Abstract The use of regulatory and obligatory heat production mechanisms were studied in juvenile birds during the development of endothermy. The development of shivering thermogenesis was studied in the pectoral and gastrocnemius muscles of the altricial domestic pigeon and in three precocial galliforms (Japanese quail, grey partridge and domestic fowl). The development of shivering was the determinant for the beginning of endothermy. Homeothermy also necessitated avoidance of excess heat loss by insulation and behavioural thermoregulation. In the precocial species, shivering thermogenesis was present in the leg muscles of the youngest age groups (1-2 d) studied. Breast muscles contributed shivering from the second post-hatching week. In the altricial pigeons, significant thermogenesis was apparent later than in the precocials, at the age of 6 d. In contrast to the precocials, the pectoral muscles of the altricials were the most significant heat production tissues. In newly-hatched partridges and pigeons, incipient shivering did not result in significant heat production. The ability to produce heat in cold by putative nonshivering thermogenesis was studied in Japanese quail chicks and domestic ducklings. In both species, three-week cold acclimation resulted in morphometric and physiological changes, but there was no clear evidence of nonshivering thermogenesis. The lack of NST was evident because an increase in shivering amplitude at least in one of the muscles studied paralleled an increase in oxygen consumption. Consequently, shivering thermogenesis was probably the only mode of regulatory heat production. The amplitudes of shivering EMGs measured during cold exposure were dependent on the coexistence of postprandial thermogenesis or exercise. Japanese quail chicks were able to substitute shivering thermogenesis partially with postprandial heat production when nourished. Bipedal exercise both inhibited shivering in pectorals directly via inhibitory neural circuits and stimulated it indirectly via decreased body temperature. Because of increased heat loss, exercise was not used as a substitute for shivering. Shivering is a flexible mode of thermogenesis and its magnitude can be adjusted according to the magnitude of obligatory thermogenesis. The adjustment works towards energy saving by avoidance of the summation of different modes of heat production. The prerequisite for successful adjustment of shivering is adequate insulation, whose role in preventing excessive heat loss is pronounced during exercise. It is concluded that the energetics of posthatching thermoregulation includes the potential for optimizations in energy use in order to avoid dissipation of waste energy as heat.

No description available.

Abstract In homeothermic birds and mammals, several thermoregulatory adaptations have evolved for surviving in unstable, food-restricted conditions. This study focuses on two adaptive mechanisms in pigeons (Columba livia) and quails (Coturnix coturnix japonica): hypothermia and the adaptive use obligatory heat production connected with feeding and digestion. The plasticity of the hypothermic response in fed and fasted birds and birds with restricted feeding was studied in laboratory and outdoor winter conditions. The other objective was to study adaptive timing of digestion, and substitution of facultative thermogenesis by obligatory heat production in cold and at thermoneutrality. The results showed that fasting has a strong influence on the level of nocturnal hypothermia in laboratory conditions: hypothermia becomes progressively deeper when fasting continues. In outdoor conditions, ambient temperature and predation risk modulated the daily body temperature (Tb) pattern of fasting pigeons. In very cold conditions, diurnal Tb of fasted birds also dropped below the normal level of the active phase. Predation risk prevented diurnal hypothermia but also attenuated the depth of nocturnal hypothermia in fasting pigeons. This study provides the first empirical effects of predation risk on hypothermia in starving birds. The study suggests that the presence of crop in pigeons allows adaptive timing of digestion. At thermoneutrality, peak digestion appeared late in the dark phase in birds with fed in the morning. Because the Tb of the birds increases to diurnal levels late in the dark phase, this obligatory heat from digestion can be used to aid re-warming by such timing. On other hand, the results of this study were partly opposite to the classical model of thermoregulatory substitution. In line with the classical model, a postprandial increase in metabolic rate (heat increment of feeding, HIF) was seen at thermoneutrality but not in cold. However, electromyographic measurements showed that there was no postprandial decrease in the intensity of shivering in the fed birds in cold. This indicates that true thermoregulatory substitution may be less common than assumed and suggests a role for facultative thermogenesis in HIF.

