Differential regulation of the Drosophila sleep homeostat by circadian and arousal inputs.

One output arm of the sleep homeostat in Drosophila appears to be a group of neurons with projections to the dorsal fan-shaped body (dFB neurons) of the central complex in the brain. However, neurons that regulate the sleep homeostat remain poorly understood. Using neurogenetic approaches combined with Ca2+ imaging, we characterized synaptic connections between dFB neurons and distinct sets of upstream sleep-regulatory neurons. One group of the sleep-promoting upstream neurons is a set of circadian pacemaker neurons that activates dFB neurons via direct glutaminergic excitatory synaptic connections. Opposing this population, a group of arousal-promoting neurons downregulates dFB axonal output with dopamine. Co-activating these two inputs leads to frequent shifts between sleep and wake states. We also show that dFB neurons release the neurotransmitter GABA and inhibit octopaminergic arousal neurons. We propose that dFB neurons integrate synaptic inputs from distinct sets of upstream sleep-promoting circadian clock neurons, and arousal neurons

Thermoregulation in exercising horses: Aspects of temperature monitoring during field exercise

Joint Degree Program between the School of Animal and Veterinary Science, University of Adelaide, and Faculty of Veterinary Medicine, Ghent University, BelgiumHyperthermia is an ongoing welfare and performance issue for all horses exercising in racing and other competitive sport events. At present, little is known about the influence of core body temperature evolvement on hyperthermia in real time during different types of exercise performed in field conditions such as racing and endurance events. Consequently, it is becoming increasingly important to establish appropriate policies regarding the detection and prevention of all types of heat stress. To achieve this, a detailed view of the variability of equine thermoregulation during field exercise and recovery is essential. To date, the vast majority of thermoregulatory studies have been conducted in indoor laboratory conditions using a treadmill and subjecting horses to specific standardized exercise tests. However, this approach cannot successfully reflect real-time field conditions. Hence, there is a need to accurately and reliably monitor equine core body temperature responses to avoid potential harm due to increasing heat load. Chapter 1 provides a review of current research into thermoregulation, hyperthermia and exertional heat illness (EHI) in exercising horses. In addition, several temperature monitoring methods in horses are described along with some relevant methods in human athletes. However, no studies have investigated the promising continuous monitoring method involving a telemetric gastrointestinal pill (GI) that can be applied in the field in all conditions. Chapter 2 outlines the scientific aims of the thesis. Chapter 3 describes a study designed to evaluate the efficacy of continuous monitoring of core body temperature using the novel telemetric GI pill during real-time field exercise for the first time. The results showed that the continuous recording of the GI core temperature in exercising horses in the field using the GI pill was non-invasive, practical and accurate. Temperature fluctuations experienced during exercise and recovery are reliably recorded, and tendencies toward EHI will be easily observed during field exercise. Importantly, the GI pill has proven to be a more accurate and precise tool to monitor core thermal response when compared with serial Tre measurements in the field. Summary 194 Chapter 4 describes the application of this novel thermoregulation monitoring method in detail. The study involved measurements conducted in both endurance horses and trotters in order to compare exercise types in real-life competitions in the field. Not only were the core body temperatures (Tc) continuously monitored during exercise and recovery, the thermoregulatory responses to the different exercise intensities were also compared. The findings of this study reported real-time temperature evolvement during real-time competition in the field. More specifically, endurance horses reached peak temperature at 75% of completion of 40 km of exercise. However, trotters reached peak temperature always during recovery. In addition, the Tc in endurance horses returned to baseline within 60 minutes into recovery while in 30% of trotters, Tc was still higher than 39°C at the end of recovery. Since endurance horses are considered as ‘fit to continue’ competition when the heartrate (HR) is 60 beats per minute or below, the finding that the mean Tc was still 38.8 ± 0.4°C at a HR of 60 bpm is of importance. Overall, the study showed that horses have very individual thermoregulatory responses which require highly accurate monitoring no matter what type of exercise is performed in the field. Chapter 5 investigated the usefulness of monitoring skin temperature in endurance horses. A large array of skin temperature methodologies recently used in the field is reviewed, mainly pre- and post-exercise at time points, In this study, to evaluate if skin temperature could be used as a proxy for core temperature, the skin temperature was continuously monitored and evaluated using an infrared monitor during a real-life endurance competition. The skin temperature was compared to the GI temperature and importantly, there was no correlation between skin and GI temperature.Thesis (Ph.D.) -- University of Adelaide, School of Animal and Veterinary Sciences, 202

