Prenatal programming of neuroendocrine reproductive function

It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the “prenatal programming” of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be “shaped” both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent “normal function”. The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential

Investigating the function of neutrophils in RSV Bronchiolitis using a novel in vitro translational model of transepithelial immune cell migration

Background: Respiratory Syncytial Virus (RSV) infects almost all children before the age of 2. In most children, RSV infection causes a mild to moderate illness, but a small percentage of children develop severe RSV bronchiolitis and require hospitalisation. A significant proportion of these acutely unwell children were previously otherwise healthy. Clinical studies of infants with severe bronchiolitis have shown a massive infiltrate of neutrophils to the airway, comprising over 80% of all cells recovered. In this thesis I explore further whether the effect of neutrophil infiltration is necessary for viral clearance or detrimental to clinical disease, by exploring the interaction between neutrophils and RSV infected airway epithelial cells (AECs). Aims: The aims of this thesis were to (i) describe neutrophil movement across RSV infected AECs, (ii) measure the effect of interaction with RSV infected AECs on neutrophil apoptosis, (iii) activation, then (iv) compare these effects between adult and cord blood neutrophils. Methods: To examine the complex relationship between the RSV infected airway and neutrophil function, this study optimises a novel in-vitro transepithelial migration model of RSV infected AECs, comprising human neutrophils, ciliated epithelial cells cultured at air-liquid interface and RSV. This has allowed real-time video microscopy of neutrophil transepithelial migration, examination of dynamic neutrophil activation and assessment of neutrophil viability and apoptosis during infection. Results and Conclusion: Three populations of neutrophils interacting with AECs were described, those basolateral to AECs, those apical and those adhered to AECs. Imaging neutrophil migration revealed adhered neutrophils appear to kill virally infected AECs during migration. Neutrophil apoptosis and activation were defined by their interaction with AECs and evidence presented in this thesis suggest physiological differences between adult and cord blood neutrophil response to RSV infected AECs may predispose to a more severe disease picture in neonates

Clothes and how to care for them

Cooperative Extension Work in Agriculture and Home Economics, University of Missouri, College of Agriculture and the United States Department of Agriculture cooperating."March, 1937 (Fourth Edition)."Title from cover

Oral Inflammation, Tooth Loss, Risk Factors, and Association with Progression of Alzheimer’s Disease

Periodontitis is a polymicrobial chronic inflammatory disease of tooth-supporting tissues with bacterial etiology affecting all age groups, becoming chronic in a subgroup of older individuals. Periodontal pathogens Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are implicated in the development of a number of inflammatory pathologies at remote organ sites, including Alzheimer’s disease (AD). The initial inflammatory hypothesis proposed that AD hallmark proteins were the main contributors of central nervous system (CNS) inflammation. This hypothesis is expanding to include the role of infections, lifestyle, and genetic and environmental factors in the pathogenesis of AD. Periodontal disease (PD) typifies a condition that encompasses all of the above factors including pathogenic bacteria. These bacteria not only are the source of low-grade, chronic infection and inflammation that follow daily episodes of bacteremia arising from everyday tasks such as brushing, flossing teeth, chewing food, and during dental procedures, but they also disseminate into the brain from closely related anatomical pathways. The long-term effect of inflammatory mediators, pathogens, and/or their virulence factors, reaching the brain systemically or otherwise would, over time, prime the brain’s own microglia in individuals who have inherent susceptibility traits. Such susceptibilities contribute to inadequate neutralization of invading agents, upon reaching the brain. This has the capacity to create a vicious cycle of sustained local inflammatory milieu resulting in the loss of cytoarchitectural integrity and vital neurons with subsequent loss of function (deterioration in memory). The possible pathways between PD and AD development are considered here, as well as environmental factors that may modulate/exacerbate AD symptoms

Swearing as a response to pain: A cross-cultural comparison of British and Japanese participants

Background and aims: Research suggests swearing can moderate pain perception. The present study assessed whether changes in pain perception due to swearing reflect a "scripting" effect by comparing swearing as a response to pain in native English and Japanese speakers. Cognitive psychology denotes a 'script' to be a sequence of learnt behaviours expected for given situations. Japanese participants were included as they rarely, if ever, swear as a response to pain and therefore do not possess an available script for swearing in the context of pain. It was hypothesised that Japanese participants would demonstrate less tolerance and more sensitivity to pain than English participants, and - due to a lack of an available script of swearing in response to pain - that Japanese participants would not experience swearword mediated hypoalgesia. Methods: Fifty-six native English (mean age = 23 years) and 39 Japanese (mean age = 21) speakers completed a cold-pressor task whilst repeating either a swear on control word. A 2 (culture; Japanese, British). ×. 2 (word; swear; non-swear) design explored whether Japanese participants showed the same increase in pain tolerance and experienced similar levels of perceived pain when a swearing intervention was used as British participants. Pain tolerance was assessed by the number of seconds participants could endure of cold-pressor exposure and self-report pain measurements. Levels of perceived pain were assessed using a 120-mm horizontal visual analogue scale anchored by descriptors in the participant's native language of "no pain" (left) and "terrible pain" (right). The participant was asked to mark a 10. mm vertical line to indicate overall pain intensity. The score was measured from the zero anchor to the participant's mark. Results: Japanese participants reported higher levels of pain (p <. 0.005) and displayed lower pain tolerance than British participants (p <. 0.05). Pain tolerance increased in swearers regardless of cultural background (p <. 0.001) and no interaction was found between word group and culture (p = 0.96), thereby suggesting that swearing had no differential effect related to the cultural group of the participant. Conclusions: The results replicate previous findings that swearing increases pain tolerance and that individuals from an Asian ethnic background experience greater levels of perceived pain than those from a Caucasian ethnic background. However, these results do not support the idea of pain perception modification due to a "scripting" effect. This is evidenced as swearword mediated hypoalgesia occurs irrespective of participant cultural background. Rather, it is suggested that modulation of pain perception may occur through activation of descending inhibitory neural pain mechanisms. Implications: As swearing can increase pain tolerance in both Japanese and British people, it may be suggested that swearword mediated hypoalgesia is a universal phenomenon that transcends socio-cultural learnt behaviours. Furthermore, swearing could be encouraged as an intervention to help people cope with acute painful stimuli

Improving Diabetes Care Delivery in an Integrated Health Clinic

Abstract People with serious mental illness (SMI), as a population, are typically underserved and likely to have barriers to accessing primary care services. When these patients do seek primary care, it is often fragmented and communication between multiple providers lacks efficiency and coordination. A co-located primary care clinic was recently established in a large behavioral health setting to improve access to primary care for this population. Prior to opening the clinic, of 499 client survey respondents, 82 indicated they needed help managing their diabetes. Multiple providers with varied backgrounds are providing care in the new clinic setting where potential gaps in the delivery of diabetes related care are likely. The purpose of this project is to evaluate the care provided to patients with type 2 diabetes mellitus in the primary care clinic by multiple providers compared to the standard of medical care for diabetes management according to the American Diabetes Association (ADA) 2015 guidelines. A retrospective chart review using a standards checklist based on the ADA guidelines was implemented to evaluate care provided by a number of different providers. Identified gaps in care, potential improvements in documentation and use of the checklist as a tool for improving delivery of care to meet standards were shared with providers in a post-study discussion