No description available.

Brown (BAT) and white (WAT) adipose tissues are significant contributors to whole-body energy homeostasis. A disturbance in their metabolic function could result in the development of obesity and subsequent metabolic complications. The energy-sensing enzyme of the cell, AMP-activated protein kinase (AMPK), has been vastly studied in skeletal muscle and liver, but its role in BAT and WAT metabolism is elusive. We generated an inducible, adipocyte-specific knockout mouse model for the two AMPK β subunits (iβ1β2AKO) and found that iβ1β2AKO mice were intolerant to cold, and resistant to β3-adrenergic activation of BAT and browning of WAT. These defects in BAT activity were not due to the AMPK-ACC axis, but instead were due to compromised integrity of mitochondria. Mitochondrial morphology, function, and autophagy were all distorted in iβ1β2AKO mice, measured via transmission electron microscopy (TEM), respiration, and immunoblotting, respectively. These findings provide strong evidence that adipocyte AMPK regulates a fine-tuned program that responds to environmental and pharmacological inputs by maintaining mitochondrial integrity through autophagy and subsequent mitochondrial biogenesis in chronic settings. / Thesis / Master of Science (MSc) / Traditionally, there are two types of adipose tissue that appear and function differently. White adipose tissue (WAT) has evolved to store away energy in an efficient manner for later use. In contrast, brown adipose tissue (BAT) is a unique organ in mammals that has evolved over time to maintain body temperature. In essence, BAT has the ability to burn away calories as heat and is a promising therapeutic target to combat obesity and metabolic diseases such as type 2 diabetes. In our study, we have identified a potential factor that not only promotes BAT activity, but also promotes WAT to function more like BAT. By targeting this factor through drugs, there is potential to increase resting metabolic rate and fight the global epidemic of obesity.

<p dir="ltr">Adipose tissue consists of adipocytes that store energy within lipid droplets and are a central component of lipid metabolism. Mammals contain white, brown and beige adipocytes, which differ in their metabolic roles. White adipocytes store energy, in the form of triglycerides, within lipid droplets and predominantly take on an energy storage role. Brown and beige adipocytes promote energy expenditure and the dissipation of energy as heat through non-shivering thermogenesis. Since energy expenditure combats excess caloric intake and overeating, non-shivering thermogenesis has become heavily researched for its potential therapeutic use in combatting the continued increase in obesity and metabolic disorders worldwide.</p><p dir="ltr">In addition to ATP synthesis, mitochondria are required for a multitude of metabolic processes that maintain cellular homeostasis, including non-shivering thermogenesis. Brown and beige adipocyte mitochondria are specialized to perform non-shivering thermogenesis in response to an environmental stressor like cold exposure. Uncoupling protein 1 (UCP1) is uniquely characteristic of brown and beige adipocyte mitochondria, because it allows oxidative phosphorylation to be uncoupled from ATP synthesis. In order to enhance non-shivering thermogenesis, ongoing molecular characterization of brown adipose tissue (BAT) is being conducted to identify proteins that regulate mitochondrial function and UCP1 activity. In this study, I explored the function of LETM1-domain containing 1 (LETMD1), a novel mitochondrial inner membrane protein with unknown function in BAT. We generated a global (<i>Letmd1</i>^<em>KO</em>) and UCP1+ cell-specific <i>(Letmd1</i>^<em>UKO</em><i>) knockout</i><i> </i>mouse model to study the whole-body and cell-autonomous role of LETMD1 in BAT, respectively. Loss-of-function studies resulted in striking, BAT-specific phenotypic differences, including whitened BAT under thermoneutral, room temperature and cold exposure. Both knockout models were cold intolerant without access to food, and became hypothermic within a few hours of fasted cold exposure. Loss of normal mitochondria structure and cristae arrangement were also evident in knockout BAT, resulting in a decreased number of mitochondria and decreased number of cristae per mitochondrion. Mitochondrial DNA copy number was also significantly decreased in both knockout models. Abnormal mitochondria morphology was supported by increased reactive oxygen species (ROS) accumulation in both knockout models and the visualization of protein aggregates and mitophagy-like morphologies in <i>Letmd1</i>^<em>UKO</em><i> </i><i>mice specifically</i>. TurboID proximity labeling of brown adipocytes revealed enrichment of several respiratory chain complex proteins, mitochondrial ribosome proteins and mitochondrial protein import machinery. Moreover, the aggregation of misfolded nuclear-encoded mitochondrial proteins, including several respiratory chain and mitochondrial ribosome proteins, suggested that LETMD1 facilitates mitochondrial protein import and mitochondrial ribosome assembly, thereby compromising respiratory chain assembly and function during non-shivering thermogenesis. Overall, this study identifies LETMD1 as a novel regulator of brown adipocyte mitochondrial structure and thermogenic function and highlights the requirement of LETMD1 for mitochondrial biogenesis.</p>

