ABSTRACT
BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.
Subject(s)
Hereditary Autoinflammatory Diseases , Lymphadenitis , Pharyngitis , Registries , Stomatitis, Aphthous , Humans , Child , Europe/epidemiology , Female , Male , Stomatitis, Aphthous/diagnosis , Stomatitis, Aphthous/epidemiology , Child, Preschool , Hereditary Autoinflammatory Diseases/diagnosis , Lymphadenitis/diagnosis , Lymphadenitis/epidemiology , Pharyngitis/diagnosis , Adolescent , Infant , Retrospective Studies , Fever/etiology , Fever/diagnosis , RecurrenceABSTRACT
The plasma metabolomic profile of elite harness horses subjected to different training programmes was explored. All horses had the same training programme from 1.5 until 2 years of age and then high-intensity training was introduced, with horses divided into high and low training groups. Morning blood samples were collected at 1.5, 2, 2.5 and 3.5 years of age. The plasma was analysed using targeted absolute quantitative analysis and a combination of tandem mass spectrometry, flow-injection analysis and liquid chromatography. Differences between the two training groups were observed at 2 years of age, when 161 metabolites and sums and ratios were lower (e.g. ceramide and several triglycerides) and 51 were higher (e.g. aconitic acid, anserine, sum of PUFA cholesteryl esters and solely ketogenic AAs) in High compared with low horses. The metabolites aconitic acid, anserine, leucine, HArg synthesis and sum of solely ketogenic AAs increased over time, while beta alanine synthesis, ceramides and indole decreased. Therefore high-intensity training promoted adaptations linked to aerobic energy production and amino acid metabolism, and potentially also affected pH-buffering and vascular and insulin responses.
Subject(s)
Aconitic Acid , Anserine , Horses , Animals , Metabolomics/methods , Tandem Mass Spectrometry , LeucineABSTRACT
OBJECTIVES: To investigate the change in feelings of loneliness among Finnish community-dwelling older people from before the COVID-19 pandemic in 2019 to during the pandemic in 2021. Moreover, we explore the changes in other dimensions of psychological well-being (PWB) during the study period. DESIGN: Questionnaires were mailed in the 2019 Helsinki Aging Study, a repeated cohort study. A follow-up interview was carried on over the telephone during the year 2021. SETTING AND PARTICIPANTS: A random sample of 2,917 home-dwelling older people aged 75-104 years residing in Helsinki, Finland were mailed the questionnaire. Altogether 898 participated in the follow-up. MEASUREMENTS: Loneliness was measured using a single item question "Do you suffer from loneliness?". Other items of psychological well-being were measured: "Are you satisfied with your life?" (yes/no), "Do you feel useful?" (yes/no), "Do you have a zest for life?" (yes/no),"Do you have plans for the future?" (yes/no), and "Do you feel depressed?"("rarely or never"/ "sometimes"/ "often or always"). RESULTS: Altogether 898 people participated both in 2019 and 2021. The subjects' mean age was 83 years and 66% were women. Between 2019 and 2021, the prevalence of experienced loneliness increased among older home-dwellers from 26% to 30%. During two years of the pandemic feelings of loneliness (RR 1.79, 95% CI: 1.30 to 2.46) and depression (RR 1.37, 95% CI: 1.12 to 1.67) increased even adjusted with various confounders. CONCLUSION: Considering the impact loneliness has on health and well-being, the finding of increased feelings of loneliness among older people is alarming. Actions to combat loneliness need to be taken.
Subject(s)
COVID-19 , Loneliness , Female , Humans , Aged , Aged, 80 and over , Male , Longitudinal Studies , Finland/epidemiology , Cohort Studies , Pandemics , COVID-19/epidemiologyABSTRACT
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.
