Sex hormone supplementation improves breathing and restores respiratory neuroplasticity following C2 hemisection in rats.

In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17ß-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7 days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2 weeks post-SCI.

Estimating the burden of illness caused by domestic waterborne Legionnaires' disease in Canada: 2015-2019.

Legionellosis is a disease caused by the bacterium Legionella that most commonly presents as Legionnaires' disease (LD), a severe form of pneumonia. From 2015 to 2019, an average of 438 LD cases per year were reported in Canada. However, it is believed that the actual number of cases is much higher, since LD may be underdiagnosed and underreported. The purpose of this study was to develop an estimate of the true incidence of illnesses, hospitalizations, and deaths associated with LD in Canada. Values were derived using a stochastic model, based on Canadian surveillance data from 2015 to 2019, which were scaled up to account for underdiagnosis and underreporting. Overall, there were an estimated 1,113 (90% CrI: 737-1,730) illnesses, 1,008 (90% CrI: 271-2,244) hospitalizations, and 34 (90% CrI: 4-86) deaths due to domestically acquired waterborne LD annually in Canada from 2015 to 2019. It was further estimated that only 36% of illnesses and 39% of hospitalizations and deaths were captured in surveillance, and that 22% of illnesses were caused by Legionella serogroups and species other than Legionella pneumophila serogroup 1 (non-Lp1). This study highlights the true burden and areas for improvement in Canada's surveillance and detection of LD.

Low level CO2 supplementation maintains isocapnia and reveals ventilatory long-term facilitation in rats.

Acute, intermittent hypoxia (AIH) induces ventilatory long-term facilitation (vLTF) in awake, freely behaving rats under poikilocapnic and isocapnic experimental conditions. Establishing pre-clinical methods for vLTF induction that more closely align with successful protocols in humans and anesthetized rats would minimize dissonance in experimental findings and improve translational aspects of vLTF. Here, we tested several levels of low-dose CO2 supplementation during and after AIH to determine 1) the lowest amount of inspired CO2 that would maintain isocapnia in rats during a vLTF protocol, and 2) the net impact of supplemental CO2 on vLTF expression. Rats received one of four levels of inspired CO2 (0%, 0.5%, 1% or 2%) administered during AIH and for the 60 min following AIH to quantify vLTF. Our findings indicated that 2% inspired CO2 was sufficient to maintain isocapnia across the AIH protocol and reveal significant vLTF. These findings provide evidence-based support for using 2% supplemental CO2 during and after AIH when assessing vLTF in rats.

A mixed-methods assessment of community-engaged learning in a Master of Public Health program.

Objective: Community-engaged learning is used in Master of Public Health programs to enhance student training, connect with communities, help solve societal issues, develop competencies, and build partnerships. However, it is unclear how much community-engaged learning components supplement existing Master of Public Health programs and prepare students in developing these competencies. Thus, the aim of this study was to apply an explanatory mixed-methods study design to evaluate a Canadian Master of Public Health program's community-engaged learning activities and propose recommendations to strengthen public health training and course delivery. Methods: We conducted a questionnaire among Master of Public Health students (n = 25), focus group discussion with a subset of these students (n = 7), and one-on-one semi-structured telephone interviews with community partners who had previously hosted Master of Public Health students for practicum placements (n = 11). Results: Community-engagement enhanced learning among Master of Public Health students, with the practicum placement, and program development capstone resulting in the largest self-reported development. Students in the focus group indicated community engagement provided skill and professional development, but also identified wanting additional curriculum coverage on various statistical software and qualitative research methods. Interviews with community partners revealed benefits of practicum placements such as mutual knowledge transfer, increased organizational capacity, and strengthened academic-community partnerships. Community partners also commented on challenges with recruitment, training, and aligning student-organization goals. Conclusion: The findings from this study suggest that an update to the Master of Public Health program curriculum, its core competencies, a combination of community-engagement activities, and future evaluations will be needed to advance education delivery.

Impact of the COVID-19 Pandemic on the Reported Incidence of Select Bacterial Enteric Diseases in Canada, 2020.

