Application of 2,3,5-triiodobenzoic acid (TIBA) at 1, 2, 4, 5 and 12 g/ha to field-grown snap beans (Phaseolus vulgaris L.) at early bloom caused a reduction in plant height and width but not dry weight. Yield differences occurred with the cultural variables of cultivar ('Sprite' and 'Dark-Seeded Provider') and row spacing (single and double rows) but not with the chemical treatment. Low soil moisture at the time of TIBA application was suspected of interfering with absorption and action of the chemical. In the winter and spring of 1981 greenhouse studies were conducted with 2 g/ha TIBA treatment of double-row snap beans grown under 3 pre-flower moisture regimes. Early yield was increased with the TIBA treatment, but the total yield did not differ due to a reduced second harvest, such that TIBA functioned as a yield catalyst under these study conditions. Environment was a more important determinant of the snap bean productivity as yield increased with more available soil moisture in both trials and decreased with warmer temperatures during the second crop trial. The importance of environmental influences on TIBA effect is discussed. / M.S.

The kidney is an organ that plays a major role in the homeostasis of the body. The kidney has several roles such as fluid management, electrolyte balance, vitamin D production, blood pressure control, removal of wastes, red blood cell production, and pH balance. Damage to the kidney can result in severe comorbidities and even mortality. Currently, kidney disease affects over 800 million individuals today (United States Renal Data System, 2022). One of the primary methods to treat kidney disease is using dialysis as a form of renal replacement. The two current dialysis modalities are peritoneal dialysis and hemodialysis. The purpose of this thesis is to establish a background in the kidney, kidney disease, and dialysis. With this background, this thesis aims to present the advantages and disadvantages of each of the three dialysis access: arteriovenous grafts, arteriovenous fistulas, and central venous catheters. By exploring the creation methods, dialysis use, and patient perspective, this thesis has demonstrated that arteriovenous fistulas are the supreme access. However, arteriovenous grafts and central venous catheters provide important alternatives and should not be ignored.

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Despite the high prevalence of chronic kidney disease, renal narratives are under-reported. Much of what is written on kidney failure is written by health care professionals for health care professionals and about patients. While medical experts and health care practitioners have one type of knowledge, their patients have another type of knowledge acquired through their experience of their own condition. From within the disability and patients’ rights movements urgent calls have been made for the authentic voices of disabled people and patients to be heard without the mediation of professional lenses. In response to this my dissertation combines personal and academic writing to explore my own experience of end-stage renal disease, dialysis, transplantation and the life after transplant. I have used autoethnography as a methodology. Autoethnography is a relatively new, somewhat postmodern form of inquiry that developed from the reflexive turn in anthropology and narrative studies in the latter part of the twentieth century. It is very useful in writing about the experience of illness and reflecting on illness narratives because, in autoethnographic writing, the observer and observed, the narrator and narrated, insider and outsider are the same person. This allows scope for exploring the problematics of representation and for finding alternatives to already existing ways of telling certain stories. Engaging with autoethnography’s postmodern aspects has allowed me to conceptualize experiences that, until I undertook this research, I have never been able