INTRODUCTION: Primary pulmonary hypertension (PH) is a progressive disease that is characterized by restricted blood flow in the pulmonary vasculature, resulting in an increase in pulmonary vascular resistance (PVR) (McLaughlin et al., 2009). Patients with sickle cell disease (SCD), a monogenic blood disorder that causes red blood cells to form a sickle shape and decreases their ability to carry oxygen to the body’s tissues, can develop secondary pulmonary hypertension. Although there is significant data showing that pulmonary hypertension secondary to SCD increases morbidity and mortality in adult patients, there is little information regarding how PH affects children with SCD (Klings & Machado et al., 2014). Although diagnosing PH requires right heart catheterization, the American College of Cardiology Foundation and the American Heart Association recommend using Doppler echocardiography as a screening test for PH (McLaughlin et al., 2009). A tricuspid valve regurgitant jet velocity (TRV) of 2.5 m/s or higher, measured by Doppler echocardiography, is suggestive of PH (McLaughlin et al., 2009). Because Doppler echocardiography is non-invasive, there is much more information available regarding TRV than right heart catheterization, an invasive procedure. This study examines the prevalence and incidence of elevated TRV (≥ 2.5 m/s) in children with SCD as well as factors that may be associated with an elevated TRV. MATERIALS AND METHODS: We conducted a retrospective longitudinal cohort study chart review for 83 subjects followed by pediatric hematology at Boston Medical Center; examining demographic information, pediatric and adult echocardiogram reports, SCD complications previously identified as being related to PH, laboratory results that have previously been identified as being related to PH while each subject was between the ages of 8 and 30 between July 31, 2003 and June 30, 2015. RESULTS: We found that 11 (13%) of our study population had one or more elevated TRV value (≥ 2.5 m/s). Elevated TRV values ranged from 2.5 – 2.83 m/s. The average age for elevated TRV was 15.9 years old. Of the subjects with elevated TRV 6 (55%) were taking HU, as compared to 53 (64%) of the general study population. No SCD complications previously reported to be related to PH were found to be significantly associated with elevated TRV in our study population. The only laboratory value that we found to be associated with elevated TRV was an elevate reticulocyte count, with an average value of 11% of red blood cells in subjects with elevated TRV and 8.41% of red blood cells in the general study population (p = 0.04). DISCUSSION/CONCLUSION: We found that 13% of children with SCD had at least one screening echocardiogram with TRV ≥ 2.5 m/s, which is in agreement with the prevalence estimates of 10-20% published by the American Thoracic Society (Klings & Machado et al., 2014). However, this is much lower than the 30% reported in the literature (Kato, Onyekwere, & Gladwin, 2007). This may be caused by more widespread use of hydroxyurea therapy at our academic institution. We also found no associated factors other than elevated reticulocyte count, while other studies found associations with a history of sepsis/bacteremia, history of ACS, history of asthma, Hb SS genotype, low hemoglobin levels, and elevated reticulocyte count (Hagar et al., 2007; Minniti et al., 2009; Pashankar et al., 2008; Ambrusko et l., 2006; Kato et al., 2007)

Crohn's disease (CD) affects 1.5 million Americans a year. Many patients refractory to standard treatments suffer from life-long detrimental symptoms that reduce quality of life. Chronic inflammation of the gastrointestinal tract, a hallmark of CD, has led to the development of drugs and interventions targeting the immune response. Recent ideology regarding the pathophysiology of CD has implicated a role for the microbiome within the human gut. The advent of metagenomics has allowed for the characterization of the microbiome of both healthy and diseased individuals. The phylogenetic bacterial makeup of the microbiome of patients with CD shows an alteration from that of healthy individuals. Therapeutic methods incorporating the re-establishment of a healthy microbiome are being investigated. Fecal microbiota transplantation (FMT) has become the "gold standard" of care for patients afflicted with Clostridium difficile (C. diff.) infection who do not respond to a standard antibiotic regimen. C. diff.-infection presents with similar symptoms and alterations of the microbiome to that observed in patients diagnosed with CD. To date, only studies of three case and two cohorts utilizing FMT in patients with CD have been reported. Results from these studies show potential usefulness for fecal microbiota transplantation as a therapy for CD. This review offers insight for improved clinical trials in which FMT and immune response therapies are adjunctively utilized to improve CD treatment.

