Impact of Increasing GLP-1 on Markers of Inflammation, Glucose Control and Cardiovascular Risk Factors in Patients With Type 2 Diabetes

There is a strong established relationship between diabetes and cardiovascular disease. Much of the latest research studies have identified a link between the inflammatory processes and the pathogenesis of both cardiovascular disease and diabetes. Specific inflammatory markers include: Interleukins 1,6,18; C-reactive protein, Fibrinogen, Tumor Necrosis Factor-α, PAI-I and cell adhesion molecules. As a result, there has been an emphasis on identifying therapeutic approaches that would improve both markers of inflammation and glucose control. The endocrine hormones known as incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropicpolypeptide (GIP), are produced in the gastrointestinal tract following ingestion of a meal. In individuals with type 2 diabetes, endothelial dysfunction associated with premature atherosclerosis has been well documented. The purpose of this paper is to determine whether increasing levels of GLP-1 reduce markers of inflammation while improving both glucose control and cardiovascular risk factors. The review of literature explored the impact of increasing GLP-1, either though DPP-IV inhibitors or GLP-1 analogues, on various inflammatory markers in patients with type 2 diabetes. The studies reviewed provided ample support for the use of DPP-IV inhibitors to improve both glycemic control and cardiovascular risk factors. GLP-1 analogues also appear to have a similar impact, but with the added benefit of weight loss. In addition, patients with type 2 diabetes frequently have coagulation abnormalities leading to a prothromboticstate. Thus the reduction in fibrinogen, C-reactive protein and plasminogen activator inhibitor observed during the review of literature supports the potential for DPP-IV inhibitors and GLP-1 agonists to exhibits an antithrombotic effect. These findings are of clinical significance as these treatments may potentially slow the progression of premature cardiovascular disease as well as reduce thrombotic events in patients with type 2 diabetes.https://commons.und.edu/pas-grad-posters/1085/thumbnail.jp

Vowel harmony decay in Old Norwegian

Vowel harmony involves the systematic correspondence between vowels in some domain for some phonological feature. Though harmony represents one of the most natural and diachronically robust phonological phenomena that occurs in human language, how and why harmony systems emerge and decay over time remains unclear. Specifically, what motivates harmony decay and the pathways by which harmony languages lose harmony remains poorly understood since no consistent historical record in any single language has yet been identified which displays the full progression of this rare sound change (McCollum 2015, 2020; Kavitskaya 2013, Bobaljik 2018). In this paper, I explore the progression and causation of vowel harmony decay in Old Norwegian (c 1100–1350). Using a grapho‐phonologically tagged database of a sample of 13th‐ to 14th‐century manuscripts, I present novel corpus methods for tracking and visualising changes to vowel co‐occurrence patterns in historical records, demonstrating that the Old Norwegian corpus provides a consistent and coherent record of harmony decay. The corpus distinguishes categorical pre‐decay harmony, probabilistic intermediate stages, and post‐decay non‐harmony. Across the Old Norwegian manuscripts, we observe a variety of pathways of harmony decay, including increasing harmony variability via the collapse of harmony classes introduced by vowel mergers, the lexicalisation of historically harmonising morphemes, and trisyllabic vowel reductions which limit harmony iterativity. This paper provides the first detailed corpus study of the full spectrum and causation of this rare sound change in progress and provides valuable empirical diagnostics for identifying and analysing harmony change in contemporary languages

Disability and health-related quality of life in patients with amyotrophic lateral sclerosis, and caregiving experience from the perspective of next of kin

