Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.

BACKGROUND: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

Current water quality guidelines across North America and Europe do not protect lakes from salinization.

Human-induced salinization caused by the use of road deicing salts, agricultural practices, mining operations, and climate change is a major threat to the biodiversity and functioning of freshwater ecosystems. Yet, it is unclear if freshwater ecosystems are protected from salinization by current water quality guidelines. Leveraging an experimental network of land-based and in-lake mesocosms across North America and Europe, we tested how salinization-indicated as elevated chloride (Cl-) concentration-will affect lake food webs and if two of the lowest Cl- thresholds found globally are sufficient to protect these food webs. Our results indicated that salinization will cause substantial zooplankton mortality at the lowest Cl- thresholds established in Canada (120 mg Cl-/L) and the United States (230 mg Cl-/L) and throughout Europe where Cl- thresholds are generally higher. For instance, at 73% of our study sites, Cl- concentrations that caused a ≥50% reduction in cladoceran abundance were at or below Cl- thresholds in Canada, in the United States, and throughout Europe. Similar trends occurred for copepod and rotifer zooplankton. The loss of zooplankton triggered a cascading effect causing an increase in phytoplankton biomass at 47% of study sites. Such changes in lake food webs could alter nutrient cycling and water clarity and trigger declines in fish production. Current Cl- thresholds across North America and Europe clearly do not adequately protect lake food webs. Water quality guidelines should be developed where they do not exist, and there is an urgent need to reassess existing guidelines to protect lake ecosystems from human-induced salinization.

Timing determines zooplankton community responses to multiple stressors.

Human activities and climate change cause abiotic factors to fluctuate through time, sometimes passing thresholds for organismal reproduction and survival. Multiple stressors can independently or interactively impact organisms; however, few studies have examined how they interact when they overlap spatially but occur asynchronously. Fluctuations in salinity have been found in freshwater habitats worldwide. Meanwhile, heatwaves have become more frequent and extreme. High salinity pulses and heatwaves are often decoupled in time but can still collectively impact freshwater zooplankton. The time intervals between them, during which population growth and community recovery could happen, can influence combined effects, but no one has examined these effects. We conducted a mesocosm experiment to examine how different recovery times (0-, 3-, 6-week) between salt treatment and heatwave exposure influence their combined effects. We hypothesized that antagonistic effects would appear when having short recovery time, because previous study found that similar species were affected by the two stressors, but effects would become additive with longer recovery time since fully recovered communities would respond to heatwave similar to undisturbed communities. Our findings showed that, when combined, the two-stressor joint impacts changed from antagonistic to additive with increased recovery time between stressors. Surprisingly, full compositional recovery was not achieved despite a recovery period that was long enough for population growth, suggesting legacy effects from earlier treatment. The recovery was mainly driven by small organisms, such as rotifers and small cladocerans. As a result, communities recovering from previous salt exposure responded differently to heatwaves than undisturbed communities, leading to similar zooplankton communities regardless of the recovery time between stressors. Our research bolsters the understanding and management of multiple-stressor issues by revealing that prior exposure to one stressor has long-lasting impacts on community recovery that can lead to unexpected joint effects of multiple stressors.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.e. the number of maternal tissue layers between placental tissue and maternal blood). The villi in these species therefore serve as a compelling evolutionary case study to explore whether placentas have developed structural adaptations to respond to the challenge of reduced nutrient availability in less invasive placentas. Here, we use three-dimensional X-ray microfocus computed tomography and electron microscopy to quantitatively evaluate key structures involved in exchange in human and equid placental villi. We find that equid villi have a higher surface area to volume ratio and deeper trophoblastic vessel indentation than human villi. Using illustrative computational models, we propose that these structural adaptations have evolved in equids to boost nutrient transfer to compensate for reduced invasiveness into maternal tissue. We discuss these findings in relation to the 'maternal-fetal conflict hypothesis' of placental evolution.

Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study.

BACKGROUND AND OBJECTIVES: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first-line therapy in the absence of available prospective clinical trials. METHODS: Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow-up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated. RESULTS: Of 159 unique KHE/TA subjects, Kasabach-Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus. CONCLUSIONS: In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.