to articulate, because the traditional (static) illness narrative forms did not speak to my experience or my understanding of my condition. The central issue in my dissertation lies in the question: How do I tell the story of chronic illness once I have had an organ transplant? Flowing from this are a number of sub-issues: Can my story change? How do I describe myself: The well, the ill, the impaired, the disabled, the afflicted? Do I describe myself living in no man’s land? In my narrative, do I oscillate between being well and ill, or do I occupy another territory entirely? And if I do, what is it? My study shows that writing the story (or stories) of chronic kidney disease is complex, nuanced and dynamic and that, far from being an extended liminal experience, kidney disease is littoral. This distinction is important in coming to narrative terms with an identity that is not damaged so much as different. Through this I hope to demonstrate to both outsiders and insiders, who often submit to narratives that are forced on them, that more satisfying alternatives can be found. / AFRIKAANSE OPSOMMING: Ondanks die hoë voorkomssyfer van chroniese nierkwale word nierverhale nie genoeg aangemeld nie. Die meerderheid van dit wat oor nierversaking geskryf word, word deur gesondheidsorgdeskundiges vir gesondheidsorgdeskundiges en oor pasiënte geskryf. Terwyl mediese deskundiges en gesondheidsorgpraktisyns een soort kennis het, het hulle pasiënte ’n ander soort kennis op grond van hulle ervaring van hulle eie toestande. Van binne die gestremdheid en pasiënteregte-bewegings het ’n dringende oproep weerklink vir die outentieke stemme van mense met gestremdhede en pasiënte om gehoor te word sonder die tussenkoms van professionele perspektiewe. In reaksie hierop kombineer my verhandeling persoonlike en akademiese beskrywings om my eie ervaring van eindstadium- nierkwale, dialise, oorplanting en die lewe na oorplanting te verken. Ek het outo-etnografie as metodologie gebruik. Outo-etnografie is ’n relatief nuwe, ietwat postmoderne vorm van ondersoek wat in die tweede deel van die twintigste eeu uit die refleksiewe wending in antropologie en narratiewe studies ontwikkel het. Dit is baie bruikbaar wanneer oor die belewenis van siekte en besinning oor siekte-narratiewe geskryf word aangesien die waarnemer en die waargeneemde, die verteller en dit wat vertel word, die ingewyde en die buitestander in outo-etnografiese skryfwerk dieselfde persoon is. Dit laat meer ruimte vir verkenning van die problematiek van voorstelling en vir die opspoor van alternatiewe vir reeds bestaande wyses om sekere stories te vertel. My bemoeienis met postmoderne aspekte van outo-etnografie het dit vir my moontlik gemaak om ervaringe wat ek tot en met hierdie navorsing nooit kon artikuleer nie, te konseptualiseer, aangesien die tradisionele (statiese) vorme van siekte-narratiewe nie tot my ervaring of my begrip van my toestand gespreek het nie. ‘Hoe vertel ek die storie van chroniese siekte nadat ek ’n orgaanoorplanting gehad het?’ is ’n sentrale vraagstuk in my verhandeling. Hieruit spruit ’n aantal newevraagstukke voort: Kan my storie verander? Hoe beskryf ek myself: Die gesonde persoon, die sieke, die verswakte, die gestremde, die aangetaste? Hoe beskryf ek myself wat in ’n niemandsland woon? Fluktueer ek in my narratief tussen gesond wees en siek wees of betrek ek ’n geheel ander gebied? En indien wel, wat is dit? My studie toon dat, om die storie (of stories) van chroniese niersiekte te skryf, kompleks, genuanseerd en dinamies is en dat niersiekte glad nie ’n uitgebreide liminale ervaring is nie, maar eerder littoraal is. Dit is belangrik wanneer daar tot ’n narratiewe verstandhouding gekom moet word met ’n identiteit wat nie soseer beskadig is nie, maar eerder anders. Hierdeur hoop ek om aan beide buitestanders en ingewydes, wat dikwels voor narratiewe wat op hulle afgedwing word, moet buig, te wys dat daar meer bevredigende alternatiewe gekry kan word.

