The effect of sub-lethal methylmercury exposure on corticosterone hormone and the glucocorticoid receptor in the Australian zebra finch (Taeniopygia guttata)

Mercury can disrupt the endocrine systems of mammals and fish, but little is known about its effects on the avian stress response. An experimental manipulation was used to show that methylmercury suppresses the stress-induced corticosterone response in birds, an effect previously unreported in the literature. Corticosterone regulates many normal metabolic processes, such as the maintenance of proper blood glucose levels during stressful daily fasting; an inability to increase corticosterone levels in response to stressors renders a bird less able to face a wide array of environmental challenges. Reproductively mature zebra finches that had been exposed to 0.0, 0.3, 0.6, 1.2, or 2.4 μg/g Hg (wet weight, ww) dietary methylmercury throughout their life (i.e. from the egg onwards) were the subjects of this study. In contrast to some field studies, no significant change in baseline plasma corticosterone concentrations was attributable to chronic methylmercury exposure. However, a comparison between the baseline corticosterone levels and levels after 30-minutes of handling stress revealed that the ability of birds to mount a stress response was reduced with increasing blood total mercury concentration. These results are consistent with adrenal corticoid disruption due to chronic mercury exposure, and mirror a similar study on free-living nestling songbirds exposed to environmental mercury. In addition, the glucocorticoid receptor in 50-day old juvenile zebra finches was studied to determine if this facet of the stress response pathway was also disrupted. No change was detected by quantitative PCR analysis in the expression of the glucocorticoid receptor in the brains of juvenile zebra finches. This result is consistent with the conclusion that mercury exposure does in fact have a significant effect on the stress response pathway, as the system is not compensating by altering receptor expression in response to abnormal hormone concentrations. More research will need to be done to determine whether the system is truly affected by mercury exposure, and whether or not it is compensating in some way for the disturbance of hormone concentrations. This project also studied the expression of the glucocorticoid receptor in zebra finch embryos of various stages, both through qPCR analysis and in situ hybridization. The purpose of studying embryos was not to compare expression among mercury treatment groups at this time, but rather to begin to characterize expression of the glucocorticoid receptor during the developmental stages of the Australian zebra finch, as there is currently no literature on this subject. The glucocorticoid receptor appears to be fairly ubiquitously expressed in zebra finch embryos from stage 17-30: more work will need to be done to continue the characterization of the expression of this receptor during the embryonic development of this species

Building Community Through Asset Mapping in an Alternate Route to Licensure Program

Teacher preparation programs in the U.S. have adopted social justice approaches in their work. However, it is necessary to investigate how teacher preparation programs foster an asset orientation in teacher candidates—particularly as Alternative Routes to Licensure have increased in popularity. The current investigation was an interview study of teacher candidates’ experiences after completing an asset mapping activity as part of their field experiences. Participants consistently described how the activity helped them to foster relationships with their students through (a) making connections, (b) humanizing students, and (c) community scaffolding. We explore the implications of these findings for teacher preparation research and practice

Distinguishing Increased Adiposity and/or Aerobic Deconditioning as Moderators of Low VO2peak in Obese Men

Peak oxygen uptake (V̇O2peak) in a cardiopulmonary exercise test (CPET) is a strong predictor of morbidity, mortality, and quality of life. V̇O2peak in obese individuals is typically below the lower limit of normal (2 transport and utilization, i.e. aerobic deconditioning; or both. We hypothesized a modified CPET, to measure the fraction of maximum isokinetic power that can be supported by aerobic metabolism, will distinguish between adiposity and deconditioning effects on V̇O2peak. PURPOSE: To compare V̇O2peak and isokinetic neuromuscular performance in obese vs non-obese men. METHODS: A modified CPET with maximal (3 s) isokinetic cycling power at baseline and the limit of ramp-incremental (RI) exercise was used to calculate: A) baseline maximum isokinetic power (Piso); B) tolerance index (TI), % of Piso at V̇O2peak; C) fatigue index (FI), % reduction in Piso per RI-watt at V̇O2peak; D) power reserve (PR), isokinetic power available at V̇O2peak expressed as % RI-wattpeak. The FRIEND nomogram was used to predict V̇O2peak. Data are mean(SD) and were assessed by t-test. RESULTS: Compared to controls (n=24), obese men (n=20) were older (32(5) vs 26(7) yr), had greater BMI (38(6) vs 23(2) kg/m2), but were not different in stature (177(5) vs 180(7) cm) or predicted V̇O2peak (3.49(0.49) vs 3.58(0.36) L/min). Obese men had lower V̇O2peak (2.84(0.42) vs 3.71(0.45) L/min, p2peak (82(15) vs 104(12) %, pIndependent of body mass, obese men had preserved leg strength (normal Piso), but the fraction of maximum isokinetic power supported by aerobic metabolism at RI intolerance was reduced (low TI) with greater fatigability (high FI); each consistent with aerobic deconditioning. A modified CPET with maximal isokinetic power measurements can distinguish the effects of increased adiposity from aerobic deconditioning on V̇O2peak in obese men

