Factors controlling the phenology and limits of hibernation in a sciurid

Thesis (Ph.D.) University of Alaska Fairbanks, 2015Animals that live in seasonal environments have a variety of adaptations to survive periods of low to no food availability. One such adaptation is hibernation, which is characterized by profound decreases in activity, metabolic rate, and in most cases, body temperature. Among animals that hibernate, only two species are known to maintain low tissue temperature while defending significant temperature gradients, and the best studied of these is the Arctic ground squirrel (Urocitellus parryii). In the first chapter, we determine the lower ambient temperature limit of hibernation for an arctic ground squirrel (-26°C), and that a maximum torpid metabolic rate exists (0.37 mL O₂/g*h). This maximum torpid metabolic rate allows animals to defend a ~26°C temperature gradient between their core and their environment. In this chapter we also demonstrate that another, temperate, hibernating species, the golden-mantled ground squirrel (Callospermophilus lateralis), is capable of continuing hibernation at sub-freezing temperatures and can defend a temperature gradient of at least 9°C. Due to the extreme environment that Arctic ground squirrels inhabit, they have a very short growing season (~3-7 months) during which they must reproduce, grow, and accumulate energy stores prior to hibernation onset. In the second chapter we investigate the roles androgens play in hibernation phenology and male aggressive behavior. We use plasma samples collected from free-living animals and radioimmunoassays to determine circulating androgen levels. We then match the peaks in androgens to the timing of the two periods of male-male aggression (testosterone in the spring and dehydroepiandrosterone in the late summer/fall). We also present evidence to support testosterone as the main factor determining the timing of spring euthermy and emergence among reproductively mature males. In the third chapter we utilize captive animals to determine the importance of a cache to male reproductive development. Using three separate experiments, we show that while the accumulation of a cache in the late summer/fall may increase the likelihood of a male undergoing reproductive development, it alone may not be enough to ensure reproductive development. Additionally, we demonstrate that simply having access to ad libitum food in the spring is not enough to ensure reproductive development, nor is a restricted spring ration enough to prevent it

Close Homolog of L1 Is an Enhancer of Integrin-mediated Cell Migration

Close homolog of L1 (CHL1) is a member of the L1 family of cell adhesion molecules expressed by subpopulations of neurons and glia in the central and peripheral nervous system. It promotes neurite outgrowth and neuronal survival in vitro. This study describes a novel function for CHL1 in potentiating integrin-dependent cell migration toward extracellular matrix proteins. Expression of CHL1 in HEK293 cells stimulated their haptotactic migration toward collagen I, fibronectin, laminin, and vitronectin substrates in Transwell assays. CHL1-potentiated cell migration to collagen I was dependent on alpha1beta1 and alpha2beta1 integrins, as shown with function blocking antibodies. Potentiated migration relied on the early integrin signaling intermediates c-Src, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase. Enhancement of migration was disrupted by mutation of a potential integrin interaction motif Asp-Gly-Glu-Ala (DGEA) in the sixth immunoglobulin domain of CHL1, suggesting that CHL1 functionally interacts with beta1 integrins through this domain. CHL1 was shown to associate with beta1 integrins on the cell surface by antibody-induced co-capping. Through a cytoplasmic domain sequence containing a conserved tyrosine residue (Phe-Ile-Gly-Ala-Tyr), CHL1 recruited the actin cytoskeletal adapter protein ankyrin to the plasma membrane, and this sequence was necessary for promoting integrin-dependent migration to extracellular matrix proteins. These results support a role for CHL1 in integrin-dependent cell migration that may be physiologically important in regulating cell migration in nerve regeneration and cortical development

Early monocyte response following local ablation in hepatocellular carcinoma

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients’ response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response

Практикоориентированное обучение – активно реализуемая сумма знаний

МЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯОБРАЗОВАНИЕ МЕДИЦИНСКОЕСТУДЕНТЫ МЕДИЦИНСКИХ УЧЕБНЫХ ЗАВЕДЕНИЙПРАКТИКО-ОРИЕНТИРОВАННОЕ ОБУЧЕНИЕЗНАНИЙ ПРИОБРЕТЕНИЯ СПОСОБНОСТ

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population: a comparison of two German registries

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared. Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total. Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19. Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease

Physicians' attitudes about obesity and their associations with competency and specialty: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Physicians frequently report negative attitudes about obesity which is thought to affect patient care. However, little is known about how attitudes toward treating obese patients are formed. We conducted a cross-sectional survey of physicians in order to better characterize their attitudes and explore the relationships among attitudes, perceived competency in obesity care, including report of weight loss in patients, and other key physician, training, and practice characteristics.</p> <p>Methods</p> <p>We surveyed all 399 physicians from internal medicine, pediatrics, and psychiatry specialties at one institution regarding obesity care attitudes, competency, including physician report of percent of their patients who lose weight. We performed a factor analysis on the attitude items and used hierarchical regression analysis to explore the degree to which competency, reported weight loss, physician, training and practice characteristics explained the variance in each attitude factor.</p> <p>Results</p> <p>The overall response rate was 63%. More than 40% of physicians had a negative reaction towards obese patients, 56% felt qualified to treat obesity, and 46% felt successful in this realm. The factor analysis revealed 4 factors–<it>Physician Discomfort/Bias, Physician Success/Self Efficacy, Positive Outcome Expectancy</it>, and <it>Negative Outcome Expectancy</it>. Competency and reported percent of patients who lose weight were most strongly associated with the <it>Physician Success/Self Efficacy </it>attitude factor. Greater skill in patient assessment was associated with less <it>Physician Discomfort/Bias</it>. Training characteristics were associated with outcome expectancies with newer physicians reporting more positive treatment expectancies. Pediatric faculty was more positive and psychiatry faculty less negative in their treatment expectancies than internal medicine faculty.</p> <p>Conclusion</p> <p>Physician attitudes towards obesity are associated with competency, specialty, and years since postgraduate training. Further study is necessary to determine the direction of influence and to explore the impact of these attitudes on patient care.</p

Radio Continuum Surveys with Square Kilometre Array Pathfinders

In the lead-up to the Square Kilometre Array (SKA) project, several next-generation radio telescopes and upgrades are already being built around the world. These include APERTIF (The Netherlands), ASKAP (Australia), e-MERLIN (UK), VLA (USA), e-EVN (based in Europe), LOFAR (The Netherlands), MeerKAT (South Africa), and the Murchison Widefield Array. Each of these new instruments has different strengths, and coordination of surveys between them can help maximise the science from each of them. A radio continuum survey is being planned on each of them with the primary science objective of understanding the formation and evolution of galaxies over cosmic time, and the cosmological parameters and large-scale structures which drive it. In pursuit of this objective, the different teams are developing a variety of new techniques, and refining existing ones. To achieve these exciting scientific goals, many technical challenges must be addressed by the survey instruments. Given the limited resources of the global radio-astronomical community, it is essential that we pool our skills and knowledge. We do not have sufficient resources to enjoy the luxury of re-inventing wheels. We face significant challenges in calibration, imaging, source extraction and measurement, classification and cross-identification, redshift determination, stacking, and data-intensive research. As these instruments extend the observational parameters, we will face further unexpected challenges in calibration, imaging, and interpretation. If we are to realise the full scientific potential of these expensive instruments, it is essential that we devote enough resources and careful study to understanding the instrumental effects and how they will affect the data. We have established an SKA Radio Continuum Survey working group, whose prime role is to maximise science from these instruments by ensuring we share resources and expertise across the projects. Here we describe these projects, their science goals, and the technical challenges which are being addressed to maximise the science return