Development of the adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as global endocrine and physiological effectors. In recent years the zebrafish has been utilized as a favorable animal model as a step towards dissecting and better understanding these postembryonic developmental processes. One of the more powerful methods utilized in zebrafish has been the identification of new gene functions through the use of mutant screens. The nutria mutant was recovered from one such screen to identify postembryonic defects in pigment pattern, growth and metamorphosis. These mutants exhibited a pigment cell defect, touch unresponsiveness and severe growth retardation. Here I will discuss my work towards dissecting the underlying developmental processes governing the phenotypic changes in nutria mutants. I characterize gross alterations in skeletal development in nutria mutants that lead to accelerated endochondral ossification but delayed intramembranous ossification. I show that the nutria phenotype results from mutations in trpm7, which encodes a transient receptor potential (TRP) family member that functions as both a cation channel and a kinase. I find trpm7 expression in the fish-specific, ion homeostasis-regulating gland known as the corpuscles of Stannius (CS), and in the mesonephric kidney. I show that mutants also develop kidney stones. Together these results suggest a role for trpm7 activity in regulation of physiological ion homeostasis. Next I confirm that role by identifying late-embryonic and early larval defects in the CS and the kidney, two organs that regulate physiological ion homeostasis. I demonstrate the early larval detection of kidney stones in trpm7 mutants and show that their appearance is presaged by decreased levels of total calcium and magnesium. Furthermore I establish a link between trpm7 function in the CS and stanniocalcin1 (stc1), a potent molecular regulator of calcium homeostasis. Finally, using transgenic overexpression and morpholino-oligonucleotide knockdown, I demonstrate that stc1 modulates calcium and magnesium levels in trpm7 mutant and wild-type backgrounds. Together these analyses establish postembryonic roles for trpm7 function in growth, skeletogenesis, kidney function, and physiological ion homeostasis. / text

The metanephric kidney consists of two types of epithelia; the Wolffian duct-derived ureteric bud and the nephrogenic components that originate from mesenchymal-toepithelial transitions in the metanephric mesenchyme. The ureteric bud forms when inductive signals from the metanephric mesenchyme stimulates the evagination of an epithelial tube from the Wolffian duct into the mesenchyme. Reciprocal signalling between the ureteric bud and the metanephric mesenchyme regulates the branching of the ureteric bud and the induction of nephron formation. Inductive and inhibitory signalling of ureteric bud growth and branching has been shown by several protein families, however, the mechanical aspects of ureteric bud branching and nephrogenesis are largely unknown. I investigated the roles of Rac1-GTPase and Rho-kinase during kidney development. These proteins are important regulators of the cytoskeleton where Rac1 is a promoter of actin filament polymerisation and Rho-kinase directly stimulates the formation and contraction of actin-myosin stress fibres. Using a cell-permeable inhibitor, Rac1 was inhibited with no effects on nephron formation or subsequent segmentation and patterning. Inhibition of active Rac1 significantly reduced the level of ureteric bud branching and also resulted in lower proliferation rates. Rho-kinase was similarly targeted using two inhibitors. Rho-kinase inhibition had important effects on nephron formation and nephron maturation. Inhibition of Rhokinase resulted in decreased levels of nephron formation and severely morphologically abnormal nephrons. The formation of apical-basal polarity was disturbed as was the development of the visceral and parietal epithelia; precursors of the renal corpuscle. Inhibition of Rho-kinase led to abnormal formation of the proximal-distal axis and abnormal segmentation of the nephron. The effects of Rho-kinase inhibition were partially mimicked by direct targeting of actin-myosin contractions using a myosin-ATPase inhibitor. This demonstrated that Rho-kinase is necessary during multiple stages of nephrogenesis and maturation, at least in part, as a result of its ability to regulate actin-myosin contraction. These results show that Rac1 and Rho-kinase play important roles during several aspects of kidney development and highlights the significance of further investigating the mechanisms involved during kidney organogenesis.

