Minimal influence of the menstrual cycle or hormonal contraceptives on performance in female rugby league athletes.

We examined performance across one menstrual cycle (MC) and 3 weeks of hormonal contraceptives (HC) use to identify whether known fluctuations in estrogen and progesterone/progestin are associated with functional performance changes. National Rugby League Indigenous Women's Academy athletes [n = 11 naturally menstruating (NM), n = 13 using HC] completed performance tests [countermovement jump (CMJ), squat jump (SJ), isometric mid-thigh pull, 20 m sprint, power pass and Stroop test] during three phases of a MC or three weeks of HC usage, confirmed through ovulation tests alongside serum estrogen and progesterone concentrations. MC phase or HC use did not influence jump height, peak force, sprint time, distance thrown or Stroop effect. However, there were small variations in kinetic and kinematic CMJ/SJ outputs. NM athletes produced greater mean concentric power in MC phase four than one [+0.41 W·kg-1 (+16.8%), p = 0.021] during the CMJ, alongside greater impulse at 50 ms at phase one than four [+1.7 N·s (+4.7%), p = 0.031] during the SJ, without differences between tests for HC users. Among NM athletes, estradiol negatively correlated with mean velocity and power (r = -0.44 to -0.50, p < 0.047), progesterone positively correlated with contraction time (r = 0.45, p = 0.045), and both negatively correlated with the rate of force development and impulse (r = -0.45 to -0.64, p < 0.043) during the SJ. During the CMJ, estradiol positively correlated to 200 ms impulse (r = 0.45, p = 0.049) and progesterone to mean power (r = 0.51, p = 0.021). Evidence of changes in testing performance across a MC, or during active HC use, is insufficient to justify "phase-based testing"; however, kinetic or kinematic outputs may be altered in NM athletes.

Analyzing atomic force microscopy images of virus-like particles by expectation-maximization.

Analysis of virus-like particles (VLPs) is an essential task in optimizing their implementation as vaccine antigens for virus-initiated diseases. Interrogating VLP collections for elasticity by probing with a rigid atomic force microscopy (AFM) tip is a potential method for determining VLP morphological changes. During VLP morphological change, it is not expected that all VLPs would be in the same state. This leads to the open question of whether VLPs may change in a continuous or stepwise fashion. For continuous change, the statistical distribution of observed VLP properties would be expected as a single distribution, while stepwise change would lead to a multimodal distribution of properties. This study presents the application of a Gaussian mixture model (GMM), fit by the Expectation-Maximization (EM) algorithm, to identify different states of VLP morphological change observed by AFM imaging.

Effect of Menstrual Cycle Phase and Hormonal Contraceptives on Resting Metabolic Rate and Body Composition.

The cyclical changes in sex hormones across the menstrual cycle (MC) are associated with various biological changes that may alter resting metabolic rate (RMR) and body composition estimates. Hormonal contraceptive (HC) use must also be considered given their impact on endogenous sex hormone concentrations and synchronous exogenous profiles. The purpose of this study was to determine if RMR and dual-energy X-ray absorptiometry body composition estimates change across the MC and differ compared with HC users. This was accomplished during a 5-week training camp involving naturally cycling athletes (n = 11) and HC users (n = 7 subdermal progestin implant, n = 4 combined monophasic oral contraceptive pill, n = 1 injection) from the National Rugby League Indigenous Women's Academy. MC phase was retrospectively confirmed via serum estradiol and progesterone concentrations and a positive ovulation test. HC users had serum estradiol and progesterone concentrations assessed at the time point of testing. Results were analyzed using general linear mixed model. There was no effect of MC phase on absolute RMR (p = .877), relative RMR (p = .957), or dual-energy X-ray absorptiometry body composition estimates (p > .05). There was no effect of HC use on absolute RMR (p = .069), relative RMR (p = .679), or fat mass estimates (p = .766), but HC users had a greater fat-free mass and lean body mass than naturally cycling athletes (p = .028). Our findings suggest that RMR and dual-energy X-ray absorptiometry body composition estimates do not significantly differ due to changes in sex hormones in a group of athletes, and measurements can be compared between MC phases or with HC usage without variations in sex hormones causing additional noise.

