Background: During the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double strand DNA breaks are produced. Subsequently, these breaks are corrected by a complexed system led mainly by the non-homologous end-joining (NHEJ). Mutations in proteins involved in this process, including the XLF/ Cernunnos gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and susseptability to inoizing radiation. Objective: To provide new clinical and immunological insights on XLF/Cernunnos deficiency, arising from a newly diagnosed patient with severe immunodeficiency. Methods: A male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic work up. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole exome sequencing (WES), TCR repertoire Vβ repertoire via flow cytometry analysis and TCR and BCR via next generation sequencing (NGS). Results: Clinical findings included microcephaly, recurrent bacterial viral pneumonia and failure to thrive. Immune workup revealed lymphopenia, reduced T cell function and hypogammaglubolinemia. A skewed TCR Vβ repertoire, TCR gamma (TRG) repertoire and BCR repertoire were determined in the patient. Genetic analysis identified a novel autosomal recessive homozygous missense mutation in XLF/Cernunnos c. A580Ins.T; p. M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT). Conclusions: A novel XLF/Cernunnos mutation is reported in a patient presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.

Luminescence, a physical phenomenon that producing cool light in vivo, has been found in bacteria, fungi and anminals but not yet in terrestrial higher plants. Through genetic engineering, it is feasible to introduce luminescence system into living plant cells as biomarkers. Recently, some plants transformed with luminescent systems can glimmer in darkness, which can be observed by our naked eyes and provide a novel lighting resource. In this review, we summarized the development of luminescence in plant cells, followed by exampling the successful cases of glowing plants transformed with diverse luminescent systems. The potential key factors to optimize a glowing plant are also discussed. Our review is useful for the creation of the optimized glowing plants, which can be used not only in scientific research, but also as promising substitutes of artificial light sources in the future.

Aim: We aimed to compare pre-voiding bladder and post-voiding residual (BV, PVR) volumes measured by portable ultrasonic scanner (PUS) in standing and supine positions. Material and Methods: A total of 436 children were included. We composed 2 groups (group-1: PUS vs. volume by catheter, group-2: PUS vs. infused volume during urodynamic study) to evaluate the agreement of PUS measurements with actual bladder volume and then third group (group-3) to analyze the correlation of PUS measurements in standing vs. supine positions. In groups 1 and 2, agreement of measurements were evaluated by paired sample T or Wilcoxon signed rank tests. Following confirmation of agreement, correlations were analyzed by Pearson’s or Spearman’s coefficients in all groups. Interpretation of coefficients were done as 0.90-1.00 (very high correlation) and 0.70-0.90 (high correlation), respectively. Results: In group-1, measurements (catheter vs. PUS) were similar (Wilcoxon Signed rank test, p= 0.976) and were highly correlated (r=0.873). In group-2, measurements of bladder volumes infused by urodynamic device and volumes by PUS were similar that revealed the agreement of PUS measurements on different volumes and highly correlated at the 25th and very highly correlated at the 50th, 75th and 100th percentiles of the EBC (estimated bladder capacity related to age). In group-3, BV and PVR measurements by PUS in standing and supine positions were highly correlated that revelaed PUS can be used in both positions. Conclusion: Measurements of BV before uroflowmetry or PVR volume by PUS in standing position gave similar results with those in supine position.

OBJECTIVE To assess the impact of the surgical delay for localized prostate cancer (PCa) on adverse pathological features and oncological outcomes. MATERIALS AND METHODS Patients who underwent surgery for localized prostate cancer were included from the Turkish Urooncology Association (TUA) Prostate Cancer database. A History of previous treatment or active surveillance (AS) were considered as exclusion criteria from the study. Patients were divided into two groups according the time period between the diagnosis and surgery; less than or equal to 90 days (group 1) or longer than 90 days (group 2). Surgical pathology results and oncological outcomes were compared between the two groups. RESULTS A total of 2454 out of 3646 patients were assessed. Pathological findings of the radical prostatectomy (RP) specimens were similar between two groups. However, there was slightly more seminal vesicle invasion in final surgical pathology in group 1 (12.9% vs. 9.3%, respectively p=0.042). 5-year biochemical recurrence free survival times were similar across all D’Amico risk categories between two groups. The regression analysis demonstrated the seminal vesicle invasion as the only factor affecting time to PSA progression in high-risk patients (p<0.001 HR:2.51 CI: 1,58-4,45). CONCLUSION In conclusion, our results in this large cohort suggest that surgical delay does not cause a deterioration for prostate cancer surgical outcomes even in high-risk group of patients. These findings may be helpful for planning the limited healthcare resources especially in conditions like the Covid-19 pandemic where the availability and optimal use of healthcare system resources is crucial.

