Molecular genetics of primary open angle glaucoma and exfoliation syndrome

Glaucoma is the second leading cause of blindness worldwide. It is a group of optic neuropathies, characterized by progressive optic nerve degeneration, excavation of the optic disc due to apoptosis of retinal ganglion cells and corresponding visual field defects. Open angle glaucoma (OAG) is a subtype of glaucoma, classified according to the age of onset into juvenile and adult- forms with a cut-off point of 40 years of age. The prevalence of OAG is 1-2% of the population over 40 years and increases with age. During the last decade several candidate loci and three candidate genes, myocilin (MYOC), optineurin (OPTN) and WD40-repeat 36 (WDR36), for OAG have been identified. Exfoliation syndrome (XFS), age, elevated intraocular pressure and genetic predisposition are known risk factors for OAG. XFS is characterized by accumulation of grayish scales of fibrillogranular extracellular material in the anterior segment of the eye. XFS is overall the most common identifiable cause of glaucoma (exfoliation glaucoma, XFG). In the past year, three single nucleotide polymorphisms (SNPs) on the lysyl oxidase like 1 (LOXL1) gene have been associated with XFS and XFG in several populations. This thesis describes the first molecular genetic studies of OAG and XFS/XFG in the Finnish population. The role of the MYOC and OPTN genes and fourteen candidate loci was investigated in eight Finnish glaucoma families. Both candidate genes and loci were excluded in families, further confirming the heterogeneous nature of OAG. To investigate the genetic basis of glaucoma in a large Finnish family with juvenile and adult onset OAG, we analysed the MYOC gene in family members. Glaucoma associated mutation (Thr377Met) was identified in the MYOC gene segregating with the disease in the family. This finding has great significance for the family and encourages investigating the MYOC gene also in other Finnish OAG families. In order to identify the genetic susceptibility loci for XFS, we carried out a genome-wide scan in the extended Finnish XFS family. This scan produced promising candidate locus on chromosomal region 18q12.1-21.33 and several additional putative susceptibility loci for XFS. This locus on chromosome 18 provides a solid starting point for the fine-scale mapping studies, which are needed to identify variants conferring susceptibility to XFS in the region. A case-control and family-based association study and family-based linkage study was performed to evaluate whether SNPs in the LOXL1 gene contain a risk for XFS, XFG or POAG in the Finnish patients. A significant association between the LOXL1 gene SNPs and XFS and XFG was confirmed in the Finnish population. However, no association was detected with POAG. Probably also other genetic and environmental factors are involved in the pathogenesis of XFS and XFG.

Markers of systemic inflammation in diagnostics and in prediction of outcome of community-acquired infection

Sepsis is associated with a systemic inflammatory response. It is characterised by an early proinflammatory response and followed by a state of immunosuppression. In order to improve the outcome of patients with infection and sepsis, novel therapies that influence the systemic inflammatory response are being developed and utilised. Thus, an accurate and early diagnosis of infection and evaluation of immune state are crucial. In this thesis, various markers of systemic inflammation were studied with respect to enhancing the diagnostics of infection and of predicting outcome in patients with suspected community-acquired infection. A total of 1092 acutely ill patients admitted to a university hospital medical emergency department were evaluated, and 531 patients with a suspicion of community-acquired infection were included for the analysis. Markers of systemic inflammation were determined from a blood sample obtained simultaneously with a blood culture sample on admission to hospital. Levels of phagocyte CD11b/CD18 and CD14 expression were measured by whole blood flow cytometry. Concentrations of soluble CD14, interleukin (IL)-8, and soluble IL-2 receptor α (sIL-2Rα) were determined by ELISA, those of sIL-2R, IL-6, and IL-8 by a chemiluminescent immunoassay, that of procalcitonin by immunoluminometric assay, and that of C-reactive protein by immunoturbidimetric assay. Clinical data were collected retrospectively from the medical records. No marker of systemic inflammation, neither CRP, PCT, IL-6, IL-8, nor sIL-2R predicted bacteraemia better than did the clinical signs of infection, i.e., the presence of infectious focus or fever or both. IL-6 and PCT had the highest positive likelihood ratios to identify patients with hidden community-acquired infection. However, the use of a single marker failed to detect all patients with infection. A combination of markers including a fast-responding reactant (CD11b expression), a later-peaking reactant (CRP), and a reactant originating from inflamed tissues (IL-8) detected all patients with infection. The majority of patients (86.5%) with possible but not verified infection showed levels exceeding at least one cut-off limit of combination, supporting the view that infection was the cause of their acute illness. The 28-day mortality of patients with community-acquired infection was low (3.4%). On admission to hospital, the low expression of cell-associated lipopolysaccharide receptor CD14 (mCD14) was predictive for 28-day mortality. In the patients with severe forms of community-acquired infection, namely pneumonia and sepsis, high levels of soluble CD14 alone did not predict mortality, but a high sCD14 level measured simultaneously with a low mCD14 raised the possibility of poor prognosis. In conclusion, to further enhance the diagnostics of hidden community-acquired infection, a combination of inflammatory markers is useful; 28-day mortality is associated with low levels of mCD14 expression at an early phase of the disease.

