Cognitive functioning and its heritability in bipolar I disorder

Bipolar I disorder is a severe psychiatric disorder characterized by episodic mood alterations that can be manic, depressive or mixed. Bipolar disorder seems to be highly genetic, but the etiology of this complex disorder has remained elusive. In recent years, studies have found that euthymic patients with bipolar disorder may have impairments particularly in executive functioning, verbal learning and memory. These impairments may be present also among some of the relatives of these patients, who may be vulnerable to the disorder. Using neuropsychological variables as endophenotypes, i.e. intermediate phenotypes between genes and the phenotypes, has been suggested to aid search for the etiological background of the disorder, but evidence is sparse on whether these variables fulfill the criteria for endophenotypes. The present thesis is part of the Genetic Epidemiology and Molecular Genetics of Severe Mental Disorders in Finland project. The specific aim was to investigate whether neuropsychological test variables would indicate genetic liability to the disorder and could therefore be regarded as endophenotypes. Thus, cognitive functions and their heritability were studied in bipolar I disorder patients and in their unaffected first-degree relatives from a population-based sample of families, comparing them to a population-based control group. In order to add homogeneity to the subgroups of bipolar disorder patients and their relatives, cognitive functions and their heritability were further studied in a group of families affected by bipolar I disorder only (bipolar families) and another group of families affected by both bipolar I disorder and schizophrenia or schizoaffective disorders (mixed families). Finally, the effect of processing speed on other cognitive functions was investigated. The study showed that especially executive functioning and processing speed fulfilled the endophenotype criteria. Impairments in these functions were found in bipolar patients and in their relatives irrespective of other severe psychopathology in the family. These functions were highly heritable in these families. Study also showed that generalized impairment in verbal memory may associate more with bipolar disorder than to vulnerability to other psychotic disorders, and be more related to fully developed disease; impairments in verbal learning and memory were found only in patients, and they were not found to be highly heritable. Finally, the most potential endophenotype, i.e. processing speed, seemed to contribute to a range of other cognitive dysfunctions seen in bipolar disorder patients. Processing speed, in particular, has also been shown to be a valid endophenotype in subsequent association analyses in psychiatric genetics in Finland and internationally. Information concerning cognitive impairments and their association with the psychosocial consequences of bipolar disorder is important in planning treatment. It is also important to understand and acknowledge that patients may have cognitive impairments that affect their everyday life. Psychosocial interventions and neuropsychological rehabilitation may supplement other conventional treatments for bipolar patients.

Toiseustarinat : äitinä suomalaisessa yhteiskunnassa

The focus of this study is to analyse the power relations on how our society normalizes motherhood and what kind techniques of power can be found in the motherhood culture. This study is an educational family research, and the aim of this study was to analyse those power frames that try to limit mothers in their motherhoods. There were seven mother participants in this study. They wrote essays about their experiences of motherhood in the Finnish society. The method of the research was qualitative, and the data was analysed by discourse analysis. The theoretical part of the research consists of distinguish in parenthood, family policy in families with children and motherhood in the Finnish society. The methodological approach is Michel Foucault´s analytic of power relations, and in this viewpoint I try to find out the different discourses of motherhood. In this study, mothers process against those assumptions of motherhood, which limit their freedom as acting in their role as mothers. Mothers locate themselves in the position of the Other that differs from those motherhood discourses which mothers were talking about. From the point of the Others , mothers processed their own motherhood, and they feel that they were always distinguished from the motherhood which they were expected to belong. Six categories were found in the motherhood assumptions: the norm of education, the myths of motherhood, the role assumptions in the motherhood, the norm of motherhood and discourse of good parenting, and discourse of project parenting. These discourses of motherhood assumptions make limitations, classifications and difference among motherhood. These assumptions were told by people for example in maternity clinics, first and security houses, judiciary systems, nursery, or by some other people. Mothers in this study made a comparison between the motherhood assumptions and themselves. In this study, mothers also criticize the culture of motherhood in the society and feel incompatible with the norms of motherhood around them. This may also increase mothers exhaustion.

