Load bearing improves the limits of agreement for repeated in vivo measures of the speed of sound in human Achilles tendon

Axial acoustic wave propagation has been widely used in evaluating the mechanical properties of human bone in vivo. However, application of this technique to monitor soft tissues, such as tendon, has received comparatively little scientific attention. Laboratory-based research has established that axial acoustic wave transmission is not only related to the physical properties of equine tendon but is also proportional to tensile load to which it is exposed (Miles et al., 1996; Pourcelot et al., 2005). The reproducibility of the technique for in vivo measurements in human tendon, however, has not been established. The aim of this study was to evaluate the limits of agreement for repeated measures of the speed of sound (SoS) in human Achilles tendon in vivo. Methods: A custom built ultrasound device, consisting of an A-mode 1MHz emitter and two regularly spaced receivers, was used to measure the SoS in the mid-portion of the Achilles tendon in ten healthy males and ten females (mean age: 33.8 years, range 23-56 yrs; height: 1.73±0.08 m; weight: 68.4±15.3 kg). The emitter and receivers were held at fixed positions by a polyethylene frame and maintained in close contact with the skin overlying the tendon by means of elasticated straps. Repeated SoS measurements were taken with the subject prone (non-weightbearing and relaxed Achilles tendon) and during quiet bipedal and unipedal stance. In each instance, the device was detached and repositioned prior to measurement. Results: Limits of agreement for repeated SoS measures during non-weightbearing and bipedal and unipedal stance were ±53, ±28 and ±21 m/s, respectively. The average SoS in the non-weightbearing Achilles tendon was 1804±198 m/s. There was a significant increase in the average SoS during bilateral (2122±135 m/s) (P < 0.05) and unilateral (2221±79 m/s) stance (P < 0.05). Conclusions: Repeated SoS measures in human Achilles tendon were more reliable during stance than under non-weightbearing conditions. These findings are consistent with previous research in equine tendon in which lower variability in SoS was observed with increasing tensile load (Crevier-Denoix et al, 2009). Since the limits of agreement for Achilles tendon SoS are nearly 5% of the changes previously observed during walking and therapeutic heel raise exercises, acoustic wave transmission provides a promising new non-invasive method for determining tendon properties during sports and rehabilitation related activities.

Abortion

Abortion remains one of the most complex and controversial issues in contemporary law and bioethics. This volume draws together key essays from leading scholars on the ethical and regulatory aspects of abortion. The essays explore the complex issues of personhood, prenatal life and reproductive rights, international perspectives on the regulation of abortion, health professionals and the provision of abortion services, and prenatal diagnosis and abortion. This volume will be an invaluable tool for all those interested in this challenging area.

Genetic technologies and the regulation of reproductive decision-making in Australia

This article provides a critical analysis of the current Australian regulatory landscape at the interface between genetics and reproductive decision- making. The authors argue that a comparative analysis with other countries and international law and a contextual examination of the way law regulates concepts such as disease and health, abnormality and normality is necessary before we can develop appropriate policy and legislative responses in this area. Specific genetic testing technologies are considered including prenatal genetic testing, preimplantation genetic diagnosis and inheritable genetic modification. An increasing number of members of the Australian community are using genetic testing technologies when they decide to have a baby. The authors argue that as concepts of disease and health vary among members of the community and the potential to test for traits other than illness increases, a new tension arises between an ethic of individual choice and a role for government in regulating reproductive decision-making.

Religion, spirituality, and mental health and social behaviour in young adulthood: A longitudinal study

