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The burgeoning adoption of modern technologies provides a great opportunity for gathering multiple modalities of comprehensive personalized data on individuals. The thesis aims to address statistical challenges in analyzing these data, including patient-specific biomarkers, digital phenotypes and clinical data available from the electronic health records (EHRs) linked with other data sources to achieve precision medicine. The first part of the thesis introduces a dimension reduction method of microbiome data to facilitate subsequent analysis such as regression and clustering. We adopt the proposed zero-inflated Poisson factor analysis (ZIPFA) model on the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) and provide valuable insights into the relation between subgingival microbiome and periodontal disease. The second part focuses on modeling the intensive longitudinal digital phenotypes collected by mobile devices. We develop a method based on a generalized state-space model to estimate the latent process of patient's health status. The application to the Mobile Parkinson's Observatory for Worldwide Evidence-based Research (mPower) data reveals the low-rank structure of digital phenotypes and infers the short-term and long-term Levodopa treatment effect. The third part proposes a self-matched learning method to learn individualized treatment rule (ITR) from longitudinal EHR data. The medical history data in EHRs provide the opportunity to alleviate unmeasured time-invariant confounding by matching different periods of treatments within the same patient (self-controlled matching). We estimate the ITR for type 2 diabetes patients for reducing the risk of diabetes-related complications using the EHRs data from New York Presbyterian (NYP) hospital. Furthermore, we include an additional example of self-controlled case series (SCCS) study on the side effect of stimulants. Significant associations between the use of stimulants and mortality are found from both FDA Adverse Event Reporting System and the SCCS study, but the latter uses a much smaller sample size which suggests high efficiency of the SCCS design.

Honey is a naturally sweet substance produced by honeybees from water, pollen, and nectar. Due to its unique nutritional and therapeutic benefits, which are ascribed to the interaction of the various chemical groups it contains, natural honey is one of the most popular consumed products. Modern-day individuals consume a lot of refined granulated sugar, either directly through foods or indirectly from other sources. The consumption of large amounts of refined granulated sugar alters hematological and physiological changes in the body. According to several scientific studies, honey can be a healthier alternative to refined granulated sugar because it does not threaten human health. Consuming natural honey raises serum iron levels and red blood cell counts since it is known that the iron in honey serves as a precursor to hemoglobin. Overconsumption of refined granulated sugar has been identified as a risk factor for metabolic disorders such as obesity, cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. This study, therefore, investigated the effect of the golden liquid from honeybees (natural honey) and refined granulated sugar on the blood glucose and serum iron levels of 25 Wistar albino rats. The experimental animals used in this study were grouped into five treatments based on the dose of natural honey and refined granulated sugar administered namely: T1 (1.02 g of honey /kg BW), T2 (1.40g of honey /kg BW), T3 (1.02 g of refined granulated sugar /kg BW), T4 (1.40g of refined granulated sugar /kg BW), rats in T5 were not administered honey, and refined granulated sugar served as the control. The blood glucose concentration of the albino rats was measured using the glucose strips with a glucometer while the serum iron analysis was conducted using Atomic Absorption Spectrophotometer. The result revealed that the mean blood glucose level of the rats was highest in T3 (112.95mg/dl), followed by T5 (92.20mg/dl) while the least value was recorded in T2 (74.86mg/dl). There was a significant difference in the blood glucose levels of albino rats orally administered natural honey and refined granulated sugar at varying levels (P0.05) among treatments. It was found that the highest serum iron level was recorded in T5 (1.31±0.395 ppm) followed by T2 (1.22± 0.115 ppm), while the least serum iron level was recorded in T1 (0.88±1.319ppm). It was observed that there were no significant differences in the serum iron levels of the albino rats (p>0.05) among treatments The use of natural honey is recommended since albino rats orally administered honey at varying doses had lower blood glucose levels than those given refined granulated sugar. This work will be a useful tool for understanding the role of honey over granulated sugars, especially among prediabetic and diabetic patients in order to control their sugar levels using diet as a source. This implies that the consumption of natural honey did not significantly increase blood glucose levels. It was therefore recommended that physicians and dietitians should advocate for natural honey use over refined granulated sugar which could be safe for consumption by diabetic patients.

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Blood sugar levels were determined in toadfish and catfish by the Folin reducing procedure and a specific enzymatic glucose procedure. The difference between the two values was considered to be the rest reduction (RR). After alloxan injection, the RR level increased greatly reaching a peak at one hour and then decreasing. The glucose level rose more slowly. An attempt was made to study these changes in blood by paper chromatography using silver nitrate to detect reducing compounds. In normal blood, glucose, an unidentified compound, and several other reducing compounds present in small amounts were separated. The large amount or RR present after alloxan could not be detected by silver nitrate. The significance of the results was discussed and future investigations were suggested. / Thesis / Master of Science (MSc)

