No Value Found With Routine Early Postoperative Radiographs after Implant Removal in Pediatric Patients.

BACKGROUND: Implants are routinely removed in pediatric patients. Fracture through the prior implant site is a common worry after implant removal. Early post-implant removal radiographs are routinely used to evaluate the prior implant removal sites and to assess when a patient may return to normal activities. To our knowledge, the value of early, routine postoperative radiographs after elective implant removal in pediatric patients has not been studied. METHODS: A retrospective patient cohort of pediatric patients who had implant removal from an extremity from 2017 to 2019 was used in this study. Data were collected for patient demographics, implant site, reason for primary surgery, complications, number of postoperative radiographs, radiation exposure, cost of imaging, and whether the postoperative plan was changed by imaging. RESULTS: Two hundred ninety patients were included in the study. Postoperative plans were changed only in 0.69% of patients (n = 2) because of abnormal 2-week radiographs and 1.72% (n = 5) because of abnormal 6-week radiographs. However, the event's proportion difference (change of management) was not statically significant ( P = 0.182) between those who had a radiograph obtained and those who did not. The mean follow-up time was 16 months. The mean number of postoperative radiographs obtained was 3.74, the mean cost per radiograph was $103, and the mean postoperative radiation exposure was 1.34 mSv. No fractures were observed after implant removal. DISCUSSION: A retrospective review of the value of early, postoperative radiographs after routine orthopaedic implant removal found that postoperative radiographs at 2 and 6 weeks did not change the postoperative plan for most of the patients. Postoperative radiographs have an average cost of $103, and radiation exposure equal to approximately 6 months of natural background radiation. LEVEL OF EVIDENCE: Level III.

The influence of tourist visitation on the heterophyl to lymphocyte ratios and trophic values of Magellanic penguins (Spheniscus magellanicus) at Martillo Island, Argentina.

Wildlife tourism is increasing worldwide and monitoring the impact of tourism on wild populations is of the utmost importance for species conservation. The Magellanic penguin Spheniscus magellanicus colony at Martillo Island, Argentina, was studied in the 2016-2020 breeding seasons. In all seasons, adults and chicks belonged to: (i) an area close to or within the tourist trail or (ii) an area far from the tourist trail and out of sight of the tourists. Blood samples were taken for carbon and nitrogen stable isotope composition, in order to estimate trophic niches, and for smears that were made in situ and were then stained in the laboratory where leucocyte counts and differentiation were made under optical microscope. Heterophil to lymphocyte ratios were used as proxies of stress. Repeated sampling showed individual stress levels reduced while wintering. In 2017, stress levels and trophic values were lower than 2018 for the same individuals. Trophic levels did not differ between tourism and no tourism areas within each season, and differed between 2017 and the remaining seasons, indicating a possible diet shift that year. Stress levels were higher for the tourism area than the no tourism area for adults and chicks in all years except for 2020, when stress levels in the tourism area were lower and similar to the no tourism area that year and previous years. Vessel transit within the Beagle Channel and tourist visitation to the penguin colony was greatly reduced in 2020 due to the Covid-19 pandemic. A combination of internal characteristics and external factors may be affecting the stress physiology of individuals. Therefore, future research should include sampling of multiple aspects of penguin physiology, behaviour and environmental context in order to evaluate each effect on Magellanic penguin stress and, ultimately, inform the conservation of this iconic species in time.

Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression.

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the DMPK gene that generates toxic RNA with a myriad of downstream alterations in RNA metabolism. A key consequence is the sequestration of alternative splicing regulatory proteins MBNL1/2 by expanded transcripts in the affected tissues. MBNL1/2 depletion interferes with a developmental alternative splicing switch that causes the expression of fetal isoforms in adults. Boosting the endogenous expression of MBNL proteins by inhibiting the natural translational repressors miR-23b and miR-218 has previously been shown to be a promising therapeutic approach. We designed antimiRs against both miRNAs with a phosphorodiamidate morpholino oligonucleotide (PMO) chemistry conjugated to cell-penetrating peptides (CPPs) to improve delivery to affected tissues. In DM1 cells, CPP-PMOs significantly increased MBNL1 levels. In some candidates, this was achieved using concentrations less than two orders of magnitude below the median toxic concentration, with up to 5.38-fold better therapeutic window than previous antagomiRs. In HSALR mice, intravenous injections of CPP-PMOs improve molecular, histopathological, and functional phenotypes, without signs of toxicity. Our findings place CPP-PMOs as promising antimiR candidates to overcome the treatment delivery challenge in DM1 therapy.

