The Human Gut Microbiome: A Physiological System Approach

2014 University Libraries Undergraduate Research Award Winner---Perhaps some of the most complex disorders that have been observed in humans are those that concern emotion and processes of the human brain. The pathway between stimulus and response in cases of depression and anxiety is one that can take many directions depending on the patient in question; for this reason, psychiatry has provided interesting modes by which pathology can be studied outside of a one-to-one causal relationship. Given the expected lifespan of the average individual and the decades through which different disorders can emerge and withdraw given changes in environment or situation, determining the cause of such pathologies as Chronic Fatigue Syndrome (CFS) or even Obsessive-Compulsive Disorder (OCD) can be daunting for any physician. How does one trace a pattern of feeling or behavior back to a causal event that may have occurred years before symptoms even emerged? In an age where Post-Traumatic Stress Disorder (PTSD) continues to gain relevance in light of a world at war, such questions must be asked. The lives of patients and their families depend on the ability of scientists to uncover pathways that can be manipulated to produce some treatment option or cure. After Dr. James Greenblatt was sought out by the parents of a young girl named Mary who had been diagnosed with a mixture of psychiatric disorders, including OCD and Attention Deficit Hyperactivity Disorder (ADHD), and treated with a range of psychotropic drugs that had remained largely unhelpful, his mode of thinking was able to change her quality of life (James 2013). He turned to her stomach as a possible root of the problem. One may not expect a trip to the psychiatrist to include a survey of questions aimed at ascertaining his or her digestive health; however, Dr. Greenblatt employed this strategy and, because of his conclusion that the symptoms that were manifesting in the emotive regions of Mary's brain might actually originate from an imbalance in her gut microflora composition, was able to prescribe a twice-daily dosage of probiotic that alleviated Mary's symptoms altogether. His assumption stemmed from an elevated level of metabolite HPHP A in her urine, a byproduct of the metabolic pathways of Clostridium species. Dr. Greenblatt's reasoning further developed from his ideas concerning the connection between the human gut and brain, an interface that had once been deemed a one-way street. By reversing this line of thinking and implementing a treatment plan that assumed a gut-to-brain avenue of communication, Dr. Greenblatt was able to treat Mary's symptoms, thereby continuing a thought that the gut microbiome plays more of a role in the human body than previously thought. While Dr. Greenblatt's treatment of Mary's condition constitutes an isolated case where an assumed role by the human gut microbiome existed, many clinical studies have also contributed to the belief behind this linkage

A comparison of selected student outcomes in community college associate degree nursing programs using a competitive admissions process versus those using a modified open admissions process

The purpose of this study was to investigate whether there were significant differences in selected student outcomes in community college associate degree nursing programs using a competitive admissions process compared to those programs using a modified open admissions process. Community college nursing faculty are attempting to reconcile a need to choose the best and brightest nursing students in an environment traditionally committed to open admissions for all students. Two admissions processes may be used to select students for entry into associate degree nursing programs - one, competitive admissions, ranks and accepts applicants ordinally on the basis of past academic achievement and potential aptitude; and two, modified open admissions, accepts qualified applicants on the basis of date of fulfillment of admission requirements until all admissions spaces are filled

A study of differential characteristics of freshmen music students in selected two-year and four-year colleges in Virginia

The purpose of this study was to determine whether differences existed between entering freshmen two-year and four-year college music students by group and by sex in personality characteristics, value structures, and musical aptitude. Three tests were given in this study--the Omnibus Personality Inventory (OPI) was given to determine personality characteristics; the Study of Values (SOV) was given to determine value structures; and the Musical Aptitude Profile (MAP) was given to determine musical aptitude. The two-year college sample consisted of students entering music programs at Virginia Western Community College and Tidewater Community College in Virginia. The four-year college sample consisted of students entering music programs at Madison College in Virginia. Both two-year colleges and the four-year college are state supported public institutions. Testing was done in freshman music theory classes

The influence of Andrew Craig Phillips on North Carolina local superintendents

Craig Phillips was the North Carolina State Superintendent of Public Instruction from 1968-1988, longer than any other holder of that office. This study investigates the impact of his tenure as state superintendent on local superintendents. Accordingly, the study had four purposes. The first was to determine to what extent Craig Phillips' behavior influenced local administrative procedure. The second purpose was to determine whether age, years in office, size of administrative unit, geographical region, or Phillips' tenure affected local superintendents' perceptions of Phillips and/or his administration. The third was to determine which statewide implemented programs during Phillips' tenure were attributed to Phillips and/or his administration. Finally, the fourth purpose was to examine how local superintendents would select the State Superintendent of Public Instruction. The study was based on interviews with local superintendents in Region 8 and a Likert-scaled survey mailed to all of the 139 local superintendents in North Carolina

UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gen

Duration of Effectiveness of Permethrin-Treated Clothing to Prevent Mosquito Bites Under Simulated Conditions

Presented for World Environmental Health Day, September 26, 2016 in Greenville, North Carolina.Biological hazards such as exposure to ticks and mosquitoes can affect worker health. Permethrin is a repellant/insecticide approved for human use by the Environmental Protection Agency. Permethrin-treated clothing is commercially available to the public. Permethrin-treated clothing (50% cotton/50% nylon) has been shown to retain repellency through 70 washings. Work attire differs between state and consulting foresters, park rangers, etc.; hence, variation in protection from vector borne disease may existThis study was funded by the Southeast Center for Agricultural Health and Injury Prevention (# 3049025288-14-060)