Population projection for Namibia 2011-2020 - With an estimation of the impact of HIV/AIDS

This study presents a population projection for Namibia for years 2011–2020. In many countries of sub-Saharan Africa, including Namibia, the population growth is still continuing even though the fertility rates have declined. However, many of these countries suffer from a large HIV epidemic that is slowing down the population growth. In Namibia, the epidemic has been severe. Therefore, it is important to assess the effect of HIV/AIDS on the population of Namibia in the future. Demographic research on Namibia has not been very extensive, and data on population is not widely available. According to the studies made, fertility has been shown to be generally declining and mortality has been significantly increasing due to AIDS. Previous population projections predict population growth for Namibia in the near future, yet HIV/AIDS is affecting the future population developments. For the projection constructed in this study, data on population is taken from the two most recent censuses, from 1991 and 2001. Data on HIV is available from HIV Sentinel Surveys 1992–2008, which test pregnant women for HIV in antenatal clinics. Additional data are collected from different sources and recent studies. The projection is made with software (EPP and Spectrum) specially designed for developing countries with scarce data. The projection includes two main scenarios which have different assumptions concerning the development of the HIV epidemic. In addition, two hypothetical scenarios are made: the first considering the case where HIV epidemic would never have existed and the second considering the case where HIV treatment would never have existed. The results indicate population growth for Namibia. Population in the 2001 census was 1.83 million and is projected to result in 2.38/2.39 million in 2020 in the first two scenarios. Without HIV, population would be 2.61 million and without treatment 2.30 million in 2020. Urban population is growing faster than rural. Even though AIDS is increasing mortality, the past high fertility rates still keep young adult age groups quite large. The HIV epidemic shows to be slowing down, but it is still increasing the mortality of the working-aged population. The initiation of HIV treatment in 2004 in the public sector seems to have had an effect on many projected indicators, diminishing the impact of HIV on the population. For example, the rise of mortality is slowing down.

mRNA-binding protein HuR in breast carcinogenesis

Breast cancer is the most common cancer among women. Although its prognosis has improved nowadays, methods to predict the progression of the disease or to treat it are not comprehensive. This thesis work was initiated to elucidate in breast carcinogenesis the role of HuR, a ubiquitously expressed mRNA-binding protein that regulates gene expression posttranscriptionally. HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm, and this nucleocytoplasmic translocation is important for its function as a RNA-stabilizing and translational regulator. HuR has been associated with diverse cellular processes, for example carcinogenesis. The specific aims of my thesis work were to study the prognostic value of HuR in breast cancer and to clarify the mechanisms by which HuR contributes to breast carcinogenesis. My ultimate goal is, by better understanding the role of HuR in breast carcinogenesis, to aid in the discovery of novel targets for cancer therapies. HuR expression and localization was studied in paraffin-embedded preinvasive (atypical ductal hyperplasia, ADH, and ductal carcinoma in situ, DCIS) specimens as well in sporadic and familial breast cancer specimens. Our results show that cytoplasmic HuR expression was already elevated in ADH and remained elevated in DCIS as well as in cancer specimens. Clinicopathological analysis showed that cytoplasmic HuR expression associated with the more aggressive form of the disease in DCIS, and in cancer specimens it proved an independent marker for poor prognosis. Importantly, cytoplasmic HuR expression was significantly associated with poor outcome in the subgroups of small (2 cm) and axillary lymph node-negative breast cancers. HuR proved to be the first mRNA stability protein the expression of which is associated in breast cancer with poor outcome. To explore the mechanisms of HuR in breast carcinogenesis, lentiviral constructs were developed to inhibit and to overexpress the HuR expression in a breast epithelial cell line (184B5Me). Our results suggest that HuR mediates breast carcinogenesis by participating in processes important in cell transformation, in programmed cell death, and in cell invasion. Global gene expression analysis shows that HuR regulates genes participating in diverse cellular processes, and affects several pathways important in cancer development. In addition, we identified two novel target transcripts (connective tissue growth factor, CTGF, and Ras oncogene family member 31, RAB31) for HuR. In conclusion, because cytoplasmic HuR expression in breast cancer can predict the outcome of the disease it could serve in clinics as a prognostic marker. HuR accumulates in the cytoplasm even at its non-invasive stage (ADH and DCIS) of the carcinogenic process and supports functions essential in cell alteration. These data suggest that HuR contributes to carcinogenesis of the breast epithelium.