Female Athlete Research Camp: A Unique Model for Conducting Research in High-Performance Female Athletes.

PURPOSE: The purpose of this study is to describe the implementation of a novel research protocol for conducting research with highly trained female athletes, including characterizing menstrual cycle (MC) function, hormonal profiles and symptoms of the participating athletes. METHODS: Twenty-four Australian First Nation female Rugby League athletes completed this study, which involved 11 wk of cycle tracking, followed by attendance at a 5-wk training camp. Throughout the study, athletes completed a daily survey, reporting their MC function and any associated symptoms. During the training camp, athletes reported to the laboratory on three occasions and provided a venous blood sample, which was analyzed for reproductive hormones. For naturally cycling athletes (athleteNC, n = 11), this included phase 1, 2, and 4 of the menstrual cycle, whereas athletes using hormonal contraception (athleteHC; n = 13) were tested at three equally spaced time points in which consistent exogenous hormone provision occurred. RESULTS: In the athleteNC cohort, just one athlete reached criteria for classification as eumenorrheic, with five athletes showing evidence of MC dysfunction. The prevalence of symptoms on any given day was similar between athleteNC (33.7%) and athleteHC (22.9%; P = 0.376); however, more symptoms were reported in athleteNC, suggesting that they were more likely to report multiple symptoms. Regardless of MC function, there was a significant, positive association between bleeding and symptoms ( P < 0.001), where athletes were more likely to report one or more symptoms on bleeding (50.1%) compared with nonbleeding days (22.0%). CONCLUSIONS: We describe an innovative strategy to investigate the effect of MC function and MC phase in a high-performance sport environment, including approaches to address the challenges of undertaking research with female athletes with MC variability and those using exogenous hormonal therapies.

Canadian COVID-19 Outbreak Surveillance System: implementation of national surveillance during a global pandemic.

SETTING: Early in the SARS-CoV-2 pandemic, the need to develop systematic outbreak surveillance at the national level to monitor trends in SARS-CoV-2 outbreaks was identified as a priority for the Public Health Agency of Canada (PHAC). The Canadian COVID-19 Outbreak Surveillance System (CCOSS) was established to monitor the frequency and severity of SARS-CoV-2 outbreaks across various community settings. INTERVENTION: PHAC engaged with provincial/territorial partners in May 2020 to develop goals and key data elements for CCOSS. In January 2021, provincial/territorial partners began submitting cumulative outbreak line lists on a weekly basis. OUTCOMES: Eight provincial and territorial partners, representing 93% of the population, submit outbreak data on the number of cases and severity indicators (hospitalizations and deaths) for 24 outbreak settings to CCOSS. Outbreak data can be integrated with national case data to supply information on case demographics, clinical outcomes, vaccination status, and variant lineages. Data aggregated to the national level are used to conduct analyses and report on outbreak trends. Evidence from CCOSS analyses has been useful in supporting provincial/territorial outbreak investigations, informing policy recommendations, and monitoring the impact of public health measures (vaccination, closures) in specific outbreak settings. IMPLICATIONS: The development of a SARS-CoV-2 outbreak surveillance system complemented case-based surveillance and furthered the understanding of epidemiological trends. Further efforts are required to better understand SARS-CoV-2 outbreaks for Indigenous populations and other priority populations, as well as create linkages between genomic and epidemiological data. As SARS-CoV-2 outbreak surveillance enhanced case surveillance, outbreak surveillance should be a priority for emerging public health threats.