Evaluation of ELISA coupled with Western blot as a surveillance tool for Trichinella infection in wild boar (Sus scrofa)

Trichinella surveillance in wildlife relies on muscle digestion of large samples which are logistically difficult to store and transport in remote and tropical regions as well as labour-intensive to process. Serological methods such as enzyme-linked immunosorbent assays (ELISAs) offer rapid, cost-effective alternatives for surveillance but should be paired with additional tests because of the high false-positive rates encountered in wildlife. We investigated the utility of ELISAs coupled with Western blot (WB) in providing evidence of Trichinella exposure or infection in wild boar. Serum samples were collected from 673 wild boar from a high- and low-risk region for Trichinella introduction within mainland Australia, which is considered Trichinella-free. Sera were examined using both an 'in-house' and a commercially available indirect-ELISA that used excretory secretory (E/S) antigens. Cut-off values for positive results were determined using sera from the low-risk population. All wild boar from the high-risk region (352) and 139/321 (43.3%) of the wild boar from the low-risk region were tested by artificial digestion. Testing by Western blot using E/S antigens, and a Trichinella-specific real-time PCR was also carried out on all ELISA-positive samples. The two ELISAs correctly classified all positive controls as well as one naturally infected wild boar from Gabba Island in the Torres Strait. In both the high- and low-risk populations, the ELISA results showed substantial agreement (k-value = 0.66) that increased to very good (k-value = 0.82) when WB-positive only samples were compared. The results of testing sera collected from the Australian mainland showed the Trichinella seroprevalence was 3.5% (95% C.I. 0.0-8.0) and 2.3% (95% C.I. 0.0-5.6) using the in-house and commercial ELISA coupled with WB respectively. These estimates were significantly higher (P < 0.05) than the artificial digestion estimate of 0.0% (95% C.I. 0.0-1.1). Real-time PCR testing of muscle from seropositive animals did not detect Trichinella DNA in any mainland animals, but did reveal the presence of a second larvae-positive wild boar on Gabba Island, supporting its utility as an alternative, highly sensitive method in muscle examination. The serology results suggest Australian wildlife may have been exposed to Trichinella parasites. However, because of the possibility of non-specific reactions with other parasitic infections, more work using well-defined cohorts of positive and negative samples is required. Even if the specificity of the ELISAs is proven to be low, their ability to correctly classify the small number of true positive sera in this study indicates utility in screening wild boar populations for reactive sera which can be followed up with additional testing. (C) 2013 Elsevier B.V. All rights reserved.

