The autonomic nervous system (ANS) controls most involuntary functions of the body. Dysfunctions of the ANS can be life-threatening. However, several critical questions related to cardiovascular and breathing regulations remain unclear. One of the open questions is how the system lose control of the vascular tones under certain circumstances. Using the septic shock model induced by lipopolysaccharide (LPS) in isolated and perfused mesenteric arterial rings, we found the vascular hyporeactivity is attributed to the decreased vasoconstriction to α-adrenoceptor agonists. The endotoxin-induced vasodilation can be intervened with endothelin-1 (ET-1), serotonin (5-HT) or vasopressin, which have never been used in clinical treatment. It is unclear how the excitability of endothelium affects vascular tones. Using optogenetics and transgenic mice with channelrhodopsin expression in endothelial cells (ECs), we found selective activation of the ECs induces a fast, robust, reproducible and long-lasting vasoconstriction in isolated and perfused hearts and kidneys. Breathing control by the ANS within the brain becomes abnormal in certain genetic diseases, such as Rett syndrome with defected norepinephrine (NE) system in locus coeruleus (LC). The LC neurons are hyperexcitable while NE release is deficient. Using optogenetics and double transgenic mice with Mecp2 null and channelrhodopsin expression in LC neurons, we found the NE-ergic modulation of hypoglossal neurons was impaired in transgenic mice, which cannot be improved with optostimulation, suggesting that LC neuronal hyperexcitability may not benefit the NE modulation in Rett syndrome. Collectively, our results provide insight into the autonomic dysfunctions using experimental interventions that have barely been used before.

As medical advances are made in the area of neonatology, more and more premature babies are surviving at younger gestational ages and lower birth weights. Growth in the survival rates of preterm infants leads to questions regarding the long term developmental trajectory of these children. The current study sought to expand on research regarding dimensions of childhood functioning and to apply it to the problem of prematurity by (a) utilizing a new instrument: the Merrill Palmer Revised edition, (b) including children of preterm and full term birth statuses from as young as 2 months of age, and (c) collecting data from parental and clinician reports. In addition to attempts to clarify the relationship between birth status and childhood dysfunction, this study also sought to augment existing literature by exploring the correlation between parental report and clinician observation of childhood dysfunction. The results of this study did not support the hypothesis that children of preterm birth will demonstrate more problems in functioning when compared to full term peers. Although there were more significant differences between preterm and full term children in the older cohort group, those differences did not consistently reflect dysfunction by the preterm children. Additionally, this study considered dimensions of dysfunction as measured by parental report and clinician observations. Notably, a lack of agreement between parent and clinician observations emerged for the young age cohort group. However, the high level of agreement for the older children suggests that parental and clinician perspectives converge with older children. Contrary to the hypothesis, birth status, gender, ethnicity, and SES did not collectively form a specific risk index for dysfunction. However, these factors did interact with each other to predict functioning on several scales. In fact, there were no significant main effects. Instead, predictors of dysfunction were interactions of variables such as birth status, age, gender, and ethnicity. This general finding illustrates the importance of taking into consideration all aspects of the childs situation when making an assessment of functioning.

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Atualmente, o nível de exigências do mercado de trabalho tem aumentado, a qualificação profissional se tornou indispensável, a concorrência está cada vez maior e por isso, o estresse ocupacional tem destaque no processo de saúde-doença do individuo em seu ambiente de trabalho. O mecanismo interno de liberação de estresse pode causar, entre outros, um aumento na tonicidade da musculatura da cabeça e do pescoço, como também dos níveis de atividade muscular parafuncional, como o bruxismo e o apertamento dentário. Assim, o cirurgião-dentista tem o papel de diagnosticar, tratar e proservar os pacientes com disfunção temporomandibular. Uma das profissões mais históricas no Brasil, ser militar, especificamente da força armada terrestre, o Exército Brasileiro tem, além de suas características de honestidade, vigor físico, responsabilidade e pontualidade, fatores