Biogeography And Systematics Of The Nerodia Clarkii/nerodia Fasciata Clade In Florida

Biogeography provides a window into the evolutionary history of populations, and helps explain the diversity and distribution of life through time. Viewed from a systematic perspective, biogeographic studies generate convincing arguments to explain the relationships among organisms and categorize them into useful taxonomies. When taxonomies do not reflect evolutionary histories, inaccurate representations of biodiversity confound future studies and conservation efforts. Two thamnophiine snakes, Nerodia clarkii and Nerodia fasciata, harbor unique morphological and ecological adaptations that obscured natural groupings, leading to controversial taxonomic delimitations. Additionally, population declines documented in N. clarkii compressicauda and N. clarkii taeniata led managers to list N. clarkii taeniata as threatened in 1977. I generated a baseline for continued biogeographic and systematic study of the Nerodia clarkii/fasciata clade. I used mitochondrial DNA to build a parsimony-based haplotype network, infer the phylogenetic relationships between the two species and their thamnophiine relatives, and estimate the divergence times of major N. clarkii/fasciata clades. With these data, I tested biogeographic and systematic hypotheses about the origin and distribution of diversity in this clade. I used principal components analyses to summarize morphological data and discuss ecological observations in search of characters that may unite genetic or taxonomic units. The analyses revealed a peninsular and a panhandle clade in Florida that appeared to iv diverge as a result of Pleistocene glacial fluctuations. I found no support genetically, morphologically, or ecologically for the current taxonomy, indicating a need for range-wide research to generate revised nomenclature. My results do not support the protection status of N. clarkii taeniat

The ontogeny of cardiorespiratory support of metabolism

The formation of the cardiovascular system and its role in gas exchange has long been speculated to occur concomitantly. Although this premise has been suggested and quoted for more than a century, there are few studies to date which have attempted to validate these claims. Furthermore, the few which do exist have been primarily concerned with two things: first, how environment may affect the functional morphology; and second, how these changes may affect hemodynamics directly. As a result, our understanding of how gas exchange is coupled with to cardiovascular function is seriously lacking; The goal of this dissertation was to understand how, or if, the cardiovascular and respiratory systems coordinate function during development. Populations of amphibians were reared in various environments which included carbon monoxide (CO). This allowed for direct assessment of the efficacy of Hb in bulk O{dollar}\sb2{dollar} transport. The results indicated that CO, and the subsequent elimination of Hb function, had few ill effects on either aerobic or anaerobic metabolism. Further, the data indicated that cardiovascular function was mildly elevated. A separate study, set out to determine what factors limit overall O{dollar}\sb2{dollar} transport in developing embryos by limiting the available quantities of gas and eliminating Hb function. The results indicated that aerobic metabolism was unaffected in all populations. Cardiovascular function was mildly elevated, but only in populations of animals exposed to CO. Finally, gas exchange was modeled in developing embryos to determine the role of diffusion and plasma transport in overall O{dollar}\sb2{dollar} uptake. Calculations of maximal O{dollar}\sb2{dollar} flux indicate that diffusion would allow for enough gas to be exchanged to support aerobic metabolism in early life. Moreover, the role of plasma transport was considered in addition to diffusion, it be came clear that their combined transport would be adequate to support metabolism for animals in late life; A separate study evaluated how body composition changes with progressive development. From this it was determined that amphibians are unlike their fish counterparts in composition. When the total energy pool available for growth and development was calculated and compared with aerobic metabolism, it was shown that energy was not a limiting resource during development; Collectively these data indicated that Hb was not essential of O{dollar}\sb2{dollar} uptake and that the cardiovascular system as a whole may play a reduced role in total O{dollar}\sb2{dollar} turnover. Furthermore, the data indicates that neither diffusion nor perfusion limits total gas exchange. In addition, the model indicate that diffusion may be a viable mean to obtain O{dollar}\sb2{dollar} early in development, and that late in development convection of plasma coupled with diffusion could support metabolism. Finally, the body composition work indicate that resource limitations were not set by available substrate

Cross Sector Differences in the Awareness of the Glass Ceiling and Recourse Options

