Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF).

AIM: Heart Failure with preserved Ejection Fraction (HFpEF) is characterized by diastolic dysfunction and reduced cardiac output, but its pathophysiology remains poorly understood. Animal models of HFpEF are challenging due to difficulties in assessing the degree of heart failure in small animals. This study aimed at inducing HFpEF in a mouse model to probe preload-dependency. METHODS: Increased body mass and arterial hypertension were induced in mice using a Western diet and NO synthase inhibition. Preload dependence was tested ex vivo. RESULTS: Mice with obesity and hypertension exhibited reduced cardiac output, indicating a failing heart. Increased left ventricular filling pressure during diastole suggested reduced compliance. Notably, the ejection fraction was preserved, suggesting the development of HFpEF. Spontaneous physical activity at night was reduced in HFpEF mice, indicating exercise intolerance; however, the cardiac connective tissue content was comparable between HFpEF and control mice. The HFpEF mice showed increased vulnerability to reduced preload ex vivo, indicating that elevated left ventricular filling pressure compensated for the rigid left ventricle, preventing a critical decrease in cardiac output. CONCLUSION: This animal model successfully developed mild HFpEF with a reduced pump function that was dependent on a high preload. A model of mild HFpEF may serve as a valuable tool for studying disease progression and interventions aimed at delaying or reversing symptom advancement, considering the slow development of HFpEF in patients.

Does the Menstrual Cycle Influence Aerobic Capacity in Endurance-Trained Women?

Purpose: The aim was to study if aerobic capacity varies during different phases of the menstrual cycle (MC) in endurance-trained female athletes. Methods: Ten endurance-trained eumenorrheic women performed a submaximal test followed by an incremental test until exhaustion three times during one MC, early follicular phase (EFP), late follicular phase (LFP), and midluteal phase (MLP). During the submaximal test, the respiratory exchange ratio (RER) and utilization of fat and carbohydrates were analyzed; and, during the incremental test, VO2 peak, maximal heart rate, utilization of fat and carbohydrates, and RER were analyzed. Lactate levels were analyzed at rest, during the submaximal test, and after the incremental test. The anaerobic threshold was determined at RER = 1. Results: No significant differences (p < .05) between the MC phases were seen in a maximal heart rate or VO2peak. Similarly, VO2, heart rate, RER, fatty acid oxidation, and carbohydrate oxidation at 70, 80, 90, and 100% of VO2peak did not differ significantly between MC phases. There were no significant differences between these phases in resting lactate before the test or during the submaximal tests, though there was a significant difference in lactate concentration 3 minutes after the incremental test between the EFP and the LFP (p = .043). Conclusion: This study did not display variations in physiological parameters between EFP, LFP, and MLP, indicating similar aerobic capacity despite hormonal variations. This knowledge may be useful when planning for competition in aerobic events.

Women's desires for mental health support following a pregnancy loss, termination of pregnancy for medical reasons, or abortion: A report from the STRONG Women Study.

OBJECTIVE: We report on women's mental health care desires following a miscarriage, medical termination, or abortion. METHOD: 689 women completed a questionnaire on reproductive history, health care following miscarriage/medical termination/abortion, and current mental health. Descriptive statistics and logistic regression analyses examined: miscarriage/termination/abortion incidence, desires for mental health support following miscarriages/terminations/abortions, and current mental health. RESULTS: Of 365 women with a pregnancy history, 37% reported ≥1 miscarriage, 9% ≥1 medical termination, 16% ≥1 abortion, and 3% endorsed all three. Current mental health did not differ between women with a history of miscarriage/termination/abortion and those with only live births (p = 0.82). Following miscarriage, 68% of women discussed options for the medical management of pregnancy loss with their provider, 32% discussed grief/loss, and 25% received mental health care recommendations. Engagement in mental health services was reported by 16% of women with a history of miscarriage, 38% after medical termination, and 19% following an abortion. Of women who became pregnant after their most recent miscarriage/termination/abortion and did not receive mental health care, 55% wished they had received services during the subsequent pregnancy. CONCLUSIONS: Women desire mental health care after miscarriages, medical terminations, or abortions, warranting improved access to mental health care for these individuals.

Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice.

Tail bleeding models are important tools in hemophilia research, specifically for the assessment of procoagulant effects. The tail vein transection (TVT) survival model has been preferred in many settings due to sensitivity to clinically relevant doses of FVIII, whereas other established models, such as the tail clip model, require higher levels of procoagulant compounds. To avoid using survival as an endpoint, we developed a TVT model establishing blood loss and bleeding time as endpoints and full anesthesia during the entire experiment. Briefly, anesthetized mice are positioned with the tail submerged in temperate saline (37°C) and dosed with the test compound in the right lateral tail vein. After 5 min, the left lateral tail vein is transected using a template guide, the tail is returned to the saline, and all bleeding episodes are monitored and recorded for 40 min while collecting the blood. If no bleeding occurs at 10 min, 20 min, or 30 min post-injury, the clot is challenged gently by wiping the cut twice with a wet gauze swab. After 40 min, blood loss is quantified by the amount of hemoglobin bled into the saline. This fast and relatively simple procedure results in consistent and reproducible bleeds. Compared to the TVT survival model, it uses a more humane procedure without compromising sensitivity to pharmacological intervention. Furthermore, it is possible to use both genders, reducing the total number of animals that need to be bred, in adherence with the principles of 3R's. A potential limitation in bleeding models is the stochastic nature of hemostasis, which can reduce the reproducibility of the model. To counter this, manual clot disruption ensures that the clot is challenged during monitoring, preventing primary (platelet) hemostasis from stopping bleeding. This addition to the catalog of bleeding injury models provides an option to characterize procoagulant effects in a standardized and humane manner.

Development and Testing of an Instrument for Summative Assessment of Practical Skill Performance: A Generalizability Theory Approach.

BACKGROUND AND PURPOSE: Many newly graduated nurses lack proficiency in practical skill performance. Presently, nursing students' practical skill is assessed by summative instruments with overarching items. The purpose of this study was to develop a more detailed instrument to use in summative assessment of nursing students' practical skill performance and to assess its psychometric properties. METHODS: A 50-item instrument was developed. Video-recorded performances were rated by experienced clinical supervisors. A multifacet measurement design was developed. Relevant parameters were estimated by generalizability analysis. RESULTS: Findings indicated that error of measurement were mainly caused by raters far more than by items. CONCLUSIONS: The present study suggested that summative assessment in realistic settings may not apply one rater only. Two to three/four raters appear necessary to dependably measure most skills.

Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock.

AIM: Cardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte-specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted. METHODS: We implanted radio transmitters in male mice with cardiomyocyte-specific Bmal1 knockout (CBK) and in control mice and recorded 24-h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo. RESULTS: Both RR and QT intervals were longer in conscious CBK than control mice (RR: 117 ± 7 vs 110 ± 9 ms, P < .05; and QT: 53 ± 4 vs 48 ± 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 ± 3 vs 16 ± 2 Hz, respectively, P < .05). CONCLUSION: The bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24-h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.

The Iceland-Faroe Slope Jet: a conduit for dense water toward the Faroe Bank Channel overflow.

Dense water from the Nordic Seas passes through the Faroe Bank Channel and supplies the lower limb of the Atlantic Meridional Overturning Circulation, a critical component of the climate system. Yet, the upstream pathways of this water are not fully known. Here we present evidence of a previously unrecognised deep current following the slope from Iceland toward the Faroe Bank Channel using high-resolution, synoptic shipboard observations and long-term measurements north of the Faroe Islands. The bulk of the volume transport of the current, named the Iceland-Faroe Slope Jet (IFSJ), is relatively uniform in hydrographic properties, very similar to the North Icelandic Jet flowing westward along the slope north of Iceland toward Denmark Strait. This suggests a common source for the two major overflows across the Greenland-Scotland Ridge. The IFSJ can account for approximately half of the total overflow transport through the Faroe Bank Channel, thus constituting a significant component of the overturning circulation in the Nordic Seas.

Discovery of an unrecognized pathway carrying overflow waters toward the Faroe Bank Channel.