Chronic disease risks and use of a smartphone application during a physical activity and dietary intervention in Australian truck drivers

- Objective This study examined chronic disease risks and the use of a smartphone activity tracking application during an intervention in Australian truck drivers (April-October 2014). - Methods Forty-four men (mean age=47.5 [SD 9.8] years) completed baseline health measures, and were subsequently offered access to a free wrist-worn activity tracker and smartphone application (Jawbone UP) to monitor step counts and dietary choices during a 20-week intervention. Chronic disease risks were evaluated against guidelines; weekly step count and dietary logs registered by drivers in the application were analysed to evaluate use of the Jawbone UP. - Results Chronic disease risks were high (e.g. 97% high waist circumference [≥94 cm]). Eighteen drivers (41%) did not start the intervention; smartphone technical barriers were the main reason for drop out. Across 20-weeks, drivers who used the Jawbone UP logged step counts for an average of 6 [SD 1] days/week; mean step counts remained consistent across the intervention (weeks 1–4=8,743[SD 2,867] steps/day; weeks 17–20=8,994[SD 3,478] steps/day). The median number of dietary logs significantly decreased from start (17 [IQR 38] logs/weeks) to end of the intervention (0 [IQR 23] logs/week; p<0.01); the median proportion of healthy diet choices relative to total diet choices logged increased across the intervention (weeks 1–4=38[IQR 21]%; weeks 17–20=58[IQR 18]%). - Conclusions Step counts were more successfully monitored than dietary choices in those drivers who used the Jawbone UP. - Implications Smartphone technology facilitated active living and healthy dietary choices, but also prohibited intervention engagement in a number of these high-risk Australian truck drivers.

Born leaders: Political selection and the relative age effect in the US Congress

We present substantial evidence for the existence of a bias in the distribution of births of leading US politicians in favour of those who were the eldest in their cohort at school. This result adds to the research on the long-term effects of relative age among peers at school. We discuss parametric and non-parametric tests to identify this effect, and we show that it is not driven by measurement error, redshirting or a sorting effect of highly educated parents. The magnitude of the effect that we estimate is larger than what other studies on ‘relative age effects’ have found for broader populations but is in general consistent with research that looks at professional sportsmen. We also find that relative age does not seem to correlate with the quality of elected politicians.

Studies On Hydrogen Bonds: Part IV. Proposed Working Criteria for Assessing Qualitative Strength of Hydrogen Bonds

The data obtained in the earlier parts of this series for the donor and acceptor end parameters of N-H. O and O-H. O hydrogen bonds have been utilised to obtain a qualitative working criterion to classify the hydrogen bonds into three categories: "very good" (VG), "moderately good" (MG) and weak (W). The general distribution curves for all the four parameters are found to be nearly of the Gaussian type. Assuming that the VG hydrogen bonds lie between 0 and ± la, MG hydrogen bonds between ± 1 and ± 2, W hydrogen bonds beyond ± 2 (where is the standard deviation), suitable cut-off limits for classifying the hydrogen bonds in the three categories have been derived. These limits are used to get VG and MG ranges for the four parameters 1 and θ (at the donor end) and ± and ± (at the acceptor end). The qualitative strength of a hydrogen bond is decided by the cumulative application of the criteria to all the four parameters. The criterion has been further applied to some practical examples in conformational studies such as α-helix and can be used for obtaining suitable location of hydrogen atoms to form good hydrogen bonds. An empirical approach to the energy of hydrogen bonds in the three categories has also been presented.