Subject(s)
Antirheumatic Agents , Osteomyelitis , Child , Adolescent , Humans , Consensus , Cytokines , Antirheumatic Agents/therapeutic use , Osteomyelitis/drug therapy , Pain/complications , Pain/drug therapy , Chronic DiseaseABSTRACT
BACKGROUND: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. AIM: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. METHODS: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. RESULTS: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children <12 yr, 6545 adolescents 12-17 yr, and 57,344 adults >17 yr) and 38,117 with COPD. Depending on age and disease group, 43-77% had performed spirometry, 36-65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. CONCLUSION: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.
ABSTRACT
BACKGROUND: Submersion time is a strong predictor for death in drowning, already 10â¯min after submersion, survival is poor. Traditional search efforts are time-consuming and demand a large number of rescuers and resources. We aim to investigate the feasibility and effectiveness of using drones combined with an online machine learning (ML) model for automated recognition of simulated drowning victims. METHODS: This feasibility study used photos taken by a drone hovering at 40â¯m altitude over an estimated 3000â¯m2 surf area with individuals simulating drowning. Photos from 2 ocean beaches in the south of Sweden were used to (a) train an online ML model (b) test the model for recognition of a drowning victim. RESULTS: The model was tested for recognition on nâ¯=â¯100 photos with one victim and nâ¯=â¯100 photos with no victims. In drone photos containing one victim (nâ¯=â¯100) the ML model sensitivity for drowning victim recognition was 91% (95%CI 84.9%-96.2%) with a median probability score that the finding was human of 66% (IQR 52-71). In photos with no victim (nâ¯=â¯100) the ML model specificity was 90% (95%CI: 83.9%-95.6%). False positives were present in 17.5% of all nâ¯=â¯200 photos but could all be ruled out manually as false objects. CONCLUSIONS: The use of a drone and a ML model was feasible and showed satisfying effectiveness in identifying a submerged static human simulating drowning in open water and favorable environmental conditions. The ML algorithm and methodology should be further optimized, again tested and validated in a real-life clinical study.
Subject(s)
Drowning , Near Drowning , Drowning/diagnosis , Feasibility Studies , Humans , Machine Learning , Sweden , WaterABSTRACT
OBJECTIVES: The aim of this study was to examine changes in the prevalence of loneliness over time from 2011 to 2017 in long-term care facilities; and its related factors. MATERIAL AND METHODS: Repeated cross-sectional studies exploring loneliness and its associated factors among residents in long-term care facilities were conducted in Helsinki, Finland in 2011 (Nâ¯=â¯4966) and 2017 (Nâ¯=â¯3767). Residents in temporary respite care or with severe cognitive impairment, and those unable or refusing to respond to the loneliness item were excluded. The total number of participants in this analysis was 1563 in 2011, and 1367 in 2017. In both samples, we used the same loneliness measurement by asking "Do you suffer from loneliness?" (never/sometimes/often or always). When comparing the samples in order to reduce the effect of confounding between them, we used propensity score matching. A multivariable logistic regression model explored the relationship between various characteristics and loneliness. RESULTS: Loneliness showed no change in prevalence over time: propensity score-adjusted loneliness was 36 % in 2011 and 2017. In the multivariate logistic regression model, feeling depressed was the only independent characteristic associated with loneliness. Of the respondents who did not feel depressed, 24 % suffered from loneliness at least sometimes. Among the respondents who felt depressed, the respective figure was 55 %. CONCLUSION: Loneliness is common in institutional settings. It remained stable, and not decreased over time. Because loneliness impairs the well-being, quality of life and health of residents, it needs to be addressed. Screening loneliness and developing interventions to alleviate it, is essential.
Subject(s)
Loneliness , Quality of Life , Cross-Sectional Studies , Finland/epidemiology , Humans , PrevalenceABSTRACT
BACKGROUND: Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. OBJECTIVES: We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. STUDY DESIGN: Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. METHODS: Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. RESULTS: COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (±s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 ± 0.38 µg/mL, and for lame horses was 5.24 ± 1.83 µg/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. MAIN LIMITATIONS: ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. CONCLUSIONS: This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.