Gender inequality affects many women in the workplace creating a wage gap. If found, a solution to this problem could dismantle barriers and close the gap. The extent to which women are aware of the glass ceiling and where to find help was studied through an online survey. One hundred and thirty eight women from the public, non-profit and private sectors completed the six-question survey. The results show that women in the non-profit sector are more likely to know of the glass ceiling but also are more likely not to know where to find help when compared to the other sectors. The survey was supplemented with an elite interview, and a simulation through participant observation. Future research on the awareness across employment sectors could potentially be beneficial in breaking through the glass ceiling and closing the wage gap completely

IL NODULO TIROIDEO SOSPETTO: VECCHI E NUOVI INDICI PREDITTIVI DI MALIGNITA'

Scopo della presente tesi è stato quello di valutare se la determinazione dei livelli circolanti di tireoglobulina (Tg), associata ad alcuni caratteri ecografici, possa avere un ruolo predittivo nella diagnosi preoperatoria di malignità dei noduli tiroidei a citologia microfollicolare ed a cellule di Hürtle. La casistica è costituita da 215 pazienti (169 femmine, 46 maschi) con diagnosi citologica di nodulo tiroideo microfollicolare ed a cellule di Hürtle, successivamente sottoposti ad intervento di tiroidectomia. Per ogni paziente è stato effettuato uno studio della funzione tiroidea, un’ecografia tiroidea ed un esame citologico sul materiale raccolto mediante aspirazione con ago sottile. L'esame citologico ha deposto per neoplasia microfollicolare in 178/215 pazienti e per neoplasia a cellule di Hürtle nei rimanenti 37/215. La diagnosi istologica definitiva ha deposto per carcinoma tiroideo in 72/215 (33%) pazienti e per la natura benigna del nodulo nei restanti 143/215 (67%). In riferimento all’istotipo dei carcinomi, il 30% è risultato essere un carcinoma papillare variante classica, il 46% un carcinoma papillare variante follicolare, il 10% un carcinoma papillare a cellule alte o trabecolare, il 14% un carcinoma follicolare o a cellule di Hürtle. Le concentrazioni sieriche della Tg sono risultate più elevate nei noduli maligni rispetto ai noduli benigni; tuttavia, tale differenza è risultata statisticamente non significativa. Un aumento del rischio di malignità, peraltro non statisticamente significativo, è stato documentato nei noduli con presenza contemporanea di margini irregolari e di microcalcificazioni. Nei noduli maligni il diametro maggiore era inferiore rispetto a quello dei noduli benigni e la differenza osservata è risultata statisticamente significativa (p=0,044). Dallo studio della relazione tra concentrazioni sieriche di Tg e caratteri ecografici del nodulo, si è pervenuti ai risultati descritti di seguito. Concentrazioni elevate di Tg, in presenza di microcalcificazioni, sono risultate associate ad una maggiore probabilità di malignità del nodulo. Tale probabilità, peraltro statisticamente non significativa, risulta ancora più elevata quando alte concentrazioni sieriche di Tg sono associate alla presenza contemporanea di microcalcificazioni e di margini irregolari del nodulo. Una differenza statisticamente significativa del valore medio delle concentrazioni sieriche di Tg tra noduli maligni e noduli benigni è stata osservata quando il diametro maggiore del nodulo è inferiore a 3 cm (p=0,037). Infine, è stato evidenziato che concentrazioni sieriche di Tg superiori a 300 ng/ml, in pazienti con noduli di dimensioni inferiori a 3 cm, sono associate ad un incremento statisticamente significativo del rischio di malignità dei noduli (p=0,001) . In conclusione, i risultati ottenuti nella presente tesi suggeriscono che: 1)i caratteri ecografici di ipoecogenicità, di margini irregolari e di microcalcificazioni - isolati o in combinazione tra loro- non sono di per sé sufficienti per predire la malignità del nodulo; 2) la prevalenza di carcinoma è più elevata nei noduli con diametro minore, indipendentemente dalla presenza degli altri caratteri ecografici studiati; 3) il riscontro di concentrazioni sieriche elevate di Tg, nei noduli di piccole dimensioni, è associato ad un alto rischio di malignità

Meeting report of the annual workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer\u27s Disease research.