Role of Different Low-Density Lipoprotein-Lowering Medications on Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients With Diabetes Mellitus.

Purpose The objective of this study was to explore the optimal cholesterol-lowering therapy for diabetic patients categorized as having a very high risk for future atherosclerotic cardiovascular disease (ASCVD) events. The primary medications under investigation were statins, ezetimibe, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (PCSK9-Is). The efficacy of different medication regimens helped to draw conclusions regarding the evolution of cholesterol management recommended under the American College of Cardiology's (ACC) 2013 and 2018 guidelines. Methods A retrospective chart review was conducted on a cohort of patients from a large, community-based cardiology practice. Inclusion criteria specified patients aged 30-82 with a past medical history of two or more ASCVD events or one ASCVD event and at least two high-risk comorbidities. Acquired data included demographics, all lipid panels, medications used, and ASCVD events between December 1, 2013, and December 31, 2019. The data were stored and encrypted on a REDCap account. Sub-group analysis was conducted on only diabetic patients, who were then categorized by medication regimen. The statistical analysis was completed using Fisher's exact test. A p-value <0.05 was considered significant. Results A total of 102 diabetic patients met the inclusion criteria. Our primary analysis determined the percentage of patients who achieved their goals on each medication regimen. The goal was defined as a low-density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dL or at least a 50% reduction from baseline levels. The results are as follows: none (0%), statin (33.9%), ezetimibe (21.1%), statin + ezetimibe (73.5%), PCSK9-Is ± statin (83.3%), and PCSK9-Is and ezetimibe ± statin (100%). There proved to be a significant difference favoring all combination regimens over statins alone; however, there was no significant difference between these advanced regimens. A follow-up analysis determined if these patients were able to maintain their goals in the subsequent lipid panel after achieving their goals. The results are as follows: none (0%), statin (61.5%), ezetimibe (50%), statin + ezetimibe (77.8%), PCSK9-Is ± statin (100%), and PCSK9-Is and ezetimibe ± statin (66.6%). The only significant difference found was between PCSK9-Is ± statins and statins alone. Conclusions Our study revealed that regimens using PCSK9 inhibitors and ezetimibe, in addition to maximally tolerated statin therapy, were more effective than statin therapy alone in achieving the goal. On extended analysis, only PCSK9 inhibitors showed superior ability in terms of maintaining the goals for diabetic patients at very high risk for future ASCVD events. This implies that statins alone may be inadequate to properly treat this specific patient population. In the context of clinical practice, physicians could have heightened consideration for dual therapy consisting of maximally tolerated statins and a secondary agent in accordance with the 2018 ACC guidelines.

Asymptotic Distribution of Certain Types of Entropy under the Multinomial Law.

We obtain expressions for the asymptotic distributions of the Rényi and Tsallis of order q entropies and Fisher information when computed on the maximum likelihood estimator of probabilities from multinomial random samples. We verify that these asymptotic models, two of which (Tsallis and Fisher) are normal, describe well a variety of simulated data. In addition, we obtain test statistics for comparing (possibly different types of) entropies from two samples without requiring the same number of categories. Finally, we apply these tests to social survey data and verify that the results are consistent but more general than those obtained with a χ2 test.

Tool parameters to minimize temperature changes in bone drilling.