Conventional techniques within the beef cattle industry involve weaning the calf from the dam when the calf is about 205 days of age. Weaning induces a stress-response that is implicated in reducing the health and productivity of newly weaned calves. Our goal was to evaluate the impact of weaning on the stress immune responses of beef calves. To that end, we 1) evaluated novel methods to quantify physiological markers of stress, 2) compared immune function and growth of calves grazing legume versus grass forages, and 3) compared the effects of abrupt versus two-stage weaning on calves. In study 1, calf, yearling, and adult beef cattle were used to assess the accuracy and precision of handheld glucometers in quantifying bovine blood glucose concentration. Precision Xtra® and ReliOn® glucometers were used chute side to quantify blood glucose concentrations in cattle and were compared to an accepted plasma glucose analysis on the same samples for validation. The Precision Xtra® glucometer was more accurate and precise than the ReliOn® glucometer. In study 2, weaned heifers were used to compare the immunomodulatory effects of grazing alfalfa versus fescue over a 30 day grazing period. No differences were detected in the interferon gamma (IFNγ) production and weight gain between the heifers on alfalfa and fescue. In study 3, effects of two-stage (fenceline) and abrupt weaning were compared. Calf weights, immune cell function, antibody production, blood glucose concentrations, fecal cortisol concentrations, and gene expression (FAS, IL-4,IL-10, and IFNγ) were measured pre- and post-weaning. On the day after weaning, the abruptly weaned calves had higher blood glucose concentrations than fenceline weaned calves. Fecal cortisol concentration and gene expression of FAS and IL-4 increased in both groups after weaning, but no differences were detected between the weaning treatments. Gene expression of IL-10 and IFNγ did not change over time. No date, treatment or treatment*date effect was detected for total weight gain or IFNγ production within the non-stimulated and the mitogen-stimulated whole blood samples. / Master of Science

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Seit Veröffentlichung der Studien von G. Van den Berghe et al. im Jahre 2001 galt es die strikte Blutzuckereinstellung in normoglykämische Bereiche bei Schwerverletzten anzustreben. Die intensivierte Insulintherapie wurde daraufhin von verschiedensten Fachgesellschaften in Leitlinien und Therapieregimen integriert, so auch auf der neurochirurgischen ITS der Universitätsklinik Leipzig. Kurze Zeit später erschienen große multizentrische Studien, die den Benefit der intensivierten Insulintherapie in Frage stellten und sogar von einer signifikant höheren Letalität bei strikt normoglykäm eingestellten Patienten berichteten. Daher wird in dieser Studie die zwiespältige aktuelle Datenlage zum Anlass genommen, die Beziehungen zwischen Blutzuckereinstellung und ITS-Regime sowie die Auswirkungen hyperglykämischer Stoffwechselsituationen und mögliche Bedeutung des Blutglukosespiegels respektive der intensivierten Insulintherapie speziell für Patienten mit isoliertem mittelschwerem und schwerem Schädel-Hirn-Trauma zu evaluieren. Mit Hilfe der Integration wird erstmalig ein Verfahren zur Blutglukosedarstellung verwendet, dass durch die Flächenberechnung (Area under the Curve (AUC-BG)) ein Abbild von Höhe und Dauer der Hyperglykämie schafft. Es konnte gezeigt werden, dass die Blutzuckereinstellung mit dem klinischen Verlauf, krankheitsspezifischen Therapiekonzepten, Komplikationen und dem Outcome der Patienten korreliert und positiv Einfluss nimmt. Von besonderem Interesse war die Auswirkung auf den Hirndruck und die Notwendigkeit von Dekompressionskraniektomien, als auch auf Infektionsereignisse, die kontrollierte Beatmung, Ernährungsform und das Outcome. Nach Einführung der intensivierten Insulintherapie wurde ein Vergleich mit konventionell therapierten Patienten herbeigeführt. Es wurden vergleichende Analysen zwischen der retrospektiven (n = 65, konventionelle Insulintherapie, Blutzucker < 10,0 mmol/l [< 180 mg/dl]) und prospektiven Gruppe (n = 65, intensivierte Insulintherapie, Blutzucker 4,4 – 6,1 mmol/l [80 – 110 mg/dl]) bezüglich Blutzuckerfläche, Intensivverlauf und Outcome durchgeführt. Nach 1:1-Matching hinsichtlich Alter und Geschlechterzugehörigkeit waren die beiden Therapiegruppen homogen und es zeigten sich keine Unterschiede bezüglich der Aufnahmecharakteristik. Schädelhirntraumatisierte Patienten profitierten von einer intensivierten Insulintherapie im Vergleich zur Kontrollgruppe, auch wenn es nicht gelang, den Blutzuckerspiegel entsprechend der initiierten Therapierichtlinie signifikant hin zur Normoglykämie zu senken. Die positiven Effekte zeigten sich deutlich in Bezug auf die Infektionsrate und Ernährungsform. Die intensivierte Insulintherapie senkte den Hirndruck und die Rate risikobehafteter Dekompressionskraniektomien mit einem deutlicheren Trend zu besseren Outcomemesswerten. Vor allem Patienten mit einem besseren initialem GCS und Nicht-Diabetiker scheinen von einer guten Blutzuckereinstellung zu profitieren. Hypoglykämien (Blutzucker ≤ 3 mmol/l) traten entgegen der Vermutung dabei nicht gehäuft auf und stellten somit kein Gegenargument einer derartigen Therapie dar. Die Senkung des Blutzuckers in einen moderaten, therapeutischen Bereich sollte das Mindestziel in der Gesamttherapie von Patienten mit einem mittelschweren und schweren Schädel-Hirn-Trauma sein, wobei ein Konsens über den optimal therapeutischen Blutzuckerzielbereich bisher noch nicht gefunden wurde und somit weitere Untersuchungen gerechtfertigt sind.

O tratamento para síndrome dos ovários policísticos (SOP) inclui como primeira linha de cuidados a mudança de estilo de vida com dieta balanceada e exercícios físicos. Dentre as intervenções nutricionais o jejum intermitente (JI) é uma estratégia alternativa. O objetivo deste estudo foi avaliar o impacto do JI em aspectos metabólicos e reprodutivos em modelo animal de SOP. A SOP experimental foi induzida por injeção subcutânea de propionato de testosterona, em período neonatal. Os animais do grupo Controle receberam injeção subcutânea de óleo de girassol. Após 90 dias de idade, instituiu-se a intervenção: grupo JI recebeu ração padrão em dias alternados enquanto o grupo controle manteve a dieta no esquema habitual. Os grupos experimentais foram: Controle ad libitum (n=10), Controle JI (n=10), SOP ad libitum (n=11) e SOP JI (n=15). Foram realizados: teste de tolerância à insulina (ITT) e à glicose (GTT), esfregaço vaginal, passagem por gaiolas metabólicas e PET/CT para avaliar atividade metabólica de tecido gorduroso. Após 4 semanas de JI, os animais foram eutanasiados e coletados tecido adiposo em região inguinal, perigonadal e mesentérica, adrenal, coração, ovários e útero. Como resultados, identificamos que a ingestão alimentar no grupo SOP foi maior em relação ao Controle, antes e depois da intervenção, assim como a sua massa corporal. Nas gaiolas metabólicas pré-jejum, a ingestão alimentar e hídrica, excreção fecal e urinária foram maiores nos animais SOP. No ITT, a glicemia basal dos animais SOP ADL apresentou-se maior que os Controle ADL. No GTT, a glicemia de jejum das ratas Controle JI era maior que as ratas Controle ADL. O peso da inguinal do grupo SOP JI era menor que SOP ADL. A gordura mesentérica se apresentou menor nos animais Controle JI em relação ao Controle ADL. Controle e SOP JI possuíam menores quantidades de perigonadal quando comparadas as ADL. O peso do coração dos animais SOP ADL era maior que os SOP JI. Grupos SOP apresentaram maior adrenal que os Controle. SOP JI possuía menor peso de ovário em relação aos grupos Controle ADL e JI. Em conclusão, o jejum intermitente reduziu os depósitos de gordura perigonadal e mesentérica dos animais Controle, e inguinal e perigonadal dos animais SOP. Além disso, o JI aumentou a glicemia basal das ratas Controle / Treatment for polycystic ovary syndrome (PCOS) includes as first line of care lifestyle change with balanced diet and exercise. Among the nutritional interventions, intermittent fasting (IF) is an alternative strategy. The objective of this study was to evaluate the impact of IF on metabolic and reproductive aspects in animal models of PCOS. Experimental PCOS was induced by subcutaneous injection of testosterone propionate in the neonatal period. Control animals received subcutaneous injection of sunflower oil. After 90 days of age, the intervention was instituted: IF group received standard ration on alternate days while the control group maintained the diet in the usual scheme. The experimental groups were: Control ad libitum (n = 10), Control IF (n = 10), PCOS ad libitum (n = 11) and PCOS IF (n = 15).The following tests were performed: insulin tolerance test (ITT) and glucose (GTT), vaginal smear, passage through metabolic cages and PET / CT to evaluate the metabolic activity of fatty tissue. After 4 weeks of IF, the animals were euthanized and collected adipose tissue in inguinal region, perigonadal and mesenteric, adrenal, heart, ovaries and uterus. As results, we identified that the food intake in the PCOS group was higher in relation to the Control, before and after the intervention, as well as their body mass. In the pre-fast metabolic cages, food and water intake, fecal and urinary excretion were higher in PCOS animals. In ITT, the basal glycemia of the PCOS ADL animals was higher than the Control ADL. In GTT, the fasting glycemia of Control IF rats was greater than the Control ADL rats. The inguinal weight of the PCOS IF group was less than PCOS ADL. Mesenteric fat was lower in Control IF animals than in Control ADL. Control and PCOS IF had smaller amounts of perigonadal when compared to ADL. The heart weight of the PCOS ADL animals was higher than the PCOS IFs. PCOS groups presented greater adrenal than Control. PCOS IF had lower ovary weight in relation to the ADL and IF Control groups. In conclusion, intermittent fasting reduced deposits of perigonadal and mesenteric fat in Control animals, and inguinal and perigonadal in PCOS animals. In addition, IF increased basal glycemia of control rats