Chronic kidney disease (CKD), defined as a decrease in renal function, is a global issue. The treatment of CKD and its comorbidities imparts a costly burden on the American healthcare system, therefore the need for therapeutics that prevent the progression of chronic kidney disease is urgent. Microarray studies have shown that the serine protease inhibitor clade A member 3 (SERPINA3) is transcriptionally upregulated in kidney injury. SERPINA3 is an extracellular protease inhibitor that maintains the homeostasis of extracellular matrix proteins. Our lab hypothesizes that SERPINA3 might not only be a transcriptional biomarker for kidney injury, but the SERPINA3 protein might act as a key upstream regulator in the advancement of renal inflammation and fibrosis. Our research characterizes the expression patterns of SERPINA3 in models of acute and chronic kidney injury through immunoblotting and immunohistochemistry. Our unilateral ureteral obstruction (UUO) model of chronic renal injury displays significant glomerular localization of SERPINA3. The adenine diet model of chronic kidney injury and the renal ischemic reperfusion injury (RIRI) model of acute kidney injury both display tubular upregulation of SERPINA3. The DOCA-salt hypertension model of chronic kidney injury was imposed on two strains of mice, C57BL/6 and 129/sv, both of which display tubular and glomerular upregulation of SERPINA3. However, the C57BL/6 strain, which is known for its resistance to glomerular sclerosis, displays higher renal localization of SERPINA3 when exposed to DOCA-salt hypertension, than does the 129/sv strain. In conclusion, our data suggests that SERPINA3 protein is upregulated in both acute and chronic kidney injury. The role of SERPINA3 in these models remains unknown, however, our lab theorizes that SERPINA3 protein may be renoprotective in certain instances of kidney injury. Functional assays must be performed to elucidate the role of SERPINA3 in these models of kidney injury. Characterizing the function of SERPINA3 in chronic and acute kidney injury might aid in the development of novel therapeutics to prevent the advancement of CKD.

Thesis advisor: Stefan Hoderlein / This dissertation is divided into two parts. Part I - Dynamic Kidney Exchange In recent years, kidney paired donation (KPD) has an emerged as an attractive alternative for end-stage renal disease patients with incompatible living donors. However, we argue that the matching algorithm currently used by organ clearinghouses is inefficient, in the sense that a larger number of patients may be reached if kidney transplant centers take into consideration how their pool of patients and donors will evolve over time. In our work Two Novel Algorithms for Dynamic Kidney Exchange, we explore this claim and propose new computational algorithms to increase the cardinality of matchings in a discrete-time dynamic kidney exchange model with Poisson entries and Geometric deaths. Our algorithms are classified into direct prediction methods and multi-armed bandit methods. In the direct prediction method, we use machine learning estimator to produce a probability that each patient-donor pair should be matched today, as op- posed to being left for a future matching. The estimators are trained on offline optimal solutions. In contrast, in multi-armed bandit methods, we use simulations to evaluate the desirability of different matchings. Since the amount of different matchings is enormous, multi-armed bandits (MAB) are employed to decrease order to decrease the computational burden. Our methods are evaluated using simulations in a variety of simulation configurations. We find that the performance of at least one of our methods, based on multi-armed bandit algorithms, is able to uniformly dominate the myopic method that is used by kidney transplants in practice. We restrict our experiments to pairwise kidney exchange, but the methods described here are easily extensible, computational constraints permitting. Part II - Econometrics In our econometric paper Heterogenous Production Functions, Panel Data, and Productivity, we present methods for identification of moments and nonparametric marginal distributions of endogenous random coefficient models in fixed-T linear panel data models. Our identification strategy is constructive, immediately leading to relatively simple estimators that can be shown to be consistent and asymptotically normal. Because our strategy makes use of special properties of “small” (measure-zero) subpopulations, our estimators are irregularly identified: they can be shown to be consistent and asymptotically Normal, but converge at rates slower than root-n. We provide an illustration of our methods by estimating first and second moments of random Cobb-Douglas coefficients in production functions, using Indian plant-level microdata. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Economics.