The dense overflow waters of the Nordic Seas are an integral link and important diagnostic for the stability of the Atlantic Meridional Overturning Circulation (AMOC). The pathways feeding the overflow remain, however, poorly resolved. Here we use multiple observational platforms and an eddy-resolving ocean model to identify an unrecognized deep flow toward the Faroe Bank Channel. We demonstrate that anticyclonic wind forcing in the Nordic Seas via its regulation of the basin circulation plays a key role in activating an unrecognized overflow path from the Norwegian slope - at which times the overflow is anomalously strong. We further establish that, regardless of upstream pathways, the overflows are mostly carried by a deep jet banked against the eastern slope of the Faroe-Shetland Channel, contrary to previous thinking. This deep flow is thus the primary conduit of overflow water feeding the lower branch of the AMOC via the Faroe Bank Channel.

Improving Clinical Nurses' Development of Supervision Skills through an Action Learning Approach.

The aim of this study was to investigate action learning as an implementation method in a large-scale project with many participants in several autonomous and geographically spread groups. The focus of the implementation was the Model of Practical Skill Performance as a learning and supervision tool in the clinical education of nursing students. Nineteen action learning groups were established, and a total of 129 clinical supervisors and 13 facilitators were involved. To evaluate the implementation process, qualitative data were generated through three focus group interviews, questionnaires, and notes. Data illuminate clinical supervisors' perceptions of value, impact, and sustainability when they participate in an action learning group to become familiar with the Model of Practical Skill Performance. The deductive data analysis was guided by central concepts from action learning. Action learning proved to be an engaging and effective tool in the implementation where the main strength seemed to be the autonomous local group supporting collective reflections on actions. Clinical supervisors had the right competences to adopt a reflective process-oriented approach, which is the hallmark of action learning. This study shows the necessity of collaboration between stakeholders in practice, education, and management to implement large-scale projects in clinical practice. The findings imply that managers should choose participants on the basis of their motivation and their voluntary wish to participate and that nurses' immersion in the project over time aids implementation.

Ocean circulation causes the largest freshening event for 120 years in eastern subpolar North Atlantic.

The Atlantic Ocean overturning circulation is important to the climate system because it carries heat and carbon northward, and from the surface to the deep ocean. The high salinity of the subpolar North Atlantic is a prerequisite for overturning circulation, and strong freshening could herald a slowdown. We show that the eastern subpolar North Atlantic underwent extreme freshening during 2012 to 2016, with a magnitude never seen before in 120 years of measurements. The cause was unusual winter wind patterns driving major changes in ocean circulation, including slowing of the North Atlantic Current and diversion of Arctic freshwater from the western boundary into the eastern basins. We find that wind-driven routing of Arctic-origin freshwater intimately links conditions on the North West Atlantic shelf and slope region with the eastern subpolar basins. This reveals the importance of atmospheric forcing of intra-basin circulation in determining the salinity of the subpolar North Atlantic.

Cardiovascular disease and long-term occupational exposure to ultrafine particles: A cohort study of airport workers.

AIM: To investigate if ischemic heart disease (IHD) and cerebrovascular disease is associated with long-term occupational exposure to ultrafine particles (UFP) outdoors at an airport. METHODS AND RESULTS: This is a register-based follow-up study based on a cohort comprising an exposed group of 6515 men employed in unskilled work at Copenhagen Airport and a reference group of 61,617 men in unskilled work in other firms in greater Copenhagen during 1990-2012. The exposure was assessed from information on proportion of time spent on the airport apron for each calendar year (apron-years) and the primary exposure measure was cumulated apron-years. The cohort was merged to the National Patient Register that includes data on all contacts to public and private hospitals in Denmark and the Register of Causes of Death. Risk estimates were provided by Poisson regression and adjusted for age, calendar year and educational level. We found no associations between cumulative apron-years and IHD (IRR, 1.00; 95%CI, 0.97-1.03) or cerebrovascular disease (IRR, 1.00; 0.98-1.02) when adjusted for confounders. CONCLUSION: In this large cohort study, we found no association between outdoor occupational exposure to UFP and IHD and cerebrovascular disease.

Occupational lifting predicts hospital admission due to low back pain in a cohort of airport baggage handlers.