The aim of this study was to describe the impact of the COVID-19 pandemic on reported cases and clusters of select enteric diseases in Canada, for the period of March 2020 to December 2020. Weekly counts of laboratory confirmed cases of Salmonella, Shigella, Shiga toxin-producing Escherichia coli (STEC), and Listeria monocytogenes were obtained from laboratory surveillance data. These data were supplemented with epidemiological information on the suspected source of illness, collected for cases identified within whole genome sequencing clusters. Incidence rate ratios were calculated for each pathogen. All data were compared with a prepandemic reference period. Decreases in the number of reported cases in 2020 compared with the previous 5-year period were noted for Salmonella, Shigella, Escherichia coli O157, and non-O157 STEC. Reported number of cases for L. monocytogenes in 2020 remained similar to those of the previous 5-year period. There was a considerable decline (59.9%) in the number of cases associated with international travel compared with a 10% decline in the number of domestic cases. Comparison of reported incidence rates of clustered versus sporadic cases for each pathogen showed little variation. This study represents the first formal assessment of the impact of COVID-19 on reported enteric diseases in Canada. Reported case counts across several pathogens saw notable declines in 2020 compared with prepandemic levels, with restrictions on international travel playing a key role. Additional research is needed to understand how limitations on social gatherings, lock downs, and other public health measures have impacted enteric diseases.

A transcriptome dataset for gonadectomy-induced changes in rat spinal cord.

Circulating sex steroid hormones are critical for neural function and development of neuroplasticity in many regions of the central nervous system. In the spinal cord, our knowledge of steroid hormone influence mostly derives from mechanistic studies of pain processing in dorsal spinal cord circuits; less is known regarding hormonal influence of ventral spinal motor function. Gonadectomy (surgical removal of the testes in males and ovaries in females) rapidly and persistently reduces circulating sex steroids in both females and males, providing a means to interrogate the role of hormones on neural function. Here we provide a next-generation RNA sequencing (RNA-seq) data set to evaluate the impact of gonadectomy on the transcriptome of ventral spinal cord tissue of adult female and male rats.

Estimated Reduction in the Burden of Nontyphoidal Salmonella Illness in Canada Circa 2019.

Nontyphoidal Salmonella (NTS) is a leading cause of acute gastrointestinal illness in Canada, and reported cases have been on the rise since the early 2000s. To address this trend, agri-food industry partners and government have worked to identify and implement interventions, guided by the enhanced information provided by whole-genome sequencing, to reduce the incidence of NTS. A substantial reduction in the number of NTS cases reported occurred in 2019. Due to underreporting and underdiagnosis factors, the observed decrease in the number of reported cases represents a fraction of the true number of illnesses averted in the community. The objective of this study was to: (1) use burden of illness estimation methodologies to estimate the true number of NTS illnesses, hospitalizations, and deaths prevented, and (2) estimate the economic savings associated with the prevention of these cases. Compared with the previous 5 years, there were an estimated 25,821 fewer illnesses, 213 fewer hospitalizations, and 2 fewer deaths attributable to NTS in 2019. This corresponds to an estimated reduction of 26.9 million Canadian dollars in the economic burden of NTS. Although causality cannot be proven by this study, the findings are suggestive that the strategically implemented suite of public health actions, including genomic-based surveillance, policy changes, and interventions by the government and industry, were successful in reducing the economic and health burden of NTS infections in Canada.

Pandemic fatigue or enduring precautionary behaviours? Canadians' long-term response to COVID-19 public health measures.