Postoperativ shivering (PAS) definieras som en serie ofrivilliga muskelrörelser som ökar den metabola värmeproduktionen i kroppen. Förekomsten av postoperativ shivering är ett problem inom den perioperativa vården. Det finns flera orsaker till shivering. Termoregulativa och icke termoregulativa. PAS förekommer i ca 5-65% av alla anestesier, men frekvensen har under åren minskat. Det är tidigare känt att anestesi sätter termoregulationen ur spel. Konsekvenserna kan leda till vårdlidande för patienten och högre kostnader för samhället. Syftet med studien är att undersöka orsaken till shivering. Arbetet utgår från en kvantitativ metod. I samarbete med SÄS utarbetades ett datainsamlingsformulär. Studien som genomfördes på tre sjukhus i västra delen av Sverige inkluderade 350 patienter &gt;18 år. Materialet analyserades i SPSS, version 19. Resultatet visade att ålder, kön, operationstid (knivtid) och vissa typer av operationsingrepp (öron- ögon- hals- käk- näs- och endoskopisk kirurgi), hade signifikans för uppkomsten av PAS. Övriga variabler som undersöktes (anestesimetod, temperatur och övriga undersökta operationsingrepp) hade ingen signifikans. Resultatet talar delvis emot tidigare forskning, som visar att anestesimetod har betydelse för uppkomsten av PAS. Studien överensstämmer med tidigare forskning gällande signifikans för kön, ålder, operationstid och temperatur. Genom identifiering av olika faktorer, som kan leda till postoperativ shivering, kan vi, som anestesisjuksköterskor, förebygga fenomenet och ge patienten en trygg och säker vård samt minska vårdlidande. / Program: Specialistsjuksköterskeutbildning med inriktning mot anestesisjukvård

Radars have been under steady development to track, identify, image, and classify targets. Modern radar systems, with the help of embedded systems, have additional comprehensive signal processing capabilities. They can extract useful information from very noisy data, e.g. interference from the environment and unwanted echoes which is collectively known as clutter in radar terms. Concerning the healthcare industry, radar applications for detection of vital signs, i.e. breathing and heart rate, have been extensively developed during the last few decades. Modern radar systems are expected to be a large part of non-intrusive monitoring in the coming smart home industry, where vital signs need to be monitored in the currently aging population. The research presented here is to break new ground in the radar-based healthcare technology, enabling detection of cold-induced shivering to such level that the micro-shivering can be clearly identified. To simplify the radar software optimization, a commercially available radar kit with demo application and a muscle model system using a vibration generator is used. The model is quantified through precise measurements. A simulated human body vital sign plus shivering is applied. By optimizing the radar software, the shivering amplitude and frequency are measured.