Metabarcoding is an important tool for understanding fungal communities. The internal transcribed spacer (ITS) rDNA is the accepted fungal barcode but has known problems. The large subunit (LSU) rDNA has also been used to investigate fungal communities but available LSU metabarcoding primers were mostly designed to target Dikarya (Ascomycota + Basidiomycota) with little attention to early diverging fungi (EDF). However, evidence from multiple studies suggests that EDF comprise a large portion of unknown diversity in community sampling. Here we investigate how DNA marker choice and methodological biases impact recovery of EDF from environmental samples. We focused on one EDF lineage, Zoopagomycota, as an example. We evaluated three primer sets (ITS1F/ITS2, LROR/LR3, and LR3 paired with new primer LR22F) to amplify and sequence a Zoopagomycota mock community and a set of 146 environmental samples with Illumina MiSeq. We compared two taxonomy assignment methods and created an LSU reference database compatible with AMPtk software. The two taxonomy assignment methods recovered strikingly different communities of fungi and EDF. Target fragment length variation exacerbated PCR amplification biases and influenced downstream taxonomic assignments, but this effect was greater for EDF than Dikarya. To improve identification of LSU amplicons we performed phylogenetic reconstruction and illustrate the advantages of this critical tool for investigating identified and unidentified sequences. Our results suggest much of the EDF community may be missed or misidentified with “standard” metabarcoding approaches and modified techniques are needed to understand the role of these taxa in a broader ecological context.

A popular measure of differentiation in biodiversity is the Bray Curtis index of dissimilarity. It has recently also been proposed for use in molecular ecology. However, this measure currently cannot be predicted under specified conditions of population size, dispersal and speciation or mutation. Here I show forecasts for Bray-Curtis for two-variant systems such as single-nucleotide polymorphisms (SNPs) (or two species ecosystems). These are derived from well-known equations in population genetics, for forecasting measures such as G_ST, and shown to be appropriate by simulation. Thus, Bray-Curtis can now be used for assessment of differentiation, in order to understand natural or artificial processes, thus complementing other measures with different sensitivities, such as Morisita-Horn/D_EST, G_ST and Shannon Mutual Information/Shannon Differentiation.

Although infrequent, drug-induced agranulocytosis can be stimulated by antibiotics. Here, we analyzed the Japanese Adverse Drug Event Report database to identify profiles of antibiotic-induced agranulocytosis. Ten of 60 antibiotics showed signals for agranulocytosis; the reporting odds ratios (95% confidence intervals) for ampicillin/sulbactam, amikacin, cefmetazole, cefozopran, clindamycin, ciprofloxacin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 2.65 (1.79–3.80), 2.49 (1.91–4.34), 4.48 (2.27–6.92), 2.77 (1.88–3.95), 1.64 (1.04–2.47), 2.01 (1.40–2.82), 2.78 (2.11–3.60), 6.05 (2.16–13.7), 2.05 (1.31–3.07), and 3.54 (2.73–4.54), respectively. The median times-to-onset of agranulocytosis for ampicillin/sulbactam, cefmetazole, cefozopran, clindamycin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 20, 6, 10, 16, 12, 3, 18, and 13 days, respectively. The 95% confidence intervals of the Weibull shape parameter β for these antibiotics were over and excluded 1, indicating that the antibiotics were the wear out failure type. These findings provided insights into the characteristics of antibiotic-induced agranulocytosis.

Livestock industry supports the livelihood of around 1.3 billion people in the world, with swine industry contributing with 30 % of total livestock production worldwide. To maintain and guarantee this production, a pivotal point according to the OIE is addressing potential biohazards. To control them, permanent sero-surveillance is crucial to achieve more focused veterinary public health intervention and prevention strategies, to break the chains of transmission, and to enable fast responses against outbreaks. Within this context, multiplex assays are powerful tools with the potential to simplify surveillance programs, since they reduce time, labour, and variability within analysis. In the present work, we developed a multiplex bead-based assay for the detection of specific antibodies to six relevant pathogens affecting swine: ASFV, CSFV, PRRSV, SIV, TB, and HEV. The most immunogenic target antigen of each pathogen was selected as the target protein to coat different microsphere regions in order to develop this multiplex assay. A total of 1544 serum samples from experimental infections as well as field samples were included in the analysis. The 6plex assay exhibited credible diagnostic parameters with sensitivities ranging from 87.0 % to 97.5 % and specificities ranging from 87.9 % to 100.0 %, demonstrating it to be a potential high throughput tool for surveillance of infectious diseases in swine.