BACKGROUND: Drilling is a common technique used in orthopedic surgery procedures but causes increases in temperature that can lead to cell damage and death. The extent of this depends largely on the magnitude of the increase in temperature. The commonly accepted limit to prevent osteonecrosis is less than 47 °C for 60 s. There is controversy when it comes to the optimal drilling parameters that limit temperature increases and cell death. In addition to this, less research has been done on the drilling effects in the osteochondral area of joints. Osteochondral tissue damage can interfere with the daily lives of patients and if severe enough will need to be treated. We hypothesize that increasing tool speed and drill bit size will increase temperature that could be above the osteonecrosis limit. METHODS: Ex-vivo experiments were conducted on porcine shoulder joints that tested the thermal effects of different tool speeds and drill bit sizes. A thermal camera was used to record and measure real time temperature changes while drilling. Three drill bit sizes and five tool speeds were used. Statistical analyses includes Welch's ANOVA with Games-Howell Post Hoc analyses, multivariate linear regression, and surface response regression were used to explore the association of tool speeds and drill bit size on temperature. RESULTS AND CONCLUSIONS: All the tool speed and drill bit size combinations lead to an increase in temperature that were under the commonly accepted limit. The highest temperature reached was 44 °C with a tool speed of 1150 RPM and 3070 RPM and drill bit size 5.159 mm. It was found that increasing the tool speed increased the temperature change and increasing the drill bit size increased the temperature change.

Potential for redistribution of post-moult habitat for Eudyptes penguins in the Southern Ocean under future climate conditions.

Anthropogenic climate change is resulting in spatial redistributions of many species. We assessed the potential effects of climate change on an abundant and widely distributed group of diving birds, Eudyptes penguins, which are the main avian consumers in the Southern Ocean in terms of biomass consumption. Despite their abundance, several of these species have undergone population declines over the past century, potentially due to changing oceanography and prey availability over the important winter months. We used light-based geolocation tracking data for 485 individuals deployed between 2006 and 2020 across 10 of the major breeding locations for five taxa of Eudyptes penguins. We used boosted regression tree modelling to quantify post-moult habitat preference for southern rockhopper (E. chrysocome), eastern rockhopper (E. filholi), northern rockhopper (E. moseleyi) and macaroni/royal (E. chrysolophus and E. schlegeli) penguins. We then modelled their redistribution under two climate change scenarios, representative concentration pathways RCP4.5 and RCP8.5 (for the end of the century, 2071-2100). As climate forcings differ regionally, we quantified redistribution in the Atlantic, Central Indian, East Indian, West Pacific and East Pacific regions. We found sea surface temperature and sea surface height to be the most important predictors of current habitat for these penguins; physical features that are changing rapidly in the Southern Ocean. Our results indicated that the less severe RCP4.5 would lead to less habitat loss than the more severe RCP8.5. The five taxa of penguin may experience a general poleward redistribution of their preferred habitat, but with contrasting effects in the (i) change in total area of preferred habitat under climate change (ii) according to geographic region and (iii) the species (macaroni/royal vs. rockhopper populations). Our results provide further understanding on the regional impacts and vulnerability of species to climate change.

Mercury and stable isotopes portray colony-specific foraging grounds in southern rockhopper penguins over the Patagonian Shelf.

Mercury pollution is a serious global environmental issue and the characterization of its distribution and its driving forces should be urgently included in research agendas. We report unusually high mercury (Hg) concentrations (>5 µg/g) along with stable isotopes values in feathers of southern rockhopper penguins (Eudyptes chrysocome) from colonies in the Southwest Atlantic Ocean. We found a highly heterogenous prevalence of Hg throughout the study area and over a three-fold higher mean Hg concentration in southernmost colonies. Variation in Hg concentrations among colonies is primarily explained by site, rather than by trophic position. We provide further support to the existence of a Hg hotspot in the food web of the Patagonian Shelf and spatially restrict it to the southern tip of South America. Our findings highlight the need for regional and colony-based seabird conservation management when high local variability and plasticity in foraging habits is evident.

Comparison of DNA methylation patterns across tissue types in infants with tetralogy of Fallot.