The long-term dynamics of COVID-19 disease incidence and public health measures may impact individuals' precautionary behaviours as well as support for measures. The objectives of this study were to assess longitudinal changes in precautionary behaviours and support for public health measures. Survey data were collected online from 1030 Canadians in each of 5 cycles in 2020: June 15-July 13; July 22-Aug 8; Sept 7-15; Oct 14-21; and Nov 12-17. Precautionary behaviour increased over the study period in the context of increasing disease incidence. When controlling for the stringency of public health measures and disease incidence, mixed effects logistic regression models showed these behaviours did not significantly change over time. Odds ratios for avoiding contact with family and friends ranged from 0.84 (95% CI 0.59-1.20) in September to 1.25 (95% CI 0.66-2.37) in November compared with July 2020. Odds ratios for attending an indoor gathering ranged from 0.86 (95% CI 0.62-1.20) in August to 1.71 (95% CI 0.95-3.09) in October compared with July 2020. Support for non-essential business closures increased over time with 2.33 (95% CI 1.14-4.75) times higher odds of support in November compared to July 2020. Support for school closures declined over time with lower odds of support in September (OR 0.66 [95% CI 0.45-0.96]), October (OR 0.48 [95% CI 0.26-0.87]), and November (OR 0.39 [95% CI 0.19-0.81]) compared with July 2020. In summary, respondents' behaviour mirrored government guidance between July and November 2020 and supported individual precautionary behaviour and limitations on non-essential businesses over school closures.

Effectiveness of non-pharmaceutical interventions to reduce SARS-CoV-2 transmission in Canada and their association with COVID-19 hospitalization rates.

Background: Non-pharmaceutical interventions (NPIs) aim to reduce the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections mostly by limiting contacts between people where virus transmission can occur. However, NPIs limit social interactions and have negative impacts on economic, physical, mental and social well-being. It is, therefore, important to assess the impact of NPIs on reducing the number of coronavirus disease 2019 (COVID-19) cases and hospitalizations to justify their use. Methods: Dynamic regression models accounting for autocorrelation in time series data were used with data from six Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Québec) to assess 1) the effect of NPIs (measured using a stringency index) on SARS-CoV-2 transmission (measured by the effective reproduction number), and 2) the effect of the number of hospitalized COVID-19 patients on the stringency index. Results: Increasing stringency index was associated with a statistically significant decrease in the transmission of SARS-CoV-2 in Alberta, Saskatchewan, Manitoba, Ontario and Québec. The effect of stringency on transmission was time-lagged in all of these provinces except for Ontario. In all provinces except for Saskatchewan, increasing hospitalization rates were associated with a statistically significant increase in the stringency index. The effect of hospitalization on stringency was time-lagged. Conclusion: These results suggest that NPIs have been effective in Canadian provinces, and that their implementation has been, in part, a response to increasing hospitalization rates of COVID-19 patients.

Salmonella enterica serovars associated with bacteremia in Canada, 2006-2019.

BACKGROUND: Members of the bacterial genus Salmonella cause salmonellosis, a disease with a spectrum of clinical presentations from a self-limiting gastroenteritis to more severe bacteremia, organ failure and sepsis. The genus consists of over 2,600 serological variants (serovars). Important differences in the pathogenesis of Salmonella serovars have been noted. OBJECTIVE: The purpose of this study was to determine which Salmonella serovars were more likely to be associated with bacteremia in Canada. METHODS: Information on the total number of Salmonella infections and blood isolations reported to the National Enteric Surveillance Program (NESP) from 2006 to 2019 was extracted for each serovar. The risk (proportion) and likelihood (odds) of bacteremia were calculated for all serovars. RESULTS: Of the 96,082 Salmonella cases reported to the NESP during the 14-year study period, 4.4% (95% CI: 4.3%-4.6%) were bacteremic. Twenty nontyphoidal Salmonella (NTS) serovars were associated with lower rates of bacteremia compared to all NTS serovars, and 19 NTS serovars were identified as having higher rates. Heidelberg, Oranienburg, Schwarzengrund, Virchow, Panama and Poona among the top 25 most commonly reported serovars in Canada during the study period. CONCLUSION: The identification of serovars associated with Salmonella bacteremia in Canada is a first step towards understanding differences in pathogenesis and disease presentation.

The long-term impact of ovariectomy on ventilation and expression of phrenic long-term facilitation in female rats.