Subject(s)
Aging , Cartilage Oligomeric Matrix Protein/metabolism , Circadian Rhythm , Horse Diseases/metabolism , Lameness, Animal , Physical Conditioning, Animal , Animals , Biomarkers , Cartilage Oligomeric Matrix Protein/blood , Cartilage Oligomeric Matrix Protein/genetics , Epitopes/genetics , Epitopes/metabolism , Female , Horse Diseases/blood , Horse Diseases/diagnosis , Horses , Longitudinal Studies , MaleABSTRACT
Novel foods could represent a sustainable alternative to traditional farming and conventional foodstuffs. Starting in 2018, Regulation (EU) 2283/2015 entered into force, laying down provisions for the approval of novel foods in Europe, including insects. This Approved Regulation establishes the requirements that enable Food Business Operators to bring new foods into the EU market, while ensuring high levels of food safety for European consumers. The present risk profile tackles the hazards for one of the most promising novel food insects, the house cricket (Acheta domesticus). The risk profile envisages a closed A. domesticus crickets rearing system, under Hazard Analysis and Critical Control Points (HACCP) and good farming practices (GFP), in contrast with open cricket farms. The methodology used involves screening the literature and identifying possible hazards, followed by adding relevant inclusion criteria for the evidence obtained. These criteria include animal health and food safety aspects, for the entire lifespan of crickets, based on the farm to fork One Health principle. When data were scarce, comparative evidence from close relatives of the Orthoptera genus was used (e.g. grasshoppers, locusts and other cricket species). Nevertheless, significant data gaps in animal health and food safety are present. Even if HACCP-type systems are implemented, the risk profile identifies the following considerable concerns: (1) high total aerobic bacterial counts; (2) survival of spore-forming bacteria following thermal processing; (3) allergenicity of insects and insect-derived products; and (4) the bioaccumulation of heavy metals (e.g. cadmium). Other hazards like parasites, fungi, viruses, prions, antimicrobial resistance and toxins are ranked as low risk. For some hazards, a need for additional evidence is highlighted.
ABSTRACT
This study examined feed intake, growth, body condition, muscle glycogen content and nutrition-related health in 16 Standardbred horses fed a high-energy, forage-only diet ad libitum and allocated to either a control training programme (C-group) or a training programme with the high-intensity training distance reduced by 30% (R-group), from January as 2-year olds until December as 3-year olds. Feed intake was recorded on 10 occasions during 3 consecutive days. Body weight was recorded once in a week and height, body condition score (BCS), rump fat thickness and thickness of the m. longissimus dorsi were measured at 7±3-week intervals throughout the study. Muscle biopsies of the m. gluteus medius were taken in December as 2-year olds and in November as 3-year olds and analysed for glycogen content. Nutrition-related health disorders were noted when they occurred. Horses consumed 1.7% to 2.6% dry matter of BW, corresponding to 19 to 28 MJ metabolisable energy/100 kg BW. There were no differences between training groups in feed intake or any of the body measurements. The pooled weekly BCS was maintained between 4.8 and 5.1 (root mean square error (RMSE)=0.4). Muscle glycogen content was 587 and 623 mmol/kg dry weight (RMSE=68) as 2- and 3-year olds, respectively, and there was no difference between training groups. When managed under normal conditions, no nutrition-related health disorders or stereotypic behaviours were observed. It was concluded that the training programme did not affect feed intake, growth, BCS or muscle glycogen content. In addition, the forage-only diet did not appear to prohibit muscle glycogen storage, growth or maintenance of body condition, and seemed to promote good nutrition-related health.