Diagnostics and treatment options in low-grade central chondrosarcomas

  The first part of my thesis concerns a multicenter study in nine different European countries of patients with one of the rare diseases Ollier disease or Maffucci syndrome. We collected clinical data to look to factors that predict prognosis and chance to develop secondary chondrosarcoma. In the second part of this thesis describes different aspects in the intralesional treatment of low-grade chondrosarcoma of long bones. In our series, we used phenol as an adjuvant therapy. First, the cell-killing effect of phenol was investigated. Also, clinical parts of the surgery were studied. We described a patients series of patients treated this way. Also, we looked to the postoperative characteristics on Gd-MRI.  Anna Fonds Noref; Nederlandse Orthopaedische VerenigingLUMC / Geneeskund

Homogeneity analysis with k sets of variables: An alternating least squares method with optimal scaling features

Homogeneity analysis, or multiple correspondence analysis, is usually applied to k separate variables. In this paper, it is applied to sets of variables by using sums within sets. The resulting technique is referred to as OVERALS. It uses the notion of optimal scaling, with transformations that can be multiple or single. The single transformations consist of three types: (1) nominal; (2) ordinal; and (3) numerical. The corresponding OVERALS computer program minimizes a least squares loss function by using an alternating least squares algorithm. Many existing linear and non-linear multivariate analysis techniques are shown to be special cases of OVERALS. Disadvantages of the OVERALS method include the possibility of local minima in some complicated special cases, a lack of information on the stability of results, and its inability to handle incomplete data matrices. Means of dealing with some of these problems are suggested (i.e., an alternating least squares algorithm to solve the minimization problem). An application of the method to data from an epidemiological survey is provided

Atypical cases of equine Glanders could form a risk for re-emerging Glanders disease worldwide

E.J.M.M. Verdegaal, L.A.A.M. van Oije

Preliminary evaluation of the veterinary EPOC® point-of-care (POC) clinical analyser in horses by comparison with in-house analysis and establishment of reference values

Abstract onlyAveray K, Nicholson A, Verdegaal EJM

Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

Recovery and the use of postoperative physical therapy after total hip or knee replacement

BACKGROUND: Total hip or knee arthroplasties (THA/TKA) show favorable long-term effects, yet the recovery process may take weeks to months. Physical therapy (PT) following discharge from hospital is an effective intervention to enhance this recovery process. To investigate the relation between recovery and postoperative PT usage, including the presence of comorbidities, 6 months after THA/TKA. METHODS: Multicenter, observational study in primary THA/TKA patients who completed preoperative and 6 months postoperative assessments. The assessments included questions on PT use (yes/no and duration; long term use defined as ≥ 12 weeks), comorbidities (musculoskeletal, non-musculoskeletal, sensory comorbidities and frequency of comorbidities). Recovery was assessed with the HOOS/KOOS on all 5 subdomains. Logistic regression with long term PT as outcome was performed adjusted for confounding including an interaction term (comorbidity*HOOS/KOOS-subdomain). RESULTS: In total, 1289 THA and 1333 TKA patients were included, of whom 95% received postoperative PT, 56% and 67% received postoperative PT ≥ 12 weeks respectively. In both THA and TKA group, less improvement on all HOOS/KOOS domain scores was associated with ≥ 12 weeks of postoperative PT (range Odds Ratios 0.97–0.99). In the THA group the impact of recovery was smaller in patient with comorbidities as non- musculoskeletal comorbidities modified all associations between recovery and postoperative PT duration (Odds Ratios range 1.01–1.05). Musculoskeletal comorbidities modified the associations between Function-in-Daily-Living-and Sport-and-recreation recovery and postoperative PT. Sensory comorbidities only had an effect on Sport-and-recreation recovery and postoperative PT. Also the frequency of comorbidities modified the relation between Function-in-Daily-Living, pain and symptoms recovery and postoperative PT. In the TKA group comorbidity did not modify the associations. CONCLUSION: Worse recovery was associated with longer duration of postoperative PT suggesting that PT provision is in line with patients’ needs. The impact of physical recovery on the use of long-term postoperative PT was smaller in THA patients with comorbidities. TRIAL REGISTRATION: Registered in the Dutch Trial Registry on March 13, 2012. TRIAL ID NTR3348; registration number: P12.047. https://www.trialregister.nl/trial/3197. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05429-z