Holistic Spirituality in the Thinking of Ellen White

Spiritualiteetti viittaa syvälliseen, inhimilliseen ulottuvuuteen ja ominaisuuteen, jonka tarkka määritteleminen on haasteellista, ellei mahdotonta. Sitä vastaa yhtäältä uskonnollisuuden kautta toteutuva, elämän tarkoitukseen ja syvemmän olemuksen etsintään liittyvä hengellisyys, mutta toisaalta myös kaikkea muuta hengen viljelyä ja mielekkään olemisen tavoittelua tarkoittava henkisyys. John Swintonin mukaan hengen ulottuvuus on se inhimilliseen olemukseen kuuluva, dynaaminen elinvoima, joka virkistää ja elävöittää ihmistä ja motivoi häntä etsimään Jumalaa, arvoja, merkitystä, tarkoitusta ja toivoa. Tämä tutkimus nostaa tarkastelun kohteeksi kokonaisvaltaisen hengellisyyden, jolloin huomio kiinnitetään niihin sidoksiin, joiden kautta hengen ulottuvuus liittyy muihin inhimillisen elämän olennaisiin toimintoihin ja näkökulmiin. Tällaisia ovat 1) ajattelu 2) teot ja käytännön toiminta 3) suhteet ja vuorovaikutusverkostot 4) tunteet ja kanssakäymistä ohjaavat asenteet 5) olemassaolon ja olemisen ulottuvuudet. Kokemusten merkitys, arvo ja mielekkyys hahmottuvat juuri hengen alueella, toisin sanoen sisäisesti, hengellisenä ja henkisenä asiana. Tutkimusmateriaalina tässä tutkimuksessa on amerikkalaisen vuosina 1827 1915 eläneen Ellen Whiten kuusi myöhäiskauden teosta vuosilta 1892 1905 ja tutkimusmenetelmänä on käytetty systemaattista analyysiä. Olennaista Whiten tavassa käsitellä uskonnon harjoitukseen liittyviä aiheita on hänen käytännöllinen ja elämän arkeen kiinteästi niveltyvä otteensa. Tutkimus paljastaa, että Martti Lutherin käsitykset ovat merkittävästi vaikuttaneet Whiten ajatteluun. Lähteistä paljastuu samankaltaisuutta hänen näkemystensä ja uusimman suomalaisen Luther-tutkimuksen Martti Lutherin tuotannosta esiin nostaman ajattelutavan välillä. Vaikka teologisen oppineisuuden kannalta White ja Luther ovat eri tasoilla, kummankin käsitys ihmisen ja Jumalan välisen suhteen perusolemuksesta on samankaltainen: Lähtökohtana sille on Jumalan rakkaus ja hänen armostaan lähtenyt toiminta. Toiseksi, ihmisen ja Kristuksen välinen, olemuksellinen yhteys, unio , on perustana sille, että Jumala hyväksyy ihmisen ja huolehtii hänestä nyt ja ikuisesti. Kolmanneksi, tämä ihmisen ja Kristuksen liittoutuminen ja yhdistyminen ilmenee yhteistoimintana ja kumppanuutena yhteisten tavoitteiden saavuttamiseksi maailmassa. White korostaa ihmisen ja Kristuksen välisen hengellisen suhteen vuorovaikutteista ja toiminnallista luonnetta, joka tulee ilmi epäitsekkyytenä, toisten ihmisten ja heidän tarpeittensa huomioimisena sekä myötätuntona ja kykynä asettua toisen asemaan. Terveellistä elämäntapaa ja kasvatusta koskevat ajatuksensa White liittää siihen laaja-alaiseen näkemykseen hengellisyydestä, jonka tavoitteena on ihmisen kokonaisvaltainen hyvinvointi. Hän ei näe spiritualiteettia elämän arjesta irrallisena tai erillisenä saarekkeena, vaan ihmistä kaikessa ohjaavana, voimaannuttavana ja mielekkyyttä tuottavana, ensisijaisena ulottuvuutena. Tutkimuksen kuluessa myös Whiten usein käyttämät Jumalalle antautumisen ja luonteen käsitteet nousevat tarkastelun kohteiksi. Hänen mukaansa ihminen ei tahdonponnistuksillaan yksin pysty tavoittamaan Jumalaa vaan hänen on lakattava Jumalan rakastavan kutsun edessä itse tahtomasta ja suostuttava liittymään Jumalan tahtoon ja tarkoitukseen. Tämä liittyy siihen sisäiseen muutokseen, jota White kuvaa luonteen käsitteen avulla. Jumalan armon vaikuttama tahdon uudelleen suuntaaminen muuttaa ihmisen olemusta, arvoja, asennoitumisen tapaa ja myötätuntoisen vuorovaikutuksen kykyä niin ettei ihminen ole enää aivan sama kuin ennen. Kysymys on toisaalta yhtäkkisestä ja kertakaikkisesta olemuksellisesta muuttumisesta, mutta samalla myös hiljaisesta, elämänmittaisesta kasvusta ja kypsymisestä. Juuri luonteen käsitteen avulla White kuvaa hengellisyyttä ja siihen kuuluvaa sisästä matkaa. Tässä tutkimuksessa spiritualiteettia lähestytään yleisinhimillisenä piirteenä ja ominaisuutena, jolloin huomio ei ole ensisijaisesti yksittäisissä opillisissa käsityksissä tai uskonnollisuuden harjoittamisen muodoissa. Tarkoituksena on luoda kokoava rakenne, jonka puitteissa holistinen spiritualiteetti voidaan selkeämmin hahmottaa ja yksilöidymmin ymmärtää.