RéSUMé: CONTEXTE: Au début de la pandémie de SRAS-CoV-2, l'Agence de la santé publique du Canada (ASPC) a déterminé comme priorité la nécessité de développer un système de surveillance systématique des éclosions à l'échelle nationale afin de suivre les tendances des éclosions de SRAS-CoV-2. Le système canadien de surveillance des éclosions de COVID-19 (SCSEC) a été établi pour surveiller la fréquence et la gravité des éclosions de SRAS-CoV-2 dans différents milieux communautaires. INTERVENTION: L'ASPC s'est engagée avec les partenaires provinciaux et territoriaux en mai 2020 pour élaborer des objectifs et des éléments de données clés pour le SCSEC. En janvier 2021, les partenaires provinciaux et territoriaux ont commencé à transmettre des listes d'éclosions cumulatives hebdomadaires. RéSULTATS: Huit partenaires provinciaux et territoriaux, représentant 93 % de la population, transmettent au SCSEC des données sur les éclosions sur le nombre de cas et les indicateurs de gravité (les hospitalisations et les décès) pour 24 types de milieux. Les données sur les éclosions peuvent être intégrées avec les données nationales sur les cas pour obtenir des informations sur la démographie des cas, les résultats cliniques, le statut vaccinal et les lignées de variants. Les données agrégées à l'échelle nationale sont utilisées pour effectuer des analyses et faire rapport des tendances sur les éclosions. Les résultats des analyses du SCSEC ont été utiles pour soutenir les enquêtes provinciales/territoriales sur les éclosions, informer les recommandations politiques et surveiller l'impact des mesures de santé publique (la vaccination, les fermetures) dans des milieux d'éclosions spécifiques. IMPLICATIONS: Le développement d'un système de surveillance des éclosions de SRAS-CoV-2 a permis de complémenter la surveillance des cas et d'approfondir notre compréhension des tendances épidémiologiques. Des efforts supplémentaires sont nécessaires pour mieux comprendre les éclosions de SRAS-CoV-2 chez les populations autochtones et d'autres populations minoritaires, ainsi que pour créer des liens entre les données génomiques et les données épidémiologiques. Comme la surveillance des éclosions de SRAS-CoV-2 a enrichi la surveillance des cas, la surveillance des éclosions devrait être une priorité pour les menaces émergentes pour la santé publique.

COVID-19 outbreak trends in Canada, 2021.

Background: In January 2021, the Public Health Agency of Canada launched an outbreak surveillance system, the Canadian COVID-19 Outbreak Surveillance System (CCOSS), with the goal of monitoring incidence and severity of coronavirus disease 2019 (COVID-19) outbreaks across various community settings and complementing case surveillance. Methods: Seven provinces were included in this report; these provinces submitted weekly cumulative COVID-19 outbreak line lists to CCOSS in 2021. Data includes administrative variables (e.g. date outbreak declared, date outbreak declared over, outbreak identifier), 24 outbreak settings, and number of confirmed cases and outcomes (hospitalization, death). Descriptive analyses for COVID-19 outbreaks across Canada from January 3, 2021, to January 1, 2022, were performed examining trends over time, severity, and outbreak size. Results: Incidence of outbreaks followed similar trends to case incidence. Outbreaks were most common in school and childcare settings (39%) and industrial/agricultural settings (21%). Outbreak size ranged from 2 to 639 cases per outbreak; the median size was four cases per outbreak. Correctional facilities had the largest median outbreak size with 18 cases per outbreak, followed by long-term care facilities with 10 cases per outbreak. During periods of high case incidence, outbreaks may be under-ascertained due to limited public health capacity, or reporting may be biased towards high-risk settings prioritized for testing. Outbreaks reported to CCOSS were dominated by jurisdictions with the largest populations. Conclusion: The trends illustrate that COVID-19 outbreaks in 2021 were reported most frequently in community settings such as schools; however, the largest outbreaks occurred in congregate living settings. The information gathered from outbreak surveillance complemented case incidence trends and furthered understanding of COVID-19 in Canada.

Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women.