Background The concept spirituality appears to be gaining increasing attention for its potential relationship to mental health, despite there being an absence of consensus on what spirituality is or whether it can be distinguished from religion (or religiousness) in operational terms. Spirituality is a term that is embraced within secular and non-secular contexts alike. As a consequence, spirituality as a concept encompasses forms of religiosity that are embedded in traditional religion and those that have little or no connection to traditional religious teachings. The emergence of religious/spiritual beliefs that depart from traditional religious thought represents one key feature of widespread religious change in contemporary societies. Non-traditional religious/spiritual beliefs need to be viewed within this context and thus be differentiated from traditional religious/spiritual beliefs when investigating connections between religion, spirituality, and mental health. Aims The current study seeks to compare the mental health of those whose beliefs are rooted in religious tradition with those whose beliefs deviate from traditional religious thought. The two main objectives of this study are: (1) to determine the extent to which religious background predicts endorsement of traditional and non-traditional religious/spiritual beliefs and church attendance in young adulthood, and; (2) to determine whether differential relationships exist between current religiosity, religious background, and mental health in young adulthood, and whether any observed differences are attributable to other characteristics of respondents like sociodemographic factors and health-risk behaviours. Methods Data were derived from the Mater-University of Queensland Study of Pregnancy, a longitudinal, prospective study of maternal and child health from the prenatal period to 21 years post-delivery. Religiosity was assessed among the study children in young adulthood from three items measured at the time of the 21-year follow-up. Religious background was assessed from information provided by the study mothers in earlier phases of the study. Young adult responses to items included in the Young Adult Self Report (Achenbach, 1997) were used to assess cases of anxiety/depression and externalising behaviour, and delusional ideation was assessed from their responses to the 21-item Peters et al. Delusions Inventory (PDI) (Peters & Garety, 1996). Results Belief in a spiritual or higher power other than God was found to be positively related to anxiety/depression, disturbed ideation, suspiciousness and paranormal ideation, high total PDI scores, as well as antisocial behaviour in young adulthood, regardless of gender. These associations persisted after adjustment for potential confounders. By contrast, young adults who maintain a traditional belief in God appear to be no different to those who reject this belief in regard to anxiety/depression. Belief in God was found to have no association with antisocial behaviour for males, but was observed to have a weak negative relationship with antisocial behaviour for females. This association failed to reach statistical significance however, after adjustment for other religious/spiritual and social characteristics. No associations were found between young adult belief in God and disturbed, suspicious or paranormal ideation, although a positive relationship was identified for high total PDI scores. Weekly church attendance was observed to reduce the likelihood of antisocial behaviour in young adulthood among males, but not females. Religious ideation was found to more prevalent among young adults who attend church on either a weekly or infrequent basis. No long-term effects on anxiety/depression or antisocial behaviour were evident from maternal belief in God, church attendance or religious affiliation in the young adults’ early lives. However, maternal church attendance predicted religious ideation in young adulthood. Offspring of mothers affiliated with a Pentecostal church in the prenatal period appear to have a high rate of religious ideation and high total PDI scores. Paranormal ideation in young adulthood appears to have no association with maternal religiosity in a young adult’s early life. Conclusion The findings from this study suggest that young adults who endorse non-traditional religious/spiritual beliefs are at greater risk for poorer mental health and aberrant social behaviour than those who reject these beliefs. These results suggest that a non-traditional religious/spiritual belief system involves more than mere rejection of traditional religious doctrine. This system of belief may be a marker for those who question the legitimacy of established societal norms and values, and whose thoughts, attitudes and actions reflect this position. This possibility has implications for mental health and wellbeing at both an individual and a societal level and warrants further research attention.

Prediction of maximal surface electromyographically based voluntary contractions of erector spinae muscles from sonographic measurements during isometric contractions

Objectives Currently, there are no studies combining electromyography (EMG) and sonography to estimate the absolute and relative strength values of erector spinae (ES) muscles in healthy individuals. The purpose of this study was to establish whether the maximum voluntary contraction (MVC) of the ES during isometric contractions could be predicted from the changes in surface EMG as well as in fiber pennation and thickness as measured by sonography. Methods Thirty healthy adults performed 3 isometric extensions at 45° from the vertical to calculate the MVC force. Contractions at 33% and 100% of the MVC force were then used during sonographic and EMG recordings. These measurements were used to observe the architecture and function of the muscles during contraction. Statistical analysis was performed using bivariate regression and regression equations. Results The slope for each regression equation was statistically significant (P < .001) with R2 values of 0.837 and 0.986 for the right and left ES, respectively. The standard error estimate between the sonographic measurements and the regression-estimated pennation angles for the right and left ES were 0.10 and 0.02, respectively. Conclusions Erector spinae muscle activation can be predicted from the changes in fiber pennation during isometric contractions at 33% and 100% of the MVC force. These findings could be essential for developing a regression equation that could estimate the level of muscle activation from changes in the muscle architecture.

Mutation of perinatal myosin heavy chain

Veugelers et al. (July 29 issue)1 report on patients with the trismus–pseudocamptodactyly syndrome as having a “Carney complex variant.” Among more than 500 patients with the Carney complex in our database, there are none with the trismus–pseudocamptodactyly syndrome.2,3...