BACKGROUND: Environmental factors may influence the development of tetralogy of Fallot (TOF), and DNA methylation patterns may reveal specific chemical signatures of perturbations during cardiac development. We investigated whether blood and buccal cells could be viable surrogates for myocardium. METHODS: We measured epigenome-wide DNA methylation at 866,895 5'-cytosine-phosphate-guanine-3' (CpG) sites in blood (n=3), buccal cells (n=3), and right ventricular myocardium (n=4) collected from infants with TOF and compared the percent of differentially methylated CpG sites across tissue types. Gene-specific DNA methylation profiles were also analyzed for ten representative genes associated with heart development. Welch's ANOVAs compared general methylation between tissue types. RESULTS: Comparison of DNA methylation profiles across blood, buccal, and myocardium suggested myocardium and buccal samples were most similar, differing in DNA methylation at only 1.3% (11,386) of CpG sites whereas myocardium and blood were most dissimilar, having 146,857 statistically dissimilar methylated CpG sites (~17% dissimilarity; adjusted p < 0.01 for each site). Buccal swabs were significantly more variable (p < .001) than either blood or myocardial samples. In gene-specific analyses, SCO2, GATA4, NOTCH4, WNT7A, and DKK2 showed conserved DNA methylation profiles across tissue types, while HAND1, JAG1, NKX2-5, TBX5 and TBX20 showed more distinctive tissue-specific patterns of DNA methylation. CONCLUSIONS: Compared with blood, buccal tissue more closely mirrors the myocardial methylome, with >10-fold similarity. Nevertheless, both buccal and blood tissue capture highly conserved DNA methylation patterns at specific genetic loci related to cardiac development. Buccal cheek swabs may be a useful surrogate tissue type for future investigations of TOF-specific epigenetic profiles.

Impact of Providing Peer Support on Medical Students' Empathy, Self-Efficacy, and Mental Health Stigma.

BACKGROUND: Peer-support programs in medical school can buffer feelings of inadequacy, anxiety, social isolation, and burnout, drawing upon the benefits of near-peer-support resources. This study examined the effects of providing support to students in a medical school peer-support program. METHODS: Using a pre-post, quasi-experimental study design, the investigators surveyed medical students who were peer supporters in their second through fourth years of medical school with four measures assessing (1) empathy, (2) self-efficacy, (3) mental health stigma, and (4) likelihood to assist peers with mental health problems to examine if serving as a volunteer peer supporter had any effect. Participants included 38 medical students that were actively enrolled peer supporters during the 2020-2021 year at a United States allopathic medical school. RESULTS: Medical students who participated as peer supporters were found to have higher ratings of empathy scores (Z = -1.964, p = 0.050, r = 0.34) and self-efficacy scores (Z = -2.060, p = 0.039, r = 0.35) after participation in the program. No significant changes were noted for mental health stigma or likelihood to assist peers with mental health problems. DISCUSSION: Peer-support programs present a low-cost, sustainable modality to promote wellbeing in medical students. There is a growing body of literature documenting the benefits of peer-support services. This brief, novel study examined the effects of providing peer support on the peer supporters and found higher self-reported ratings of empathy and self-efficacy after participation. These findings underscore peer-support programs as a valuable wellness resource not only for medical students who use the services but for those who provide them as well.

Entropy Estimators in SAR Image Classification.

Remotely sensed data are essential for understanding environmental dynamics, for their forecasting, and for early detection of disasters. Microwave remote sensing sensors complement the information provided by observations in the optical spectrum, with the advantage of being less sensitive to adverse atmospherical conditions and of carrying their own source of illumination. On the one hand, new generations and constellations of Synthetic Aperture Radar (SAR) sensors provide images with high spatial and temporal resolution and excellent coverage. On the other hand, SAR images suffer from speckle noise and need specific models and information extraction techniques. In this sense, the G0 family of distributions is a suitable model for SAR intensity data because it describes well areas with different degrees of texture. Information theory has gained a place in signal and image processing for parameter estimation and feature extraction. Entropy stands out as one of the most expressive features in this realm. We evaluate the performance of several parametric and non-parametric Shannon entropy estimators as input for supervised and unsupervised classification algorithms. We also propose a methodology for fine-tuning non-parametric entropy estimators. Finally, we apply these techniques to actual data.