A Transmission Assay of 'Candidatus Liberibacter asiaticus' Using Citrus Phloem Sap and Topical Feeding to Its Insect Vector, Diaphorina citri.

'Candidatus Liberibacter asiaticus', the putative causal agent of citrus greening disease, is transmitted by the Asian citrus psyllid, Diaphorina citri, in a propagative, circulative, and persistent manner. Unfortunately, 'Ca. L. asiaticus' is not yet available in pure culture to carry out Koch's postulates and to confirm its etiology. When a pure culture is available, an assay to test its infectivity in both the insect vector and the plant host will be crucial. Herein, we described a transmission assay based on the use of phloem sap extracted from infected citrus plants and topical feeding to D. citri nymphs. Phloem sap was collected by centrifugation, diluted with 0.1 M phosphate buffer pH 7.4 containing 20% (wt/vol) sucrose and 0.1% ascorbic acid (wt/vol) as an antioxidant, and delivered to third through fifth instar nymphs by placing droplets on the mouthparts. Nymphs unfolded the stylets and acquired the phloem sap containing the bacterial pathogen. Nymphs were then placed onto Citrus macrophylla seedlings (10 nymphs per seedling) for an inoculation period of 2 weeks. A transmission rate of up to 80% was recorded at 6 months postinoculation. The method could be a powerful tool to test the transmissibility of the bacterial pathogen after various treatments to reduce the viability of the bacteria or to block its transmission. In addition, it might be a potent assay to achieve Koch's postulates if a pure culture of 'Ca. L. asiaticus' becomes available.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Impacts of sequential salinity and heat stress are recovery time-specific in freshwater crustacean, Daphnia pulicaria.

Stressors can interact to affect animal fitness, but we have limited knowledge about how temporal variation in stressors may impact their combined effect. This limits our ability to predict the outcomes of pollutants and future dynamic environmental changes. Elevated salinity in freshwater ecosystems has been observed worldwide. Meanwhile, heatwaves have become more frequent and intensified as an outcome of climate change. These two stressors can jointly affect organisms; however, their interaction has rarely been explored in the context of freshwater ecosystems. We conducted lab experiments using Daphnia pulicaria, a key species in lakes, to investigate how elevated salinity and heatwave conditions collectively affect freshwater organisms. We also monitored the impacts of various recovery times between the two stressors. Daphnia physiological conditions (metabolic rate, Na+-K+-ATPase (NKA) activity, and lipid peroxidation level) and life history traits (survival, fecundity, and growth) in response to salt stress as well as mortality in heat treatment were examined. We found that Daphnia responded to elevated salinity by upregulating NKA activity and increasing metabolic rate, causing a high lipid peroxidation level. Survival, fecundity, and growth were all negatively affected by this stressor. These impacts on physiological conditions and life history traits persisted for a few days after the end of the exposure. Heat treatments caused mortality in Daphnia, which increased with rising temperature. Results also showed that individuals that experienced salt exposure were more susceptible to subsequent heat stress, but this effect decreased with increasing recovery time between stressors. Findings from this work suggest that the legacy effects from a previous stressor can reduce individual resistance to a subsequent stressor, adding great difficulties to the prediction of outcomes of multiple stressors. Our work also demonstrates that cross-tolerance/susceptibility and the associated mechanisms remain unclear, necessitating further investigation.

Pupil Size and Reactivity in Pediatric Patients With Sickle Cell Disease.

Pupil size and reactivity have been studied to objectively measure pain utilizing pupillometry measurements. Given the challenges associated with treating vaso-occlusive pain in pediatric patients with sickle cell disease, better assessment tools are needed. The objective of this study is to establish normative values for pupil size and reactivity in pediatric patients with sickle cell disease with the hope that pupillometry can be used as a tool to objectively measure pain and response to treatment with analgesic medications. Readings were performed using a NeurOptics PLR-2000 pupillometer. Forty-four males and 38 females, all black, were studied. Their median age was 11 years (range: 2 to 21). When comparing our participants with white participants in a previously published pediatric study, there was a significant difference in maximum constriction velocity ( t =3.45, P =0.009), maximum pupil size ( t =-5.57 mm, P <0.0001), and minimum pupil size ( t =-3.24, P =0.002). There was no significant difference in pupil size and reactivity between patients with sickle cell disease and black patients without the disease when compared with the previously published study. Therefore, further investigation of pupillometry within the black population during vaso-occlusive crisis and in the "well state" is warranted in pediatric patients with sickle cell disease.