Dielectric-lined rectangular metal waveguide

The propagation characteristics of electromagnetic waves in a dielectric-lined rectangular metal waveguide have been studied. The lining on the two side walls (E-plane) together with the air space in between them is considered as a homogeneous equivalent dielectric medium whose equivalent dielectric constant is derived by using electrostatic theory. The theoretical work is based on the fact that LSE and LSM modes can be propagated in a rectangular metal waveguide lined in the two longer sides (H-plane) by dielectric lining. Experimental verification of the guide wavelength at 'X', 'ku' and 'Ka' bands and cut-off frequency are reported.

Measuring the expressed emotion in Chinese family caregivers of persons with dementia: Validation of a Chinese version of the Family Attitude Scale

- Background Expressed emotion (EE) captures the affective quality of the relationship between family caregivers and their care recipients and is known to increase the risk of poor health outcomes for caregiving dyads. Little is known about expressed emotion in the context of caregiving for persons with dementia, especially in non-Western cultures. The Family Attitude Scale (FAS) is a psychometrically sound self-reporting measure for EE. Its use in the examination of caregiving for patients with dementia has not yet been explored. - Objectives This study was performed to examine the psychometric properties of the Chinese version of the FAS (FAS-C) in Chinese caregivers of relatives with dementia, and its validity in predicting severe depressive symptoms among the caregivers. - Methods The FAS was translated into Chinese using Brislin's model. Two expert panels evaluated the semantic equivalence and content validity of this Chinese version (FAS-C), respectively. A total of 123 Chinese primary caregivers of relatives with dementia were recruited from three elderly community care centers in Hong Kong. The FAS-C was administered with the Chinese versions of the 5-item Mental Health Inventory (MHI-5), the Zarit Burden Interview (ZBI) and the Revised Memory and Behavioral Problem Checklist (RMBPC). - Results The FAS-C had excellent semantic equivalence with the original version and a content validity index of 0.92. Exploratory factor analysis identified a three-factor structure for the FAS-C (hostile acts, criticism and distancing). Cronbach's alpha of the FAS-C was 0.92. Pearson's correlation indicated that there were significant associations between a higher score on the FAS-C and greater caregiver burden (r = 0.66, p < 0.001), poorer mental health of the caregivers (r = −0.65, p < 0.001) and a higher level of dementia-related symptoms (frequency of symptoms: r = 0.45, p < 0.001; symptom disturbance: r = 0.51, p < 0.001), which serves to suggest its construct validity. For detecting severe depressive symptoms of the family caregivers, the receiving operating characteristics (ROC) curve had an area under curve of 0.78 (95% confidence interval (CI) = 0.69–0.87, p < 0.0001). The optimal cut-off score was >47 with a sensitivity of 0.720 (95% CI = 0.506–0.879) and specificity of 0.742 (95% CI = 0.643–0.826). - Conclusions The FAS-C is a reliable and valid measure to assess the affective quality of the relationship between Chinese caregivers and their relatives with dementia. It also has acceptable predictability in identifying family caregivers with severe depressive symptoms.