PURPOSE: To examine if occupational lifting assessed as cumulative years as a baggage handler is associated with first-time hospital diagnosis or treatment for low back disorders. METHODS: This study is based on the Copenhagen Airport Cohort consisting of male baggage handlers performing heavy lifting every day and a reference group of unskilled men from the greater Copenhagen area during the period 1990-2012. We followed the cohort in the National Patient Register and Civil Registration System to obtain information on diagnoses, surgery, mortality, and migration. The outcomes were first-time hospital diagnosis or surgery for (1) lumbar disc herniation or (2) low back pain (LBP). RESULTS: Baggage handlers (N = 3473) had a higher incidence rate of LBP, but not of lumbar disc herniation, compared to the reference group (N = 65,702). Baggage handlers with longer employment had a higher incidence of LBP compared to baggage handlers with shorter employment. The linear association of cumulative years as a baggage handler on LBP was significantly increased with an incidence rate ratio of 1.16 (95% CI 1.07-1.25) for a 5-year increase of employment as baggage handler. CONCLUSIONS: In this large cohort study, we found an increased incidence of LBP among baggage handlers compared to the reference group with indications of a dose-response relationship between years of employment and the outcome. For baggage handlers working on the apron, the incidence was particularly increased before introduction of technical lifting equipment, suggesting that preventive measures to reduce cumulative work load may have a positive effect.

Psychoactive substances in natural and unnatural deaths in Norway and Sweden - a study on victims of suicide and accidents compared with natural deaths in psychiatric patients.

BACKGROUND: The extent of post-mortem detection of specific psychoactive drugs may differ between countries, and may greatly influence the national death register's classification of manner and cause of death. The main objective of the present study was to analyse the magnitude and pattern of post-mortem detection of various psychoactive substances by the manner of death (suicide, accidental, undetermined and natural death with a psychiatric diagnosis) in Norway and Sweden. METHODS: The Cause of Death Registers in Norway and Sweden provided data on 600 deaths in 2008 from each country, of which 200 were registered as suicides, 200 as accidents or undetermined manner of death and 200 as natural deaths in individuals with a diagnosis of mental disorder as the underlying cause of death. We examined death certificates and forensic reports including toxicological analyses. RESULTS: The detection of psychoactive substances was commonly reported in suicides (66 and 74% in Norway and Sweden respectively), accidents (85 and 66%), undetermined manner of deaths (80% in the Swedish dataset) and in natural deaths with a psychiatric diagnosis (50 and 53%). Ethanol was the most commonly reported substance in the three manners of death, except from opioids being more common in accidental deaths in the Norwegian dataset. In cases of suicide by poisoning, benzodiazepines and z-drugs were the most common substances in both countries. Heroin or morphine was the most commonly reported substance in cases of accidental death by poisoning in the Norwegian dataset, while other opioids dominated the Swedish dataset. Anti-depressants were found in 22% of the suicide cases in the Norwegian dataset and in 29% of suicide cases in the Swedish dataset. CONCLUSIONS: Psychoactive substances were detected in 66 and 74% of suicides and in 85 and 66% of accidental deaths in the Norwegian and Swedish datasets, respectively. Apart from a higher detection rate of heroin in deaths by accident in Norway than in Sweden, the pattern of detected psychoactive substances was similar in the two countries. Assessment of a suicidal motive may be hampered by the common use of psychoactive substances in suicide victims.

Low back pain and associated disability in Swedish adolescents.

INTRODUCTION: Low back pain (LBP) defined as ache or pain in the lowest part of the back is a common experience among people all over the world. The lifetime prevalence is reported to be as high as 84%, and the prevalence of LBP seems to be almost the same among adolescents as among adults. The risk for having LBP later in life if you experienced LBP in adolescence is high. MATERIAL AND METHODS: In this cross-sectional study of 2550 students aged 16-20 years, we used the Standardized Nordic Questionnaire for the analysis of musculo-skeletal symptoms. We studied gender difference, prevalence, and disability of Low back pain. We also studied differences in LBP in adolescent athletes depending on hours spent on sports or physical activity. RESULTS: Significantly, more girls than boys had had problems sometimes during their life. Those who participated in sports reported LBP to a significantly higher extent than those who were physically inactive in their spare time. Gender and spare time sports were important risk factors for getting LBP some time in life. There was a higher risk for girls to have low back pain problems more than 30 days or daily the last year if they had had low back pain some time earlier in life. CONCLUSION: This study shows that low back pain (LBP) is common among Swedish adolescents, more common among girls than boys. High sport activity was associated with the risk of having LBP, length of time with LBP, and disability due to LBP.