High-Intensity Interval Training is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).

A mixed-methods exploration of attitudes towards pregnant Facebook fitness influencers.

BACKGROUND: Exercise during pregnancy is associated with various health benefits for both mother and child. Despite these benefits, most pregnant women do not meet physical activity recommendations. A known barrier to engaging in exercise during pregnancy is a lack of knowledge about appropriate and safe exercise. In our current era of social media, many pregnant women are turning to online information sources for guidance, including social media influencers. Little is known about attitudes towards pregnancy exercise information provided by influencers on social media platforms. This study aimed to explore attitudes towards exercise during pregnancy depicted by social media influencers on Facebook, and user engagement with posted content. METHODS: A mixed-methods approach was used to analyse data from 10 Facebook video posts of social media influencers exercising during pregnancy. Quantitative descriptive analyses were used to report the number of views, shares, comments and emotive reactions. Qualitative analysis of user comments was achieved using an inductive thematic approach. RESULTS: The 10 video posts analysed were viewed a total of 12,117,200 times, shared on 11,181 occasions, included 13,455 user comments and 128,804 emotive icon reactions, with the most frequently used icon being 'like' (81.48%). The thematic analysis identified three themes associated with attitudes including [1] exercise during pregnancy [2] influencers and [3] type of exercise. A fourth theme of community was also identified. Most user comments were associated with positive attitudes towards exercise during pregnancy and the influencer. However, attitudes towards the types of exercise the influencer performed were mixed (aerobic and body weight exercises were positive; resistance-based exercise with weights were negative). Finally, the online community perceived by users was mostly positive and recognised for offering social support and guidance. CONCLUSIONS: User comments imply resistance-based exercise with weights as unsafe and unnecessary when pregnant, a perception that does not align with current best practice guidelines. Collectively, the findings from this study highlight the need for continued education regarding exercise during pregnancy and the potential for social media influencers to disseminate evidence-based material to pregnant women who are highly receptive to, and in need of reliable health information.

Client and Clinician Experiences and Perspectives of Exercise Physiology Services During the COVID-19 Pandemic: Qualitative Study.

BACKGROUND: The COVID-19 pandemic led to changes in the delivery of exercise physiology services. The lived experience of those who continued to provide or receive exercise physiology services during the heightened public health restrictions of the inaugural year of the COVID-19 pandemic has received little attention to date. Acquiring this knowledge will be fundamental in addressing whether telehealth is a viable option for service delivery in exercise care, research, and policy. This is especially pertinent in the wake of the COVID-19 pandemic and subsequent global interest in digital health delivery of health care services. OBJECTIVE: This study aims to explore the clinician and client experiences and perspectives of exercise physiology services delivered in person or via telehealth during the inaugural year of the COVID-19 pandemic (after January 25, 2020; the date of the first confirmed case in Australia). METHODS: Eligible participants for this study were adult (aged 18 years or older; capable of understanding and writing in English) clients who received and clinicians who delivered 1 or more exercise physiology sessions in Australia during the first year of the COVID-19 pandemic (June 2020 to June 2021). The data collection period spanned from January 20, 2021, to September 24, 2021. A total of 18 semistructured individual interviews were conducted with accredited exercise physiologists (n=7) and clients (n=11) who engaged with exercise physiology services during this period. All interviews were digitally recorded and transcribed verbatim. Thematic analysis was conducted with themes and subthemes derived using deductive and inductive approaches. RESULTS: A total of 3 dominant themes, each with 2 subthemes, were identified. The first theme was that telehealth enables access to services but limits the use of some clinical tools. Remote access to services was valued by both clinicians and clients, but the exercise clinical environment could not be replicated over telehealth. This was especially true regarding access to exercise equipment. Second, engagement and the "relational space" are limited by telehealth. Perceived challenges regarding social interactions and a sense of community were a limitation for clients, and difficulties fostering clinician-client report were noted by clinicians. Finally, technological challenges are pervasive in the telehealth delivery of exercise services. Both clinicians and clients noted that systems necessary to facilitate telehealth frequently disrupted delivery, and client-based technical issues were influenced by digital health literacy. CONCLUSIONS: Shared client and accredited exercise physiologist experiences highlight key considerations for the ongoing implementation of telehealth to facilitate the uptake and effectiveness of exercise physiology services. These findings imply that the co-design of solutions to client-perceived limitations of telehealth delivery is warranted.