NEW FINDINGS: What is the central question of this study? Would ovariectomy cause prolonged changes in ventilation and sustained loss of acute, intermittent hypoxia-induced neuroplasticity or would these outcomes be restored with time? What is the main finding and its importance? Our main findings demonstrate that ovariectomy elicits minimal alteration in overall breathing function but impairs acute, intermittent hypoxia-induced plasticity for ≤ 12 weeks. ABSTRACT: Sex hormones are necessary to enable respiratory neuroplasticity, including phrenic long-term facilitation (pLTF), a form of respiratory motor plasticity elicited by acute, intermittent hypoxia (AIH). Female rats exhibit a progressive increase in phrenic nerve amplitude after AIH characteristic of pLTF only during pro-oestrus, the stage of the oestrous cycle notable for elevated circulating oestradiol levels. Removal of the ovaries [ovariectomy (OVX)], the primary source of circulating oestradiol, also eliminates AIH-induced pLTF after 1 week. Ovariectomy is used routinely as a model to examine the impact of sex hormones on CNS structure and function, but the long-term impact of OVX is rarely examined. Extra-ovarian sites of oestradiol synthesis, including multiple CNS sites, have been identified and might possess the capacity to restore oestradiol levels, in part, over time, impacting respiratory function and the expression of respiratory neuroplasticity. We examined both ventilation in awake, freely behaving female rats, using barometric plethysmography, and the expression of AIH-induced pLTF in anaesthetized, ventilated female rats 2 and 12 weeks after OVX and compared them with age-matched ovarian-intact female rats. Our findings indicate that chronic OVX had little impact on baseline breathing or in the response to respiratory challenge (10% O2 , 5% CO2 , balance N2 ) during plethysmography. However, OVX rats at both 2 and 12 weeks demonstrated a persistent loss of AIH-induced pLTF relative to control animals (P < 0.01), suggesting that other sources of oestradiol synthesis were insufficient to restore pLTF. These data are consistent with our previous work indicating that oestradiol plays a key role in expression of AIH-induced respiratory neuroplasticity.

Pulmonary carcinoid presenting in pregnancy with an unusual radiological feature.

Pulmonary carcinoid tumours are a rare form of malignancy that often present with clinical heterogeneity and are challenging to diagnose. Diagnosis during pregnancy is further complicated by delays in imaging and procedures to minimise harm to the fetus. This case describes a primigravid healthcare worker who was diagnosed with pulmonary carcinoid in her first trimester of pregnancy, with particular focus on the unique radiological findings of subpleural blebs as a feature.

Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).

INTRODUCTION: This is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method. METHODS AND ANALYSIS: We will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached. Participants will be administered a single dose of liposomal curcumin (LipoCurc, SignPath Pharma) via their existing TIPC as a sequential enrolling case series with the following dose cohorts: 100, 200 and 300 mg/m2. Primary endpoints are determination of the maximum tolerated dose within the predetermined dose range, and determination of the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC. Secondary endpoints include determination of the safety and tolerability of intrapleural administration of liposomal curcumin, median overall survival, effects on quality of life and on feelings of breathlessness, and the pharmacokinetics and concentrations of curcumin from the plasma and the pleural fluid. Important inclusion criteria include age ≥18 years, an existing TIPC, a pleural biopsy or pleural fluid cytology-proven diagnosis of malignant pleural effusion and for whom no antitumour therapy of proven benefit is available or has been previously declined, eastern cooperative group performance status <2. ETHICS AND DISSEMINATION: The study protocol has been approved by the Southern Adelaide Local Health Network Human Research Ethics Committee (HREC) (approval number: HREC/20/SAC/11). Study results will be published in peer-reviewed journals, and presented at conferences, in field of medical oncology and respiratory medicine. TRIAL REGISTRATION NUMBER: ACTRN12620001216909. PROTOCOL VERSION NUMBER: V.1.0.

Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice.

Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6-8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury.

Exploring the percentage of COVID-19 cases reported in the community in Canada and associated case fatality ratios.