Migration is often thought to be driven by poor environmental conditions during one season and to permit avoidance of harsh weather or resource shortage and tracking of more favourable conditions. Here, we tested this hypothesis in seabirds at the global scale by quantifying niche occupancy during the breeding and non-breeding periods over multiple marine ecoregions and exploring whether the niche dynamics reflects changes in environmental conditions at the breeding and non-breeding grounds. We demonstrate that migratory species exhibit more divergent seasonal niches than resident and dispersive ones. In most cases, migratory status was not related to unavailability of favourable conditions at the breeding or non-breeding grounds, suggesting that niche availability is not the main driver of migration. We hypothesize that this unexpected pattern might arise from strong constraints imposed on seabirds by scarcity of suitable sites breeding which constrain the range of environments available for optimizing reproductive success.

Monogenean infection of the internal organs is extremely rare when compared to external infections. This study describes mass mortality of Nile tilapia (Oreochromis niloticus L.) originating from co-infection with Enterogyrus spp. and Aeromonas jandaei following transport stress. The first fish deaths occurred on day 1 post-transport, while cumulative mortality reached approximately 90% by day 10 post-stocking. An atypical amount of pale (whitish) faeces floating on the surface of the water as well as typical clinical signs of motile Aeromonas septicemia, were reported. Adult monogeneans and countless eggs of monogeneans were found in the stomachs and the intestines of both moribund and dead fish, respectively. Two strains of A. jandaei were isolated from the kidneys. Scanning electron microscope microphotographs of the stomach revealed the presence of numerous monogeneans penetrating deep into the gastric tissue, and diffuse lesions filled with bacilliform bacteria. This is the first report of co-infection by Enterogyrus spp. and A. jandaei in Nile tilapia and the first report of E. coronatus, E. foratus, and E. malbergi parasitizing tilapia in Brazil. These findings indicate that synergic co-infection by Monogenean stomach parasites (E. coronatus, E. foratus, and E. malbergi) and A. jandaei may induce high mortalities in tilapia following transport stress.

Objective: Seasonal inactivated influenza vaccine (IIV) is recommended during pregnancy to protect both mothers and infants from severe infection. Most studies have evaluated the risk of major structural birth defects in infants associated with prenatal administration of pandemic IIV. Our aim was to estimate the risk in infants associated with prenatal administration of seasonal IIV. Design: Retrospective population-based observational study Setting: Western Australia Population or sample: All pregnant women with a singleton birth from 2012-2016 Methods: 125,866 singleton births were linked to the state’s registers for congenital anomalies and a state prenatal vaccination database. We estimated prevalence ratios (PR) of any major structural birth defect and defects by organ system. Inverse probability treatment weighting factored for baseline probability for vaccination. Bonferroni correction was applied to account for multiple comparisons. Main outcome measures: Prevalence ratios by vaccination and major structural birth defects categories or specific birth defects diagnosed within one month of birth or within six years of life. Results: 3.9% of births had a major structural birth defect. IIV exposure during the first trimester was not associated with diagnosis of any major structural birth defect diagnosed within one month of birth (PR 0.98, 95% CI: 0.77, 1.28) or within six years of life (PR 1.02, 95% CI: 0.78, 1.35). We identified no increased risk in specific birth defects associated with IIV. Conclusions: Results suggest there is no association between maternal influenza vaccination and risk of major structural birth defects. These results support the safety of IIV administration during pregnancy.