This study examined the association between dietary Vitamin K1 intake with fracture-related hospitalizations over 14.5 years in community-dwelling older Australian women (n = 1373, ≥70 years). Dietary Vitamin K1 intake at baseline (1998) was estimated using a validated food frequency questionnaire and a new Australian Vitamin K nutrient database, which was supplemented with published data. Over 14.5 years, any fracture (n = 404, 28.3%) and hip fracture (n = 153, 10.7%) related hospitalizations were captured using linked health data. Plasma Vitamin D status (25OHD) and the ratio of undercarboxylated osteocalcin (ucOC) to total osteocalcin (tOC) from serum was assessed at baseline. Estimates of dietary Vitamin K1 intake were supported by a significant inverse association with ucOC : tOC; a marker of Vitamin K status (r = -0.12, p < 0.001). Compared to women with the lowest Vitamin K1 intake (Quartile 1, <61 µg d-1), women with the highest Vitamin K1 intake (Quartile 4, ≥99 µg d-1) had lower hazards for any fracture- (HR 0.69 95%CI 0.52-0.91, p < 0.001) and hip fracture-related hospitalization (HR 0.51 95%CI 0.32-0.79, p < 0.001), independent of 25OHD levels, as part of multivariable-adjusted analysis. Spline analysis suggested a nadir in the relative hazard for any fracture-related hospitalizations at a Vitamin K1 intake of approximately 100 µg day-1. For hip fractures, a similar relationship was apparent. Higher dietary Vitamin K1 is associated with lower long-term risk for any fracture- and hip fracture-related hospitalizations in community-dwelling older women.

miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging.

Satellite cell-dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age-related dysfunction and defective muscle regeneration. In this study, we demonstrated an age-related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR-24 in regenerating muscle from adult mice and downregulation of miR-24 during muscle regeneration in old mice. FACS-sorted satellite cells were characterized by decreased levels of miR-24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR-24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR-24 expression indicate miR-24 plays a role in fine-tuning Prdx6 expression. Changes in miR-24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated-H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR-24 were more pronounced in myogenic progenitors from old mice, suggesting a context-dependent role of miR-24 in these cells, with miR-24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR-24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways.

Exercise and Heat Stress: Inflammation and the Iron Regulatory Response.

This study determined the impact of heat stress on postexercise inflammation and hepcidin levels. Twelve moderately trained males completed three, 60-min treadmill running sessions under different conditions: (a) COOL, 18 °C with speed maintained at 80% maximum heart rate; (b) HOTHR, 35 °C with speed maintained at 80% maximum heart rate; and (c) HOTPACE, 35 °C completed at the average running speed from the COOL trial. Venous blood samples were collected pre-, post-, and 3-hr postexercise and analyzed for serum ferritin, interleukin-6 (IL-6), and hepcidin concentrations. Average HR was highest during HOTPACE compared with HOTHR and COOL (p < .001). Running speed was slowest in HOTHR compared with COOL and HOTPACE (p < .001). The postexercise increase in IL-6 was greatest during HOTPACE (295%; p = .003). No differences in the IL-6 response immediately postexercise between COOL (115%) and HOTHR (116%) were evident (p = .992). No differences in hepcidin concentrations between the three trials were evident at 3 hr postexercise (p = .407). Findings from this study suggest the IL-6 response to exercise is greatest in hot compared with cool conditions when the absolute running speed was matched. No differences in IL-6 between hot and cool conditions were evident when HR was matched, suggesting the increased physiological strain induced from training at higher intensities in hot environments, rather than the heat per se, is likely responsible for this elevated response. Environmental temperature had no impact on hepcidin levels, indicating that exercising in hot conditions is unlikely to further impact transient alterations in iron regulation, beyond that expected in temperate conditions.

Refining Treatment Strategies for Iron Deficient Athletes.