Subject(s)
Eating , Glycogen/metabolism , Horses/physiology , Physical Conditioning, Animal , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Horses/growth & development , Male , Muscle, Skeletal/metabolism , PoaceaeABSTRACT
This study examined the effect of increasing BW ratio (BWR) between rider and horse, in the BWR range common for Icelandic horses (20% to 35%), on heart rate (HR), plasma lactate concentration (Lac), BWR at Lac 4 mmol/l (W4), breathing frequency (BF), rectal temperature (RT) and hematocrit (Hct) in Icelandic horses. In total, eight experienced school-horses were used in an incremental exercise test performed outdoors on an oval riding track and one rider rode all horses. The exercise test consisted of five phases (each 642 m) in tölt, a four-beat symmetrical gait, at a speed of 5.4±0.1 m/s (mean±SD), where BWR between rider (including saddle) and horse started at 20% (BWR20), was increased to 25% (BWR25), 30% (BWR30), and 35% (BWR35) and finally decreased to 20% (BWR20b). Between phases, the horses were stopped (~5.5 min) to add lead weights to specially adjusted saddle bags and a vest on the rider. Heart rate was measured during warm-up, the exercise test and after 5, 15 and 30 min of recovery and blood samples were taken and BF recorded at rest, and at end of each of these aforementioned occasions. Rectal temperature was measured at rest, at end of the exercise test and after a 30-min recovery period. Body size and body condition score (BCS) were registered and a clinical examination performed on the day before the test and for 2 days after. Heart rate and BF increased linearly (P0.05), but negative correlations (P<0.05) existed between body size measurements and Hct. While HR, Hct and BF recovered to values at rest within 30 min, Lac and RT did not. All horses had no clinical remarks on palpation and at walk 1 and 2 days after the test. In conclusion, increasing BWR from 20% to 35% resulted in increased HR, Lac, RT and BF responses in the test group of experienced adult Icelandic riding horses. The horses mainly worked aerobically until BWR reached 22.7%, but considerable individual differences (17.0% to 27.5%) existed that were not linked to horse size, but to back BCS.
Subject(s)
Gait/physiology , Heart Rate/physiology , Horses/physiology , Animals , Body Weight/physiology , Exercise Test/veterinary , Female , Hematocrit/veterinary , Iceland , Lactic Acid/blood , Male , Physical Conditioning, Animal/physiology , Respiration , Weight-Bearing/physiologyABSTRACT
This study investigated the effects of rider weight in the BW ratio (BWR) range common for Icelandic horses (20% to 35%), on stride parameters in tölt in Icelandic horses. The kinematics of eight experienced Icelandic school horses were measured during an incremental exercise test using a high-speed camera (300 frames/s). Each horse performed five phases (642 m each) in tölt at a BWR between rider (including saddle) and horse starting at 20% (BWR20) and increasing to 25% (BWR25), 30% (BWR30), 35% (BWR35) and finally 20% (BWR20b) was repeated. One professional rider rode all horses and weight (lead) was added to saddle and rider as needed. For each phase, eight strides at speed of 5.5 m/s were analyzed for stride duration, stride frequency, stride length, duty factor (DF), lateral advanced placement, lateral advanced liftoff, unipedal support (UPS), bipedal support (BPS) and height of front leg action. Stride length became shorter (Y=2.73-0.004x; P0.05). In conclusion, increased BWR decreased stride length and increased DF proportionally to the same extent in all limbs, whereas BPS increased at the expense of decreased UPS. These changes can be expected to decrease tölt quality when subjectively evaluated according to the breeding goals for the Icelandic horse. However, beat, symmetry and height of front leg lifting were not affected by BWR.