Phylogenetic trees have been extensively used in community ecology. However, how the phylogenetic reconstruction affects ecological inferences is poorly understood. In this study, we reconstructed three different types of phylogenetic trees (a synthetic-tree generated using VPhylomaker, a barcode-tree generated using rbcL+matK+trnH-psbA and a genome-tree generated from plastid genomes) that represented an increasing level of phylogenetic resolution among 580 woody plant species from six dynamic plots in subtropical evergreen broadleaved forests of China. We then evaluated the performance of each phylogeny in estimations of community phylogenetic structure, turnover and phylogenetic signal in functional traits. As expected, the genome-tree was most resolved and most supported for relationships among species. For local phylogenetic structure, the three trees showed consistent results with Faith’s PD and MPD; however, only the synthetic-tree produced significant clustering patterns using MNTD for some plots. For phylogenetic turnover, contrasting results between the molecular trees and the synthetic-tree occurred only with nearest neighbor distance. The barcode-tree agreed more with the genome-tree than the synthetic-tree for both phylogenetic structure and turnover. For functional traits, both the barcode-tree and genome-tree detected phylogenetic signal in maximum height, but only the genome-tree detected signal in leaf width. This is the first study that uses plastid genomes in large-scale community phylogenetics. Our results highlight the outperformance of genome-trees over barcode-trees and synthetic-trees for the analyses studied here. Our results also point to the possibility of Type I and II errors in estimation of phylogenetic structure and turnover and detection of phylogenetic signal when using synthetic-trees.

Abstract Objective Surgery is the main treatment of visual loss related to cataracts. There are multiple intraocular lens (IOL) options with certain advantages. Patient education on IOL types is necessary to achieve a successful shared decision making process and meet the expectations of the individual patient. Decision aids (DAs) are used for patient education and we developed a novel DA to assist patients during IOL type selection for their cataract surgery. Methods The Ottawa Personal Decision Guide and the ‘Workbook on Developing and Evaluating Patient Decision Aids’ were used in the development of this DA. General characteristics of cataracts, surgical treatment, and details including advantages and disadvantages of varying IOLs were included in the content of the DA. The DA was further evaluated by 3 physicians (Delphi assessment- International Patient Decision Aid Standards (IPDAS) Collaboration standards) and 25 patients (questionnaire of 6 questions with Five-point Likert scale). Results The DA was finalized with feedbacks from the experts. A total score of 50/54 was achieved in Delphi group assessment. Patient perception of the DA was favorable and patients also recommended its use by other patients. Conclusions This novel DA to assist IOL selection for cataract surgery was well accepted by the patients. There is a potential to improve patients’ level of knowledge and diminish decisional conflicts. This potential can also increase patients’ contribution on the shared decision making process. A further prospective randomized trial to compare with the standard patient informing process is also planned.

Background: The aim of this study is to evaluate the importance of ischemia changed albumin, in foreseeing fetal asphyxia and comparing it between normal and preeclamptic pregnant. Method: We planned our study as a prospective case-controlled study between May 2011 and June 2013. We recruited 104 pregnant women complicated by preeclampsia and 110 healthy pregnant women in the study. Doppler ultrasonography, non-stress test and fetal biometric measurements were performed. Venous blood samples taken to measure ischemia modified albumin (IMA). The presence of fetal hypoxia/acidosis was analyzed by conducting post-natal cord blood gas examination and 1.-5. minutes APGAR scoring. Results: IMA levels in the preeclamptic group were found statistically high (p<0,0001). The correlations between umbilical artery doppler systolic/diastolic (S/D) ratio, brain sparing effect, non stress test and IMA analyzed. We have found IMA statistically high when S/D ratio is above 2 standard deviations (preeclampsia; 11.83±1.33 vs 19.62±1.56 p<0.001, control; 10.28±1.57 vs 18.09±2.13 p<0.001) or brain sparing effect started (preeclampsia; 25.59±2.48 vs 9.16±1.99 p<0.001, control; 16.37±1.97 vs 6.72± 1.53 p<0.001) or abnormal NST findings occurred (preeclampsia; 10.69±1.92 vs 20.72±1.15 p<0.001, control; 7,42±1,94 vs 9,72±2,19 p<0.001). Conclusions: Maternal IMA levels are found high in preeclamptic pregnant women and it can be used as a biomarker for determining fetal wellbeing. What’s already known about this topic? Hypertensive disease of pregnancy is the most frequently complication of pregnancy, being 5-10%. It is the most important reason for perinatal morbidity and mortality. Preeclampsia develops in an abnormal hypoxic intrauterine environment characterized by reperfusion and oxidative stress. To determine the fetal wellbeing, various tests were suggested, yet many of them provided a few benefits. What does this article add? The detected elevations in serum concentrations of IMA propose that measurements of this biomarker may be useful in assessing fetal hypoxia and predicting pregnancies which preeclampsia may develop

Double chambered left ventricle is an exceedingly rare congenital anomaly. We report a case diagnosed prenatally at 24 weeks of gestation and its postnatal evolution to left ventricular dysfunction.