Mercury exposure driven by geographic and trophic factors in Magellanic penguins from Tierra del Fuego.

Penguins accumulate mercury due to their long-life span together with their high trophic position. We sampled adult and juveniles' feathers from three colonies of Spheniscus magellanicus from Tierra del Fuego along an inshore-offshore corridor. We integrated toxicological information (mercury concentrations) and foraging biomarkers (δ13C, δ15N) into a common data analysis framework (isotopic niche analysis) to evaluate the influence of age, location, and foraging behaviors on mercury concentrations. Adults had higher feather mercury concentrations, δ13C, and δ15N values compared to juveniles. Also, adult and juvenile feather mercury concentrations differed between colonies, with lower mercury concentrations at the nearest inshore colony relative to the farther offshore colonies. Trophic position and the isotopic niche analyses suggest that this geographic gradient in mercury concentrations is due to differences in colonies' foraging areas. Understanding penguins' exposure to mercury derived from local food webs is a crucial first step in evaluating the impacts of this heavy metal on their conservation status.

Sex-specific spatial use of the winter foraging areas by Magellanic penguins and assessment of potential conflicts with fisheries during winter dispersal.

Magellanic penguins (Spheniscus magellanicus) disperse widely during winter and are a major consumer of marine resources over the Patagonian Shelf. Magellanic penguins were equipped with geolocators at Martillo Island in late February- early March 2017 and recaptured at the beginning of the next breeding season to recover the devices and to collect blood samples for stable carbon (δ13C) and nitrogen (δ15N) isotope analysis. We evaluated their whole winter dispersal and their trophic niche by sex during the last month of the winter dispersal. Also, we evaluated their spatial overlap with bottom trawl and shrimp fisheries using data from satellite fisheries monitoring. Penguins dispersed northwards up to 42°S and showed latitudinal spatial segregation between sexes during May to August (females were located further north than males). In contrast, during the last month of the winter dispersal females were located more southerly and showed lower trophic position than males. Also, females did not dive as deep as males during winter. We found high overlap between both fisheries and penguin's spatial use in regions with documented interaction. However, no sex-specific statistical differences with fisheries overlap were found. Our results highlight the importance of understanding the spatial domains of each sex and assessment of their potential conflicts with bottom trawl fishery and shrimp fishery during the winter period.

Effects of voluntary attendance patterns on first-year medical students' wellness and academic performance during COVID-19.

There is increasing evidence that attendance is not a reliable predictor of academic performance, which invites the question of whether attendance may have alternative positive effects such as increased student wellness. While conducting an observational cohort study on the relationship of attendance to performance and wellness, the COVID-19 pandemic lockdown changed the ability of students to attend class. Matriculating medical students were recruited to participate at the beginning of their first year in August 2019. In-person attendance was collected prospectively until the lockdown began in March 2020. This was then correlated with performance on course final examinations and responses to two separate incidences of a survey on stress, burnout, social isolation, and loneliness. The first survey was deployed January through February 2020 (pre-COVID) and the second June 2020 (during COVID lockdown). Attendance declined across the year (76.0%-25.0%). There was a small positive correlation of attendance to performance in module 1 (r = 0.235, P = 0.035) with none in the remaining two modules (P = 0.870, P = 0.410). The high attenders at the time of the lockdown had no decline in their performance when attendance was no longer possible. Attendance negatively correlated with stress and loneliness but not with the remainder of the wellness metrics. There was no significant change in any of the wellness metrics between the pre-COVID and during COVID time points. While the data support the conclusion that attendance is not required to maintain performance in this population, these data suggest a small protective effect against stress and loneliness.