L'encéphalopathie hypoxique ischémique néonatale (EHI) reste la cause principale de mortalité chez le nouveau-né à terme. Un tiers des survivants vont développer des séquelles neurologiques, dont la paralysie cérébrale (PC), l'épilepsie et un retard intellectuel. Afin d'améliorer leur pronostic, ces nouveau-nés sont soumis à l'hypothermie thérapeutique (HT) qui débute au plus tard 6 heures après la naissance, pour une durée totale de 72 heures, suivie d'un réchauffement graduel (0.5°C/h). Il a été démontré que cette thérapie à effet neuroprotecteur diminue considérablement l'étendue des lésions cérébrales et la fréquence des séquelles neurologiques. Or, des études animales suggèrent que l'hypothermie sans sédation avec opioïdes n'est pas bénéfique. Selon les observations qui ont été réalisées, les porcelets traités avec la thérapie, mais sans l’administration d’analgésique ont manifesté des signes d’instabilités et de tremblements exagérés. On ignorait jusqu’à présent dans quelle mesure ces résultats tirés des expérimentations animales pouvaient être généralisables au nouveau-né. Ainsi, mon projet de maîtrise vise à mieux comprendre les facteurs qui risquent de compromettre les effets bénéfiques de la thérapie de refroidissement, dans le but d’optimiser la neuroprotection et d’améliorer le développement des nourrissons atteints d’EHI. Nous avons comme objectif principal d’évaluer l’association entre les doses d’opioïdes consommées pendant l’HT, le degrée de tremblement, et l’évolution de l’index de discontinuité à l’EEG au fil des 72h de l’HT, du réchauffement et jusqu’à 12 heures post-HT. Pour répondre à l’objectif, nous avons conduit une étude chez 21 nouveau-nés avec EHI soumis à l’HT, et dont les principaux résultats ont montré des associations significatives entre les fortes doses d’opioïdes administrés à l’enfant (r = - 0.493, p = 0.023), les frissons réduits pendant l’HT (r = 0.513, p = 0.017) et l’amélioration du rythme cérébrale d’EEG. Ces résultats sont décrits de manière plus approfondie dans le Chapitre 2 qui présente la version de l’article soumis à la revue Journal of Pediatrics, et le Chapitre 3 qui présente un retour sur la littérature à la lumière de nos trouvailles. Quant au Chapitre 4, nous y élaborons les possibilités de perspectives futures et les retombées cliniques de nos résultats. À long terme, nous espérons que nos travaux permettront l’ouverture d’une nouvelle piste d’amélioration de la neuroprotection, en favorisant systématiquement une meilleure prise en charge de la douleur et du stress induit par le refroidissement. / Neonatal hypoxic-ischemic encephalopathy (HIE) remains the leading cause of death and mortality in the term infant. A third of the survivors will develop neurological sequelae including cerebral palsy (CP), epilepsy and mental retardation. In order to improve their prognosis, these newborns undergo therapeutic hypothermia (TH), which begins no later than 6 hours after birth, maintained for a total duration of 72 hours and followed by gradual rewarming (0.5°C/h). This neuroprotective therapy has been shown to significantly decrease the extent of brain injury and the frequency of neurological sequelae. Results from animal studies revealed that ongoing hypothermia without proper anesthesia is not beneficial. Based on the observations that have been reported, piglets treated with TH with no analgesics have shown signs of instability and excessive tremors. Until now, the extent to which these results from animal experiments could be generalized to the newborn remained unknown. Thus, the purpose of my master’s project was to better understand the clinical factors that may compromise the beneficial effects of TH, in an attempt to optimize neuroprotection and improve the neurological outcome of HIE infants. Our main objective was to assess the associations between opioid doses consumed during TH, shivering recorded during TH, and the evolution of EEG discontinuity index over the course of TH, rewarming and up to 12 hours post-TH. To meet the objective, we conducted a study in 21 newborns with HIE undergoing TH, and the results have shown significant associations between high doses of opioid administered (r = - 0.493, p = 0.023), reduced shivering stress (r = 0.513, p = 0.017) and improved EEG background activity. The key findings of the study are described in more detail in Chapter 2, which presents the original manuscript submitted for publication to the “Journal of Pediatrics”, and Chapter 3, which presents a review of the literature in light of our results. In Chapter 4, we discuss future perspectives and the clinical significance of our results. At last, we hope that our study will open up new avenues for improving neuroprotection, by systematically promoting a better management of pain and cooling-induced stress.