Perinatal mortality and maternal health in rural China

Background and context Since the economic reforms of 1978, China has been acclaimed as a remarkable economy, achieving 9% annual growth per head for more than 25 years. However, China's health sector has not fared well. The population health gains slowed down and health disparities increased. In the field of health and health care, significant progress in maternal care has been achieved. However, there still remain important disparities between the urban and rural areas and among the rural areas in terms of economic development. The excess female infant deaths and the rapidly increasing sex ratio at birth in the last decade aroused serious concerns among policy makers and scholars. Decentralization of the government administration and health sector reform impacts maternal care. Many studies using census data have been conducted to explore the determinants of a high sex ratio at birth, but no agreement has been so far reached on the possible contributing factors. No study using family planning system data has been conducted to explore perinatal mortality and sex ratio at birth and only few studies have examined the impact of the decentralization of government and health sector reforms on the provision and organization of maternal care in rural China. Objectives The general objective of this study was to investigate the state of perinatal health and maternal care and their determinants in rural China under the historic context of major socioeconomic reforms and the one child family planning policy. The specific objectives of the study included: 1) to study pregnancy outcomes and perinatal health and their correlates in a rural Chinese county; 2) to examine the issue of sex ratio at birth and its determinants in a rural Chinese county; 3) to explore the patterns of provision, utilization, and content of maternal care in a rural Chinese county; 4) to investigate the changes in the use of maternal care in China from 1991 to 2003. Materials and Methods This study is based on a project for evaluating the prenatal care programme in Dingyuan county in 1999-2003, Anhui province, China and a nationwide household health survey to describe the changes in maternal care utilization. The approaches used included a retrospective cohort study, cross sectional interview surveys, informant interviews, observations and the use of statistical data. The data sources included the following: 1) A cohort of pregnant women followed from pregnancy up to 7 days after birth in 20 townships in the study county, collecting information on pregnancy outcomes using family planning records; 2) A questionnaire interview survey given to women who gave birth between 2001 and 2003; 3) Various statistical and informant surveys data collected from the study county; 4) Three national household health interview survey data sets (1993-2003) were utilized, and reanalyzed to described the changes in maternity care utilization. Relative risks (RR) and their confidence intervals (CI) were calculated for comparison between parity, approval status, infant sex and township groups. The chi-square test was used to analyse the disparity of use of maternal care between and within urban and rural areas and its trend across the years in China. Logistic regression was used to analyse the factors associated with hospital delivery in rural areas. Results There were 3697 pregnancies in the study cohort, resulting in 3092 live births in a total population of 299463 in the 20 study townships during 1999-2000. The average age at pregnancy in the cohort was 25.9 years. Of the women, 61% were childless, 38% already had one child and 0.3% had two children before the current pregnancy. About 90% of approved pregnancies ended in a live birth while 73% of the unapproved ones were aborted. The perinatal mortality rate was 69 per thousand births. If the 30 induced abortions in which the gestational age was more than 28 weeks had been counted as perinatal deaths, the perinatal mortality rate would have been as high as 78 per thousand. The perinatal mortality rate was negatively associated with the wealth of the township. Approximately two thirds of the perinatal deaths occurred in the early neonatal period. Both the still birth rate and the early neonatal death rate increased with parity. The risk of a stillbirth in a second pregnancy was almost four times that for a first pregnancy, while the risk of early neonatal deaths doubled. The early neonatal mortality rate was twice as high for female as for male infants. The sex difference in the early neonatal mortality rate was mainly attributable to mortality in second births. The male early neonatal mortality rate was not affected by parity, while the female early neonatal mortality rate increased dramatically with parity: it was about six times higher for second births than for first births. About 82% early neonatal deaths happened within 24 hours after birth, and during that time, girls were almost three times more likely to die than boys. The death rate of females on the day of birth increased much more sharply with parity than that of males. The total sex ratio at birth of 3697 registered pregnancies was 152 males to 100 females, with 118 and 287 in first and second pregnancies, respectively. Among unapproved pregnancies, there were almost 5 live-born boys for each girl. Most prenatal and delivery care was to be taken care of in township hospitals. At the village level, there were small private clinics. There was no limitation period for the provision of prenatal and postnatal care by private practitioners. They were not permitted to provide delivery care by the county health bureau, but as some 12% of all births occurred either at home or at private clinics; some village health workers might have been involved. The county level hospitals served as the referral centers for the township hospitals in the county. However, there was no formal regulation or guideline on how the referral system should work. Whether or not a woman was referred to a higher level hospital depended on the individual midwife's professional judgment and on the clients' compliance. The county health bureau had little power over township hospitals, because township hospitals had in the decentralization process become directly accountable to the township government. In the township and county hospitals only 10-20% of the recurrent costs were funded by local government (the township hospital was funded by the township government and the county hospital