Introdução: A prevalência de doença renal crônica na faixa etária pediátrica ainda é desconhecida. O tratamento de escolha é o transplante renal, independente da idade. Os principais objetivos do tratamento são a manutenção do desenvolvimento físico, neurológico e esquelético, prevenção da doença do metabolismo mineral e ósseo (DMMO), adequada maturação sexual e da função endócrina. O déficit de crescimento está relacionado com a idade de surgimento da insuficiência renal e ocorre devido à má-nutrição energético-calórica, DMMO e uso de corticoide, além dos efeitos deletérios da anemia, uremia e resistência ao hormônio do crescimento. Causas relacionadas ao paciente como retardo de crescimento intra-uterino e malformações congênitas também estão relacionadas. Objetivos: avaliar o desenvolvimento pondero-estatural dos pacientes pediátricos submetidos a transplante renal no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC FMRP-USP). Casuística: revisão dos prontuários dos pacientes pediátricos submetidos a transplante renal no HC FMRP-USP e análise do desenvolvimento pondero-estatural comparando os score-z altura para idade e índice de massa corporal (IMC) para idade durante o acompanhamento. As variáveis analisadas foram sexo, faixa etária, uso de Basiliximab, realização ou não de diálise, tipo de transplante realizado (doador falecido ou doador vivo relacionado), hipertensão arterial, dose de manutenção de prednisona. Resultados: foi possível avaliar os dados de 31 pacientes, 10 femininos e 21 masculinos. Ao longo do tempo houve ganho significativo em peso (p< 0,0001) e estatura (p< 0,0001) mas nenhuma das variáveis analisadas mostrou diferença estatisticamente significativa. Houve interação significativa do uso de Basiliximab e da faixa etária sobre o IMC e do uso de Basiliximab, faixa etária e dose de prednisona utilizada sobre a evolução da estatura. A estatura manteve abaixo da média padrão durante todo o acompanhamento e nenhum paciente atingiu a altura final esperada. O IMC estava abaixo da média padrão na ocasião do transplante mas a partir do primeiro ano recuperou e manteve estável em torno do percentil 0. Conclusões: a doença renal crônica na infância compromete o desenvolvimento ponderoestatural dos pacientes afetados. / Introduction: The prevalence of chronic kidney disease in the pediatric age range is still unknown. The treatment of choice is a renal transplant, regardless of age. The main objectives of treatment are the maintenance of physical, neurological and skeletal development, the prevention of renal osteodystrophy, and appropriate sexual and endocrine function maturation. The growth deficit is related to the age at onset of renal failure and is due to energy-calorie malnutrition, to renal osteodystrophy and to corticoid use, in addition to the deleterious effects of anemia, uremia and of resistance to growth hormone. Additional patient-related causes are intrauterine growth retardation and congenital malformations. Objectives: to assess the weight-height development of pediatric patients submitted to renal transplantation at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HC FMRP-USP). Patients: The medical records of pediatric patients submitted to renal transplantation at HC FMRP-USP were reviewed and weight-height development was analyzed by comparing the zscores for height for age and body mass index (BMI) for age during follow-up. The variables analyzed were: sex, age range, use of Basiliximab, having undergone dialysis or not, type of transplant performed (cadaver donor or related live donor), arterial hypertension, and maintenance dose of prednisone. Results: it was possible to assess the data of 31 patients, 10 girls and 21 boys. A significant weight gain (p<0.0001) and height (p<0.0001) occurred over time but none of the variables analyzed showed a statistically significant difference. There was a significant interaction between age range and BMI, between the use of Basiliximab and age range and between the prednisone dose used and height evolution. Height was below the standard mean value throughout follow-up and no patient reached the expected final height. BMI was below the standard mean value at the time of transplantation, but recovered after the first year and remained stable at a value of about 0. Conclusions: renal failure during childhood compromises the weight-height development of affected patients.

A ingestão excessiva de fluoreto por um longo período de tempo pode resultar em fluorose, que pode causar manifestações dentárias e esqueléticas. Danos metabólicos, funcionais e estruturais causados pela fluorose crônica tem sido relatados em vários tecidos. O objetivo deste estudo foi avaliar os efeitos do fluoreto administrado na água de beber, da administração de fluoreto na água de beber na defesa antioxidante de ratos. Quatro grupos de ratos wistar foram usados (n=10/grupo). Os animais receberam água de beber contendo 0 (controle), 5, 15 ou 50 ppm de fluoreto durante 60 dias. Eles foram eutanasiados e os tecidos (fígado, rins e coração) e plasma foram coletados e homogenizados. Superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa reduzida (GSH), substâncias antioxidantes totais (SAT), substâncias reativas ao ácido tiobarbitúrico (TBARS), hidroperóxido de lipídios (HL) e fluoreto foram análisadas. Dados foram analisados por ANOVA e teste de Tukey ou Kruskal-Wallis e teste de Dunn (p<0,05). Nos rins, SOD, GPx, GSH e SAT diminuiram e fluoreto e HL aumentaram significantivamente. No fígado, CAT e TBARS diminuiram, SOD, HL e SAT aumentaram significativamente. No coração, GPx aumentou significativamente. No plasma, SOD e HL diminuiram significativamente. Em resumo, esses resultados mostram que a administração crônica de fluoreto altera o sistema antioxidante de ratos. Nosso dados sugerem que a exposição em níveis elevados de fluoreto, a conversão do ânion superóxido em água nos rins parecem ocorrer principalmente através da SOD e CAT, com baixa participação do sistema glutationa, diferindo do que parece ocorrer no fígado. / Excessive fluoride intake over a long period of time could result in fluorosis, which can lead to dental and skeletal manifestations. Metabolic, functional and structural damages caused by chronic fluorosis have been reported in many tissues. The aim of this study was to evaluate the effect of fluoride, administered in drinking water, in the antioxidant defense of rats. Four groups of Wistar rats were included (n=10/group). The animals received drinking water containing 0 (control), 5, 15 or 50 ppm of fluoride during 60 days. They were euthanized and the tissues (liver, kidney and heart) and plasma were collected and homogenized. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), antioxidants, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide (LH), and fluoride were analyzed. Data were analyzed by ANOVA and Tukeys test or Kruskal-Wallis and Dunns tests (p<0.05). In the kidney SOD, GPx, GSH and SAT decreased and fluoride and LH increased significantly. In the liver, CAT and TBARS decreased and fluoride, SOD, LH and SAT increased significantly. In the heart, GPx increased significantly. In the plasma, SOD and LH decreased significantly. In summary, these results show that chronic fluoride administration alters the antioxidant system of the rats. Our data suggest that upon exposure to high levels of fluoride, the conversion of the superoxide anion to water in the kidney seems to occur mainly through the SOD and CAT, with a low participation of the glutathione system, differing from what seems to occur in the liver.

Acute kidney injury (AKI) is a major risk factor for chronic kidney disease (CKD). For patients who recover from AKI, there is a 25% increase in the risk of CKD, and a mortality rate of up to 50% after 10 years. Nuclear factor kappa-B (NF-κB) is a family of transcription factors that regulates the transcription of many proteins that play a key role in inflammation. Inhibitor of IκB kinase (IKK) is directly upstream of NF-κB. My aim was to investigate a) the role of IKK in the progression of AKI to CKD, and b) whether its inhibition attenuates renal fibrosis. In this thesis I used a model of unilateral renal ischaemia-reperfusion injury with contralateral nephrectomy, to firstly map the acute time course of AKI. From the data generated from the time course, I decided to treat the animals at 24 h post reperfusion with the IKK inhibitor, IKK16, as i) this was at the peak of renal dysfunction (24 h post reperfusion), and ii) prior to the activation of NF-κB (48 h post reperfusion). The inhibition of IKK at 24 hours post reperfusion, as a delayed treatment, successfully attenuated renal dysfunction, NF-κB activation and renal structural damage. I subsequently increased the recovery time after ischaemia-reperfusion in my rat model to 28 days to study the development of fibrosis post AKI. The inhibition of IKK at 24 hours post reperfusion successfully attenuated the development of fibrosis, formation of myofibroblasts, macrophage infiltration, the expression of pro-fibrotic markers and the deposition of extracellular matrix components at 28 days post reperfusion. In addition, the delayed inhibition of IKK at days 7-13 post unilateral ureteral obstruction in a rat model, successfully attenuated the development of fibrosis, formation of myofibroblasts, macrophage infiltration, the expression of pro-fibrotic markers and the deposition of extracellular matrix components. These data indicate that the activation of the IKK complex drives tubulointerstitial fibrosis, and suggests that the inhibition of IKK could be a useful pharmacological tool for the creation of therapies to combat AKI and the subsequent development of fibrosis, via the reduction of both inflammation and the prevention of the expression of pro-fibrotic markers.