Iron deficiency (ID) is a prevailing nutritional concern amongst the athletic population due to the increased iron demands of this group. Athletes' ability to replenish taxed iron stores is challenging due to the low bioavailability of dietary sources, and the interaction between exercise and hepcidin, the primary iron-regulatory hormone. To date, copious research has explored the link between exercise and iron regulation, with a more recent focus on optimising iron treatment applications. Currently, oral iron supplementation is typically the first avenue of iron replacement therapy beyond nutritional intervention, for treatment of ID athletes. However, many athletes encounter associated gastrointestinal side-effects which can deter them from fulfilling a full-term oral iron treatment plan, generally resulting in sub-optimal treatment efficacy. Consequently, various strategies (e.g. dosage, composition, timing) of oral iron supplementation have been investigated with the goal of increasing fractional iron absorption, reducing gastric irritation, and ultimately improving the efficacy of oral iron therapy. This review explores the various treatment strategies pertinent to athletes and concludes a contemporary strategy of oral iron therapy entailing morning supplementation, ideally within the 30 min following morning exercise, and in athletes experiencing gut sensitivity, consumed on alternate days or at lower doses.

Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration.

Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruch's membrane (BM), however, the diseased native BM and related structures still leave potential for transplanted cells to succumb to disease. In this proof-of-concept work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the underside was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for 2 weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This could allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function two-fold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.

miR-181a regulates p62/SQSTM1, parkin, and protein DJ-1 promoting mitochondrial dynamics in skeletal muscle aging.

One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during aging concomitant with dysregulation of miR-181a target interactions. Using functional approaches and mito-QC assay, we have established that miR-181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1, and DJ-1 in vitro. Downregulation of miR-181a with age was associated with an accumulation of autophagy-related proteins and abnormal mitochondria. Restoring miR-181a levels in old mice prevented accumulation of p62, DJ-1, and PARK2, and improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA-based interventions for age-related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics.

The Effectiveness of Daily and Alternate Day Oral Iron Supplementation in Athletes With Suboptimal Iron Status (Part 2).

The authors compared the effectiveness of daily (DAY) versus alternate day (ALT) oral iron supplementation in athletes with suboptimal iron. Endurance-trained runners (nine males and 22 females), with serum ferritin (sFer) concentrations <50 µg/L, supplemented with oral iron either DAY or ALT for 8 weeks. Serum ferritin was measured at baseline and at fortnightly intervals. Hemoglobin mass (Hbmass) was measured pre- and postintervention in a participant subset (n = 10). Linear mixed-effects models were used to assess the effectiveness of the two strategies on sFer and Hbmass. There were no sFer treatment (p = .928) or interaction (p = .877) effects; however, sFer did increase (19.7 µg/L; p < .001) over the 8-week intervention in both groups. In addition, sFer was 21.2 µg/L higher (p < .001) in males than females. No Hbmass treatment (p = .146) or interaction (p = .249) effects existed; however, a significant effect for sex indicated that Hbmass was 140.85 g higher (p = .004) in males compared with females. Training load (p = .001) and dietary iron intake (p = .015) also affected Hbmass. Finally, there were six complaints of severe gastrointestinal side effects in DAY, but only one in ALT. In summary, both supplement strategies increased sFer in athletes with suboptimal iron status; however, the ALT approach was associated with lower incidence of gastrointestinal upset.

The Effectiveness of Transdermal Iron Patches in Athletes With Suboptimal Iron Status (Part 1).

The authors compared the effectiveness of two modes of daily iron supplementation in athletes with suboptimal iron stores: oral iron (PILL) versus transdermal iron (PATCH). Endurance-trained runners (nine males and 20 females), with serum ferritin concentrations <50 µg/L, supplemented with oral iron or iron patches for 8 weeks, in a parallel group study design. Serum ferritin was measured at baseline and fortnightly intervals. Hemoglobin mass and maximal oxygen consumption (V˙O2max) were measured preintervention and postintervention in PATCH. A linear mixed effects model was used to assess the effectiveness of each mode of supplementation on sFer. A repeated-measures analysis of variance was used to assess hemoglobin mass and V˙O2max outcomes in PATCH. There was a significant time effect (p < .001), sex effect (p = .013), and Time × Group interaction (p = .009) for sFer. At Week 6, PILL had significantly greater sFer compared with PATCH (15.27 µg/L greater in PILL; p = .019). Serum ferritin was 15.53 µg/L greater overall in males compared with females (p = .013). There were no significant differences in hemoglobin mass (p = .727) or V˙O2max (p = .929) preintervention to postintervention in PATCH. Finally, there were six complaints of severe gastrointestinal side effects in PILL and none in PATCH. Therefore, this study concluded that PILL effectively increased sFer in athletes with suboptimal iron stores, whereas PATCH showed no beneficial effects.

