No abstract

Genetic differentiation has been observed in marine species even when no obvious barriers to gene flow exist, and understanding such differentiation is essential for effective fisheries management. Highly differentiated outlier loci can provide information on how genetic variation might not only contribute to local adaptation but may also be affected by historical demographic events. A locus which aligned to a predicted zona pellucida sperm-binding protein 3 gene (ZP3) in Atlantic cod (Gadus morhua) was previously identified as the highest outlier based on F ST in a RADseq study of Pacific cod (Gadus macrocephalus) across the West Coast of North America.However, because of the limited length of the RAD sequence and restricted geographic area of sampling, no conclusion on the functional significance of the observed variation was possible. In other marine species, ZP3 is involved in reproductive isolation, local adaptation, and has neofunctionalized as an antifreeze gene, and so it may provide important insights in functional population structure of Pacific cod. Here, we sequenced a 544-bp region of ZP3 in 230 Pacific cod collected from throughout their geographic range. We observed striking patterns of spatial structuring of ZP3 haplotypes, with a sharp break near Kodiak, Alaska, USA where populations within ~200 km of each other are nearly fixed for different haplotypes, contrasting a pattern of isolation by distance at other genetic markers in this region (F ST = 0.003).Phylogenetic analysis of ZP3 haplotypes revealed that the more southern haplotypes appear to be ancestral, with the northern haplotype evolving more recently, potentially in response to a novel selective pressure as Pacific cod recolonized northern latitudes after glaciation. The sharp break in haplotype frequencies suggests strong selective pressures are operating on small spatial scales and illustrates that selection can create high divergence even in marine species with ample opportunities for gene flow.

Objectives: Respiratory rate (RR) measurement is critical to diagnosing pneumonia in resource-constrained settings, but accurate RR measurement is challenging. The acute lower respiratory illness treatment and evaluation (ALRITE) mobile phone application (app), designed to help healthcare workers (HCWs) manage pediatric respiratory illnesses, includes a semiautomated RR counter. This study aimed to evaluate the accuracy and usability of the ALRITE RR counter and a commercially available RR counter app, RRate, with a reference standard.Methods: This was a cross-sectional observational study of HCWs. Participants used both apps to measure the RR of pediatric patients from standardized videos. The reference standard was determined by consensus of a manual 1-min count by two providers. We assessed agreement using Spearman's rank correlation coefficient and constructed Bland-Altman plots to determine bias and limits of agreement.Participants completed a usability survey.Results: Thirty-nine HCWs participated. The agreement between the apps and reference standard (Spearman's coefficient) was 0.83 (95% confidence interval [CI]: 0.78-0.87) for ALRITE and 0.62 (95% CI: 0.52-0.70) for RRate. ALRITE had a bias of −2 breaths/min (lower limit of agreement [LoA] −16 to +12) and RRate had a bias of −0.4 breaths/min (LoA −24 to +23) compared to the reference standard. Both apps had a poorer agreement at higher RRs. Based on usability survey responses, 95% found ALRITE easy to use.

Background: Methemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and potentially life-threatening cause of cyanosis in newborns that can be caused by either cytochrome B 5 reductase or hemoglobin variants known as Hemoglobin M. Case presentation:A term male infant developed cyanosis and hypoxia shortly after birth after an uncomplicated pregnancy, with oxygen saturations persistently 70-80% despite 1.0 FiO2 and respiratory support of CPAP+ 6 cm H2O. Pre-and post-ductal saturations were equal and remained below 85%. Initial radiographic and echography imaging was normal. Capillary blood gas values were reassuring with normal pH and an elevated pO2. Investigations to rule out hemolysis and end-organ dysfunction were within acceptable range. Given the absence of clear cardiac or pulmonary etiology of persistent cyanosis, hematologic causes such as methemoglobinemia were explored. No family history was available at the time of transfer to our institution. Unconjugated hyperbilirubinemia > 5 mg/dL (442 μmol/L) interfered with laboratory equipment measurement, making accurate methemoglobin levels unattainable despite multiple attempts. Initial treatment with methylene blue or ascorbic acid was considered. However, upon arrival of the presumed biological father, a thorough history revealed an extensive paternal family history of neonatal cyanosis due to a rare mutation resulting in a hemoglobin M variant. Given this new information, hematology recommended supportive care as well as further testing to confirm the diagnosis of congenital methemoglobinopathy. Whole genome sequencing revealed a likely pathogenic variation in hemoglobin. The neonate was discharged home at 2 weeks of age on full oral feeds with 0.25 L/min nasal cannula as respiratory support, with close outpatient followup. By 5 weeks of age, he was weaned off respiratory support. Conclusion:Congenital methemoglobinemia should be considered in the differential diagnosis for newborns with persistent hypoxemia despite normal imaging and laboratory values. Accurate quantification of methemoglobin concentrations is challenging in neonates due to the presence of other substances that absorb light at similar wavelengths, including HbF, bilirubin, and lipids.