Requeening queenright honey bee colonies with queen cells in honey supers.

Many Canadian beekeepers replace a subset of their honey bee queens annually. However, introducing a new queen to a honey bee colony is a management practice with a high degree of uncertainty. Despite the consensus that it is most effective to introduce queens to queenless colonies, some commercial beekeepers claim success with introducing queen cells into the honey super of queenright colonies. We tested the success rate of this practice by introducing queen cells to 100 queenright colonies in southern Alberta during a honey flow. The genotypes of the resultant offspring drones were determined using the microsatellite marker A76 to identify their laying queen mothers. Our results show that new queens successfully supersede original queens in 6% of queenright colonies, suggesting that the practice does not result in the new queen taking over leadership in most colonies. Additionally, supersedure by daughter queens is more common (13%) than new queen supersedure when introducing queen cells to queenright colonies during a honey flow. However, there could be a benefit to the practice of requeening queenright colonies with queen cells in honey supers if the colonies that accepted a new queen (whether a daughter of or unrelated to the old queen) were colonies with a failing queen.

Grief, COVID-19, and the South: Considerations and Recommendations.

PURPOSE: COVID-19 has devastated the United States (U.S.). One of the more notably impacted areas is the South. Compared to the rest of the U.S., the South is characterized by increased rurality, lowered access to healthcare, older populations, and higher religiosity, all of which might predispose its residents to more detrimental effects of COVID-19, including COVID-related fatalities. As such, this paper provides important considerations for individuals engaging in work with Southern, rural Americans dealing with COVID-related grief and loss. METHODS: A review of the literature addressing the impact of Southern legislature, rurality, cross-country factors, and faith on COVID-related grief among Southerners was conducted, with applicable considerations expressed. CONCLUSIONS: Care should be taken by providers working with rural, Southern residents to attend to tangible and intangible losses experienced as a result of COVID-19. These considerations can help inform work with rural Southerners dealing with grief during the pandemic.

Safety and efficacy of exercise training in children and adolescents with congenital heart disease: A systematic review and descriptive analysis.

BACKGROUND: While exercise training is beneficial in the prevention and management of many chronic diseases, the role of exercise training in children and adolescents with congenital heart disease is less understood. We sought to determine the safety and efficacy of exercise training in children and adolescents with congenital heart disease. METHODS: We conducted a systematic search of the following databases: PubMed, CINAHL, EMBASE, Web of Science and SportDiscus. We included randomised controlled trials that incorporated an exercise intervention compared with a non-exercising comparator group and examined safety and efficacy in children and adolescents with congenital heart disease. A descriptive analysis of the included trials was then conducted. RESULTS: A total of 9 articles from 6 trials (642 participants with varying conditions and disease severity) were included. Significant variability of study participants and outcomes were observed across the trials. No adverse events linked to the exercise interventions were stated. The articles reported numerous positive changes to clinically relevant fitness measures. Exercise capacity improved with exercise training in 3 of 4 trials in which it was measured. Cardiorespiratory fitness showed improvements in 3 of 4 trials. Neuromuscular fitness increased in 1 of 2 trials. Physiological and metabolic parameters were improved, and negative changes were not observed to several clinically important measures (e.g. muscular oxygenation, cardiac measures) in 2 of 2 trials. Physical activity increased in 1 of 3 trials. No articles reported on changes in measures of body composition. Outcomes are varied with little consensus on measurements or assessment methods. CONCLUSIONS: Exercise training appears to be safe and efficacious for improving physical fitness in children and adolescents with congenital heart disease who have been appropriately screened by their medical team. However, the certainty of the evidence for these findings is low to moderate.

