine associated risk factors, and highlight female life history strategies that likely optimize reproduction and survival. Our data suggest that females can reset both the timing and energetic demands of reproduction through fetal loss, pup abandonment, or early weaning as part of specific physiologic checkpoints during each reproductive cycle. Females appear to preload nutritionally during delayed implantation and gestation to increase fitness and reproductive success. We found that ELS was a major cause of death, affecting 56% of enrolled adult females. Peak ELS prevalence occurred in late spring, possibly reflecting the population trend toward fall/winter pupping. Increasing age and number of pregnancies were associated with a higher risk of ELS. Although the proportion of ELS females was highest in areas with dense sea otter populations, cases were recovered throughout the range, suggesting that death from ELS is associated with, but not solely caused by, population resource limitation.

Oral papillomatosis caused by Enhydra lutris papillomavirus 1 (ElPV-1) in southern sea otters (Enhydra lutris nereis) in California, USA.

The southern sea otter (Enhydra lutris nereis) is a threatened marine sentinel. During postmortem investigations of stranded sea otters from 2004 to 2013 in California, US, papillomas were detected in the oral cavity of at least seven otters via necropsy and histopathology. Next-generation sequencing of viral particles purified from a single papilloma revealed a novel papillomavirus, Enhydra lutris papillomavirus 1 (ElPV-1). The genome of ElPV-1 was obtained, representing the first fully sequenced viral genome from southern sea otters. Phylogenetic analysis of the entire L1 gene, as well as a concatenated protein identities plot of all papillomaviral genes revealed that ElPV-1 is a λ-papillomavirus, related to a raccoon papillomavirus (Procyon lotor papillomavirus type 1) and a canine oral papillomavirus. Immunohistochemical staining, using a cross-reactive bovine papillomavirus antibody, suggested that ElPV-1 is present in intranuclear inclusions and intracytoplasmic keratin granules. Virus-infected cells were scattered throughout the stratum granulosum and stratum spinosum of the gingival and buccal papillomas. Using ElPV-1-specific PCR, we confirmed viral DNA in oral papillomas from all seven stranded sea otters, with identical L1 sequences. This virus is associated with the development of oral papillomatosis in southern sea otters.

Coccidioidomycosis and other systemic mycoses of marine mammals stranding along the central California, USA coast: 1998-2012.

A wide range of systemic mycoses have been reported from captive and wild marine mammals from North America. Examples include regionally endemic pathogens such as Coccidioides and Blastomyces spp., and novel pathogens like Cryptococcus gattii, which appear may have been introduced to North America by humans. Stranding and necropsy data were analyzed from three marine mammal stranding and response facilities on the central California coast to assess the prevalence, host demographics, and lesion distribution of systemic mycoses affecting locally endemic marine mammals. Between 1 January 1998 and 30 June 2012, >7,000 stranded marine mammals were necropsied at the three facilities. Necropsy and histopathology records were reviewed to identify cases of locally invasive or systemic mycoses and determine the nature and distribution of fungal lesions. Forty-one animals (0.6%) exhibited cytological, culture- or histologically confirmed locally invasive or systemic mycoses: 36 had coccidioidomycosis, two had zygomycosis, two had cryptococcosis, and one was systemically infected with Scedosporium apiospermum (an Ascomycota). Infected animals included 18 California sea lions (Zalophus californianus), 20 southern sea otters (Enhydra lutris nereis), two Pacific harbor seals (Phoca vitulina richardsi), one Dall's porpoise (Phocoenoides dalli), and one northern elephant seal (Mirounga angustirostris). Coccidioidomycosis was reported from 15 sea lions, 20 sea otters, and one harbor seal, confirming that Coccidioides spp. is the most common pathogen causing systemic mycosis in marine mammals stranding along the central California coast. We also report the first confirmation of C. gattii infection in a wild marine mammal from California and the first report of coccidioidomycosis in a wild harbor seal. Awareness of these pathogenic fungi during clinical care and postmortem examination is an important part of marine mammal population health surveillance and human health protection. Temporal-spatial overlap may be observed for pathogenic mycoses infecting coastal marine mammals and adjacent human populations.

Enteric bacterial pathogen detection in southern sea otters (Enhydra lutris nereis) is associated with coastal urbanization and freshwater runoff.

Although protected for nearly a century, California's sea otters have been slow to recover, in part due to exposure to fecally-associated protozoal pathogens like Toxoplasma gondii and Sarcocystis neurona. However, potential impacts from exposure to fecal bacteria have not been systematically explored. Using selective media, we examined feces from live and dead sea otters from California for specific enteric bacterial pathogens (Campylobacter, Salmonella, Clostridium perfringens, C. difficile and Escherichia coli O157:H7), and pathogens endemic to the marine environment (Vibrio cholerae, V. parahaemolyticus and Plesiomonas shigelloides). We evaluated statistical associations between detection of these pathogens in otter feces and demographic or environmental risk factors for otter exposure, and found that dead otters were more likely to test positive for C. perfringens, Campylobacter and V. parahaemolyticus than were live otters. Otters from more urbanized coastlines and areas with high freshwater runoff (near outflows of rivers or streams) were more likely to test positive for one or more of these bacterial pathogens. Other risk factors for bacterial detection in otters included male gender and fecal samples collected during the rainy season when surface runoff is maximal. Similar risk factors were reported in prior studies of pathogen exposure for California otters and their invertebrate prey, suggesting that land-sea transfer and/or facilitation of pathogen survival in degraded coastal marine habitat may be impacting sea otter recovery. Because otters and humans share many of the same foods, our findings may also have implications for human health.