The line transect method for estimating densities of large mammals in a tropical deciduous forest: An evaluation of models and field experiments

We have evaluated techniques of estimating animal density through direct counts using line transects during 1988-92 in the tropical deciduous forests of Mudumalai Sanctuary in southern India for four species of large herbivorous mammals, namely, chital (Axis axis), sambar (Cervus unicolor), Asian elephant (Elephas maximus) and gaur (Bos gauras). Density estimates derived from the Fourier Series and the Half-Normal models consistently had the lowest coefficient of variation. These two models also generated similar mean density estimates. For the Fourier Series estimator, appropriate cut-off widths for analysing line transect data for the four species are suggested. Grouping data into various distance classes did not produce any appreciable differences in estimates of mean density or their variances, although model fit is generally better when data are placed in fewer groups. The sampling effort needed to achieve a desired precision (coefficient of variation) in the density estimate is derived. A sampling effort of 800 km of transects returned a 10% coefficient of variation on estimate for chital; for the other species a higher effort was needed to achieve this level of precision. There was no statistically significant relationship between detectability of a group and the size of the group for any species. Density estimates along roads were generally significantly different from those in the interior af the forest, indicating that road-side counts may not be appropriate for most species.

Evaluation of regional and distant metastases in head and neck squamous cell carcinoma patients with special reference to the assessment of regional lymph nodes in oral cancer

For optimal treatment planning, a thorough assessment of the metastatic status of mucosal squamous cell carcinoma of the head and neck (HNSCC) is required. Current imaging methods do not allow the recognition of all patients with metastatic disease. Therefore, elective treatment of the cervical lymph nodes is usually given to patients in whom the risk of subclinical metastasis is estimated to exceed 15-20%. The objective of this study was to improve the pre-treatment evaluation of patients diagnosed with HNSCC. Particularly, we aimed at improving the identification of patients who will benefit from elective neck treatment. Computed tomography (CT) of the chest and abdomen was performed prospectively for 100 patients diagnosed with HNSCC. The findings were analysed to clarify the indications for this examination in this patient group. CT of the chest influenced the treatment approach in 3% of patients, while CT of the abdomen did not reveal any significant findings. Our results suggest that CT of the chest and abdomen is not indicated routinely for patients with newly diagnosed HNSCC but can be considered in selected cases. Retrospective analysis of 80 patients treated for early stage squamous cell carcinoma of the oral tongue was performed to investigate the potential benefits of elective neck treatment and to examine whether histopathological features of the primary tumour could be used in the prediction of occult metastases, local recurrence, or/and poor survival. Patients who had received elective neck treatment had significantly fewer cervical recurrences during the follow-up when compared to those who only had close observation of the cervical lymph nodes. Elective neck treatment did not result in survival benefit, however. Of the histopathological parameters examined, depth of infiltration and pT-category (representing tumour diameter) predicted occult cervical metastasis, but only the pT-category predicted local recurrence. Depth of infiltration can be used in the identification of at risk patients but no clear cut-off value separating high-risk and low-risk patients was found. None of the histopathological parameters examined predicted survival. Sentinel lymph node (SLN) biopsy was studied as a means of diagnosing patients with subclinical cervical metastases. SLN biopsy was applied to 46 patients who underwent elective neck dissection for oral squamous cell carcinoma. In addition, SLN biopsy was applied to 13 patients with small oral cavity tumours who were not intended to undergo elective neck dissection because of low risk of occult metastasis. The sensitivity of SLN biopsy for finding subclinical cervical metastases was found to be 67%, when SLN status was compared to the metastatic status of the rest of the neck dissection specimen. Of the patients not planned to have elective neck dissection, SLN biopsy revealed cervical metastasis in 15% of the patients. Our results suggest that SLN biopsy can not yet entirely replace elective neck dissection in the treatment of oral cancer, but it seems beneficial for patients with low risk of metastasis who are not intended for elective neck treatment according to current treatment protocols.