Pseudoaneurysms of the aorta are rare complications of cardiac surgery, and sternal re-entry to address the pathology is particularly challenging. In this case, we describe a rare presentation of thoracic aortic pseudoaneurysm due to chronic erosion from a sternal wire, 10 years following the index operation. The patient was treated in two-stages, including carotid-subclavian bypass, followed by sternal re-entry with total arch replacement and frozen elephant trunk, employing cardiopulmonary bypass via femoral and axillary cannulation. Despite the high risks of rupture/haemorrhage associated with sternal re-entry, operative success for aortic pseudoaneurysms can be achieved with careful planning and safe bypass strategies.

Clinical Images:

Microalgae have emerged as one of the most promising options for biodiesel production over the past few decades. Lipid extraction from microalgae for biodiesel production as a bottleneck of biodiesel production technology was the main purpose of this study. In this study different methods of the cell wall disruption were compared. Then, two methods of ultrasound and bead mill were used as methods of the cell wall disruption. The maximum lipid extracted by ultrasound was 17.10% and by bead mill was 15.16% (based on microalgae biomass dry weight). After the cell wall disruption of microalgae, for lipid extraction, chloroform-methanol solvent combination was used as a high extraction method and hexane-ethanol solvent combination was used as an environmentally friendly method. In this regard, the effect of solvent to biomass ratio, temperature and extraction time was investigated and the optimal results for chloroform-methanol solvent combination were 8 ml/g, 45°C and 60 minutes, respectively, and for hexane-ethanol combination were 6 ml/g, 35◦C and 73 minutes, respectively. Under these optimal conditions, the highest amount of extracted lipid from Chlorella vulgaris with a moisture content of 87.50%, and ultrasound as a cell wall disruption method were obtained 20.39% and 16.41% (based on microalgae dry weight) with a combination of chloroform-methanol solvents and hexane-ethanol respectively. Also the highest extraction rates of 17.63% and 13.85% were obtained for the combination of chloroform-methanol and hexane-ethanol solvents, respectively by bead milling as cell wall disruption method

Background: The ability to perceive bronchial obstruction is variable in asthma. This is one of the main causes of inaccurate asthma control assessment, on which therapeutic strategies are based. Objective: Primary: To evaluate the ability of a clinical and spirometric telemonitoring device to characterize symptom perception profile in asthmatic children. Secondary: To evaluate its impact on asthma management (control, treatment, respiratory function variability) and the acceptability of this telemonitoring system. Method: 26 asthmatic children aged 6-18 years equipped with a portable spirometer and a smartphone application were monitored remotely for 3 months. Clinical and spirometric data were automatically transmitted to a secure internet platform. A medical team contacted the patient to optimize management. Three physicians blindly and independently classified the patients according to their perception profile. The impact of telemonitoring on the quantitative data was assessed at the beginning (T0) and end (T3 months) of telemonitoring, using matched statistical tests. Results: Patients could initially be classified according to their perception profile, with a concordance between the 3 observers of 64% (kappa coefficient: 0.55, 95%CI [0.39; 0.71]). After further discussion, a consensus was reached and resulted in 97% concordance (kappa coefficient: 0.97, 95%CI [0.91; 1.00]). There was a trend towards improvement in the ACT score, and a significant > 40% decrease in FEV1 and PEF variability, with good acceptance of the device. Conclusion: Clinical and spirometric telehome monitoring is applicable and can help define the perception profile of bronchial obstruction in asthmatic children. The device was generally well accepted.

Left ventricular pseudoaneurysm is a complication of acute myocardial infarction, especially after involvement of the inferior wall. The signs and symptoms are nonspecific. We report a case of a 69-year-old patient admitted for clinically important dyspnea. Transthoracic echocardiography showed pseudoaneurysm in the apical region, measuring 96x116 mm. Surgical correction was performed, using bovine pericardium and anchoring the ventricular orifice with 3-0 polypropylene sutures. It was not possible to perform coronary artery bypass grafting, as the distal beds of the proposed vessels were calcified. The patient was referred to the intensive care unit and discharged on the 17th postoperative day.