BACKGROUND: Arterial stiffness, or the loss of compliance of the large arteries, is a major independent predictor of cardiovascular events. Obesity induced by a high fat, high sucrose (HFHS) diet, in mice, causes the development of arterial stiffness, diabetes, and hypertension. Along with the resulting metabolic syndrome, inflammation and oxidants are increased in vascular smooth muscle (VSM) cells of HFHS-fed mice. Sirtuin 1 (SirT1), an important cellular homeostatic regulator, has been shown to prevent inflammation and obesity-associated metabolic impairment in animal models. This deacetylase is involved in histone and transcription factor regulation, thereby affecting a wide range of physiological mechanisms. However, whether SirT1 affects obesity-induced arterial stiffness is unknown. Therefore, we aimed to investigate the effects of SirT1 on arterial stiffening in a setting of diet-induced obesity. METHODS: The polyphenolic SirT1 activators, resveratrol and S17834, were added to HFHS diet fed to WT mice for 8 months. Arterial stiffness was measured in vivo, by pulse wave velocity (PWV), at baseline, 4 months, and 8 months. In another experiment, a highly selective SirT1 activator, SRT1720, was administered to mice in HFHS diet for one week following 8 months of HFHS diet, and PWV was measured before and after treatment. To study the role of VSM SirT1 in HFHS-induced arterial stiffness, resveratrol was supplemented to HFHS diet-fed mice lacking SirT1 in VSM (SMKO), and PWV was measured in comparison to control HFHS-fed mice. Additionally, mice overexpressing SirT1 in VSM specifically (SMTG) were generated and placed on HFHS diet, and PWV was measured at baseline, 4 months, and 8 months. The effects of SirT1 on oxidant production and inflammation in the different experimental groups were assessed by staining aortic sections for oxidants and performing Western blots of inflammatory markers (phospho-p65 NFκB, VCAM1) on isolated aortic and VSM cell lysates. RESULTS: Administering resveratrol and S17834 completely prevented the development HFHS-induced arterial stiffness over 8 months. Similarly, elevated PWV due to 8 months of HFHS diet was reversed by one-week treatment with SRT1720. SirT1 knockout in VSM partially prevented resveratrol’s effect in lowering arterial stiffness. Mice overexpressing SirT1 in VSM (SMTG) did not develop arterial stiffness and were protected from HFHS-induced oxidant production and inflammation (upregulation of phospho-p65 NFκB and VCAM1). CONCLUSIONS: VSM SirT1 can prevent the development of arterial stiffness in settings of obesity by opposing oxidants and inflammation in the aortic wall. SirT1 activators represent a potential therapeutic approach to alleviate the burden of cardiovascular disease in obese individuals with metabolic syndrome. / 2018-06-16T00:00:00Z

This study has been carried out amidst new developments made at global, regional and local levels regarding the practice of Female Genital Mutilations (FGM). The declarations, conventions and articles agreed and implemented by the UN member states and the regional organs such as the African Union have put in place strategies to eliminate FGM. Moreover, the respective state governments have passed legislation against FGM. Following these developments and initiatives there has been increased social paradigm shift targeting the essence of the FGM practice. The shift has discouraged some parents from sending their girls for circumcision, but also has pushed FGM underground. The open initiation rites where boys and girls were pronounced adults, and which served as a strong social support for the circumcised women have been dismantled. Against this background, this thesis explores the experience of Wagogo women who have undergone FGM and the knowledge, attitudes and practice of former circumcisers in Dodoma Tanzania. The study has employed a constructivist-interpretivist theoretical stance, approaching it through explorative qualitative design involving 25 circumcised women and three former circumcisers. Data were gathered using semi-structured interviews within the broader feminist perspective; and were analysed thematically. The findings suggest that, indeed women circumcised under a patriarchy experience both overt and covert pain. Within the social paradigm shift there is weakening of social support; hence, destabilization of engagement coping strategies that used to assist circumcised women to cope with the overt pain. Consequently, more women are suffering from covert pain because of untreated overt pain but also due to failed engagement coping strategies. Subsequently, more circumcised women have resorted to disengagement strategies to alleviate covert pain. While new developments safeguard girls who are yet to be circumcised, none of them consider the predicament of circumcised women. Hence, the study seeks to empower the latter so that their plight and voice can be heard.