was funded by the county government) and the hospitals collected user fees to balance their budgets. Also the staff salaries depended on fee incomes by the hospital. The hospitals could define the user charges themselves. Prenatal care consultations were however free in most township hospitals. None of the midwives made postnatal home visits, because of low profit of these services. The three national household health survey data showed that the proportion of women receiving their first prenatal visit within 12 weeks increased greatly from the early to middle 1990s in all areas except for large cities. The increase was much larger in the rural areas, reducing the urban-rural difference from more than 4 times to about 1.4 times. The proportion of women that received antenatal care visits meeting the Ministry of Health s standard (at least 5 times) in the rural areas increased sharply from 12% in 1991-1993 to 36% in 2001-2003. In rural areas, the proportion increase was much faster in less developed areas than in developed areas. The hospital delivery rate increased slightly from 90% to 94% in urban areas while the proportion increased from 27% to 69% in rural areas. The fastest change was found to be in type 4 rural areas, where the utilization even quadrupled. The overall difference between rural and urban areas was substantially narrowed over the period. Multiple logistic regression analysis shows that time periods, residency in rural or urban areas, income levels, age group, education levels, delivery history, occupation, health insurance and distance from the nearest health care facilities were significantly associated with hospital delivery rates. Conclusions 1. Perinatal mortality in this study was much higher than that for urban areas as well as any reported rate from specific studies in rural areas of China. Previous studies in which calculations of infant mortality were not based on epidemiological surveys have been shown to underestimate the rates by more than 50%. 2. Routine statistics collected by the Chinese family planning system proved to be a reliable data source for studying perinatal health, including still births, neonatal deaths, sex ratio at birth and among newborns. National Household Health Survey data proved to be a useful and reliable data source for studying population health and health services. Prior to this research there were few studies in these areas available to international audiences. 3.Though perinatal mortality rate was negatively associated with the level of township economic development, the excess female early neonatal mortality rate contributed much more to high perinatal mortality rate than economic factors. This was likely a result of the role of the family planning policy and the traditional preferences for sons, which leads to lethal neglect of female newborns and high perinatal mortality. 4. The selective abortions of female foetuses were likely to contribute most to the high sex ratio at birth. The underreporting of female births seemed to have played a secondary role. The higher early neonatal mortality rate in second-born as compared to first-born children, particularly in females, may indicate that neglect or poorer care of female newborn infants also contributes to the high sex ratio at birth or among newborns. Existing family planning policy proved not to effectively control the steadily increased birth sex ratio. 5. The rural-urban gap in service utilization was on average significantly narrowed in terms of maternal healthcare in China from 1991 to 2003. This demonstrates that significant achievements in reducing inequities can be made through a combination of socio-economic development and targeted investments in improving health services, including infrastructure, staff capacities, and subsidies to reduce the costs of service utilization for the poorest. However, the huge gap which persisted among cities of different size and within different types of rural areas indicated the need for further efforts to support the poorest areas. 6. Hospital delivery care in the study county was better accepted by women because most of women think delivery care was very important while prenatal and postnatal care were not. Hospital delivery care was more systematically provided and promoted than prenatal and postnatal care by township hospital in the study area. The reliance of hospital staff income on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care, since delivery care generated much profits than prenatal and postnatal care . Recommendations 1. It is essential for the central government to re-assess and modify existing family planning policies. In order to keep national sex balance, the existing practice of one couple one child in urban areas and at-least-one-son a couple in rural areas should be gradually changed to a two-children-a-couple policy throughout the country. The government should establish a favourable social security policy for couples, especially for rural couples who have only daughters, with particular emphasis on their pension and medical care insurance, combined with an educational campaign for equal rights for boys and girls in society. 2. There is currently no routine vital-statistics registration system in rural China. Using the findings of this study, the central government could set up a routine vital-statistics registration system using family planning routine work records, which could be used by policy makers and researchers. 3. It is possible for the central and provincial government to invest more in the less developed and poor rural areas to increase the access of pregnant women in these areas to maternal care services. Central government together with local government should gradually provide free maternal care including prenatal and postnatal as well as delivery care to the women in poor and less developed rural areas. 4. Future research could be done to explore if county and the township level health care sector and the family planning system could be merged to increase the effectiveness and efficiency of maternal and child care. 5. Future research could be done to explore the relative contribution of maternal care, economic development and family planning policy on perinatal and child health using prospective cohort studies and community based randomized trials. Key words: perinatal health, perinatal mortality, stillbirth, neonatal death, sex selective abortion, sex ratio at birth, family planning, son preference, maternal care, prenatal care, postnatal care, equity, China