Background: Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease leading to progressive muscle weakness resulting in respiratory failure and death. The average survival time from diagnosis is two to three years. The use of tracheostomy invasive ventilation (TIV) may, however, prolong life by several years. ALS has a major impact on the lives of both the patients and their next of kin/ informal caregivers. There is no cure for ALS and the cornerstone of management is symptomatic treatment to alleviate symptoms and improve health-related quality of life (HRQL). Aims: The aims of this thesis were to explore aspects of disability, contextual fac- tors and HRQL in patients with ALS, and to explore the caregiving experiences and HRQL in their next of kin/informal caregivers. In addition, this thesis aimed to investigate the experiences of being next of kin to patients with ALS undergoing TIV. Material and methods: Sixty patients with ALS were included at baseline (Study I) and followed-up every 6 months for three years, unless participants had deceased or declined participation (Study II). Data on disability, contextual factors and HRQL were collected from medical records, and by study-specific protocols and standardized questionnaires administrated during home visits. Forty-nine next of kin/informal caregivers to patients with ALS were included to explore caregiving experience, HRQL and life satisfaction (Study III). Data were collected by study- specific protocols and standardized questionnaires. Multivariate regression analy- ses were used to explore factors associated with patients’ HRQL (Study I) and informal caregivers’ HRQL and life satisfaction (Study III). Descriptive statistics and correlation analyses were used to present and explore data on disability and contextual factors over three years (Study II). Eight next of kin were included to investigate the experiences of being next of kin to patients with ALS undergoing TIV (Study IV). Semi-structured face-to-face interviews were conducted and ana- lyzed with qualitative content analysis with an inductive approach. Results: Regardless of disease severity, fatigue, anxiety, depression and pain were commonly and concurrently present in patients with ALS. Furthermore, activity limitations and participation restrictions were frequently reported. The health con- dition, i.e. high disease severity; the impairments fatigue, anxiety and/or depres- sion; participation restrictions, i.e. low frequency of social and life style activities; and the contextual factors weak coping capacity and mechanical ventilator use (non-invasive and TIV) were associated with worse HRQL in patients with ALS. Both positive and negative caregiver experiences were reported by the informal caregivers. Positive experience and older age in the informal caregiver were associated with better HRQL, while negative caregiving experiences and anxiety and/or depression in the patient with ALS were associated with worse HRQL in informal caregivers. As for life satisfaction, older age in the informal caregiver and not cohabiting with the patient were associated with being satisfied with “life as a whole”. Being next of kin to patients with ALS undergoing TIV involved experi- ences of a turbulent care process aiming to extend life, a struggle to cope with the strains of everyday life, and of conflicting roles as next of kin and carer. Conclusion: Patients with ALS need, throughout the course of the disease, to be regularly screened for commonly present impairments, activity limitations, partici- pation restrictions and perceived HRQL, so that person-centred care can be applied at the right time. There is a need to consider the individual caregiver’s experience when planning services, care and support. Furthermore, it is important to adopt person-centred care, not only for patients but also for their informal caregivers, as factors related to both parties were associated with the informal caregivers’ HRQL and life satisfaction. It is important to involve next of kin to patients with ALS undergoing TIV throughout the whole care process, and to consider the specific needs of the next of kin. Furthermore, specific support interventions for next of kin to facilitate their everyday life and to ease their burden need to be developed

Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage

Glycogenin is considered to be an essential primer for glycogen biosynthesis. Nevertheless, patients with glycogenin-1 deficiency due to biallelic GYG1 (NM_004130.3) mutations can store glycogen in muscle. Glycogenin-2 has been suggested as an alternative primer for glycogen synthesis in patients with glycogenin-1 deficiency. OBJECTIVE: The objective of this article is to investigate the importance of glycogenin-1 and glycogenin-2 for glycogen synthesis in skeletal and cardiac muscle. DESIGN, SETTING, AND PATIENTS: Glycogenin-1 and glycogenin-2 expression was analyzed by Western blot, mass spectrometry, and immunohistochemistry in liver, heart, and skeletal muscle from controls and in skeletal and cardiac muscle from patients with glycogenin-1 deficiency. RESULTS: Glycogenin-1 and glycogenin-2 both were found to be expressed in the liver, but only glycogenin-1 was identified in heart and skeletal muscle from controls. In patients with truncating GYG1 mutations, neither glycogenin-1 nor glycogenin-2 was expressed in skeletal muscle. However, nonfunctional glycogenin-1 but not glycogenin-2 was identified in cardiac muscle from patients with cardiomyopathy due to GYG1 missense mutations. By immunohistochemistry, the mutated glycogenin-1 colocalized with the storage of glycogen and polyglucosan in cardiomyocytes. CONCLUSIONS: Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers. Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy

Phylogenetic relationships in the subgenus Mus ( genus Mus, family Muridae, subfamily Murinae): examining gene trees and species trees

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75415/1/j.1095-8312.2005.00462.x.pd

An Examination of the Approach to the Object and its Surface

An examination of the approach to the object and its surface uses as examples two forms of art which in surface appearances are the antithesis of one another, Abstract Expressionism and Trompe-l&rsquo;oeil. Abstract Expressionism is a contemporary art movement, a virile movement, which is little understood by the general public. Trompe-l&rsquo;oeil is an art form which has always appealed to the public. The &ldquo;New York School&rdquo; is used as an example of American Abstract Expressionism and William Harnett is used as the example of American Trompe-l&rsquo;oeil. The difference in time between the two (a difference of approximately fifty years) is actually small when one considers the whole of art. Since Harnett no artist working with Trompe-l&rsquo;oeil has contributed anything of significance to this painting form. The roots for Abstract Expressionism lie in Europe in the period of in which Harnett was working in Europe (1878-1885). Considering the painting of the &ldquo;New York School&rdquo; and Harnett, in the light of the concept of the object and its surface, is a means of re-examining by comparison and contrast some of the basic principles of painting and the superficial differences in these two forms of painting. By using two forms of art which in appearance are very different it has been possible to avoid certain similarities which in art forms more closely related have been taken as absolutes, the danger of the &ldquo;academy.&rdquo; Also it has been possible to take a point of view towards these art forms which is new in its approach.</p

Feature specifications and contrast in vowel harmony: the orthography and phonology of Old Norwegian height harmony