abstract: Exercise serves as a powerful stimulus to induce skeletal muscle adaptation. For instance, it is well understood that aerobic exercise (AE) elicits an adaptive response ultimately leading to increased fatigue resistance and capillarization, whereas resistance exercise (RE) is known to elicit an adaptive response leading to increased muscle strength and size. However, the precise molecular mechanisms mediating these unique adaptations to different forms of exercise remain to be completely resolved. The purpose of this study was to investigate the adaptive cellular response of skeletal muscle following acute AE and RE. Specifically, this study focused on two molecular processes: 1) mammalian/mechanistic target of rapamycin (mTOR) signaling pathway, a regulator of muscle protein synthesis, and 2) autophagy, a process through which proteins and organelles are broken down in the muscle fiber. In a counterbalanced, crossover design, six healthy, recreationally active young men (27±3 yr) completed acute AE (40 min of cycling ~70% maximal HR) and acute RE [8 sets, 10 reps, ~65% 1-repetition maximum (1RM)] separated by ~1wk. Muscle biopsies (vastus lateralis) were obtained before, at 1 and 4h post exercise and western blot analyses were used to examine the phosphorylation of mTOR signaling proteins and various markers of autophagy. Phosphorylation of mTORSer2448 increased only following RE at 4h (P < 0.05). However, phosphorylation of p70S6K1Thr389, a downstream marker of mTOR, increased following both AE and RE at 4h (P < 0.05). However, p70S6K1Thr389 was phosphorylated to a greater extent at 1h following RE compared to AE (P < 0.05). LC3BII was decreased at 1h and 4h postexercise in response to both AE and RE (P < 0.05). These data indicate that both acute AE and RE stimulate, to some degree, mTOR signaling in skeletal muscle, a pathway associated with increased muscle protein synthesis. Further, based on markers examined in the current study, both acute AE and RE similarly stimulate autophagy, which is associated with muscle protein breakdown. These data indicate that, at least in the immediate hours post exercise, the unique adaptations to AE and RE exercise may be mediated through cellular pathways other than mTOR and autophagy. / Dissertation/Thesis / Masters Thesis Exercise and Wellness 2019

abstract: Obesity and arthritis are risk factors for falls. Little is known about the effects of weight loss on balance in people with arthritis. The Group Lifestyle Balance (GLB) ProgramTM is an evidence-based, lifestyle change program for weight loss in individuals with prediabetes but it hasn’t been evaluated in people with arthritis. The purpose of this pilot study was to evaluate the effectiveness of an adapted version of the GLB on balance outcomes among overweight (Body Mass Index (BMI) >27) individuals with arthritis. A single-group, quasi- experimental design was used to examine the effects of the adapted GLB program on measures of balance and function. All participants (N=17) received the GLB program and completed the following assessments at baseline, 12 weeks and six months: the Timed-Up-and-Go (TUG), 10 Meter gait speed, Fullerton Advanced Balance Scale (FAB) and the Activity Based Confidence survey (ABC). Repeated measures analysis of variance (ANOVAs) were used to examine changes over time in SPSS Version 24. Participants (mean age = 71.7 years) were primarily female (82%), white (94%), and college educated (94%). There was a linear (F1=14.82, p=.002) and quadratic (F1=7.20, p=.017) effect of time for the TUG. There was a linear effect of time on the FAB (F1=7.10, p=.017), and on both the customary (F1=5.44, p=.033) and fast walking pace (F1=7.59, p=.014) 10-meter gait speed assessments. There were no significant changes on the ABC. The Group Lifestyle Balance program may be an effective way to improve balance and function among overweight and obese individuals with arthritis. / Dissertation/Thesis / Masters Thesis Exercise and Wellness 2019