Geriatrisen lääkehoidon koulutustarpeet perusterveydenhuollossa - Moniammatillisen täydennyskoulutuksen suunnittelu LOST-alueen kotihoidon henkilöstölle

Sosiaali- ja terveysministeriön 2006 julkaiseman vanhustyön ja geriatrisen lääkehoidon kehittämistä koskevan selvityksen yhtenä tärkeänä huolenaiheena oli iäkkäiden lääkehoidon useat epäkohdat, kuten iäkkäitä hoitavien hoitajien lääkeosaamiseen liittyvät puutteet ja ongelmat. Yksi keino parantaa iäkkäitä hoitavien eri tahojen lääkehoito-osaamista on täydennyskoulutus, johon kaikilla sosiaali- ja terveydenhuollon ammattiryhmillä on oikeus ja velvollisuus. Täydennyskoulutuksella pystytään myös kehittämään organisaatioiden toimintaa ja tuottamaan uusia, parempia palveluita. Tutkimuksessa selvitettiin Lohjan, Siuntion, Inkoon ja Karjalohjan muodostaman sosiaali- ja terveydenhuollon yhteistoiminta-alueen LOSTin kotihoidon yksiköiden iäkkäiden lääkehoitoihin liittyviä koulutustarpeita. Tämän tutkimuksen avulla syvennettiin samalle tutkimusryhmälle tehdyn kyselytutkimuksen tuloksia. Tutkimusaineistona käytettiin LOST-alueen kotihoidon yksiköiden hoitajille (n=150) farmaseutin lopputyönä tehtyä kyselyaineistoa sekä työntekijöille (n=6) ja esimiehille (n=6) tehtyjä erillisiä ryhmäkeskusteluja. Lisäksi näkökulman laajentamiseksi ja moniammatillisuuden korostamiseksi aineistona käytettiin kotihoidon asiakkaita hoitavien lääkärien (n=4) teemahaastatteluja. Kyselyaineistosta analysoitiin erikseen sairaanhoitajien, lähihoitajien ja kodinhoitajien koulutustarpeet. Samat asiat nousivat esille kunkin ammattiryhmän tuloksissa. Tärkeimpinä lääkehoito-osaamiseen liittyvinä teoreettisina koulutettavina asioina kyselystä nousivat esille iäkkäiden farmakokinetiikka ja lääkkeiden käyttöön liittyvät erityispiirteet, lääkkeiden vaikutukset, lääkkeiden haittavaikutukset sekä lääkkeiden yhteisvaikutukset ja yhteensopivuus. Lisäksi teoreettisista taidoista nousi hoitotyön etiikkaan liittyvät tarkkuus ja huolellisuus työssä. Käytännön taidoista tärkeimpinä koulutettavina aiheina kyselystä nousivat asiakkaiden lääkehoidon ja voinnin seuranta, lääkkeiden jakaminen sekä lääkkeiden annosteluun liittyen se, että annostellaan oikeaa lääkettä ja vahvuutta, oikea annos ja oikeaan aikaan sekä oikeat antotavat. Ryhmäkeskusteluista ja lääkärien teemahaastatteluista haettiin syvempää ymmärrystä kyselyn tuloksiin. Yksi tärkeimmistä tämän laadullisen tutkimuksen löydöksistä oli kotihoidon yhteistyöhön liittyvät epäkohdat. Lääkehoitojen toteuttamista ja seurantaa voitaisiin tulosten perusteella parantaa lääkärien ja kotihoidon hoitajien yhteisellä koulutuksella. Tärkeimpiä sairauksia tai oireita, joihin hoitajat toivoisivat yhteisiä toimintakäytäntöjä, ovat diabetes, sydän- ja verisuonisairaudet, kipu, muistisairaudet sekä psyykensairaudet. Lisäksi koulutusaiheiksi tutkimuksesta nousivat iäkkäiden lääkehoidon erityispiirteet, lääkkeiden antoreitit ja lääkemuodot. Kyselyn sekä ryhmäkeskustelujen ja lääkärien teemahaastattelujen tuloksista tehtiin lopuksi synteesi, jonka lopputuloksena LOST-alueen kotihoidon hoitohenkilöstölle sekä kotihoidon lääkäreille koottiin yhteinen tarvelähtöinen täydennyskoulutussuunnitelma. Suunnitelma tehtiin aineistosta nousseiden koulutusaiheiden pohjalta, eikä siihen lisätty aiheita tutkimuksen ulkopuolelta.