Developmental origins of psychological vulnerability factors for mental disorders

Premature birth and associated small body size are known to affect health over the life course. Moreover, compelling evidence suggests that birth size throughout its whole range of variation is inversely associated with risk for cardiovascular disease and type 2 diabetes in subsequent life. To explain these findings, the Developmental Origins of Health and Disease (DOHaD) model has been introduced. Within this framework, restricted physical growth is, to a large extent, considered either a product of harmful environmental influences, such as suboptimal nutrition and alterations in the foetal hormonal milieu, or an adaptive reaction to the environment. Whether inverse associations exist between body size at birth and psychological vulnerability factors for mental disorders is poorly known. Thus, the aim of this thesis was to study in three large prospective cohorts whether prenatal and postnatal physical growth, across the whole range of variation, is associated with subsequent temperament/personality traits and psychological symptoms that are considered vulnerability factors for mental disorders. Weight and length at birth in full term infants showed quadratic associations with the temperamental trait of harm avoidance (Study I). The highest scores were characteristic of the smallest individuals, followed by the heaviest/longest. Linear associations between birth size and psychological outcomes were found such that lower weight and thinness at birth predicted more pronounced trait anxiety in late adulthood (Study II); lower birth weight, placental size, and head circumference at 12 months predicted a more pronounced positive schitzotypal trait in women (Study III); and thinness and smaller head circumference at birth associated with symptoms of attention-deficit hyperactivity disorder (ADHD) in children who were born at term (Study IV). These associations occured across the whole variation in birth size and after adjusting for several confounders. With respect to growth after birth, individuals with high trait anxiety scores in late adulthood were lighter in weight and thinner in infancy, and gained weight more rapidly between 7 and 11 years of age, but weighed less and were shorter in late adulthood in relation to weight and height measured at 11 years of age (Study II). These results suggest that a suboptimal prenatal environment reflected in smaller birth size may affect a variety of psychological vulnerability factors for mental disorders, such as the temperamental trait of harm avoidance, trait anxiety, schizotypal traits, and symptoms of ADHD. The smaller the birth size across the whole range of variation, the more pronounced were these psychological vulnerability factors. Moreover, some of these outcomes, such as trait anxiety, were also predicted by patterns of growth after birth. The findings are concordant with the DOHaD model, and emphasise the importance of prenatal factors in the aetiology of not only mental disorders but also their psychological vulnerability factors.

Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Ultrasound of paediatric appendicitis and its secondary sonographic signs: Providing a more meaningful finding

Sonography is an important clinical tool in diagnosing appendicitis in children as it can obviate both exposure to potentially harmful ionising radiation from computed tomography scans and the need for unnecessary appendicectomies. This review examines the diagnostic accuracy of ultrasound in the identification of acute appendicitis, with a particular focus on the the utility of secondary sonographic signs as an adjunct or corollary to traditionally examined criteria. These secondary signs can be important in cases where the appendix cannot be identified with ultrasound and a more meaningful finding may be made by incorporating the presence or absence of secondary sonographic signs. There is evidence that integrating these secondary signs into the final ultrasound diagnosis can improve the utility of ultrasound in cases where appendicitis is expected, though there remains some conjecture about whether they play a more important role in negative or positive prediction in the absence of an identifiable appendix.

Characterization of the TRIM37 gene and mutations underlying mulibrey nanism

Mulibrey nanism is a hereditary developmental disorder, characterized by prenatal onset growth failure without postnatal catch-up growth, distinctive craniofacial features, progressive cardiopathy and failure of sexual maturation. In addition, the patients develop insulin resistance syndrome and type 2 diabetes and they have an increased risk of developing tumors. The TRIM37 gene that underlies mulibrey nanism encodes for a member of the tripartite motif (TRIM) protein family. The physiological function of TRIM37 and the pathogenetic mechanisms leading from TRIM37 dysfunction to the mulibrey nanism phenotype are unknown. However, TRIM37 localizes at least partially to peroxisomes, and possesses ubiquitin E3-ligase activity. Thus, it may mediate ubiquitin dependent protein degradation, suggesting that accumulation of yet unknown substrate proteins may underlie the disease pathogenesis. In this study, the TRIM37 gene was characterized in detail. A transcription initiation window, with several separate transcription start sites, was identified and the putative promoter region immediately upstream from the transcription initiation window was shown to possess basal promoter activity. Further, several alternative splice variants of the gene were identified, including a highly expressed testis specific variant, encoding for an identical protein product with the main transcript. Expression of TRIM37 mRNA was detected in several different tissues, with highest expression seen in testis and in brain, when the expression patterns of the two major transcripts in different human tissues were studied by quantitative real-time PCR. Several mulibrey nanism patients were studied and thirteen novel mutations in TRIM37 were found, including three mutations (p.Gly322Val, p.Cys109Ser, p.Glu271_Ser287), that are likely to express mutant TRIM37 proteins. These mutations were further shown to alter the subcellular localization of the mutant proteins. Most of the mulibrey nanism associated mutations however, lead to premature termination codons and degradation of mRNA. All the TRIM37 mutations identified to date predict loss-of-function alleles, and thus no phenotype-genotype correlation is seen among the patients. In order to understand the pathogenetic mechanisms underlying mulibrey nanism, an animal model for the disorder is needed. For the development of a Trim37 knock-out mouse, the mouse Trim37 gene was characterized. Alternative splice variants, were identified, including a testis specific variant predicting a longer protein product. Further, a strictly tissue and cell-specific pattern of Trim37 expression was observed in developing and adult mouse tissues, when studied by immunohistochemical methods. This distribution of Trim37 expression in mouse tissues is in agreement with the clinical findings in human mulibrey nanism patients. This thesis work gives new tools for the diagnostics of mulibrey nanism as well as for studying the molecular pathogenesis behind this interesting disorder.