In this thesis, I provide a new approach to the role of phonological patterning in determining the featural content of phonological relations and the size and shape of sound inventories. The empirical scope of this project has particular focus on vowel harmony and vocalic features with an extended case study of Old Norwegian. Vowel harmony, simply defined, is a process where vowels in a word show systematic correspondence for some feature. Because of its many moving parts and obvious class behaviour, vowel harmony and harmony languages provide one of the best laboratories for exploring the emergence, acquisition, specification, and common patterning of phonological features. In chapter 1 I provide an introduction to Old Norwegian vowel harmony and some unexplained harmony exceptions. This chapter explores parallel phenomena in the typology of harmony languages and the theoretical challenges these patterns pose. In particular, I illustrate that non-harmonising segments display three distinct behaviours with respect to phonological activity and visibility while the core components of popular grammatical and representational approaches to vowel harmony commonly only predict two. I suggest the solution to this problem lies in the representation and definition of phonological contrastivity. Chapter 2 presents the principal components of a new approach to the acquisition and specification of features using a version of Contrastive Hierarchy Theory (Dresher, Piggott & Rice 1994; D. C. Hall 2007; Dresher 2003, 2009) which incorporates emergent and substance-free features and feature-nodes (Iosad 2017a). In this chapter I argue that phonological features, segments, feature classes, and whole sound inventories emerge according to the Correlate Contrastivist Hypothesis which holds that a language’s phonemic inventory is defined by the set of active phonological features required to express the language’s phonological regularities. Drawing insights from Westergaard’s (2009, 2013, 2014) model of micro-cues, I posit that language learners generalise small pieces of abstract linguistic structures (‘micro-cues’) in the form of features and feature co-occurrence restrictions while parsing linguistic input. In the course of language acquisition, these micro-cues accumulate, and the sum of these cues defines a sound inventory. I argue a segment’s feature specifications and the shape of feature classes in a language are determined by a version of the Successive Division Algorithm (Dresher 2009, §7.8; D. C. Hall 2007, §1.2.7; Mackenzie 2013, 2016) which takes an ordered set of representational micro-cues as its input and returns a contrastively specified segment inventory as its output. Finally, this chapter demonstrates how these components combined with the hierarchical organisation of features afforded by the contrastive hierarchy architecture recapitulates all the important insights of feature geometry, providing an economical and principled model of phonological representations which narrowly vary cross-linguistically. In chapter 3 I present a formal model of harmony using a licensing approach, adapted from Iosad (2017a) and Walker (2005), inspired by the recipient-oriented model of Nevins (2010). Using a detailed study of cross-dialectal microvariation in harmony and harmony neutrality in Yoruba (Atlantic-Congo), I demonstrate that this framework makes the right predictions, affording a ternary contrast in the behaviour of non-alternating harmony segments without any necessary additional grammatical mechanisms. A principal assumption of Contrastive Hierarchy Theory is that the hierarchical scope of features is cross-linguistically variable, and this chapter illustrates how variable feature ordering predicts common asymmetries across harmony languages in the presence or absence of required agreement for orthogonal features (so-called ‘parasitic harmony’). Specifically, the contrastive hierarchy derives parasitic harmony languages by nesting harmony feature contrasts within other featural divisions. This chapter closes with an exploration of the predicted typology of non-/parasitic systems and provides explicit diagnostics for identifying true vs. false parasitic harmony. The theoretical chapters present a coherent, limited, and highly predictive model of phonological representations and vowel harmony, but the real value of a theory is whether it can provide new insights on questions which have otherwise resisted explanation. Old Norwegian vowels and vowel harmony represent such an example. Old Norwegian vowel harmony displays remarkably complex patterns, and its analysis is considerably complicated by the philological nature of available evidence. Chapter 4 presents the materials and methods I employ for the automated collection and phonological annotation of Old Norwegian vowel sequences in a corpus of mid-to-late 13th-century manuscripts. The corpus study’s data set is freely available online at http://dx.doi.org/10.17613/ gj6n-js33. Chapter 5 provides a grapho-phonological study of the Old Norwegian vowel inventory and segmental phonological patterns. This corpus study shows that Old Norwegian manuscripts display robust (pre-decay), transitional, and decayed vowel harmony, which provides invaluable empirical evidence for the otherwise poorly documented decay of harmony systems. The rest of the chapter provides a detailed survey of pre-decay Old Norwegian surface harmony patterns and their interaction with other sound processes and sound changes (e.g. umlauts, vowel deletions, and vowel mergers). A major goal of this project has been to develop tangible heuristics for the reconstruction of historical phonological representations on the basis of phonological patterns evidenced in textual source material. Tying together this thesis’ theoretical and empirical components, I show in chapter 6 how the active vocalic features and feature co-occurrence restrictions in Old Norwegian can be discerned according to the Correlate Contrastivist Hypothesis. In turn, the intricate harmony and neutral harmony patterns in Old Norwegian receive a straightforward explanation following these representational generalisations. This case study illustrates how even complex harmony systems such as Old Norwegian can be reduced to simple emergent effects of the categorisation and co-occurrence of features in contrastive feature hierarchies. This chapter concludes with a historical phonological investigation of the implications of this harmony system for the status of other Old Norwegian sound patterns. The main features of this thesis’ theoretical component and useful abstract schemata are provided in chapter 7 to aid in applying this framework to new data. For ease of comparison, I provide an appendix with contrastive hierarchies and summaries of each harmony language cited in this thesis. The unique contribution of Old Norwegian neutral harmony patterns within the typology of vowel harmony languages provides important evidence for the role of feature specifications and contrastivity in phonology. This thesis’ broad typological and narrow empirical studies confirm the descriptive and explanatory adequacy of the proposed framework in providing novel insights on new and old problems regarding the link between phonological representations and phonological patterns