Supervised Exercise Immediately After Bariatric Surgery: the Study Protocol of the EFIBAR Randomized Controlled Trial.

BACKGROUND: Previous studies have investigated weight loss caused by exercise following bariatric surgery. However, in most cases, the training program is poorly reported; the exercise type, volume, and intensity are briefly mentioned; and the sample size, selection criteria, and follow-up time vary greatly across studies. PURPOSE: The EFIBAR study aims to investigate over 1 year the effects of a 16-week supervised exercise program, initiated immediately after bariatric surgery, on weight loss (primary outcome), body composition, cardiometabolic risk, physical fitness, and quality of life in patients with severe/extreme obesity. MATERIAL AND METHODS: The EFIBAR study is a parallel-group, superiority, randomized controlled trial (RCT), comprising 80 surgery patients. Half of the participants, randomly selected, perform a 16-week supervised exercise program, including both strength and aerobic training, starting immediately after the surgery (7-14 days). For each participant, all primary and secondary outcomes are measured at three different time points: (i) before the surgery, (ii) after the intervention (≈4 months), and (iii) 1 year after the surgery. CONCLUSION: The EFIBAR study will provide new insights into the multidimensional benefits of exercise in adults with severe/extreme obesity following bariatric surgery. TRIAL REGISTRATION: EFIBAR randomized controlled trial was prospectively registered at Clinicaltrials.gov (NCT03497546) on April 13, 2018.

The dynamic trophic niche of an island bird of prey.

Optimal foraging theory predicts an inverse relationship between the availability of preferred prey and niche width in animals. Moreover, when individuals within a population have identical prey preferences and preferred prey is scarce, a nested pattern of trophic niche is expected if opportunistic and selective individuals can be identified. Here, we examined intraspecific variation in the trophic niche of a resident population of striated caracara (Phalcoboenus australis) on Isla de los Estados (Staten Island), Argentina, using pellet and stable isotope analyses. While this raptor specializes on seabird prey, we assessed this population's potential to forage on terrestrial prey, especially invasive herbivores as carrion, when seabirds are less accessible. We found that the isotopic niche of this species varies with season, age, breeding status, and, to a lesser extent, year. Our results were in general consistent with classic predictions of the optimal foraging theory, but we also explore other possible explanations for the observed pattern. Isotopic niche was broader for groups identified a priori as opportunistic (i.e., nonbreeding adults during the breeding season and the whole population during the nonbreeding season) than it was for individuals identified a priori as selective. Results suggested that terrestrial input was relatively low, and invasive mammals accounted for no more than 5% of the input. The seasonal pulse of rockhopper penguins likely interacts with caracara's reproductive status by constraining the spatial scale on which individuals forage. Niche expansion in spatially flexible individuals did not reflect an increase in terrestrial prey input; rather, it may be driven by a greater variation in the types of marine prey items consumed.

Metapopulation dynamics and foraging plasticity in a highly vagile seabird, the southern rockhopper penguin.

Population connectivity is driven by individual dispersal potential and modulated by natal philopatry. In seabirds, high vagility facilitates dispersal yet philopatry is also common, with foraging area overlap often correlated with population connectivity. We assess the interplay between these processes by studying past and current connectivity and foraging niche overlap among southern rockhopper penguin colonies of the coast of southern South America using genomic and stable isotope analyses. We found two distinct genetic clusters and detected low admixture between northern and southern colonies. Stable isotope analysis indicated niche variability between colonies, with Malvinas/Falklands colonies encompassing the species entire isotopic foraging niche, while the remaining colonies had smaller, nonoverlapping niches. A recently founded colony in continental Patagonia differed in isotopic niche width and position with Malvinas/Falklands colonies, its genetically identified founder population, suggesting the exploitation of novel foraging areas and/or prey items. Additionally, dispersing individuals found dead across the Patagonian shore in an unusual mortality event were also assigned to the northern cluster, suggesting northern individuals reach southern localities, but do not breed in these colonies. Facilitated by variability in foraging strategies, and especially during unfavorable conditions, the number of dispersing individuals may increase and enhance the probability of founding new colonies. Metapopulation demographic dynamics in seabirds should account for interannual variability in dispersal behavior and pay special attention to extreme climatic events, classically related to negative effects on population trends.