The effects of exercise on the bone health of people with cancer: a systematic review and meta-analysis.

PURPOSE: To determine the pooled effect of exercise on the bone health of people diagnosed with cancer. METHODS: Four electronic databases were systematically searched. Controlled trials that assessed the effect of exercise on the bone mineral density (BMD) or content (BMC) measured by dual-energy x-ray absorptiometry or peripheral quantitative computed tomography in people who had been diagnosed with cancer were included in the study. Random-effect meta-analyses of effect size (ES) were conducted. Sub-group analyses were performed to explore the influence of intervention duration, prescription and participant characteristics. RESULTS: Of 66 full-text articles screened, 22 studies, from 21 interventions, were included (primarily breast/prostate cancer, sample range n = 36-498). When all interventions were grouped, a significant pooled ES was observed for exercise on hip (ES = 0.112, 95% CI: 0.026 to 0.198; p = 0.011) and lumbar spine BMD (ES = 0.269, 95% CI: 0.036 to 0.501; p = 0.024) compared to control. There was also an influence of sex, where females had greater improvements in hip (ES = 0.120, 95% CI: 0.017 to 0.223; p = 0.022) and spine BMD (ES = 0.415, 95% CI: 0.056 to 0.774; p = 0.23) compared to males. CONCLUSION: Overall, exercise regimens of studies included in this review appear to improve bone health at the hip and spine in people diagnosed with cancer. Sub-analyses suggest some influence of sex, where females had greater improvements in BMD compared to males. It is essential that future studies evaluate the dose-response of exercise training on bone health and create exercise protocols that better align with the laws of bone modelling to enhance osteogenic potential.

Similar zooplankton responses to low pH and calcium may impair long-term recovery from acidification.

Throughout much of the 20th century, unprecedented industrial emissions have led to widespread acidification of regions in North America and Europe and, as lake water pH dropped, aquatic ecosystems have experienced dramatic declines in biodiversity. International emission-control agreements have led to sweeping increases in lake pH, however acid-structured zooplankton communities still persist in many lakes. Concomitantly, calcium concentrations have been declining as a legacy of acidification and are approaching or have reached concentrations that could represent a barrier to the re-establishment of zooplankton communities similar to those in non-acidified or circumneutral reference lakes. To understand how declining calcium may influence the re-establishment of zooplankton in acid-damaged lakes we manipulated calcium and pH using a factorial in-lake mesocosm experiment and assessed their individual and combined effects on a regionally diverse zooplankton assemblage. We found that the impacts of low calcium on zooplankton species were similar to those of acidification and, consequently, may prevent the recovery of acid-structured communities. Abundance of the larger bodied and acid-sensitive Daphnia pulex/pulicaria increased in high pH treatments, albeit nonsignificantly yet, by the end of our experiment, only two individuals were sampled among our 10 low calcium enclosures. In contrast, small acid-tolerant cladocerans, such as Daphnia catawba, Daphnia ambigua, and eubosminids maintained significantly higher abundances in low calcium treatments relative to all other treatment combinations. Although we did not detect an effect of calcium on mean body size, the disproportionately high abundance of small cladocerans in low calcium treatments resulted in low calcium communities with higher overall abundance and lower cladoceran evenness. Our results, along with a landscape comparison demonstrating parallel changes in zooplankton relative abundance from 34 historically acidified lakes, suggests that declining calcium will be an important, on-going factor that may limit the recovery of zooplankton, despite regional improvements in lake pH.

How we approach coagulopathy with vascular anomalies.

Some vascular anomalies can present with challenging hematologic aberrations. Kaposiform hemangioendothelioma (KHE) may be complicated with Kasabach-Merritt phenomenon (KMP) and stagnant blood flow in slow-flow malformations can promote activation and consumption of coagulation factors, which results in bleeding and clotting known as localized intravascular coagulopathy (LIC). These patients can experience significant morbidity secondary to pain due to thrombosis and are at higher risk of hematologic complications during surgical procedures. No standard of care has been established to prevent or manage these complications. This review focuses on the management of coagulopathy in children and adults with vascular anomalies.