<p> Objectives: The purpose was to evaluate pain scores (SF-36 BPS) among pre-diabetic patients on metformin or placebo to determine if patients on metformin therapy report less pain (higher SF-36 BPS) than patients on placebo. </p><p> Study design: A descriptive retrospective review of pain scores was conducted using secondary data analyses of the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) conducted from 1996 to 2008. Patients were randomly assigned to placebo, low (850 mg/day) or high dose (1700 mg/day) metformin groups. Pain scores using the SF-36 BPS standard version were taken before randomization and annually (year one through four). </p><p> Results: Out of 3,819 patients that participated in the original study, 1,056 patients met the current study criteria. The metformin group included 506 patients and the placebo group included 550 patients. With an alpha level of 0.05 for all analyses, baseline pain scores between the metformin group and placebo group showed no significant difference. Year two showed significance between placebo and metformin pain scores (75.2 vs 78.6). All other years were not significant. Comparing low and high dose metformin and placebo groups, years one, two and three displayed significant differences in pain scores. In years one and two, the high dose metformin group reported less pain than the placebo group (80.7 vs 77.7; 80.1 vs 75.2) and the low dose metformin group (80.7 vs 71.8; 80.1 vs 68.6). In year three, the high dose metformin group had less pain than the low dose metformin group (78.4 vs 70.5).</p><p> Conclusion: A high metformin dose is associated with lower reported pain in pre- diabetic patients. This study plays an important part in further advancing the exploration of metformin&rsquo;s potential for relieving chronic pain.</p>

Tutkimuksen tarkoituksena oli kuvailla ja selittää odottavan perheen suun omahoitoon sitoutumista ja siihen yhteydessä olevia tekijöitä Kainuun sosiaali- ja terveydenhuollon kuntayhtymän alueella. Tavoitteena oli lisätä tietoa odottavan perheen suun omahoitoon sitoutumiseen vaikuttavista tekijöistä, joita voidaan hyödyntää suun terveyden edistämisessä odottavien vanhempien perhevalmennuksessa ja omahoidon ohjauksessa. Tutkimusaineisto kerättiin tätä tutkimusta varten muokatulla hoitoon sitoutumisen mittarilla Kainuun sosiaali- ja terveydenhuollon kuntayhtymän alueella maaliskuussa 2014. Lomake jaettiin kaikille odottaville vanhemmille (n=114), joiden laskettu aika oli toukokuussa 2014. Vastausprosentti oli 42. Vastauksia tarkasteltiin frekvenssi- ja prosenttijakaumina sekä ristiintaulukoinnein. Tilastollista merkitsevyyttä tutkittiin Mann Whitneyn U-testillä ja Kruskall-Wallis-testillä. Odottavista vanhemmista yli kolme neljäsosaa oli hyvin sitoutunut suun omahoitoon. Naiset huolehtivat suun ja hampaiden puhdistuksesta miehiä paremmin. Hammasvälien säännöllinen puhdistus oli vähäistä odottavien vanhempien keskuudessa. Suun omahoitoon sitoutumiseen vaikuttivat halu huolehtia suun terveydestä ja sitoutuminen suun hoito-ohjeisiin. Nämä tekijät olivat yhteydessä säännölliseen hampaiden harjaukseen. Puolison tuki, yhteistyö hammaslääkärin, suuhygienistin ja hammashoitajan kanssa ovat yhteydessä suun omahoitoon sitoutumiseen. Tulokset haastavat kehittämään suun terveyden edistämisen keinoja, jotka ottavat huomioon suun omahoitoon sitoutumiseen yhteydessä olevat tekijät. / The purpose of this study was to describe and explain the expectant family’s adherence to oral self-care and related factors in Kainuu health and social care federation of municipalities. The aim was to raise awareness of the expectant family’s adherence to oral self-care of contributing factors that can be used to promote the oral health of family coaching and self-care management. The study was conducted with a modified adherence instrument in Kainuu health and social care federation of municipalities in March 2014. Questionnaire was distributed to all expectant parents (n=114), with child’s expected date was in May 2014. Response rate was 42 %. Responses were frequencies, percentages and cross-tabulation. Statistical significance was examined Mann-Whitney U test and the Kruskal-Wallis test. Research showed that more than three quarters of the parents were very committed to the oral self-care. Women take care of the mouth and teeth cleaning better than men. Cleaning the interdental was low among expectant parents. Urge to take care of oral health and oral care instructions were factors indicating adherence to oral self-care. These factors were associated with brushing. Spousal support, co-operation with the dentist, dental hygienist and dental assistant are associated with adherence to oral self-care. The results challenge to develop of oral health promotion, that take into account factors related to adherence to oral self-care.

