A post-occupancy evaluation of a neighbourhood park: : Using PPGIS methods for mapping users’ experiences in Hyväntoivonpuisto Park

In densely built areas, neighbourhood parks have a close relationship with the residents and are an integral part of their everyday activity. However, the presence of the park itself does not ensure its use. Some of the major factors that affect park use are park facilities, proximity, location, environment quality, and park design. Despite all, the extent to which the park is used can only be determined once the park comes to use. Therefore, this thesis aims to research the factors that affect the park use and park activities based on users’ activity and their experiences in the park environment by conducting a post-occupancy evaluation in Hyväntoivonpuisto Park in Jätkäsaari. By analysing the questionnaire data collected in Jätkäsaari, Helsinki, Finland in 2022, through the PPGIS method, this thesis aims to examine what kind of activities take place in Hyväntoivonpuisto park, and how do the park location and design facilitate these activities. The types of activities in the park will be discussed in terms of Jan Gehl’s categories of activities. Additionally, this thesis aims to research the relation between users’ aesthetic experiences, their perception of safety, and their activity in the Hyväntoivonpuisto park. Furthermore, it aims to reveal the collective public image of Hyväntoivonpuisto park by operationalising Kevin Lynch’s theory of ‘the city and its elements’. The data for this study was collected using the PPGIS (Public participation Geographical Information Systems) method using Maptionnaire. The PPGIS study website consisted of 11 pages, with mapping tasks, open-ended questions, and general nonspatial questions. The data collection for the study was conducted between 17th March and 12th April 2022. There were 218 survey participants, among which responses from 200 participants were suitable for analysis. The survey participants marked a total of 934 locations. The data analysis was done using QGIS (Quantum GIS) and Microsoft Excel. This thesis found that the location and the design of the park do influence the type of activities that take place in the Hyväntoivonpuisto park. The aesthetic value of the park has a stronger influence on park activity in park areas that are left open for spontaneous activities and has a smaller impact on park facilities with specified uses. When people's perceptions of their safety are positive, they had a beneficial impact on park use, but when they were negative, they had little impact on park activities. Additionally, the design features strongly influence the public image of the park, and especially nodes and landmarks strongly define the identity of the park

Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria

Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Variations in the activities of these enzymes may modulate adverse ASA-related symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6, CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The genotypes of 148 subjects with AIU (AIU group) and 260 normal healthy control subjects (NC group) were analyzed with respect to the following single nucleotide polymorphisms: CYP2C9 -1188T>C and CYP2C9*3A1075C; UGT1A6 T181A A>G and UGT1A6 R184S A>C; and NAT2 9796A>T, NAT2 197G>A, NAT2 286G>A, NAT2 9601A>G, and NAT2 9306A>G. There were significant differences in the allele frequencies for the CYP2C9 polymorphisms between the two groups. The frequency of the minor allele CYP2C9 -1188T>C was significantly higher in the AIU group than in the NC group (P=0.005). The frequency of the variant genotype CC was higher in the AIU group compared with the controls in both the co-dominant (P=0.007) and recessive models (P=0.012). The frequency of haplotype 2 [CA] was also significantly higher in the AIU group in both the co-dominant (P=0.006) and dominant models (P=0.012). There was no significant difference in genotype frequencies for any of the UGT1A6 or NAT2 polymorphisms between the two groups. Clinical parameters did not differ according to genotype. These results suggest that the C allele of CYP2C9 -1188T>C may be associated with AIU

Major histocompatibility complex and coronary artery disease : Special emphasis on Chlamydia pneumoniae, and periodontitis