While surveillance can identify changes in COVID-19 transmission patterns over time and space, sections of the population at risk, and the efficacy of public health measures, reported cases of COVID-19 are generally understood to only capture a subset of the actual number of cases. Our primary objective was to estimate the percentage of cases reported in the general community, considered as those that occurred outside of long-term care facilities (LTCFs), in specific provinces and Canada as a whole. We applied a methodology using the delay-adjusted case fatality ratio (CFR) to all cases and deaths, as well as those representing the general community. Our second objective was to assess whether the assumed CFR (mean = 1.38%) was appropriate for calculating underestimation of cases in Canada. Estimates were developed for the period from March 11th, 2020 to September 16th, 2020. Estimates of the percentage of cases reported (PrCR) and CFR varied spatially and temporally across Canada. For the majority of provinces, and for Canada as a whole, the PrCR increased through the early stages of the pandemic. The estimated PrCR in general community settings for all of Canada increased from 18.1% to 69.0% throughout the entire study period. Estimates were greater when considering only those data from outside of LTCFs. The estimated upper bound CFR in general community settings for all of Canada decreased from 9.07% on March 11th, 2020 to 2.00% on September 16th, 2020. Therefore, the true CFR in the general community in Canada was likely less than 2% on September 16th. According to our analysis, some provinces, such as Alberta, Manitoba, Newfoundland and Labrador, Nova Scotia, and Saskatchewan reported a greater percentage of cases as of September 16th, compared to British Columbia, Ontario, and Québec. This could be due to differences in testing rates and criteria, demographics, socioeconomic factors, race, and access to healthcare among the provinces. Further investigation into these factors could reveal differences among provinces that could partially explain the variation in estimates of PrCR and CFR identified in our study. The estimates provide context to the summative state of the pandemic in Canada, and can be improved as knowledge of COVID-19 reporting rates and disease characteristics are advanced.

Is Bigger Really Better? Comparison of Ultraportable Handheld Ultrasound with Standard Point-of-Care Ultrasound for Evaluating Safe Site Identification and Image Quality prior to Pleurocentesis.

BACKGROUND: Pleural effusions remain a common medical problem which often requires diagnostic pleurocentesis to determine the underlying cause. Pleurocentesis is a frequently performed procedure worldwide with improved safety using ultrasound (US) technology. OBJECTIVES: This prospective, single-center study evaluated the use of an ultraportable handheld (UPHH) US compared with standard point-of-care (SPOC) US in determining a safe site for pleurocentesis. In addition, US image quality and factors impacting on image quality were assessed using both UPHH and SPOC US. METHODS: Paired US assessments were performed by thoracic physicians using UPHH and SPOC US on patients with unilateral pleural effusions to determine a safe site for pleurocentesis (defined as >2 cm of pleural fluid, >2 cm from a solid organ/diaphragm, and <7 cm chest wall depth). Distance measurements for key structures and image quality scores (using a 5-point Likert rating scale) were obtained at the time of US assessment. Factors affecting image quality were analyzed using univariate analysis. RESULTS: In 52 of the 54 included patients (96.3%), UPHH US was able to identify a safe site for pleurocentesis. Distance measurements between UPHH and SPOC US were not statistically different (all <0.5 cm with values of p > 0.05), but image quality was reduced in UPHH compared with SPOC US by 1 point on a 5-point Likert rating scale (p < 0.002). Increasing body mass index was associated with a reduction in image quality in both UPHH and SPOC US (all p < 0.01). CONCLUSIONS: Although image quality was lower in UPHH than SPOC US, a safe site was found in 96.3% of patients, which suggests that UPHH US may be a useful tool for diagnostic pleuro-centesis when SPOC US is not available (http://www.anzctr.org.au/, Australia New Zealand Clinical Trials Registry, No. ACTRN12618001592235).

An analysis of antibiotic prescribing practices for enteric bacterial infections within FoodNet Canada sentinel sites.