Nonlocal scale effects on wave propagation in multi-walled carbon nanotubes

This paper represents the effect of nonlocal scale parameter on the wave propagation in multi-walled carbon nanotubes (MWCNTs). Each wall of the MWCNT is modeled as first order shear deformation beams and the van der Waals interactions between the walls are modeled as distributed springs. The studies shows that the scale parameter introduces certain band gap region in both flexural and shear wave mode where no wave propagation occurs. This is manifested in the wavenumber plots as the region where the wavenumber tends to infinite (or group speed tends to zero). The frequency at which this phenomenon occurs is called the ``Escape frequency''. The analysis shows that, for a given N-walled carbon nanotube (CNT). the nonlocal scaling parameter has a significant effect on the shear wave modes of the N - 1 walls. The escape frequencies of the flexural and shear wave modes of the N-walls are inversely proportionl to the nonlocal scaling parameter. It is also shown that the cut-off frequencies are independent of the nonlocal scale parameter. (C) 2009 Elsevier B.V. All rights reserved.

Men´s health behaviour, health beliefs and need for health counselling : A study amongst 40-year-old males from one Helsinki City region

Tavoitteena oli tutkia 40-vuotiaiden miesten terveyskäyttäytymistä, terveysuskomuksia ja miesten saamaa terveysneuvontaa Helsingissä. 273 miestä vastasi kyselyyn ja osallistui terveystutkimuksiin. Terveydentilan perusteella miehet arvioitiin matalan (n=145) ja korkean (n=128) riskin ryhmiin. Khin neliö-testillä tutkittiin elämäntapa- ja riskitekijöitä koetun terveyden (hyvä, keskinkertainen/huono) luokissa ja verrattiin matalan ja korkean riskin ryhmiä em. tekijöiden osalta. Askeltavalla logistisella regressiomallilla analysoitiin tulosmuuttujia taustatekijöiden, terveyskäyttäytymisen, terveysuskomusten ja kliinisten riskitekijöiden avulla sekä arvioitiin oireiden ja vaivojen suhdetta koettuun terveydentilaan. Korkeassa riskissä olevien terveyttä seurattiin vuosina 2001–2004 analysoimalla mini-intervention vaikutusta terveysriskeihin ja elintapoihin varianssianalyysin avulla (ANOVA) (n=46). Matalasta vastausprosentista johtuen (39.6%), ei-vastanneiden aineistoa kerättiin käyttämällä syvähaastattelua (n=28) sekä puhelinkyselyä (n=40). Lopullinen aineisto koostui 341 miehestä. Tulokset osoittivat, että miehillä oli sydän- ja verisuonitautiriskejä. Kaksi kolmesta osallistuneista oli ylipainoisia tai lihavia, yli kolmanneksella vyötärönympärys oli ≥100 cm, ja yli 40%:llä oli diastolinen verenpaine ≥90 mmHg. Yli puolet tupakoi päivittäin ja 40% käytti alkoholia runsaasti. Ristiriitaisuutta ilmensi se, että huolimatta riskitekijöistä noin puolet miehistä koki terveydentilansa hyväksi. Sairauden tai vamman puute, hyvä suun terveydentila ja normaali vyötärönympärys olivat yhteydessä hyväksi koettuun terveydentilaan. Suora yhteys voitiin havaita omaisten tarjoaman neuvonnan ja vähäisen alkoholin käytön välillä. Masennus ja unettomuus olivat voimakkaasti yhteydessä loppuun palamiseen. Miehillä oli erilaisia fyysisiä ja psyykkisiä oireita, jotka korreloivat voimakkaasti masennuksen kanssa. Pieni määrä miehistä koki saaneensa terveysneuvontaa hoitohenkilökunnalta verrattuna perheenjäseniltä saatuun ohjaukseen. Korkeariskisten miesten (n=46) arvot parantuivat merkitsevästi lyhyellä aikavälillä. Kolesteroliarvoja lukuunottamatta ne palautuivat kolmen vuoden kuluttua alkumittausarvoja kohti. Laadullinen tutkimus osoitti, että “ei-vastanneet“ eivät osallistuneet projektiin, sillä he olivat oireettomia tai kiireisiä. Heillä todettiin samoja terveysriskejä kuin projektiin osallistuneilla. Syvähaastattelussa miehet toivat esille kokemuksiaan huolista, vihan tunteista, peloista ja yksinäisyydestä. Hoidonantajien on tärkeää ymmärtää ristiriidat miesten subjektiivisen ja objektiivisen terveydentilan välillä, mikä auttaa havaitsemaan esteitä terveyskäyttäytymiselle. Yhä enemmän tarvitaan yhteistyötä yksityisen ja julkisen terveydenhuollon välillä varmistamaan terveystottumusten jatkuminen miesten keskuudessa.

Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers’ knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects’ height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.

Infections in lung and heart transplant recipients : Studies on the impact of bronchoscopy in the diagnosis of respiratory infections and detection of viral infections in blood and bronchoalveolar lavage fluid

Infection is a major cause of mortality and morbidity after thoracic organ transplantation. The aim of the present study was to evaluate the infectious complications after lung and heart transplantation, with a special emphasis on the usefulness of bronchoscopy and the demonstration of cytomegalovirus (CMV), human herpes virus (HHV)-6, and HHV-7. We reviewed all the consecutive bronchoscopies performed on heart transplant recipients (HTRs) from May 1988 to December 2001 (n = 44) and lung transplant recipients (LTRs) from February 1994 to November 2002 (n = 472). To compare different assays in the detection of CMV, a total of 21 thoracic organ transplant recipients were prospectively monitored by CMV pp65-antigenemia, DNAemia (PCR), and mRNAemia (NASBA) tests. The antigenemia test was the reference assay for therapeutic intervention. In addition to CMV antigenemia, 22 LTRs were monitored for HHV-6 and HHV-7 antigenemia. The diagnostic yield of the clinically indicated bronchoscopies was 41 % in the HTRs and 61 % in the LTRs. The utility of the bronchoscopy was highest from one to six months after transplantation. In contrast, the findings from the surveillance bronchoscopies performed on LTRs led to a change in the previous treatment in only 6 % of the cases. Pneumocystis carinii and CMV were the most commonly detected pathogens. Furthermore, 15 (65 %) of the P. carinii infections in the LTRs were detected during chemoprophylaxis. None of the complications of the bronchoscopies were fatal. Antigenemia, DNAemia, and mRNAemia were present in 98 %, 72 %, and 43 % of the CMV infections, respectively. The optimal DNAemia cut-off levels (sensitivity/specificity) were 400 (75.9/92.7 %), 850 (91.3/91.3 %), and 1250 (100/91.5 %) copies/ml for the antigenemia of 2, 5, and 10 pp65-positive leukocytes/50 000 leukocytes, respectively. The sensitivities of the NASBA were 25.9, 43.5, and 56.3 % in detecting the same cut-off levels. CMV DNAemia was detected in 93 % and mRNAemia in 61 % of the CMV antigenemias requiring antiviral therapy. HHV-6, HHV-7, and CMV antigenemia was detected in 20 (91 %), 11 (50 %), and 12 (55 %) of the 22 LTRs (median 16, 31, and 165 days), respectively. HHV-6 appeared in 15 (79 %), HHV-7 in seven (37 %), and CMV in one (7 %) of these patients during ganciclovir or valganciclovir prophylaxis. One case of pneumonitis and another of encephalitis were associated with HHV-6. In conclusion, bronchoscopy is a safe and useful diagnostic tool in LTRs and HTRs with a suspected respiratory infection, but the role of surveillance bronchoscopy in LTRs remains controversial. The PCR assay acts comparably with the antigenemia test in guiding the pre-emptive therapy against CMV when threshold levels of over 5 pp65-antigen positive leukocytes are used. In contrast, the low sensitivity of NASBA limits its usefulness. HHV-6 and HHV-7 activation is common after lung transplantation despite ganciclovir or valganciclovir prophylaxis, but clinical manifestations are infrequently linked to them.