Most of the genes in the MHC region are involveed in adaptive and innate immunity, with essential function in inflammatory reactions and in protection against infections. These genes might serve as a candidate region for infection and inflammation associated diseases. CAD is an inflammatory disease. The present set of studies was performed to assess whether the MHC region harbors genetic markers for CAD, and whether these genetic markers explain the CAD risk factors: e.g., C. pneumoniae, periodontitis, and periodontal pathogens. Study I was performed using two separate patient materials and age- and sex-matched healthy controls, categorizing them into two independent studies: the HTx and ACS studies. Both studies consistently showed the HLA-A3– B35– DR1 (35 ancestral haplotype) haplotype as a susceptible MHC genetic marker for CAD. HLA-DR1 alone was associated not only with CAD, but also with CAD risk factor diseases, e.g., diabetes mellitus, and hyperlipidemia. The ACS study further showed the HLA-B*07 and -DRB1*15 -related haplotype as a protective MHC haplotype for CAD. Study II showed that patients with CAD showed signs of chronic C. pneumoniae infection when compared to age- and sex-matched healthy controls. HLA-B*35 or -related haplotypes associated with the C. pneumoniae infection markers. Among these haplotype carriers, males and smokers associated with elevated C. pneumoniae infection markers. Study III showed that CAD patients with periodontitis had elevated serum markers of P. gingivalis and occurrence of the pathogen in saliva. LTA+496C strongly associated with periodontitis, while HLA-DRB1*01 with periodontitis and with the elevated serum antibodies of P. gingivalis. Study IV showed that the increased level of C3/C4 ratio was a new risk factor and was associated with recurrent cardiovascular end-points. The increased C3 and decreased C4 concentrations in serum explained the increased level of the C3/C4 ratio. Both the higher than cut-off value (4.53) and the highest quartile of the C3/C4 ratio were also associated with worst survival, increased end-points, and C4 null alleles. The presence of C4 null alleles associated with decreased serum C4 concentration, and increased C3/C4 ratio. In conclusion, the present studies show that the CAD susceptibility haplotype (HLA-A3− B35− DR1 -related haplotypes, Study I) partially explains the development of CAD in patients possessing several recognized and novel risk factors: diabetes mellitus, increased LDL, smoking, C4B*Q0, C. pneumnoiae, periodontitis, P. gingivalis, and complement C3/C4 ratio (Study II, III, and IV).Human leukocyte antigen (HLA)-geenit sijaitsevat kromosomin 6 Major Histocompatibility Complex (MHC)-alueella. Monet näistä geeneistä säätelevät hankittua ja luonnollista immuunivastetta sekä tulehdusreaktioita. HLA-geenit sopivatkin ehdokasgeeneiksi monille tulehdus- ja infektiosairauksille, myös sepelvaltimotaudille. Tämän väitöskirjan tavoitteena oli selvittää altistavatko MHC-alueen geenit tai geenipoikkevuudet sepelvaltimotaudille. Lisäksi haluttiin tutkia onko sepelvaltimotautiin liittyvillä tulehduksilla (Chlamydia pneumoniae -bakteeri tai hampaan juurikalvon tulehduksella) ja MHC-alueen geeneillä yhdessä yhteyttä sepelvaltimotautiin. Kirjan ensimmäisessä osatyössä käytettiin kahta potilasmateriaalia, jossa ensimmäisessä tutkittiin eri indikaatioilla hoidettuja sydänsiirtopotilaita ja toisessa vertailtiin akuutti koronaarisyndroomapotilaita ikä- ja sukupuolivakioituihin kontrolleihin. Molemmat tutkimukset osoittivat johdonmukaisesti, että haplotyyppi HLA-A3–B35–DR1 altistaa sepelvaltimotaudille. Tämän lisäksi osoitettiin, että HLA-DR1 liittyi sepelvaltimotaudin lisäksi myös sen riskitekijöihin, kuten diabetekseen, veren korkeaan kolesterolipitoisuuteen ja tupakointiin sekä C4B-puutokseen. Akuutti koronaarisyndrooma -työssä todettiin myös, että sepelvaltimotaudilta suojaavissa haplotyypeissä olivat HLA-B*07 ja -DRB1*15 alleelit. Toisessa osajulkaisussa tutkittiin Chlamydia pneumoniae-infektion yhteyttä HLA-alueeseen ja sepelvaltimotautiin. Chlamydia pneumoniae vasta-ainemääriä vertailtiin akuutti koronaarisyndrooma-potilaiden ja ikä- ja sukupuolivakioitujen verrokkien välillä. Tutkimus osoitti, että HLA-B*35 liittyi sepelvaltimotautipotilailla Chlamydia pneumoniae-infektioon. Lisäksi todettiin, että miessukupuoli ja tupakointi voimistivat tätä yhteyttä. HLA-B*35 saattaa olla yhteinen tekijä sepelvaltimotaudin ja Chlamydia.pneumoniae-infektion välillä. Kolmas osatyö keskittyi sepelvaltimotautipotilaisiin, joilla oli hampaan juurikalvon tulehdus eli parodontiitti. Aineistona oli 106 akuutti koronaarisyndroomapotilasta, joiden hampaat oli tutkittu sairaalaan tulovaiheessa panoramisella tomografialla ja potilaista oli otettu sylki- ja seeruminäytteet. Syljestä viljeltiin bakteerit, seerumista määritettiin muun muassa Porphyromonas gingivalis vasta-aineet ja parodontiiti määritettiin tomografialla. Löydöksiä verrattiin MHC-alueen geeneihin. Tärkeimpänä löydöksenä oli se, että LTA+496C tekijä assosioitui parodontiittiin. HLA-DRB1*01 esiintyi puolestaan potilailla, joilla oli sekä paradontiittia että Porphyromonas gingivalis -vasta-ainetta seerumissa. Neljännessä osatyössä selvitettiin akuutti koronaarisyndroomapotilailla seerumin komplementtiproteiinien C3 ja C4-suhteen (C3/C4-suhde) merkitystä sepelvaltimotautikohtausten uusiutumiseen. Tutkimuksessa pystyttiin osoittamaan, että kohonnut C3/C4-suhde on uusi riskitekijä uusivalle akuutille koronaarisyndroomalle. Sekä kohonnut C3- että alentunut C4 -pitoisuuden vaikuttivat kohonneeseen C3/C4-suhteeseen. Tämän lisäksi C4-puutokset alentuneen C4 -pitoisuus kanssa nostivat C3/C4-suhdetta. Väitöskirjan työt osoittivat, että haplotyyppi HLA-A3– B35– DR1 altistaa sepelvaltimotaudille ja liittyy niin perinteisiin kuin uusiin sepelvaltimotaudin riskitekijöihin, joita ovat mm. diabetes, veren suuri kolesterolipitoisuus, tupakointi, C4B*Q0-alleeli, Chlamydia pneumoniae, paradontiitti, Porphyromonas gingivalis, sekä komplementin C3/C4 -suhde

