Innovative levers for sustainable integration of gender medicine into medical school curricula

Efforts to integrate gender medicine into medical school curricula have focused largely on the work of individual champions. Online sex and gender materials for undergraduate courses have also been developed and disseminated. Success has been sporadic, with varying uptake across schools within and between countries. International trends in medical school accreditation processes and the growing force of the millennial student voice offer untapped opportunities to promote more systematic integration of gender medicine on a national and international level. In this commentary, the president and CEO of the Association of Faculties of Medicine of Canada and the Scientific Director of the Institute of Gender and Health of the Canadian Institutes of Health Research jointly reflect on top-down and bottom-up levers for sustainable innovation in gender medicine for undergraduate medical training.     

Arbovirus surveillance using FTATM cards in modified CO2‐baited encephalitis virus surveillance traps in the Northern Territory,Australia

In 2016, modified CO₂‐baited encephalitis virus surveillance (EVS) traps were evaluated for flavivirus surveillance in the Northern Territory, Australia. The traps were fitted with honey‐soaked nucleic acid preservation cards (FTA^TM) for mosquitoes to expectorate virus while feeding on the cards. Cards were tested for the presence of selected arboviruses, with two cards testing positive for Kunjin virus and Alfuy, while sentinel chickens tested in parallel also showed Kunjin virus activity at the same time. The results from the cards and vector mosquito feeding rates indicate that CO₂‐baited EVS traps coupled with honey‐baited FTA^TM cards are an effective tool for broad‐scale arbovirus surveillance.     

The potential of biobanked liquid based cytology samples for cervical cancer screening using Raman spectroscopy

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and ?25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated with no disease (cytology negative). The data indicates that samples stored at ?80°C are not suitable for assessment by Raman spectroscopy due to a lack of cellular material and the presence of cellular debris. However, the technology can be applied to fresh LBC samples and those stored at ?25°C and is, moreover, effective in the discrimination of negative samples from those where CIN 3 has been confirmed. Pooled fresh and biobanked samples are also amenable to the technology and achieve a similar sensitivity and specificity for CIN 3. This study demonstrates that cervical cytology samples stored within biobanks at temperatures that preclude cell lysis can act as a useful resource for Raman spectroscopy and will facilitate research and translational studies in this area.      

The pathogenic fungus Cryptococcus neoformans expresses two functional GDP-mannose transporters with distinct expression patterns and roles in capsule synthesis

Cryptococcus neoformans is a fungal pathogen that is responsible for life-threatening disease, particularly in the context of compromised immunity. This organism makes extensive use of mannose in constructing its cell wall, glycoproteins, and glycolipids. Mannose also comprises up to two-thirds of the main cryptococcal virulence factor, a polysaccharide capsule that surrounds the cell. The glycosyltransfer reactions that generate cellular carbohydrate structures usually require activated donors such as nucleotide sugars. GDP-mannose, the mannose donor, is produced in the cytosol by the sequential actions of phosphomannose isomerase, phosphomannomutase, and GDP-mannose pyrophosphorylase. However, most mannose-containing glycoconjugates are synthesized within intracellular organelles. This topological separation necessitates a specific transport mechanism to move this key precursor across biological membranes to the appropriate site for biosynthetic reactions. We have discovered two GDP-mannose transporters in C. neoformans, in contrast to the single such protein reported previously for other fungi. Biochemical studies of each protein expressed in Saccharomyces cerevisiae show that both are functional, with similar kinetics and substrate specificities. Microarray experiments indicate that the two proteins Gmt1 and Gmt2 are transcribed with distinct patterns of expression in response to variations in growth conditions. Additionally, deletion of the GMT1 gene yields cells with small capsules and a defect in capsule induction, while deletion of GMT2 does not alter the capsule. We suggest that C. neoformans produces two GDP-mannose transporters to satisfy its enormous need for mannose utilization in glycan synthesis. Furthermore, we propose that the two proteins have distinct biological roles. This is supported by the different expression patterns of GMT1 and GMT2 in response to environmental stimuli and the dissimilar phenotypes that result when each gene is deleted.     

Birth defects interstate data exchange: a battle worth fighting?