associados que podem gerar o estresse ocupacional, como o risco à vida, sujeição a preceitos rígidos de hierarquia e disciplina, disponibilidade permanente, mobilidade geográfica, formação específica e aperfeiçoamento constante, além das consequências para a família. Nesse contexto, o objetivo desta pesquisa foi investigar a presença de estresse ocupacional em uma população de militares no município de Ribeirão Preto, Estado de São Paulo, Brasil e analisar sua relação com os achados clínicos de DTM e o exame eletromiográfico dos músculos mastigatórios. A amostra foi composta por 30 sujeitos da pesquisa, militares da 5ª CSM. A presença de DTM foi investigada por meio de questionário anamnésico (ProDTMMulti) e de exame clínico odontológico (RDC/TMD; Helkimo). O estresse ocupacional foi investigado por meio de questionário específico, Maslach Burnout Inventory (MBI). Os exames eletromiográficos e de força de mordida foram realizados no gabinete odontológico da 5ª CSM por cirurgiã-dentista experiente, a qual participa ativamente do serviço como profissional militar contratada pela instituição. Os resultados mostraram que no exame clínico, 90% dos militares não foi classificável pelo RDC e apenas 20% foram classificados com disfunção severa (grupo 3) do Índice de HELKIMO. Pelo Protocolo ProDTMMulti: 46,66% dos militares se enquadraram no grau zero (ausência de DTM), 40% no grau 1 (DTM leve) e apenas 13,33% dos militares relataram sintomas um pouco mais acentuados, ficando no grau 2 (DTM moderada). Com relação ao estresse, a única correlação existente foi com a patente: quanto maior a patente, menor o estresse. Pela análise eletromiográfica nos testes estáticos e dinâmicos da mandíbula, observou-se simetria entre os lados direito e esquerdo, e um padrão mastigatório equilibrado entre os lados. No teste de força máxima de mordida, a força também se apresentou equilibrada entre os lados. Concluiu-se que o estresse ocupacional está presente nesta amostra, porém não se correlacionou com os achados clínicos de DTM e com o exame eletromiográfico dos músculos mastigatórios dos militares da 5ª CSM do município de Ribeirão Preto/SP. / As the labor market requirements have increased, professional qualification has been taken as essential and the work competition keeps heightening, occupational stress has become prominent in the health-disease process of the working person. Among other things, the internal mechanism of stress release can cause an increased tonicity of head and neck muscles and increased levels of muscular parafunctional activity such as teeth grinding (bruxism) and teeth clenching. The dentist has the role in diagnosing, treating and following-up patients with temporomandibular dysfunction. One of the most historic occupations in Brazil, the military career at the Brazilian Army, besides characteristics of honesty, physical force, responsibility and punctuality, has associated factors that can lead to occupational stress, as the risk of death, to be under precepts of strict discipline and hierarchy, permanent availability, geographic mobility, specific training and continuous improvement, and the resulting consequences for the family. The objective of this research was to study the relation between occupational stress and degree of TMD in soldiers of Ribeirão Preto, State of São Paulo, Brazil. The study sample had 30 military volunteers from the 5th CSM. The presence of TMD was investigated by use of an anamnestic questionnaire (ProDTMMulti) and dental clinical examination (RDC/TMD; Helkimo). Occupational stress was investigated by means of a specific questionnaire, Maslach Burnout Inventory (MBI). Electromyographic and bite force tests were held in the dental office of the 5ª CSM by a qualified dentist who participates actively in the service as a military professional hired by the institution. Results of clinical examination showed that 90% of the studied subjects were not classifiable by the RDC and only 20% were classifiable as having severe dysfunction (Group 3) by HELKIMO Index. By the ProDTMMulti Protocol, 46,66% of the individuals were classified in Grade 0 (absence of TMD), 40% in Grade I (light TMD) and only 13,33% reported symptoms a little more pronounced being in Grade II (moderate TMD). Regarding stress, the only identified correlation was with the military rank: higher the rank, lower the stress. By electromyography analysis in mandible static and dynamic tests, it was observed symmetry between right and left sides, and a balanced masticatory pattern between sides. In the maximal bite force test, the force between the sides also stayed balanced. It was concluded that occupational stress is present in this sample, but it does not correlate with the clinical findings of TMD and the electromyography examination of masticatory muscles in military personnel from the 5th CSM of the city of Ribeirão Preto/Brazil.