Maternal and Paternal Genomes Differentially Affect Myofibre Characteristics and Muscle Weights of Bovine Fetuses at Midgestation

Postnatal myofibre characteristics and muscle mass are largely determined during fetal development and may be significantly affected by epigenetic parent-of-origin effects. However, data on such effects in prenatal muscle development that could help understand unexplained variation in postnatal muscle traits are lacking. In a bovine model we studied effects of distinct maternal and paternal genomes, fetal sex, and non-genetic maternal effects on fetal myofibre characteristics and muscle mass. Data from 73 fetuses (Day153, 54% term) of four genetic groups with purebred and reciprocal cross Angus and Brahman genetics were analyzed using general linear models. Parental genomes explained the greatest proportion of variation in myofibre size of Musculus semitendinosus (80-96%) and in absolute and relative weights of M. supraspinatus, M. longissimus dorsi, M. quadriceps femoris and M. semimembranosus (82-89% and 56-93%, respectively). Paternal genome in interaction with maternal genome (P<0.05) explained most genetic variation in cross sectional area (CSA) of fast myotubes (68%), while maternal genome alone explained most genetic variation in CSA of fast myofibres (93%, P<0.01). Furthermore, maternal genome independently (M. semimembranosus, 88%, P<0.0001) or in combination (M. supraspinatus, 82%; M. longissimus dorsi, 93%; M. quadriceps femoris, 86%) with nested maternal weight effect (5-6%, P<0.05), was the predominant source of variation for absolute muscle weights. Effects of paternal genome on muscle mass decreased from thoracic to pelvic limb and accounted for all (M. supraspinatus, 97%, P<0.0001) or most (M. longissimus dorsi, 69%, P<0.0001; M. quadriceps femoris, 54%, P<0.001) genetic variation in relative weights. An interaction between maternal and paternal genomes (P<0.01) and effects of maternal weight (P<0.05) on expression of H19, a master regulator of an imprinted gene network, and negative correlations between H19 expression and fetal muscle mass (P<0.001), suggested imprinted genes and miRNA interference as mechanisms for differential effects of maternal and paternal genomes on fetal muscle.

Serotonergic neuroplasticity in alcohol addiction

Alcohol addiction is a debilitating disorder producing maladaptive changes in the brain, leading drinkers to become more sensitive to stress and anxiety. These changes are key factors contributing to alcohol craving and maintaining a persistent vulnerability to relapse. Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter widely expressed in the central nervous system where it plays an important role in the regulation of mood. The serotonin system has been extensively implicated in the regulation of stress and anxiety, as well as the reinforcing properties of all of the major classes of drugs of abuse, including alcohol. Dysregulation within the 5-HT system has been postulated to underlie the negative mood states associated with alcohol use disorders. This review will describe the serotonergic (5-HTergic) neuroplastic changes observed in animal models throughout the alcohol addiction cycle, from prenatal to adulthood exposure. The first section will focus on alcohol-induced 5-HTergic neuroadaptations in offspring prenatally exposed to alcohol and the consequences on the regulation of stress/anxiety. The second section will compare alterations in 5-HT signalling induced by acute or chronic alcohol exposure during adulthood and following alcohol withdrawal, highlighting the impact on the regulation of stress/anxiety signalling pathways. The third section will outline 5-HTergic neuroadaptations observed in various genetically-selected ethanol preferring rat lines. Finally, we will discuss the pharmacological manipulation of the 5-HTergic system on ethanol- and anxiety/stress-related behaviours demonstrated by clinical trials, with an emphasis on current and potential treatments.