OBJECTIVES: Understanding the current state of antibiotic treatment guidelines and prescribing practices for bacterial enteric infections is critical to inform antibiotic stewardship initiatives. This study aims to add to the current understanding through three objectives: (i) to identify and summarize published treatment guidelines for bacterial enteric infections; (ii) to describe observed antibiotic prescribing practices for bacterial enteric infections across three sentinel sites in Canada; and (iii) to assess concordance between observed antibiotic prescribing and treatment guidelines. METHODS: An environmental scan of treatment guidelines for bacterial enteric infections was conducted and recommendations were collated. A descriptive analysis of cases of bacterial enteric illnesses captured in FoodNet Canada's sentinel site surveillance system between 2010 and 2018 was performed. Antibiotic-use data were self-reported by cases via an enhanced questionnaire. RESULTS: Ten treatment guidelines were identified in the environmental scan. There was substantial variation between guidelines for both when to prescribe antibiotics and which antibiotics were recommended. Of the 5877 cases of laboratory-confirmed bacterial enteric illness in the three sites, 49% of cases reported having received an antibiotic prescription. Of particular significance was the finding that 21% of verotoxigenic Escherichia coli cases received a prescription. Of the 17 antibiotics recommended in the guidelines, 14 were used in practice. In addition to these, 18 other antibiotics not included in any of the guidelines reviewed were also prescribed. CONCLUSIONS: Our study suggests that a substantial proportion of enteric bacterial infections in Canada are prescribed antibiotics. These findings highlight the need to standardize treatment guidelines for enteric illnesses and could be used to inform future stewardship programme development.

Development of ventilatory long-term facilitation is dependent on estrous cycle stage in adult female rats.

Ventilatory long-term facilitation (vLTF) is a form of respiratory plasticity characterized by a progressive and sustained increase in minute ventilation over time following acute, intermittent hypoxia (AIH). Though vLTF has been repeatedly demonstrated in adult males (rats and humans), few studies have assessed vLTF in adult females and no studies have explored differential expression of vLTF across the normal female estrous cycle. We recently reported that AIH-induced plasticity of phrenic motor output (phrenic long-term facilitation, pLTF), a phenotypically similar form of respiratory plasticity presenting as a sustained increase in phrenic nerve amplitude, develops in adult female rats only during the proestrus stage of the estrous cycle, notable for high levels of serum estrogen. Here, we tested the hypothesis that AIH-induced vLTF would also be estrous-stage dependent; developing in female rats during proestrus, but not estrus. Barometric plethysmography in adult (4-5 months), normally cycling female rats revealed a progressive increase in minute ventilation for 60 min following AIH (5 × 5 min episodes; 10% O2) during proestrus indicative of vLTF, while estrus rats showed no changes in minute ventilation over the same time period. The development of vLTF in proestrus rats was driven by changes in tidal volume production versus respiratory frequency consistent with prior studies. These data are the first to investigate differential vLTF expression across the estrous cycle in adult female rats and highlight the importance of female estrous cycle stage as a critical physiological variable to consider in studies of AIH-induced plasticity.

Predicting Malignancy Risk of Screen-Detected Lung Nodules-Mean Diameter or Volume.

OBJECTIVE: In lung cancer screening practice low-dose computed tomography, diameter, and volumetric measurement have been used in the management of screen-detected lung nodules. The aim of this study was to compare the performance of nodule malignancy risk prediction tools using diameter or volume and between computer-aided detection (CAD) and radiologist measurements. METHODS: Multivariable logistic regression models were prepared by using data from two multicenter lung cancer screening trials. For model development and validation, baseline low-dose computed tomography scans from the Pan-Canadian Early Detection of Lung Cancer Study and a subset of National Lung Screening Trial (NLST) scans with lung nodules 3 mm or more in mean diameter were analyzed by using the CIRRUS Lung Screening Workstation (Radboud University Medical Center, Nijmegen, the Netherlands). In the NLST sample, nodules with cancer had been matched on the basis of size to nodules without cancer. RESULTS: Both CAD-based mean diameter and volume models showed excellent discrimination and calibration, with similar areas under the receiver operating characteristic curves of 0.947. The two CAD models had predictive performance similar to that of the radiologist-based model. In the NLST validation data, the CAD mean diameter and volume models also demonstrated excellent discrimination: areas under the curve of 0.810 and 0.821, respectively. These performance statistics are similar to those of the Pan-Canadian Early Detection of Lung Cancer Study malignancy probability model with use of these data and radiologist-measured maximum diameter. CONCLUSION: Either CAD-based nodule diameter or volume can be used to assist in predicting a nodule's malignancy risk.