Työn tarkoituksena oli tutkia paaston vaikutusta supikoirien kypsien luusolujen eli osteosyyttien rakenteeseen tutkimalla paastonneiden ja aktiivisena pysyneiden supikoirien luunäytteistä näiden solujen morfologiaa. Supikoirista puolet olivat paastonneet ja puolet syöneet normaalisti 10 viikon ajan. Supikoirien luista otettiin näytteet, jotka valettiin epoksimuoviin, johon lisättiin kuljetuksen yhteydessä fluoresoivaa rodamiini-6G-väriainetta. Tämä mahdollisti näytteiden kuvantamisen konfokaalimikroskoopilla (CLSM) ja osteosyyttien lakuuna-kanalikulirakenteet (OLCS) visualisoinin. CLSM:n kuvista segmentoitiin lakuuna- ja kanalikulirakenteet ja näille laskettiin kolmiulotteisia rakenneparametreja kuten tilavuus, muotoindeksi, tiheys ja paksuus. Ryhmien välisiä eroja vertailtiin Mann Whitneyn U-testillä. Tutkimuksen päätuloksena todettiin, että paasto- ja kontrolliryhmien välillä ei ollut merkitseviä eroja osteosyyttien rakennetta kuvaavien parametrien välillä. Tämä tukee ajatusta siitä, että supikoirille on kehittynyt luuta paaston aikana suojaava mekanismi evoluution tuloksena. Normaalioloissa supikoirat nukkuvat talviunta ja altistuvat siten paastolle. Ihmisillä vajaaravitsemus altistaa osteoporoosille, joka on merkittävä kansanterveyttä heikentävä ja kustannuksia aiheuttava sairaus. Mikäli supikoirien luuta suojaava mekanismi pystyttäisiin selvittämään, voisi siitä olla hyötyä myös osteoporoositutkimuksessa. Tämä vaatii kuitenkin lisää tutkimuksia.

This thesis analyses the oral health of elderly people living in Arkhangelsk, Russia. Complex oral health assessment includes objective, standardized dental tests and indices recommended by WHO. The aim of the study was to determine the alterations in dental, periodontal, salivary, glossal and immune status of oral health in elderly persons, the influence of possible unhealthy habits on the health of oral cavity and to compare these indicators with literary sources. The research focuses on elderly people older than 60 years old, who reside in a home for the elderly in Arkhangelsk. Modern world social and health tendencies dictate the necessity of ongoing research of the aging population problem. Aging is a natural phenomenon and an inevitable process but when the number of old-aged people exceeds the number of working-age population it causes serious modifications in health care, economics, social support and so forth. The socio-demographic situation in the Arkhangelsk region is characterized by a considerable increase in the number of retirement age people who suffer from severe somatic disorders. Organs and tissues of the mouth do not represent an exception, so the elderly experience serious problems with their oral health as well. The hypothesis of the study has proved to be mostly true: our conclusion is that the young-old and the old demonstrate poor oral health. We have observed 100% prevalence of caries and decayed, missed, filled teeth index (DMFT) = 24,5 with predominance of missing teeth; the level of hygiene equals to 3,4; poor condition of dentures; high prevalence of periodontal diseases and oral mucosa lesions; low salivary flow rate (0,08 ml/min) and pH (6,0), high saliva viscosity and deterioration of the oral immunity indicators such as interleukin-8 (IL-8), immunoglobulin G (IgG), tumor necrosis factor alpha (TNF-α), secretory immunoglobulin A (SIgA) and cortisol. This study may be used to formulate recommendations for the elderly, social workers and health management bodies to improve the oral wellbeing of this group of people. The data received during this study can be also be of use for other countries of the Barents region in two similar respects: dental features of the aging population and the influence of living conditions in the North on oral health.