Evidence of Pathogen-Induced Immunogenetic Selection across the Large Geographic Range of a Wild Seabird.

Over evolutionary time, pathogen challenge shapes the immune phenotype of the host to better respond to an incipient threat. The extent and direction of this selection pressure depend on the local pathogen composition, which is in turn determined by biotic and abiotic features of the environment. However, little is known about adaptation to local pathogen threats in wild animals. The Gentoo penguin (Pygoscelis papua) is a species complex that lends itself to the study of immune adaptation because of its circumpolar distribution over a large latitudinal range, with little or no admixture between different clades. In this study, we examine the diversity in a key family of innate immune genes-the Toll-like receptors (TLRs)-across the range of the Gentoo penguin. The three TLRs that we investigated present varying levels of diversity, with TLR4 and TLR5 greatly exceeding the diversity of TLR7. We present evidence of positive selection in TLR4 and TLR5, which points to pathogen-driven adaptation to the local pathogen milieu. Finally, we demonstrate that two positively selected cosegregating sites in TLR5 are sufficient to alter the responsiveness of the receptor to its bacterial ligand, flagellin. Taken together, these results suggest that Gentoo penguins have experienced distinct pathogen-driven selection pressures in different environments, which may be important given the role of the Gentoo penguin as a sentinel species in some of the world's most rapidly changing environments.

Phylogeography, Population Structure, and Species Delimitation in Rockhopper Penguins (Eudyptes chrysocome and Eudyptes moseleyi).

Rockhopper penguins are delimited as 2 species, the northern rockhopper (Eudyptes moseleyi) and the southern rockhopper (Eudyptes chrysocome), with the latter comprising 2 subspecies, the western rockhopper (Eudyptes chrysocome chrysocome) and the eastern rockhopper (Eudyptes chrysocome filholi). We conducted a phylogeographic study using multilocus data from 114 individuals sampled across 12 colonies from the entire range of the northern/southern rockhopper complex to assess potential population structure, gene flow, and species limits. Bayesian and likelihood methods with nuclear and mitochondrial DNA, including model testing and heuristic approaches, support E. moseleyi and E. chrysocome as distinct species lineages with a divergence time of 0.97 Ma. However, these analyses also indicated the presence of gene flow between these species. Among southern rockhopper subspecies, we found evidence of significant gene flow and heuristic approaches to species delimitation based on the genealogical diversity index failed to delimit them as species. The best-supported population models for the southern rockhoppers were those where E. c. chrysocome and E. c. filholi were combined into a single lineage or 2 lineages with bidirectional gene flow. Additionally, we found that E. c. filholi has the highest effective population size while E. c. chrysocome showed similar effective population size to that of the endangered E. moseleyi. We suggest that the current taxonomic definitions within rockhopper penguins be upheld and that E. chrysocome populations, all found south of the subtropical front, should be treated as a single taxon with distinct management units for E. c. chrysocome and E. c. filholi.

Lamotrigine-Valproic Acid Interaction Leading to Stevens-Johnson Syndrome.

Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens-Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Hereby, we present the case of an 8-year-old boy who suffered from SJS and other complications two weeks after LTG was added to his VPA treatment in order to control his seizures. VPA is known to decrease LTG clearance via reduced glucuronidation. In this case, the minor elimination pathway of LTG would play a more important role, and the formation of an arene oxide metabolite would be enhanced. As this reactive metabolite is detoxified mainly by enzymatic reactions, involving microsomal epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or GSH-S-transferases is either defective or inhibited or a depletion of intracellular glutathione levels is taking place. VPA can cause inhibition of epoxide hydrolase enzymes and/or depletion of glutathione levels leading to adverse cutaneous reactions.