Subject(s)
Gait/physiology , Horses/physiology , Animals , Biomechanical Phenomena , Body Weight/physiology , Breeding , Exercise Test/veterinary , Extremities , Female , Forelimb , Iceland , Male , Weight-Bearing/physiologyABSTRACT
BACKGROUND: Drowning leading to out-of-hospital cardiac arrest (OHCA) and death is a major public health concern. Submersion with duration of less than 10min is associated with favorable neurological outcome and nearby bystanders play a considerable role in rescue and resuscitation. Drones can provide a visual overview of an accident scene, their potential as lifesaving tools in drowning has not been evaluated. AIM: The aim of this simulation study was to evaluate the efficiency of a drone for providing earlier location of a submerged possible drowning victim in comparison with standard procedure. METHOD: This randomized simulation study used a submerged manikin placed in a shallow (<2m) 100×100-m area at Tylösand beach, Sweden. A search party of 14 surf-lifeguards (control) was compared to a drone transmitting video to a tablet (intervention). Time from start to contact with the manikin was the primary endpoint. RESULTS: Twenty searches were performed in total, 10 for each group. The median time from start to contact with the manikin was 4:34min (IQR 2:56-7:48) for the search party (control) and 0:47min (IQR 0:38-0:58) for the drone-system (intervention) respectively (p<0.001). The median time saved by using the drone was 3:38min (IQR 2:02-6:38). CONCLUSION: A drone transmitting live video to a tablet is feasible, time saving in comparison to traditional search parties and may be used for providing earlier location of submerged victims at a beach. Drone search can possibly contribute to earlier onset of CPR in drowning victims.
Subject(s)
Aircraft , Drowning , Emergency Medical Services/methods , Geographic Information Systems/instrumentation , Out-of-Hospital Cardiac Arrest/therapy , Time Factors , Cardiopulmonary Resuscitation , Computer Simulation , Humans , Manikins , Mobile Applications , Out-of-Hospital Cardiac Arrest/etiology , Prospective Studies , Random AllocationABSTRACT
The horse is a non-ruminant herbivore adapted to eating plant-fibre or forage-based diets. Some horses are stabled for most or the majority of the day with limited or no access to fresh pasture and are fed preserved forage typically as hay or haylage and sometimes silage. This raises questions with respect to the quality and suitability of these preserved forages (considering production, nutritional content, digestibility as well as hygiene) and required quantities. Especially for performance horses, forage is often replaced with energy dense feedstuffs which can result in a reduction in the proportion of the diet that is forage based. This may adversely affect the health, welfare, behaviour and even performance of the horse. In the past 20 years a large body of research work has contributed to a better and deeper understanding of equine forage needs and the physiological and behavioural consequences if these are not met. Recent nutrient requirement systems have incorporated some, but not all, of this new knowledge into their recommendations. This review paper amalgamates recommendations based on the latest understanding in forage feeding for horses, defining forage types and preservation methods, hygienic quality, feed intake behaviour, typical nutrient composition, digestion and digestibility as well as health and performance implications. Based on this, consensual applied recommendations for feeding preserved forages are provided.
Subject(s)
Animal Feed , Eating , Horses/physiology , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Digestion , Female , SilageABSTRACT
OBJECTIVES: To correlate clinical findings of Non-bacterial Osteitis (NBO) with whole-body MRI (WB-MRI) findings and determine a radiologic index for NBO (RINBO) which allows standardized reporting of WB-MRI. METHODS AND MATERIALS: In a prospective study, 40 patients with diagnosis of NBO underwent clinical examination and WB-MRI in which STIR- and T1- weighted images were assessed for NBO-typical lesions. Parameters of interest for RINBO were: number of radiologically active lesions (RAL), size of the patients' maximum RAL presence of extramedullary and spinal involvement. Results were tested for statistical agreement of clinical and MR-based lesion detection. RINBO was tested for correlation with clinical activity. RESULTS: 62/95 clinically/radiologically active lesions were found in 30/33 patients. In 45 % of the cohort, more active lesions were detected by WB-MRI than by clinical examination. RINBO was a significant predictor for the presence of clinically active lesions. CONCLUSION: WB-MRI is a powerful diagnostic tool for patients with NBO which can reveal asymptomatic disease activity. With RINBO a standardized evaluation approach is proposed which helps assessing radiologic disease burden and predicts clinical disease activity. KEY POINTS: ⢠Whole body MRI is a powerful diagnostic tool for patients with non-bacterial Osteitis. ⢠Whole body MRI can reveal asymptomatic disease activity. ⢠The radiologic index RINBO offers a standardized evaluation approach.