Previous studies suggested that the Functional Activities Questionnaire (FAQ-10) has minimal ethnic bias and that a shorter version (FAQ-6) can equally diagnose MCI and dementia. Objective: We analyzed whether FAQ-6 is similar to FAQ-10 in diagnosing MCI and dementia. We examined their applicability across European Americans (EA) and Hispanic Americans, and how scores correlated to beta amyloid. Method: 222 participants (116 EA) completed a neuropsychological battery, FAQ, and PET scans, and were classified as cognitively normal (CN), MCI, or dementia. The diagnostic capacity of FAQ-10 and FAQ-6 were compared for the total sample and across ethnic groups. Scores were correlated to beta amyloid. Results: Both versions showed good item discrimination. Ethnicity did not affect scores when controlling for diagnosis and education. Both versions classified CN and dementia, and positively correlated to beta amyloid. Conclusions: Results suggest FAQ-6 and FAQ-10 similarly predict diagnosis and is adequate in these ethnic groups. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Tenascin X (TNX) is a matricellular protein involved in regulating cellular functions by interacting with other extracellular matrix (ECM) proteins within the cell matrix and has anti-adhesive properties evidenced in tumours and wound healing. TNX is the only member of the tenascin family that is lost in Joint Hypermobility Syndrome (JHS) and exerts a crucial architectural function. Of importance, TNX deficient and JHS patients have gastrointestinal (GI) dysfunction. Despite this association no study has described the role of TNX in the GI tract. Thus, the aim of this thesis was to characterise the expression of TNX in the stomach and colon in mouse and human tissue. Second, we aimed to elucidate the functional role of TNX using TNX knockout (TNX KO) mice. Expression studies revealed TNX in vagal afferent endings in the mouse, and myenteric cell bodies in human stomach. In colon, TNX strongly associated with cholinergic submucous and myenteric neurons in both species, however, was not found in CGRP positive fibres. Cell bodies in nodose ganglia, dorsal root ganglia, ventral and dorsal horn were also TNX positive. Functional studies in stomach, using single fibre electrophysiology showed TNX KO mice had increased vagal afferent mechanoreceptor sensitivity. Octanoic acid breath test revealed rapid gastric emptying in TNX KO. Colonic manometry showed the amplitude and frequency of colonic contractions were reduced in TNX KO mice, particularly in the distal colon. Ussing chamber studies measuring changes in ion flux (indirect measure of secretion) showed no major difference between TNX KO and wild type (WT) mice. The specific localisation of TNX with neuronal structures in the gut is shown here for the first time suggesting that TNX is more than just an architectural protein. Indeed, its role in specific GI functions supports this observation and provides a mechanism for GI symptoms in JHS.

Telomere dysfunction is one mechanism of cellular and tissue ageing. Dysfunctional telomeres in fibroblasts are recognised as DNA double-strand breaks (DSBs) and trigger the DNA damage pathway of senescence. However, telomere uncapping in normal human epidermal keratinocytes, via expression of the dominant negative mutant of the telomere repeat-binding factor 2 (TRF2!B!M), resulted in a senescent-like arrest without a significant DNA damage response (DDR). This suggests that either keratinocytes are unusually sensitive to telomere uncapping and the low DDR is sufficient to induce senescence or that dysfunctional telomeres may also be signalled through an alternative pathway. Subsequent analysis revealed genes HIST2H2BE, ICEBERG, S100A7 and HOPX as potential markers for telomere dysfunction-induced senescence (TDIS) since they were induced by telomere uncapping and seemed to be regulated by telomerase. The aim of this project was to assess the specificity of these candidate markers for TDIS and to select the most promising for use as a biomarker. To this end, keratinocytes were exposed to doses of ionising radiation, capable of generating transient or permanent damage to the DNA, or transduced with retroviral constructs expressing p14ARF, p16INK4a, p53 or TRF2!B!M and the gene expression levels of the candidates assessed after a recovery period or at the early stages of senescence. Whilst S100A7, HOPX or ICEBERG were not induced by a transient or persistent DDR or by p16INK4a, ICEBERG and HOPX were induced by p53 and p14ARF when these were ectopically expressed at higher levels. Thus, S100A7 seems to be the most specific early marker for telomere dysfunction in keratinocytes since it was selectively induced by telomere uncapping via expression of TRF2!B!M and not by DSBs or by over expression of p14ARF, p53 or p16INK4a. S100A7 may have the potential to identify cells with telomere dysfunction in human epithelia and body fluids.