The Impact of Morning versus Afternoon Exercise on Iron Absorption in Athletes.

PURPOSE: This study examined postexercise inflammatory, hepcidin, and iron absorption responses to endurance exercise performed in the morning versus the afternoon. METHODS: Sixteen endurance-trained runners (10 male, 6 female) with serum ferritin (sFer) < 50 µg·L completed a 90-min running protocol (65% vV˙O2max) in the morning (AM), or the afternoon (PM), in a crossover design. An iron-fortified fluid labeled with stable iron isotopes (Fe or Fe) was administered with a standardized meal 30 min following the exercise and control conditions during each trial, serving as a breakfast and dinner meal. Venous blood samples were collected before, immediately after, and 3 h after the exercise and control conditions to measure sFer, serum interleukin-6 (IL-6), and serum hepcidin-25. A final venous blood sample was collected 14 d after each trial to determine the erythrocyte iron incorporation, which was used to calculate iron absorption. Linear mixed-modeling was used to analyze the data. RESULTS: Overall, exercise significantly increased the concentrations of IL-6 (4.938 pg·mL; P = 0.006), and hepcidin-25 concentrations significantly increased 3 h after exercise by 0.380 nM (P < 0.001). During the PM trial, hepcidin concentrations exhibited diurnal tendency, increasing 0.55 nM at rest (P = 0.007), before further increasing 0.68 nM (P < 0.001) from prerun to 3 h postrun. Fractional iron absorption was significantly greater at breakfast after the AM run, compared with both the rested condition (0.778%; P = 0.020) and dinner in the AM run trial (0.672%; P = 0.011). CONCLUSIONS: Although exercise resulted in increased concentrations of IL-6 and hepcidin, iron was best absorbed in the morning after exercise, indicating there may be a transient mechanism during the acute postexercise window to promote iron absorption opposing the homeostatic regulation by serum hepcidin elevations.

Outbreaks of Norovirus and Acute Gastroenteritis Associated with British Columbia Oysters, 2016-2017.

Two outbreaks of norovirus and acute gastroenteritis took place in Canada between November 2016 and April 2017. Both outbreaks were linked to oysters from British Columbia (BC) coastal waters. This paper describes the multi-agency investigations to identify the source and control the outbreak. Public health officials conducted interviews to determine case exposures. Traceback was conducted by collecting oyster tags from restaurants and analyzing them to determine the most common farms. Oyster samples were collected from case homes, restaurants, and harvest sites and tested for the presence of norovirus. Potential environmental pollution sources were investigated to identify the source of the outbreak. Four hundred and 49 cases were identified as part of the two outbreak waves. The oysters were traced to various geographically dispersed farms in BC coastal waters. Twelve farms were closed as a result of the investigations. No environmental pollution sources could be identified as the cause of the outbreak. Similarities in the timeframe, genotype, and geographic distribution of identified oyster farms indicate that they may have been one continuous event. Genotype data indicate that human sewage contamination was the likely cause of the outbreak, although no pollution source was identified.

Evaluation of whole-genome sequencing for outbreak detection of Verotoxigenic Escherichia coli O157:H7 from the Canadian perspective.