Kuka on potilas? : Suomalaisen sikiöseulontakäytännön sosiaalieettistä tarkastelua

Who is the patient? A social-ethical study of the Finnish practice of prenatal screening. The aim of this study is to examine the Finnish practice of prenatal screening from a social-ethical perspective. Analyzing ethical problems in medicine and medical practice only on a general scale may conceal relevant ethical dilemmas. Previous studies have suggested that many pregnant women view the prenatal screening practices customary in the Finnish maternal care system as intimidating and oppressive. This study analyzes the ethical questions of prenatal screening by focusing on the experiences and decision-making of a pregnant woman. Finnish women s experiences of and decision-making on the most common prenatal screening methods are reflected in the basic principles of biomedical ethics described by Tom L. Beauchamp and James F. Childress in Principles of Biomedical Ethics. To concretize women s experiences I refer to studies of Finnish women s experiences of prenatal screenings. This study shows that the principles of autonomy, non-maleficence and beneficence seem to materialize rather poorly in the Finnish practice of prenatal screening. The main ethical problem with prenatal screening is that the likelihood of a foetal cure is very limited and, upon detection of an affected foetus, the choice is usually whether to continue with the pregnancy or to undergo an abortion. Although informed consent should be required, women s participation in prenatal testing is, in many cases at least, not based on their active decision. Many women experience severe anxiety when they receive a positive screening result and must wait for the final results. Medical studies indicate that long- term anxiety may negatively influence the foetus and the mother-child relationship. This study shows that the practice of prenatal screening as such may cause more harm than benefit to many pregnant women and their foetuses. This study examines the decision-making process of a pregnant woman by using the theory of medical casuistry described in Jonsen, Siegler and Winslade s Clinical Ethics. This study focuses on each of the four points of view recommended by the theory. The main problem seems to be the question of whom the patient of prenatal screening is and whom the practice is intended to benefit: the mother, the foetus, the family or society? This study shows that the concepts of health in Finnish maternal care in general, and of the prenatal screening system in particular, differ considerably. It also demonstrates that the purpose and the aims of prenatal screening, aside from the woman s right to choose, has been expressed neither in Finnish public health programmes nor in the public recommendations of prenatal screening. This study suggests that the practice of prenatal screening is a statement, though unexpressed, of public health policy and as such comprises part of the policy of disability. This study further demonstrates that through a single explicit aim (the woman s right to choose) society actually evades its obligation to women by saddling pregnant women with the entire moral responsibility as well as the possible negative consequences of her choice, such as sorrow, regrets and moral balancing. The study reveals several ethical problems in the Finnish practice of prenatal screening. Such problems should be dealt with as the Finnish practice of prenatal screening advances.

Children and adolescents in full-time special education : an epidemiological and magnetic resonance imaging study

The need for special education (SE) is increasing. The majority of those whose problems are due to neurodevelopmental disorders have no specific aetiology. The aim of this study was to evaluate the contribution of prenatal and perinatal factors and factors associated with growth and development to later need for full-time SE and to assess joint structural and volumetric brain alterations among subjects with unexplained, familial need for SE. A random sample of 900 subjects in full-time SE allocated into three levels of neurodevelopmental problems and 301 controls in mainstream education (ME) provided data on socioeconomic factors, pregnancy, delivery, growth, and development. Of those, 119 subjects belonging to a sibling-pair in full-time SE with unexplained aetiology and 43 controls in ME underwent brain magnetic resonance imaging (MRI). Analyses of structural brain alterations and midsagittal area and diameter measurements were made. Voxel-based morphometry (VBM) analysis provided detailed information on regional grey matter, white matter, and cerebrospinal fluid (CSF) volume differences. Father’s age ≥ 40 years, low birth weight, male sex, and lower socio-economic status all increased the probability of SE placement. At age 1 year, one standard deviation score decrease in height raised the probability of SE placement by 40% and in head circumference by 28%. At infancy, the gross motor milestones differentiated the children. From age 18 months, the fine motor milestones and those related to speech and social skills became more important. Brain MRI revealed no specific aetiology for subjects in SE. However, they had more often ≥ 3 abnormal findings in MRIs (thin corpus callosum and enlarged cerebral and cerebellar CSF spaces). In VBM, subjects in full-time SE had smaller global white matter, CSF, and total brain volumes than controls. Compared with controls, subjects with intellectual disabilities had regional volume alterations (greater grey matter volumes in the anterior cingulate cortex bilaterally, smaller grey matter volume in left thalamus and left cerebellar hemisphere, greater white matter volume in the left fronto-parietal region, and smaller white matter volumes bilaterally in the posterior limbs of the internal capsules). In conclusion, the epidemiological studies emphasized several factors that increased the probability of SE placement, useful as a framework for interventional studies. The global and regional brain MRI findings provide an interesting basis for future investigations of learning-related brain structures in young subjects with cognitive impairments or intellectual disabilities of unexplained, familial aetiology.