BACKGROUND: Regardless of where infants and children are delivered, diagnosed, or treated, an important aspect of population-based birth defects surveillance is ensuring the inclusion of children with birth defects in the catchment area. However, little is known as to how the lack of interstate birth defects data exchange affects program surveillance, monitoring, prevention, and referral activities. The study objectives were to determine the status of interstate birth defects data exchange agreements and to quantify statewide data on resident births occurring in nonresident states. METHODS: In 2004, surveys were distributed to all population-based birth defects programs in the United States to determine: 1) the types of interstate birth defects data exchange agreements that exist among birth defects programs, 2) perceived barriers in establishing exchange agreements, and 3) the extent to which out-of-state births affect a program's catchment area. The National Center for Health Statistics (NCHS) data for 2002 on live birth residency were used to determine the actual frequency of out-of-state live birth occurrence. RESULTS: Of the 52 states and territories that were surveyed, 65% (n = 34) responded. Approximately 21% (n = 7) of those that responded had an interstate data exchange agreement that allowed sharing of birth defects data with another state or a facility within another state. Approximately 53% (n = 18) of responding states indicated plans to develop an interstate birth defects data exchange agreement with other states, hospitals, or both. The NCHS data showed that the actual percentage of resident out-of-state live births ranged from 0.16 to 11.51. NCHS data also reveal that 78% of states would be able to capture >75% of their out-of-state births by sharing data on out-of-state births with the three neighboring states ranking highest in terms of such occurrences. CONCLUSIONS: Few states have interstate birth defects data exchange agreements, though all states have resident births occurring out of state. While suggestive, data beyond residency of live births are needed to quantify the degree to which the objectives of state-based birth defects programs are compromised. Resources exist to guide programs in establishing interstate data exchange agreements. Efforts to establish such agreements with only a few neighboring states could be a large step toward improving birth defects surveillance on a state, regional, and national level.     

FMRP mediates mGluR5-dependent translation of amyloid precursor protein

Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Aβ) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome. Here we show that FMRP binds to the coding region of APP mRNA at a guanine-rich, G-quartet–like sequence. Stimulation of cortical synaptoneurosomes or primary neuronal cells with the metabotropic glutamate receptor agonist DHPG increased APP translation in wild-type but not fmr-1 knockout samples. APP mRNA coimmunoprecipitated with FMRP in resting synaptoneurosomes, but the interaction was lost shortly after DHPG treatment. Soluble Aβ₄₀ or Aβ₄₂ levels were significantly higher in multiple strains of fmr-1 knockout mice compared to wild-type controls. Our data indicate that postsynaptic FMRP binds to and regulates the translation of APP mRNA through metabotropic glutamate receptor activation and suggests a possible link between Alzheimer disease and fragile X syndrome.     

Wind turbine noise limits propagation of greater prairie‐chicken boom chorus,but does it matter?

Acoustic signals are often critical elements of mating displays, and lekking male greater prairie‐chickens (Tympanuchus cupido pinnatus) use their boom vocalization for this purpose. We quantified the acoustic characteristics of the boom chorus created by multiple male greater prairie‐chickens vocalizing simultaneously at leks in Brown County, NE, USA, in 2013 and 2014. We used these data to evaluate (a) the role of the boom chorus in prairie‐chicken breeding dynamics and (b) the impact of a wind energy facility on the acoustic signal of the boom chorus. We sampled the chorus using audio recorders placed in transects extending from leks; the chorus exhibited an average peak frequency of 297 ± 13 Hz. The mean chorus signal‐to‐noise ratio declined from 15.7 dB (50 m) to 2.6 dB (800 m), and wind speed and direction, topography, and relative humidity caused variation in signal‐to‐noise ratio at a given distance and location. Chorus recordings from leks within 1,000 m of a wind turbine had lower signal‐to‐noise ratio (β_turbine = ?5.659, SE = 1.289) than leks farther from turbines. The chorus signal‐to‐noise ratio increased slightly with more males present on the lek (~0.1 dB for each additional male; β_males = 0.177; SE = 0.037) and considerably more as more females visited the lek (~1.4 dB for each additional female; β_females = 2.498, SE = 0.235; β_females² = ?0.309, SE = 0.039). Our results provide support for the signal enhancement hypothesis that proposes the boom chorus is influenced notably by male–male competition for females on the lek, rather than functioning solely to advertise the presence of the lek to recruit females. Our results also suggest the choruses emanating from small leks have the greatest potential to be masked by anthropogenic (wind turbine) noise, which may affect the breeding success of male and female prairie‐chickens.