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objective The objective of this study was to investigate the effect of preoperative diastolic dysfunction on postoperative mortality and morbidity after cardiovascular surgery. Methods We systematically searched for articles that assessed the prognostic role of diastolic dysfunction on cardiovascular surgery in PubMed, Cochrane Library, Web of Science, Embase and Scopus until February 2016. Twelve studies (n=8224) met our inclusion criteria. Due to scarcity of outcome events, fixed-effects meta-analysis was performed using the Mantel-Haenszel method. Results Preoperative diagnosis of diastolic dysfunction was associated with higher postoperative mortality (OR 2.41, 95% CI 1.54-3.71; p<0.0001), major adverse cardiac events (MACE) (OR 2.07, 95% CI 1.55-2.78; p <=0.0001) and prolonged mechanical ventilation (OR 2.08, 95% CI 1.04-4.16; p=0.04) in comparison to patients without diastolic dysfunction among patients who underwent cardiovascular surgery. The odds of postoperative myocardial infarction (OR: 1.29, 95% CI 0.82, 2.05; p=0.28) and atrial fibrillation (OR: 2.67; 95% CI 0.49-14.43; p=0.25) did not significantly differ between the two groups. Severity of preoperative diastolic dysfunction was associated with increased postoperative mortality (OR 21.22, 95% CI 3.74 -120.33; p=0.0006) for Grade 3 diastolic dysfunction compared with patients with normal diastolic function. Inclusion of left ventricular ejection fraction (LVEF) <40% accompanying diastolic dysfunction, did not further impact postoperative mortality (p=0.27; I2 =18%) when compared with patients with normal LVEF and diastolic dysfunction. Conclusions Presence of preoperative diastolic dysfunction was associated with higher postoperative mortality and MACE, regardless of LVEF. Mortality was significantly higher in grade III diastolic dysfunction. Keywords Diastolic dysfunction; cardiovascular surgical procedures; mortality; meta-analysis / Revisión por pares

Male sexual dysfunction is considered to be a problematic discursive site due to the diverse ways in which it is constructed and therapeutically conceptualised. Under-researched within the discipline of counselling psychology to date, this diagnostic category needs to be explored to identify ways in which counselling psychologists construct this presenting problem. Therefore the aim of this research was to interrogate how a volunteer group of counselling psychologists understood and worked with male sexual dysfunction in order to make visible some of the masked discursive practices related to its diverse constructions. Ten counselling psychologists were interviewed and a Foucauldian discourse analysis conducted, which interrogated the discursive power games implicated in these participants' accounts. The findings produced firstly identified the wider contextual cultural norms that seemed to regulate male sexuality within gendered masculinity discourses. Secondly, three distinct discursive therapeutic subject positions and their related power games were identified as talked about by these participants. Overall, it is argued that these findings indicate that for these counselling psychologists, male sexual dysfunction is a mutable, diversely power-laden, and thereby problematic, construct. Furthermore this analysis may be understood as a contribution to counselling psychology in raising practitioners' awareness to the power games in their talk about working with male sexual dysfunction.

The intracellular Ca2+ handling system in a cardiac myocyte is of crucial importance. It regulates the contraction and relaxation of the myocyte during the excitation-contraction (EC) coupling. A normal intracellular Ca2+ handling system keeps the contraction of the heart orderly, which represents a powerful force to pump blood to the whole body. However, disarrayed or remodelled cellular structure associated with the intracellular Ca2+ handling system at the subcellular level, such as loss of T-tubule network in diseased conditions, may promote abnormal cardiac EC coupling, leading to genesis of cardiac arrhythmias impairing cardiac mechanical functions. Up to date, it is still incompletely understood how the intracellular Ca2+ handling system is altered by changes in subcellular structures of Ca2+ handling systems. In this thesis, biophysically detailed computational models for the intracellular Ca2+ handling system of a cardiac cell were developed, providing a powerful platform to investigate the spatio-temporal complexity associated with the intracellular Ca2+ handling, and its role in generating abnormal cardiac EC coupling. First, a well-validated single cell model was used to investigate how the diastolic and systolic Ca2+ concentration responded to alterations in the model parameters related to the Ca2+ handling system, from which the mechanisms underlying the rate-dependence of EC coupling were analysed. Then, a novel single cell model, with a 2D presentation of the spatial structures of subcellular Ca2+ handling and membrane action potential, of a sheep atrial myocyte was developed for simulating the abnormal intracellular Ca2+ regulation system due to the loss of T-tubules during atrial fibrillation. Variant scenarios of T-tubule loss were considered to investigate the role of the T-tubule in affecting the intracellular Ca2+ regulation. Furthermore, membrane currents' alterations due to the electrical remodelling arising from atrial fibrillation were considered together with the loss of T-tubule. Three typical types of abnormal Ca2+ cycling phenomenon, namely intracellular Ca2+ alternans, spontaneous Ca2+ sparks and intracellular Ca2+ waves were observed in AF conditions. The relationship between T-tubule loss, AF-remodelling and the genesis of delayed afterdepolarizations (DADs) was also investigated. It was shown that the loss of T-tubule in AF condition played an important role in disturbing the Ca2+ regulation system, which increases the risk for a cell to generate impaired contraction.