BACKGROUND: Rapid and accurate identification of Verotoxigenic Escherichia coli (VTEC) O157:H7 is dependent on well-established, standardized and highly discriminatory typing methods. Currently, conventional subtyping tests for foodborne bacterial pathogen surveillance are rapidly being replaced with whole-genome sequencing (WGS) in public health laboratories. The capacity of WGS to revolutionize global foodborne disease surveillance has positioned this tool to become the new gold standard; however, to ensure evidence standards for public health decision making can still be achieved, the performance of WGS must be thoroughly validated against current gold standard methods prior to implementation. Here we aim to verify the performance of WGS in comparison to pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem repeat analysis (MLVA) for eight retrospective outbreaks of VTEC O157:H7 from the Canadian perspective. Since real-time implementation and routine use of WGS in public health laboratories is highly reliant on standardized data analysis tools, we also provide a comparative analysis of two popular methodologies for WGS analyses; an in-house developed single nucleotide variant phylogenomics (SNVPhyl) pipeline and the BioNumerics whole genome multilocus sequence typing (wgMLST) tool. To provide a useful and consistent starting point for examining laboratory-based surveillance data for VTEC O157:H7 in Canada, we also aim to describe the number of genetic differences observed among outbreak-associated isolates. RESULTS: WGS provided enhanced resolution over traditional subtyping methods, and accurately distinguished outbreak-related isolates from non-outbreak related isolates with high epidemiological concordance. WGS also illuminated potential linkages between sporadic cases of illness and contaminated food, and isolates spanning multiple years. The topologies generated by SNVPhyl and wgMLST were highly congruent with strong statistical support. Few genetic differences were observed among outbreak-related isolates (≤5 SNVs/ < 10 wgMLST alleles) unless the outbreak was suspected to be multi-strain. CONCLUSIONS: This study validates the superiority of WGS and indicates the BioNumerics wgMLST schema is suitable for surveillance and cluster detection of VTEC O157:H7. These findings will provide a useful and consistent starting point for examining WGS data for prospective laboratory-based surveillance of VTEC O157:H7, but however, the data will continue to be interpreted according to context and in combination with epidemiological and food safety evidence to inform public-health decision making in Canada.

Age-related changes in skeletal muscle: changes to life-style as a therapy.

As we age, there is an age-related loss in skeletal muscle mass and strength, known as sarcopenia. Sarcopenia results in a decrease in mobility and independence, as well as an increase in the risk of other morbidities and mortality. Sarcopenia is therefore a major socio-economical problem. The mechanisms behind sarcopenia are unclear and it is likely that it is a multifactorial condition with changes in numerous important mechanisms all contributing to the structural and functional deterioration. Here, we review the major proposed changes which occur in skeletal muscle during ageing and highlight evidence for changes in physical activity and nutrition as therapeutic approaches to combat age-related skeletal muscle wasting.

Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia.

Adults presenting with sporadic hypophosphatemia and elevations in circulating fibroblast growth factor-23 (FGF23) concentrations are usually investigated for an acquired disorder of FGF23 excess such as tumor induced osteomalacia (TIO). However, in some cases the underlying tumor is not detected, and such patients may harbor other causes of FGF23 excess. Indeed, coding-region and 3'UTR mutations of phosphate-regulating neutral endopeptidase (PHEX), which encodes a cell-surface protein that regulates circulating FGF23 concentrations, can lead to alterations in phosphate homeostasis, which are not detected until adulthood. Here, we report an adult female who presented with hypophosphatemic osteomalacia and raised serum FGF23 concentrations. The patient and her parents, who were her only first-degree relatives, had no history of rickets. The patient was thus suspected of having TIO. However, no tumor had been identified following extensive localization studies. Mutational analysis of the PHEX coding-region and 3'UTR was undertaken, and this revealed the patient to be heterozygous for a novel germline PHEX mutation (c.2158G>T; p.Ala720Ser). In vitro studies involving the expression of WT and mutant PHEX proteins in HEK293 cells demonstrated the Ala720Ser mutation to impair trafficking of PHEX, with ~20% of the mutant protein being expressed at the cell surface, compared to ~80% cell surface expression for WT PHEX (p<0.05). Thus, our studies have identified a pathogenic PHEX mutation in a sporadic case of adult-onset hypophosphatemic osteomalacia, and these findings highlight a role for PHEX gene analysis in some cases of suspected TIO, particularly when no tumor has been identified.