Overnight staffing in Canadian neonatal and pediatric intensive care units

AimInfants and children who require specialized medical attention are admitted to neonatal and pediatric intensive care units (ICUs) for continuous and closely supervised care. Overnight in-house physician coverage is frequently considered the ideal staffing model. It remains unclear how often this is achieved in both pediatric and neonatal ICUs in Canada. The aim of this study is to describe overnight in-house physician staffing in Canadian pediatric and level-3 neonatal ICUs (NICUs) in the pre-COVID-19 era.MethodsA national cross-sectional survey was conducted in 34 NICUs and 19 pediatric ICUs (PICUs). ICU directors or their delegates completed a 29-question survey describing overnight staffing by resident physicians, fellow physicians, nurse practitioners, and attending physicians. A comparative analysis was conducted between ICUs with and without in-house physicians.ResultsWe obtained responses from all 34 NICUs and 19 PICUs included in this study. A total of 44 ICUs (83%) with in-house overnight physician coverage provided advanced technologies, such as extracorporeal life support, and included all ICUs that catered to patients with cardiac, transplant, or trauma conditions. Residents provided the majority of overnight coverage, followed by the Critical Care Medicine fellows. An attending physician was in-house overnight in eight (15%) out of the 53 ICUs, seven of which were NICUs. Residents participating in rotations in the ICU would often have rotation durations of less than 6 weeks and were often responsible for providing care during shifts lasting 20–24 h.ConclusionMost PICUs and level-3 NICUs in Canada have a dedicated in-house physician overnight. These physicians are mainly residents or fellows, but a notable variation exists in this arrangement. The potential effects on patient outcomes, resident learning, and physician satisfaction remain unclear and warrant further investigation

Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription Factor

It is not understood why only some infections with Entamoeba histolytica result in disease. The calcium-regulated transcription factor upstream regulatory element 3-binding protein (URE3-BP) was initially identified by virtue of its role in regulating the expression of two amebic virulence genes, the Gal/GalNac lectin and ferredoxin. Here we tested whether this transcription factor has a broader role in regulating virulence. A comparison of in vivo to in vitro parasite gene expression demonstrated that 39% of in vivo regulated transcripts contained the URE3 motif recognized by URE3-BP, compared to 23% of all promoters (P < 0.0001). Amebae induced to express a dominant positive mutant form of URE3-BP had an increase in an elongated morphology (30% ± 6% versus 14% ± 5%; P = 0.001), a 2-fold competitive advantage at invading the intestinal epithelium (P = 0.017), and a 3-fold increase in liver abscess size (0.1 ± 0.1 g versus 0.036 ± 0.1 g; P = 0.03). These results support a role for URE3-BP in virulence regulation

Timing of Moderate Level Prenatal Alcohol Exposure Influences Gene Expression of Sensory Processing Behavior in Rhesus Monkeys

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections

A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats

ABSTRACT Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log 10 total PFU and 2.7 log 10 PFU/g of tissue, respectively, compared to those in unvaccinated animals ( P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats

Examining the transport to school patterns of New Zealand adolescents by home-to-school distance and settlement types

Background: Scholarship on active transport to school has largely focused on children, (large) urban areas, the umbrella term of “active transport” which considered walking and cycling together and without taking into account walking and/or cycling distance. This research examined adolescents’ patterns of transport to school in diverse settlement types and in relation to home-to-school distance in the Otago region of Aotearoa New Zealand. Methods: Patterns of transport to school by home-to-school distance, and across school locations, are described for a sample of 2,403 adolescents (age: 15.1 ± 1.4 years; 55% females) attending 23 out of 27 schools in large urban areas (n = 1,309; 11 schools), medium urban areas (n = 265; three schools), small urban areas (n = 652; four schools) and rural settings (n = 177; five schools). Empirical data were collected through an online survey, in which adolescents reported sociodemographic characteristics, travel to school, and perceptions of walking and cycling. Home-to-school distance was measured on the shortest route determined using Geographic Information Systems (GIS)-based network analysis. Results: Transport to school patterns differed significantly by home-to-school distance and across settlement types. Profiles of different transport user groups showed significant variability in sociodemographic characteristics, family factors, average distance to school, self-reported physical activity, and perceived health. Conclusions: Initiatives to promote active transport and reduce reliance on car transport to school, whether to improve health and the environment or to reduce greenhouse gas emissions, need to pay closer attention to the settlement types, distance to school, and characteristics of different transport user modes

Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy

In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with “cone-first” retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs∗2];[Glu529Valfs∗2], and c.[401delT(;)3354G>A], p.[Leu134Argfs∗45(;)Trp1118∗]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543∗) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families

Implementation of a Shared Data Repository and Common Data Dictionary for Fetal Alcohol Spectrum Disorders Research

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed due to both structural differences in the collected data as well as difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly amongst different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data which conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, collected using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository