Tutkielmassa selvitetään, mitkä bariatriset toimenpiteet ovat tehokkaimpia lihavuuden hoidossa, tavoitetasapainon saavuttamisessa ja painonhallinnassa 1 vuoden seurantajaksolla. Lisäksi tarkastellaan leikkausmenetelmän vaikutusta liitännäissairauksien vähenemisiin. Kyseessä on rekisteritutkimus. Aineistona käytettiin kaikkia OYS:n gastroenterologisen kirurgian osastolla leikattuja potilaita vuosilta 2013–2014, joiden toimenpidekoodeina olivat JDF11 (LGBP), JDF97 (LGS) tai JFD03 (LDS) ja ICD-10-tautiluokituksena E66.8 (sairaalloinen lihavuus). Tilastojen tarkastelussa käytettiin SPSS v.23.0 -ohjelmaa. Tutkielmassa käytetty kirjallisuus etsittiin PubMed- ja Cochrane-palveluista. Tilastomenetelminä käytettiin yhdensuuntaista varianssianalyysiä ja Post Hoc -korjauksina Tamhane’s T2 ja Tukey-testiä. Kahden ryhmän välisiä muuttujia tarkasteltiin Khiin neliötestillä ja p-arvoja arvioitiin tarvittaessa Fischerin testillä. 2-luokkamuuttujissa käytettiin McNemarin testiä. Yksittäismuuttujina laskettiin keskiarvo ja mediaani. Tuloksia verrattiin kansainväliseen tasoon. Clavien-Dindo-luokituksen mukaisia komplikaatioita oli LGBP-leikatuilla 4,7 % (5), LSG-leikatuilla 0 % ja LDS-leikatuilla 14,3 % (1). Liitännäissairauksien remissioasteet selvitettiin 12 kuukautta postoperatiivisella kontrollijaksolla. Tyypin 2 diabeteksen remissioaste oli LGBP-leikatuilla 75,0 % (p<0,0001), LSG-leikatuilla 66,7 % ja LDS-leikatuilla 100 %. Depression remissio oli LGBP-leikatuilla 33,3 % (p=0,004) ja LSG-leikatuilla 100 %. Hypertension remissio oli LGBP-leikatuilla 37,1 % (p<0,0001), LSG-leikatuilla 14,3 % ja LDS-leikatuilla 0 %. Uniapnean remissio oli LGBP-leikatuilla 30,0 % (p=0,004), LSG- ja LDS-leikatuilla 0 %. Ylipainon muutos 12 kuukauden seurantajaksolla oli LGBP-leikatuilla keskimäärin -34,5 kg, LSG-leikatuilla -46,8 kg ja LDS-leikatuilla -54,2 kg. Keskimääräinen painoindeksi LGBP-leikatuilla ennen ENE-ruokavaliota oli 45,2, LSG-leikatuilla 71,1 ja LDS-leikatuilla 49,5 ja 12 kuukautta leikkauksesta vastaavasti 33,1 (LGBP), 43,4 (LSG) ja 31,3 (LDS). Bariatrinen kirurgia on tehokas laihdutusmenetelmä potilaille, jotka ovat epäonnistuneet konservatiivisessa laihduttamisessa. Lisäksi siitä on hyötyä potilaille, joilla on liitännäissairauksia. Eri leikkausmenetelmien välillä on eroja tuloksien kannalta, mikä kannattaa huomioida jokaisen potilaan kohdalla erikseen.

Tutkielmassa tarkasteltiin D-vitamiinin yhteyttä tyypin 1 diabeteksen patogeneesiin. On esitetty, että D-vitamiini voisi vaikuttaa estävästi tyypin 1 diabeteksen kehitykseen. D-vitamiinin saantimäärällä tai valmisteella saattaa myös olla merkitystä. Kirjallisuuskatsausta varten kerättiin laaja kokoelma viimeisiltä vuosikymmeniltä julkaisuja, jotka käsittelevät tutkimuskysymyksen aihepiiriä. Julkaisut kerättiin PubMed tietokannasta. Tutkimukset rajattiin tarkasti systemaattista ja kuvailevaa kirjallisuuskatsauksen metodia käyttäen. Finkin mallilla systemaattista osaa prosessoitiin vaiheittain. Tutkielmassa perehdytään 18:aan tutkimukseen, joista suurin osa on kohortti- ja tapaus-verrokkitutkimuksia ja loput interventio- ja poikkileikkaustutkimuksia. Tutkimusten perusteella on mahdollista, että D-vitamiini vaikuttaa ehkäisevästi tyypin 1 diabeteksen kehitykseen ja, että D-vitamiinin saantimäärällä ja -muodolla on merkitystä. Maailmanlaajuisesti auringonvalosta saatu D-vitamiini ei näyttäisi riittävän suositeltujen D-vitamiinivarastojen ylläpitoon. Kalanmaksaöljy voisi olla jopa parempi D-vitamiinin lähde kuin puhdas D-vitamiini. Useat tahot haluaisivat nostaa D-vitamiinin suositeltuja pitoisuuksien viitevälejä, sillä näyttää siltä, että nykyisiä suosituksia suurempi D-vitamiinin saanti kehittäisi paremman suojaavan vaikutuksen tyypin 1 diabetesta vastaan.

Breast cancer is the second most common type of cancer among women. The serine-threonine protein kinase CK2 is overexpressed in many cancers, including lung, prostate, hematologic cancers, and breast (Pinna, 2013). Here, we examined the potential of CK2 inhibition alone and in combination with chemotherapy to treat breast cancer. We performed cell viability assays on five breast cancer cell lines treated with CK2 chemical inhibitors or small interfering RNAs, and chemotherapeutic drugs, to test if a synergistic effect could be attained. We also tested if CK2 inhibition would change the stem-like phenotype, epithelial-to-mesenchymal (EMT) marker expression, and CK2 subunit gene expression in the HS578T cell line. We concluded that in the five cell lines utilized, CK2 inhibition had no synergistic effect with chemotherapeutic drugs. CK2 inhibition had no effect on the stem-like phenotype of HS578T cells. However, CK2 inhibition did show a pattern of inhibition of EMT marker expression. Finally, we found that CK2 inhibition appears to activate a compensatory feedback loop for the transcription of the alpha subunit. This may explain the lack of synergy, and bears further investigation in future studies.

Sickle cell disease consists of a group of disorders that have a similar mutation in at least one of the beta-globin chains of hemoglobin. This results in a change of the hemoglobin to sickle shaped cells when in the deoxygenated state. It is these sickled cells that lead to the symptoms and complications characteristic of sickle cell disease, including vaso-occlusion. The recurrence of sickling and polymerization in the blood vessels throughout the body ultimately results in tissue and organ damage that increases the mortality of patients. Pulmonary hypertension is the increase in blood pressure in the pulmonary vasculature causing less blood to reach the lungs. The right side of the heart has to pump harder to compensate for this, which can ultimately lead to right heart failure. With vaso-occlusion being the major complication in sickle cell disease and affecting many tissues and organs like the lungs, pulmonary hypertension has become a major risk factor in these patients, especially in children. Most research has been with adults so the seriousness of this condition is still being discovered in children. This review will cover the important aspects of both sickle cell disease and pulmonary hypertension then discuss how pulmonary hypertension has become a significant risk factor for death in those with sickle cell disease. From there the importance of this finding in children will be discussed and a plan for future endeavors will be proposed.

Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are rare diseases that cause hypocholesterolemia. Studying FHBL and ABL is essential to furthering the field of cholesterol research and has provided many therapeutic targets for hypercholesterolemia. ABL is an autosomal, recessive disease caused by a mutation in MTP, a chaperone protein in the ER that helps fold nascent apoB and transfers lipids onto apoB. FHBL is an autosomal, codominant disease caused by a mutation in APOB, which usually causes a truncated apoB with loss-of-function. ABL and homozygous FHBL have the same clinical symptoms: steatorrhea, neurological dysfunction, vision problems, and non-alcoholic fatty liver. Implementing a low-fat diet routine along with vitamin supplementations will ameliorate most symptoms except for hepatic steatosis. Both ABL and FHBL carry a reduced risk of cardiovascular diseases due to the reduction of atherosclerosis. Many new therapeutic targets for hypercholesterolemia have been inspired by FHBL and ABL. Lomitapide is an MTP (microsomal triglyceride transfer protein) inhibitor that mimics ABL's mutant mechanism. Mipomersen is an apoB synthesis inhibitor, which mimics FHBL's mutant mechanism. The purpose of both drugs is to treat familial hypercholesterolemia. This literature review suggests other targets: a molecule to permanently bind apoB to MTP which mimics an FHBL mutation, a molecule to prevent PDI from binding to the large M subunit in the heterodimer MTP, and a method to truncate apoB to mimic FHBL mutations. Two new recently-discovered diseases have similar phenotypes as ABL and FHBL: PCSK9 deficiency and familial combined hypolipidemia. Both cause hypocholesterolemia. However, PCSK9 does not have the negative systemic effects such as steatorrhea and neurological dysfunction. In addition, no fatty liver develops. More research into these new diseases can contribute to the field of hypocholesterolemia, which provides new therapeutic targets for hypercholesterolemia.

Aortic stenosis or narrowing of the aortic valve is the most common cause for surgical valvular replacement in the United States. The disease of aortic stenosis has a long asymptomatic latency period followed by a quickly progressing symptomatic phase. Symptoms of the disease include dyspnea, syncope, angina, and heart failure. The disease affects mostly the elderly and, as the United States population ages, and life expectancy increases, there is an increased prevalence of the disease. The main cause of aortic stenosis is calcification of the leaflets of the aortic valve. There are currently no pharmaceutical interventions to combat or slow the processes of the disease. The only treatment for the disease is the surgical replacement of the aortic valve. The original aortic valve replacement (AVR) was done in 1952, after that time this was the only surgical intervention until 2002 with the advent of transcatheter aortic valve replacement (TAVR). TAVR has since been approved by the Food and Drug Administration (FDA) for use in patients who are not candidates for AVR or who are at high risk for AVR. The initial studies of TAVR showed an elevated risk of stroke in those undergoing surgery but it provided similar relief of symptoms, and similar patient mortality at one and two year follow up. With the increased risk of stroke there was evaluation of cause and mechanism of the cerebral events. After concluding that the strokes were due to emboli released during mechanical movement during surgery, new technologies have begun to be developed to combat the stroke risk. One device that is used is a deflection device that ensures that an embolus does not have access to cerebral circulation. Through the study of current literature it can be concluded that the patient long-term outcomes are much improved in TAVR verse AVR for the subgroup of the population who are not candidates for surgery. There are comparable patient outcomes for those who are at a high risk for surgery, but the risk for stroke with TAVR doubled compared to AVR, which continues to be investigated. TAVR carries the benefit of a less invasive surgery, shorter hospital stays and reported increased quality of life one-year post operation. This study demonstrates that there is still a need for further development of technology, surgical technique and long term patient follow up to ensure high quality outcome for those undergoing TAVR.

As the major circulating androgen in men, testosterone holds a significant role in the maturation and maintenance of male characteristics. Some of its effects include inducing significant growth of the penis and testes early in development, producing sperm, and contributing to bone mass and muscle strength. Testosterone is synthesized in the testes and released into the circulation where it exerts its effects across the body. Its negative feedback on the hypothalamus and pituitary glands serve as regulation of the hypothalamic-pituitary-testosterone axis. Starting around age 30, testosterone levels have been shown to annually decline approximately 1-2% in men. Decline may eventually lead to a deficiency, presenting as reduced sex drive, erectile dysfunction, low sperm count, or decreased muscle bulk and strength. Many symptoms of testosterone deficiency coincide with old age. Also, the threshold of low testosterone at which symptoms manifest can vary from person to person. For these reasons, diagnosing testosterone deficiency has proven difficult. Nevertheless, certain guidelines have defined late-onset hypogonadism (LOH) as testosterone levels below about 200-300 ng/dl with the simultaneous presentation of at least one related symptom. Increasing diagnosis of late-onset hypogonadism, colloquially known as "Low T", has led to the enormous growth of the testosterone replacement therapy (TRT) market. Testosterone replacement therapy is the administration of either synthetic or endogenous testosterone to restore "above threshold" testosterone levels and improve the negative symptoms associated with deficiency. TRT comes in a wide variety of formulations and its use has risen steeply over the past decade, with a market currently worth around $1.8 billion. Reports estimate that the market for TRT may surpass $5 billion by 2018. However, there is plenty of cause for concern. In its current state, LOH is a loosely defined phenomenon whose treatment with TRT has not been confirmed in the research-standard large, randomized, placebo-controlled, trial. Furthermore, two recent retrospective database studies by Vigen et al. (2013) and Finkle et al. (2014) have reported increases in cardiovascular disease risk and mortality with TRT use in men with LOH. These studies were preceded with a meta-analysis by Xu et al. (2013) reviewing cardiovascular risk of TRT as well as another study measuring TRT effectiveness in elderly men by Basaria et al. (2010), which was prematurely halted due to an unsafe number of adverse events. The four studies above were analyzed and evaluated as the argument against TRT and its potential risk to cardiovascular health. On the other hand, there is plenty of evidence associating low endogenous testosterone levels with adverse effects and the benefits of TRT in treating LOH. This study summarized and evaluated the available evidence of the effects of endogenous testosterone levels and testosterone replacement therapy on cardiovascular health, including coronary artery disease, congestive heart failure, factors of atherosclerosis, and risk factors of cardiovascular disease such as obesity, type 2 diabetes mellitus, dyslipidemia, and inflammatory markers. Additionally, this thesis was written in the midst of a recent controversy concerning the field of TRT. Mainstream reporting on the results of the aforementioned studies by Vigen et al. (2013) and Finkle et al. (2014) led to increasing public concern about the safety of testosterone therapy. The results of these studies were met with heavy criticism by the medical field due to their shortcomings in design and conduct. The consumer rights advocacy group Public Citizen petitioned the FDA to add a black box warning of cardiovascular risk to TRT medications on the market. The Androgen Study Group, a group of medical experts and societies committed to accurate reporting of information about androgens, countered with a letter of their own to the FDA as well as a letter to JAMA requesting that they retract the article by Vigen et al (2013). The FDA is currently evaluating these requests as well as the overall risk of testosterone replacement therapy on cardiovascular health and mortality. The analysis of this thesis proved the argument against testosterone replacement therapy unreliable. The four studies contained significant flaws in methodology, substandard presentation of data, and were initially built upon a weak foundation of evidence. Current evidence shows that low endogenous testosterone levels are associated with increased cardiovascular risk, while the results of testosterone replacement therapy in treating LOH are predominantly positive. Many of these studies are epidemiological in nature, have small sample sizes, and vary in methodology and potential confounding factors. Thus, although the advantages reported for testosterone replacement therapy seems to trend positive, the need for randomized controlled trial(s) still remains. Diagnosis of LOH and prescription of TRT should be approached with caution and on an individualized basis.

OBJECTIVE: The purpose of this study is to assess whether there are significant differences between pre-surgical and bracing patients with Adolescent Idiopathic Scoliosis (AIS) in parent and child functioning including pre-operative pain, pre-operative anxiety, parent pain catastrophizing, and parent protectiveness over child's pain symptoms. METHODS: Eligible patients were recruited from the Boston Children's Hospital Orthopedics Department. Retrospective chart reviews were conducted to identify patients aged ten through seventeen with AIS who were recommended for brace treatment or spinal fusion surgery. The study included thirty-five participants and their parents, seventeen pre-surgical participants and eighteen bracing participants. REDcap questionnaires were sent to parents and their children to fill out. The questionnaires included the following measures of interest for this study: Adult Responses to Children's Symptoms (ARCS), the Pain Catastrophizing Scale (PCS), the Multidimensional Anxiety Scale for Children (MASC), and the Numeric Rating Scale (NRS) for pain. One-way ANOVAs were used to determine if there were statistically significant differences between the two groups on the following variables: age and sex of the child, sex of the parent, race and ethnicity of the parent and child, degree of curvature of the spine (Cobb angle), and on the above mentioned parent and child measures. RESULTS: The group demographics were representative of the typical AIS population. Significant differences in age, Cobb angle, and sex of the child were determined between groups and represent potential confounding factors. There was a significant difference between groups for PCS magnification and a trend towards significance for PCS helplessness and the total PCS score. Other measure differences were statistically insignificant. CONCLUSIONS: Potential differences in parent and child measures were assessed to investigate parent and child functioning in the context of two medical interventions used to treat AIS. Bracing treatment and spinal fusion surgery were chosen with the intent to determine if the severity of an intervention has adverse effects on parent and child functioning. It is important to consider these results in a preliminary context due to the small sample size. Nonetheless, the results suggest that pre-surgical patients and their families are affected differently by the additional stressors and life-altering factors that come with spinal fusion surgery. There seems to be greater emphasis placed on their child's pain as well as a sense of helplessness. Both factors may have adverse effects on their child's ability to cope with the stress of surgery, which may also translate into a more difficult recovery period.

Barrett's esophagus is a metaplasia of the epithelium of the lower esophagus from a normal squamous appearance to a columnar appearance more typically found in the stomach. It is normally caused by prolonged gastric reflux. While Barrett's esophagus is not usually the direct cause of adverse symptoms, it does put a person at greater risk for developing esophageal adenocarcinoma, one of the least treatable cancers currently known. While the progression from gastric reflux to Barrett's esophagus is fairly clear, the relationship between Barrett's esophagus and esophageal adenocarcinoma is not as well understood. Not all patients diagnosed with Barrett's esophagus will go on to develop esophageal adenocarcinoma. There are several factors that may have some impact on this progression, including obesity, lifestyle, and genetic predisposition. The purpose of this study was to evaluate the literature to determine the potential impacts of each of these factors on development of esophageal adenocarcinoma. While obesity and lifestyle clearly have some impact on development of esophageal adenocarcinoma, it was found that the exact nature of that impact is still unclear. Obesity leads to several consequences, including increased gastroesophageal reflux, hormonal changes, and reduction in the bacterium H. pylori, all of which have been shown to have some impact on metaplasia in the esophagus. Lifestyle choices, including alcohol or tobacco use, also have been shown to have at least some effect on development of esophageal adenocarcinoma. The literature also reveals that inherited risk factors, namely genetic predisposition, may play a role in development of esophageal adenocarcinoma. Genetic predisposition to obesity may have some impact, but other studies have identified genetic variations that seem to directly influence development of esophageal adenocarcinoma. While it is clear that there are several factors that influence development of esophageal adenocarcinoma, we do not yet understand the complete etiology. By continuing to study these risk factors, we will be able to develop new treatments to combat the rising incidence of Barrett's esophagus and esophageal adenocarcinoma.

Human Papillomavirus is one of the most common sexually transmitted infections (STI) worldwide and is associated with more than 70% of invasive cervical cancer (ICC) cases. Vaccines against high-risk HPV infections have been developed: Gardasail, a quadrivalent vaccine protecting against HPV 16, 18, 6, and 11, and Cervarix for types 16 and 18 only. Although these vaccines have proven to be safe and effective in preventing HPV, vaccine coverage in the US remains much lower than other developed countries including Australia, the UK, and Canada. This thesis focuses on the implications of low HPV vaccine uptake and strategies to increase coverage in the US, specifically alternative venues for vaccine provision. Results from the literature search showed that common barriers to HPV vaccine uptake include lack of knowledge about HPV and the vaccines and lack of physician recommendation. With regards to alternative vaccination provision sites, the literature search showed the most evidence for mass vaccination in schools, particularly in Australia where government funded school-based vaccination programs have increased the national HPV vaccine coverage to 70%. Further, the literature search showed that pharmacies are another promising alternative venue for HPV vaccine administration because of their high accessibility and convenience. &#8195;