Poststroke survival and ischemic stroke recurrence : the cerebral small-vessel disease perspective

The aim of the present study was to investigate the influence of different manifestations of cerebral SVD on poststroke survival and ischemic stroke recurrence in long-term follow-up. The core imaging features of small-vessel disease (SVD) are confluent and extensive white matter changes (WMC) and lacunar infarcts. These are associated with minor motor deficits but a major negative influence on cognition, mood, and functioning in daily life, resulting from small-vessel lesions in the fronto-subcortical brain network. These sub-studies were conducted as part of the Helsinki Stroke Aging Memory (SAM) study. The SAM cohort consisted of 486 consecutive patients aged 55 to 85 years who were admitted to Helsinki University Central Hospital with acute ischemic stroke. The study included comprehensive clinical, neuropsychological, psychiatric and radiological assessment three months poststroke. The patients were followed up up for 12 years using extensive national registers. The effect of different manifestations of cerebral SVD on poststroke survival and stroke recurrence was analyzed controlling for factors such as age, education, and cardiovascular risk factors. Poststroke dementia and cognitive impairment relate to poor long-term survival. In particular, deficits in executive functions as well as visuospatial and constructional abilities predict poor outcome. The predictive value of cognitive deficits is further underlined by the finding that depression-executive dysfunction syndrome (DES), but not depression in itself, is associated with poor poststroke survival. Delirium is not independently associated with increased risk for long-term poststroke mortality, although it is associated with poststroke dementia. Furthermore, acute index stroke attributable to SVD is associated with poorer long-term survival and a higher risk for cardiac death than other stroke subtypes. Severe WMC, a surrogate of SVD, is independently related to an increased risk of stroke recurrence at five years. In summary, cognitive poststroke outcomes reflecting changes in the executive network brain, and the presence of cerebral SVD are important determinants of poststroke mortality and ischemic stroke recurrence, regardless of whether SVD is the cause of the index stroke or a condition concurrent to some other etiology.

Snoring and sleep apnea in children

Snoring is a primary and major clinical symptom of upper airway obstruction during sleep. Sleep-disordered breathing ranges from primary snoring to significant partial upper airway obstruction, and obstructive sleep apnea. Adult snoring and obstructive sleep apnea have been extensively studied, whereas less is known about these disorders in children. Snoring and more severe obstructive sleep apnea have been shown to have a harmful effect on the neurobehavioral development of children, but the mechanisms of this effect remains unknown. Furthermore, the correlation of this effect to objective sleep study parameters remains poor. This study evaluated the prevalence of snoring in preschool-aged children in Finland. Host and environmental risk factors, and neurobehavioral and neurocognitive symptoms of children suffering from snoring or obstructive sleep apnea were also investigated. The feasibility of acoustic rhinometry in young children was assessed. The prevalence and risk factors of snoring (I) were evaluated by a questionnaire. The random sample included 2100 children aged 1-6 years living in Helsinki. All 3- to 6-year-old children whose parents reported their child to snore always, often, or sometimes were categorized as snorers, and invited to participate to the clinical study (II-IV). Non-snoring children whose parents were willing to participate in the clinical study were invited to serve as controls. Children underwent a clinical ear-nose-throat examination. Emotional, behavioral, and cognitive performances were evaluated by Child Behavioral Checklist (CBCL), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) and NEPSY-A Developmental Neuropsychological Assessment (NEPSY). Nasal volume was measured by acoustic rhinometry, and nasal resistance by rhinomanometry. Lateral and posteroanterior cephalometry were performed. A standard overnight ambulatory polysomnography was performed in the home environment. Twenty-six healthy children were tested in order to assess the feasibility of acoustic rhinometry in young children (V). Snoring was common in children; 6.3% of children snored always or often, whereas 81.3% snored never or occasionally. No differences were apparent between snorers and non-snorers regarding age, or gender. Pediatric snoring was associated with recurrent upper respiratory infections, otitis media, and allergic rhinitis. Exposure to parental tobacco smoke, especially maternal smoking, was more common among snorers. Rhinitis was more common among children who exposured to tobacco smoke. Overnight polysomnography (PSG) was performed on 87 children; 74% showed no signs of significant upper airway obstruction during sleep. Three children had obstructive apnea/hypopnea index (OAHI) greater than 5/h. Age, gender, or a previous adenoidectomy or tonsillectomy did not correlate with OAHI, whereas tonsillar size did correlate with OAHI. Relative body weight and obesity correlated with none of the PSG parameters. In cephalometry, no clear differences or correlations were found in PSG parameters or between snorers and non-snorers. No correlations were observed between acoustic rhinometry, rhinomanometry, and PSG parameters. Psychiatric symptoms were more frequent in the snoring group than in the nonsnoring group. In particular, anxious and depressed symptoms were more prevalent in the snoring group. Snoring children frequently scored lower in language functions. However, PSG parameters correlated poorly with neurocognitive test results in these children. This study and previous studies indicate that snoring without episodes of obstructive apnea or SpO2 desaturations may cause impairment in behavioral and neurocognitive functions. The mechanism of action remains unknown. Exposure to parental tobacco smoke is more common among snorers than non-snorers, emphasizing the importance of a smoke-free environment. Children tolerated acoustic rhinometry measurements well.

Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates

Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, and were found to be subgroup I specific and possess long RNA patterns (M. Sukumaran, K. Gowda, P. P. Maiya, T. P. Srinivas, M. S. Kumar, S. Aijaz, R. R. Reddy, L. Padilla, H. B. Greenberg, and C. D. Rao, Arch. Virol. 126:239-251, 1992). Three of these strains were adapted to tissue culture and found by serotype analysis and neutralization assays to be of serotype 10, a serotype commonly found in cattle but infrequently found in humans and not previously identified in neonates. By RNA-RNA hybridization, a high level of relatedness to a serotype 10 bovine rotavirus strain and a low-to-medium level of relatedness to a human rotavirus strain were observed. Since this human isolate shares a genogroup with bovine rotavirus, it is likely that it originated by interspecies transmission. A human rotavirus strain isolated from asymptomatic neonates and similar to bovine rotavirus might represent a good vaccine candidate.

Precarious Pregnancies : Alcohol, drugs and the regulation of risks

Since the 1970s alcohol and drug use by pregnant women has become a target of political, professional and personal concern. The present study focuses on prenatal substance use and the regulation of risks by examining different kinds of societal responses to prenatal alcohol and drug use. The study analyses face-to-face encounters between professionals and service users at a specialised maternity clinic for pregnant women with substance abuse problems, medical and political discourses on the compulsory treatment of pregnant women as a means of FAS prevention and official recommendations on alcohol intake during pregnancy. Moreover, the study addresses the women s perspective by asking how women who have used illicit drugs during pregnancy perceive and rank the dangers linked to drug use. The study consists of five empirical sub-studies and a summary article. Sub-study I was written in collaboration with Dorte Hecksher and Sub-study IV with Riikka Perälä. Theoretically the study builds on the one hand, on the socio-cultural approach to the selection and perception of risks and on the other on governmentality studies which focus on the use of power in contemporary Western societies. The study is based on an ethnographic approach and makes use of the principles of multi-sited ethnography. The empirical sub-studies are based on three different types of qualitative data: ethnographic field notes from a maternity clinic from a period of 7 months, documentary material (medical journals, political documents, health education materials, government reports) and 3) interviews from maternity clinics with clients and members of staff. The study demonstrates that the logic of the regulation of prenatal alcohol use in Finland is characterised by the rise of the foetus , a process in which the urgency of protecting the foetus has gradually gained a more prominent role in the discourses on alcohol-related foetal damage. An increasing unwillingness to accept any kinds of risks when foetal health is at stake is manifested in the public debate on the compulsory treatment of pregnant women with alcohol problems and in the health authorities decision to advise pregnant women to refrain from alcohol use during pregnancy (Sub-studies I and II). Secondly, the study suggests that maternity care professionals have an ambivalent role in their mundane encounters with their pregnant clients: on the one hand professionals focus on the well-being of the foetus, but on the other, they need to take into account the women s needs and agency. The professionals daily encounters with their clients are thus characterised by hybridisation: the simultaneous use of technologies of domination and technologies of agency (Sub-studies III and IV). Finally, the study draws attention to the women s understanding of the risks of illicit drug during pregnancy, and shows that the women s understanding of risk differs from the bio-medical view. The study suggests that when drug-using pregnant women seek professional help they can feel that their moral worth is threatened by professionals negative attitudes which can make service-use challenging.