INTRODUCTION: The second annual 5-day workshop on Principles and Techniques for Improving Preclinical to Clinical Translation in Alzheimer\u27s Disease Research was held October 7-11, 2019, at The Jackson Laboratory in Bar Harbor, Maine, USA, and included didactic lectures and hands-on training. Participants represented a broad range of research across the Alzheimer\u27s disease (AD) field, and varied in career stages from trainees and early stage investigators to established faculty, with attendance from the United States, Europe, and Asia. METHODS: In line with the National Institutes of Health (NIH) initiative on rigor and reproducibility, the workshop aimed to address training gaps in preclinical drug screening by providing participants with the skills and knowledge required to perform pharmacokinetic, pharmacodynamics, and preclinical efficacy experiments. RESULTS: This innovative and comprehensive workshop provided training in fundamental skill sets for executing in vivo preclinical translational studies. DISCUSSION: The success of this workship is expected to translate into practical skills that will enable the goals of improving preclinical to clinical translational studies for AD. HIGHLIGHTS: Nearly all preclinical studies in animal models have failed to translate to successful efficacious medicines for Alzheimer\u27s disease (AD) patients. While a wide variety of potential causes of these failures have been proposed,deficiencies in knowledge and best practices for translational research are not being sufficiently addressed by common training practices. Here we present proceedings from an annual NIA-sponsored workshop focused specifically on preclinical testing paradigms for AD translational research in animal models aimed at enabling improved preclinical to clinical translation for AD

Manometric evaluation of internal anal sphincter after fissurectomy and anoplasty for chronic anal fissure: a prospective study

Chronic anal fissure (CAF) is a common painful clinical disease and its pathogenesis remains poorly understood. After failure of pharmacological therapy, that is the first-line treatment, sur- gical sphincterotomy remains the treatment of choice although it is followed by a high rate of anal incontinence resulting from the sphincter damage; therefore, the research of a sphincter-saving surgical option has become an important goal. The aim of this study was to evaluate the mano- metric modifications and the incidence of anal incontinence after fissurectomy and anoplasty with advancement skin flap in patients affected by CAF with hypertonia of the internal anal sphincter (IAS). Fifteen patients affected by CAF with hypertonia of IAS, unresponsive to medical therapy, were enrolled. All subjects underwent fissurectomy and anoplasty with advancement skin flap. Anorectal manometry was performed preoperatively and after 6 and 12 months from surgery. Maximum resting pressure (MRP), maximum squeeze pressure (MSP), ultraslow wave activity (USWA), fissure healing, anal continence, and postoperative complications were recorded. All patients healed within 30 days from surgery. No intra- or postoperative complications were recorded except for a case of partial donor site break. No significant modifications of MSP were detected. Six months after surgery, MRP was higher with respect to healthy subjects but signif- icantly reduced in comparison to baseline levels. At 12 months, it was higher have versus 6-month values but significantly lower versus preoperative values. USWA was significantly represented in patients with CAF versus healthy subject. Both at 6 and 12 months, they decreased significantly with respect to preoperative values without significant differences versus healthy subjects. Both at 6 and 12 months, anal continence did not differ with respect to preoperative time. The fissurectomy with anoplasty resulted in a high healing rate without surgical sequelae or anal incontinence. Also, it was able to reduce IAS pressure in the same manner as surgical sphincterotomy or forceful dilatation

Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection Versus Insulin Alone in Type 2 Diabetes

Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial glucose uptake alone or in combination with insulin compared to insulin alone in metformin-treated Type 2 diabetes mellitus. Design Comparison of myocardial fuel utilization after 3 months of treatment with insulin detemir, liraglutide, or combination detemir+liraglutide. Setting Academic hospital Participants Type 2 diabetes treated with metformin plus oral agents or basal insulin. Interventions Insulin detemir, liraglutide, or combination added to background metformin Main Outcome Measures Myocardial blood flow, fuel selection and rates of fuel utilization evaluated using positron emission tomography, powered to demonstrate large effects. Results We observed greater myocardial blood flow in the insulin-treated groups (median[25th, 75th percentile]: detemir 0.64[0.50, 0.69], liraglutide 0.52[0.46, 0.58] and detemir+liraglutide 0.75[0.55, 0.77] mL/g/min, p=0.035 comparing 3 groups and p=0.01 comparing detemir groups to liraglutide alone). There were no evident differences between groups in myocardial glucose uptake (detemir 0.040[0.013, 0.049], liraglutide 0.055[0.019, 0.105], detemir+liraglutide 0.037[0.009, 0.046] µmol/g/min, p=0.68 comparing 3 groups). Similarly there were no treatment group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusions These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection

Bilateral spermatic cord en bloc ligation by laparoendoscopic single-site surgery: preliminary experience compared to conventional laparoscopy

BACKGROUND: Laparo Endoscopic Single-site Surgery (LESS) represents an evolution of minimally invasive surgery and aims to improve cosmetic outcome and reduce surgical trauma and complications associated with traditional laparoscopy. This study was performed to present our preliminary experience in bilateral spermatic cord ligation with the LESS technique and compare the results with the outcomes of conventional laparoscopic surgery. METHODS: Between June 2007 and May 2013, 24 patients were referred to our institute for bilateral varicocelectomy. The indications for this type of procedure were bilateral varicocele with impairment of semen parameters or chronic bilateral testicular pain. All procedures were performed via the same surgeon. The patients were divided into two groups according to the type of laparoscopic surgery. Group A included 10 patients underwent LESS technique while group B included the remaining 14 patients that underwent conventional laparoscopy. RESULTS: The comparison between the two techniques showed some important advantages for LESS: shorter operating time (45.4 min vs. 88.3 (P\u2009<\u2009.001), shorter hospital stay (16.6 hours vs. 51.4 hours) (P\u2009<\u2009.001), early return to the normal activity (2.3 days vs. 4.7 days) and better cosmetic outcomes. No conversions from LESS to conventional laparoscopy were necessary and blood loss was insignificant in all patients.All patients in the LESS group reported full satisfaction with the cosmetic outcome, whereas 85.7% of patients after conventional laparoscopy were fully satisfied with cosmesis. CONCLUSIONS: Bilateral spermatic cord ligation with LESS is an alternative to conventional laparoscopy. The procedure was successfully performed in all patients. The trans-umbilical approach offers the advantage of a better cosmetic result, shorter hospital stay and less postoperative pain

Characterization of A Type 1 Collagen Targeted PET Tracer

poster abstractRenal fibrosis occurs in many diseases of the kidney, including chronic kidney disease (CKD). Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components, mainly type I collagen. Determination of the presence and extent of renal fibrosis may aid in the prediction of the long-term outcome of renal function in CKD. Biopsy is considered the gold standard in the diagnosis of renal fibrosis; however biopsy is inherently invasive and does not easily lend itself to following the disease thru time. A noninvasive technique such as PET would both allow the detection and monitoring of renal fibrosis progression. A type I collagen-specific cyclic peptide, EP-3533, has been identified and used as a contrast agent in MRI after conjugation with three Gd-DOTA chelates (Caravan et al 2007). To explore the potential for imaging with PET, which can provide a quantitative assessment of regional peptide localization, we have prepared an EP-3533 conjugate incorporating the NODAGA chelating agent at its amine terminus, and radiolabeled that conjugate with generator-produced positron-emitting 68Ga (68-minute half-life). In vitro association kinetics binding of the labeled peptide was performed in collagen type 1 coated plates, where 68GaDOTA-EP-3533 exhibited a Kd of 0.2 M for type I collagen. To better characterize the tracer in an animal model, renal fibrosis was induced in male Wistar rats by clamping the renal artery and vein of the left kidney for 50 minutes. Thus providing both a diseased and control kidney in each animal. Approximately 10 weeks after surgery both left (fibrotic) and right (normal) kidneys were resected and frozen and mounted in OTC for cryotomy. Longitudinal sections obtained from each kidney were used for autoradiography. ROI analysis found an approximate two- to four-fold region-dependent increase in binding in fibrotic tissue compared to normal. Collagen and non-collagen protein levels were determined in the same kidney sections that had been used for autoradiography using a commercially available staining assay. This assay yielded a 1.7-fold difference in collagen levels between normal and fibrotic tissue. Additionally, representative slices were stained with Sirius Red for histological evaluation. Preliminary data indicates that 68Ga-NODAGA-EP-3533 binds to collagen-rich tissue, consistent with the literature for Gd-DOTA-EP-3533. In vivo studies in an animal model of fibrosis are needed to further characterize this tracer and its potential for PET tracer detection and monitoring of Renal Fibrosis