Impact of aperture separation on wind-driven single-sided natural ventilation

This paper presents a study of the impact of horizontal aperture separation in single-sided ventilation flows with two apertures (SS2). The study is based on wind tunnel measurements and dimensional analysis. The results show that the SS2 ventilation flow rate, scaled with incoming wind velocity and aperture area, depends on the incoming wind angle relative to the aperture façade, $θ$, and on the aperture separation scaled by building width, $s$′. For most wind angles, the ventilation flow increases as the square-root of $s$′. This study also identified a novel flow driving mechanism – vortex shedding: when the ventilation openings are on the leeward side of the building and the wind is nearly head-on, the flow is driven by a pumping mechanism due to vortex shedding.The authors gratefully acknowledge the contribution of staff at CPP Wind Engineering, Inc., for running the wind tunnel tests that produced the data used to develop our model; and financial support for one of us (GCG) from Instituto Dom Luiz (UID/GEO/50019/ 2013). The work described in this paper was carried out under California Energy Commission contract 500-10-025, and their financial support is gratefully acknowledged

Electroanalytical point-of-care detection of gold standard and emerging cardiac biomarkers for stratification and monitoring in intensive care medicine - a review

Determination of specific cardiac biomarkers (CBs) during the diagnosis and management of adverse cardiovascular events such as acute myocardial infarction (AMI) has become commonplace in emergency department (ED), cardiology and many other ward settings. Cardiac troponins (cTnT and cTnI) and natriuretic peptides (BNP and NT-pro-BNP) are the preferred biomarkers in clinical practice for the diagnostic workup of AMI, acute coronary syndrome (ACS) and other types of myocardial ischaemia and heart failure (HF), while the roles and possible clinical applications of several other potential biomarkers continue to be evaluated and are the subject of several comprehensive reviews. The requirement for rapid, repeated testing of a small number of CBs in ED and cardiology patients has led to the development of point-of-care (PoC) technology to circumvent the need for remote and lengthy testing procedures in the hospital pathology laboratories. Electroanalytical sensing platforms have the potential to meet these requirements. This review aims firstly to reflect on the potential benefits of rapid CB testing in critically ill patients, a very distinct cohort of patients with deranged baseline levels of CBs. We summarise their source and clinical relevance and are the first to report the required analytical ranges for such technology to be of value in this patient cohort. Secondly, we review the current electrochemical approaches, including its sub-variants such as photoelectrochemical and electrochemiluminescence, for the determination of important CBs highlighting the various strategies used, namely the use of micro- and nanomaterials, to maximise the sensitivities and selectivities of such approaches. Finally, we consider the challenges that must be overcome to allow for the commercialisation of this technology and transition into intensive care medicine. Graphical abstract: [Figure not available: see fulltext.

Nano-molecularly imprinted polymers for serum creatinine sensing using the heat transfer method

Serum creatinine concentration is an important clinical measure of kidney function. However, standard methods of detection, such as the Jaffe method or enzymatic assays, suffer several disadvantages, including non-specificity and procedural complexity, or high cost, respectively. In this work, we propose the use of nano-molecularly imprinted polymers (nMIPs) in conjunction with the novel Heat Transfer Method (HTM) as a promising alternative sensing platform to these existing methods for measuring serum creatinine concentration. More specifically, it is shown that creatinine-imprinted nMIPs can be produced using a solid-phase templating method, and that simple drop-casting onto a cheap, disposable substrate can be used in conjunction with HTM to detect creatinine with a limit-of-detection of (7.0 ± 0.5) μM in buffer solutions. Furthermore, the nMIPs are shown to selectively bind creatinine in comparison to several similar molecules, and the sensing platform is demonstrated to be able to detect changes in creatinine concentration in complex blood plasma samples

Human Immunodeficiency Virus-1 Uses the Mannose-6-Phosphate Receptor to Cross the Blood-Brain Barrier

HIV-1 circulates both as free virus and within immune cells, with the level of free virus being predictive of clinical course. Both forms of HIV-1 cross the blood-brain barrier (BBB) and much progress has been made in understanding the mechanisms by which infected immune cells cross the blood-brain barrier BBB. How HIV-1 as free virus crosses the BBB is less clear as brain endothelial cells are CD4 and galactosylceramide negative. Here, we found that HIV-1 can use the mannose-6 phosphate receptor (M6PR) to cross the BBB. Brain perfusion studies showed that HIV-1 crossed the BBB of all brain regions consistent with the uniform distribution of M6PR. Ultrastructural studies showed HIV-1 crossed by a transcytotic pathway consistent with transport by M6PR. An in vitro model of the BBB was used to show that transport of HIV-1 was inhibited by mannose, mannan, and mannose-6 phosphate and that enzymatic removal of high mannose oligosaccharide residues from HIV-1 reduced transport. Wheatgerm agglutinin and protamine sulfate, substances known to greatly increase transcytosis of HIV-1 across the BBB in vivo, were shown to be active in the in vitro model and to act through a mannose-dependent mechanism. Transport was also cAMP and calcium-dependent, the latter suggesting that the cation-dependent member of the M6PR family mediates HIV-1 transport across the BBB. We conclude that M6PR is an important receptor used by HIV-1 to cross the BBB