Animals are expected to select a breeding habitat using cues that should reflect, directly or not, the fitness outcome of the different habitat options. However, human-induced environmental changes can alter the relationship between habitat characteristics and their fitness consequences, leading to a maladaptive habitat choice. The most severe case of such nonideal habitat selection is the ecological trap, which occurs when individuals prefer to settle in poor-quality habitats while better ones are available. Here we studied the adaptiveness of nest box selection in a tree swallow (Tachycineta bicolor) population breeding over a 10-year period in a network of 400 nest boxes distributed along a gradient of agricultural intensification in southern Québec, Canada. We first examined the effects of multiple environmental and social habitat characteristics on nest box preference to identify potential settlement cues. We then assessed the links between those cues and habitat quality as defined by the reproductive performance of individuals that settled early or late in nest boxes. We found that tree swallows preferred nesting in open habitats with high cover of perennial forage crops, high spring insect biomass, and high density of house sparrows, their main competitors for nest sites. They also preferred nesting where the density of breeders and their mean number of fledglings during the previous year were high. Additionally, we detected mismatches between preference and habitat quality for several environmental variables. The density of competitors and conspecific social information showed severe mismatches, as their relationships to preference and breeding success went in opposite direction under certain circumstances. Spring food availability and agricultural landscape context, while related to preferences, were not related to breeding success. Overall, our study emphasizes the complexity of habitat selection behavior and provides evidence that multiple mechanisms may potentially lead to an ecological trap in farmlands.

Background: Asian Woollyneck Ciconia episcopus is large wading bird whose conservation status has been recently down-listed, despite a lack of general knowledge on its nesting ecology and breeding success. Thus, in this study we conducted the most comprehensive survey on the nesting ecology of this species to date. Methods: We located 39 nesting sites across 18 districts of Nepal and recorded nest tree characteristics for the nine tree species they nested in. We also used Maxent modelling to further understand factors important for nesting habitat suitability and to identify new areas for future surveys. Results: They most commonly nested in Simal Bombax ceiba (n =21), followed by Sal Shorea robusta (n=6) and Salla Pinus roxburghii (n=4). The mean height of the nesting tree, nest height and tree diameter were 29.8 ± 5.8m (±SD), 1.03 ± 0.35m & 25.3 ± 5.8 m respectively. Nesting and fledging success were additionally recorded from 31 nesting attempts at 19 of these nesting sites between 2016 and 2020. Woollyneck had an estimated nesting success probability of 0.81 ± 0.07 and a mean fledging success of 1.94 ± 0.25 (±SE) chicks per nest. MaxEnt modelling identified a total potential suitable nesting habitat area of 9.64 % (14228km2) of total area in Nepal, with this located within 72 districts (out of 77), mostly in the western part of Nepal. The modelling parameters suggest that slope, land-use, precipitation and forest were important determinants of nesting habitat suitability. Conclusions: The most likely district reported by the model for Woollyneck nesting habitat has not previously reported nests which suggests additional survey effort in this region is warranted. We recommend that priority should be given to conserve taller trees close to settlements and cropland, and future studies should consider the potential impact of climate change on nesting suitability of this species.

Freeman-Sheldon syndrome (FSS) is characterized by multiple joint contractures, characteristic facial features, such as microtia, defects of the hands and feet, such as clubfoot, and skeletal malformations. This report illustrates the case of a patient with FSS who was managed under local anesthesia with intravenous sedation for oral surgery.

Genetic differentiation has been observed in marine species even when no obvious barriers to gene flow exist. The study of highly differentiated outlier loci can provide information on how genetic variation might contribute to local adaptation. A locus which aligned to a predicted zona pellucida sperm-binding protein 3 gene (ZP3) in Atlantic cod was previously identified in Pacific cod populations as a high differentiation outlier. In other marine species, ZP3 is involved in reproductive isolation, local adaptation, and has neofunctionalized as an antifreeze gene, but the function of this genomic region is not understood in Pacific cod. We sequenced a 544 bp region of ZP3 in 230 Pacific cod collected from throughout their geographic range. Here we show that ZP3 haplotypes exhibit strong spatial structure and there is evidence for divergent selection at this locus in samples collected from the Bering Sea region. The potential for adaptation to different thermal regimes is particularly relevant given that Pacific cod have demonstrated high natural mortality during recent ocean warming events.