経口投与されたニコチンアミドリボシドとニコチンアミドモノヌクレオチドの生体内における代謝経路

富山大学・富医薬博甲第395号・Sailesh Palikhe・2022/03/23・★論文非公開★富山大

Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis

Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1*301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach

No evidence of association between interleukin-13 gene polymorphism in aspirin intolerant chronic urticaria

Aspirin-intolerant chronic urticaria (AICU) is a common condition among the chronic urticaria population, but the genetic mechanism is not yet understood. In this study, the genotypes and haplotypes of three interleukin (IL)-13 polymorphisms, -1510 A>C, -1055C>T, and Arg110Gln (110G>A), as well as their respective clinical phenotypes were examined to determine whether genetic variants of IL-13 play a role in AICU. Single-nucleotide polymorphism (SNP) genotyping was used to compare IL-13 genotype and allele frequencies among 135 patients with AICU, 146 with aspirin-tolerant chronic urticaria (ATCU), and 430 normal controls (NC). Relationships among the AICU phenotype, atopy, and total IgE level were also investigated. The results failed to show a significant difference in the allele or genotype frequencies between the AICU group and either the ATCU or NC group (P>0.05, respectively). Haplotype analysis confirmed that there was no significant difference among the three study groups (P>0.05), nor was there a significant difference in atopy or total IgE level according to the three genetic polymorphisms (P>0.05, respectively). Our data lead to the conclusion that there is no evidence supporting genetic polymorphisms in IL-13 as a genetic risk factor for the development of AICU