National injury prevention measures in team sports should focus on knee, head, and severe upper limb injuries.

PURPOSE: To examine acute injuries in licensed floorball, football, handball, and ice hockey players in all ages nationwide in Sweden, and to identify the most common and severe injuries in each body location and recommend injury prevention measures. METHODS: Using national sport insurance data from years 2006-2015 was the incidence and proportion of acute injuries, and injuries leading to permanent medical impairment (PMI), calculated in the four team sports. The most common injury type and injured body part was identified, with a particular focus of the severe injuries. Comparison between sexes was made. RESULTS: In total, there were 92,162 registered injuries in all sports together. Knee injuries were most common, and also had the highest incidence of PMI, in all ball sports and in female ice hockey players. In male ice hockey, the most common injury was a dental and face injury, and PMI injuries were mostly in the shoulder. The most severe PMI injuries were rare and most often a face/eye injury in male floorball and ice hockey, a concussion in female ice hockey, and a knee injury in female floorball, and in both sexes in football and handball. CONCLUSIONS: To achieve the greatest impact in reducing the adverse effects of acute sport injuries nationwide in Sweden, preventive measures should focus on knee injuries in all the investigated team sports. The severe head/face and upper limb injuries also need attention. Protective equipment, neuromuscular training programs, rules enforcements, and fair-play interventions may reduce the incidence of injuries.

A Nationwide Follow-up Survey on the Effectiveness of an Implemented Neuromuscular Training Program to Reduce Acute Knee Injuries in Soccer Players.

BACKGROUND: A cruciate ligament (CL) injury is a severe injury in soccer. Neuromuscular training programs have a well-documented preventive effect, but there are few studies on the effectiveness of such a program at a national level. The Swedish Knee Control Program (KCP) was found to be effective in preventing CL injuries in youth female soccer players. The KCP was implemented nationwide in Sweden in 2010. PURPOSE: To evaluate the effectiveness of the Swedish KCP in reducing acute knee injuries in soccer players at a nationwide level. STUDY DESIGN: Descriptive epidemiology study. METHODS: All licensed soccer players in Sweden are covered by the same insurance company. Using this insurance database, around 17,500 acute knee injuries that were reported to the insurance company between 2006 and 2015 were included in the study. By matching the number of licensed soccer players with the number of reported injuries each year, the annual incidence of knee and CL injuries was able to be calculated. To evaluate the spread of the KCP nationally, a questionnaire was sent to all 24 Swedish district football associations (FAs) with questions regarding KCP education. The number of downloads of the KCP mobile application (app) was obtained. RESULTS: The incidence of CL injuries decreased during the study period for both male (from 2.9 to 2.4 per 1000 player-years) and female players (from 4.9 to 3.9 per 1000 player-years). The overall incidence of knee injuries decreased in both male (from 5.6 to 4.6 per 1000 player-years) and female players (from 8.7 to 6.4 per 1000 player-years). Comparing before and after the nationwide implementation of the KCP, there was a decrease in the incidence of CL injuries by 6% (rate ratio [RR], 0.94 [95% CI, 0.89-0.98]) in male players and 13% (RR, 0.87 [95% CI, 0.81-0.92]) in female players and a decrease in the incidence of knee injuries by 8% (RR, 0.92 [95% CI, 0.89-0.96]) and 21% (RR, 0.79 [95% CI, 0.75-0.83]), respectively (P < .01 for all). This trend corresponded to a reduction of approximately 100 CL injuries each year in Sweden. A total of 21 of 24 district FAs held organized KCP educational courses during the study period. The percentage of district FAs holding KCP courses was between 46% and 79% each year. There were 101,236 downloads of the KCP app. CONCLUSION: The KCP can be considered partially implemented nationwide, and the incidence of knee and CL injuries has decreased in both sexes at a nationwide level.