Selective Review of Proton Magnetic Resonance Spectroscopy in Schizophrenia

Magnetic Resonance Spectroscopy (MRS) offers a unique opportunity to measure brain metabolites in-vivo, and in doing so enables one to understand the brain function and cellular processes implicated in the pathophysiology of psychiatric disorders. MRS, in addition to being non-invasive, is devoid of radioactive tracers and ionizing radiation, a distinct advantage over other imaging modalities like positron emission tomography and single photon emission computed tomography. With advances in MRS technique it is now possible to quantify concentrations of relevant compounds like neurotransmitters, neuronal viability markers and pharmacological compounds. Majority of the MRS studies have examined the neurometabolites in schizophrenia, a common and debilitating psychiatric disorder. Abnormalities in N Acetyl aspartate and Glutamate are consistently reported while the reports regarding the myoinsoitol and choline are inconsistent. These abnormalities are not changed across the illness stages and despite treatment. However, multiple technical challenges have limited the widespread use of MRS in psychiatric disorders. Guidelines for uniform acquisition and preprocessing are need of the hour, which. would increase the replicability and validity of MRS measures in psychiatry. Finally long term, prospective, longitudinal studies are required in different psychiatric disorders for potential clinical applications.

Lateralisation abnormalities in obsessive-compulsive disorder: a line bisection study

Objective Asymmetry in brain structure and function is implicated in the pathogenesis of psychiatric disorders. Although right hemisphere abnormality has been documented in obsessive-compulsive disorder (OCD), cerebral asymmetry is rarely examined. Therefore, in this study, we examined anomalous cerebral asymmetry in OCD patients using the line bisection task. Methods A total of 30 patients with OCD and 30 matched healthy controls were examined using a reliable and valid two-hand line bisection (LBS) task. The comparative profiles of LBS scores were analysed using analysis of covariance. Results Patients with OCD bisected significantly less number of lines to the left and had significant rightward deviation than controls, indicating right hemisphere dysfunction. The correlations observed in this study suggest that those with impaired laterality had more severe illness at baseline. Conclusions The findings of this study indicate abnormal cerebral lateralisation and right hemisphere dysfunction in OCD patients.

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.

SYNGAP1: Mind the Gap

A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein) has been shown to cause Intellectual Disability (ID) with comorbid Autism Spectrum Disorder (ASD) and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngapl mouse models, have provided deeper insights into how downstream signaling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.

SYNGAP1: Mind the Gap

A cardinal feature of early stages of human brain development centers on the sensory, cognitive, and emotional experiences that shape neuronal-circuit formation and refinement. Consequently, alterations in these processes account for many psychiatric and neurodevelopmental disorders. Neurodevelopment disorders affect 3-4% of the world population. The impact of these disorders presents a major challenge to clinicians, geneticists, and neuroscientists. Mutations that cause neurodevelopmental disorders are commonly found in genes encoding proteins that regulate synaptic function. Investigation of the underlying mechanisms using gain or loss of function approaches has revealed alterations in dendritic spine structure, function, and plasticity, consequently modulating the neuronal circuit formation and thereby raising the possibility of neurodevelopmental disorders resulting from synaptopathies. One such gene, SYNGAP1 (Synaptic Ras-GTPase-activating protein) has been shown to cause Intellectual Disability (ID) with comorbid Autism Spectrum Disorder (ASD) and epilepsy in children. SYNGAP1 is a negative regulator of Ras, Rap and of AMPA receptor trafficking to the postsynaptic membrane, thereby regulating not only synaptic plasticity, but also neuronal homeostasis. Recent studies on the neurophysiology of SYNGAP1, using Syngapl mouse models, have provided deeper insights into how downstream signaling proteins and synaptic plasticity are regulated by SYNGAP1. This knowledge has led to a better understanding of the function of SYNGAP1 and suggests a potential target during critical period of development when the brain is more susceptible to therapeutic intervention.