Subject(s)
Osteitis/pathology , Adolescent , Adult , Biomarkers/metabolism , Child , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Physical Examination/methods , Prospective Studies , Whole Body Imaging/methods , Young AdultABSTRACT
HOXA9, MEIS1 and FLT3 are genes frequently upregulated in human acute myeloid leukemia. Hoxa9 and Meis1 also cooperate to induce aggressive AML with high Flt3 expression in mice, suggesting an important role for Flt3 in Hoxa9/Meis1-induced leukemogenesis. To define the role of Flt3 in AML with high Hoxa9/Meis1, we treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL-/-) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9. Flt3 inhibition by AC220 did not delay AML development in mice transplanted with bone marrow cells overexpressing Hoxa9 and Meis1. In addition, Hoxa9/Meis1 cells induced AML in FL-/- mice as rapid as in wild-type mice. However, FL-/- mice had reduced organ infiltration compared with wild-type mice, suggesting some Flt3-dependent effect on leukemic invasiveness. Interestingly, leukemic Hoxa9/Meis1 cells from sick mice expressed high levels of Flt3 regardless of presence of its ligand, showing that Flt3 is a passive marker on these cells. In line with this, combined engineered overexpression of Flt3 and Hoxa9 did not accelerate the progression to AML. We conclude that the Hoxa9- and Meis1-associated upregulation of Flt3 is not a requirement for leukemic progression induced by Hoxa9 and Meis1.
Subject(s)
Homeodomain Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Neoplasm Proteins/genetics , fms-Like Tyrosine Kinase 3/genetics , Animals , Benzothiazoles/pharmacology , Biomarkers , Cell Proliferation/drug effects , Cell Proliferation/genetics , Disease Models, Animal , Gene Expression , Gene Expression Regulation, Leukemic , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/mortality , Mice , Mice, Knockout , Myeloid Ecotropic Viral Integration Site 1 Protein , Phenylurea Compounds/pharmacology , Prognosis , Signal Transduction/drug effects , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , fms-Like Tyrosine Kinase 3/metabolismABSTRACT
This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50:50 forage:oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT ( = 0.008, = 0.020, = 0.010, and = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT ( = 0.034) and greater for the FONLY than for the FOATS ( = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS ( = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS ( = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should preferably be included in the experimental design, because horses are likely to be transported before a competition.
Subject(s)
Diet/veterinary , Horses/metabolism , Physical Conditioning, Animal , Transportation , Animals , Avena , Drinking , Exercise Test/veterinary , Fatty Acids, Nonesterified/blood , Female , Heart Rate , Hydrocortisone/blood , Lactic Acid/bloodABSTRACT
The aim of this study was to document effects of two high-intensity training regimes on horse health. Sixteen Standardbred horses in training from September as 1-year-olds with the goal to race as 3-year-olds were used in a 2.5 year study. Horses were trained in either a control training program (C-group) or in a program with 30% reduced high intensity distance compared to the C-group (R-group). Clinical examinations were performed nine times. Locomotion asymmetry was registered with a sensor-based system 17 times. There was no difference in health scores, locomotion asymmetry or veterinary treatments between groups. Subjective lameness score and objective front limb locomotion asymmetry increased during the spring both as 2- and 3-year-olds after introduction of speed- and uphill interval training but decreased during winter. Hind limb locomotion asymmetry increased during spring as 2-year-olds and was still above initial level in December as 3-year-olds. Horses that qualified for races early had less asymmetric front limb locomotion and were less lame in clinical examinations (0.7 ± 0.3 vs. 1.6 ± 0.2 degrees [AAEP scale], P = 0.04) than late qualifiers. Days lost to training were higher in C-group than in R-group (27 ± 3% and 17 ± 3%, P = 0.029). It is concluded that (1) less days may be lost to training by reducing the high intensity training distance and (2) the introduction of new training may alter locomotion asymmetry and this can be detected with objective locomotion analysis.