Homozygous disruption of P450 side-chain cleavage (CYP11A1) is associated with prematurity, complete 46,XY sex reversal, and severe adrenal failure

Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations of the CYP11A1 gene is thought to be incompatible with fetal survival because of impaired progesterone production by the fetoplacental unit. We present a 46, XY patient with a homozygous disruption of CYP11A1.The child was born prematurely with complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single nucleotide deletion leading to a premature termination at codon position 288. This mutation will delete highly conserved regions of the P450scc enzyme and thus is predicted to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation.Our report demonstrates that severe disruption of P450scc can be compatible with survival in rare instances. Furthermore, defects in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote carriers can be healthy and fertile. The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned

USTOPIA REQUIREMENTS THOUGHTS ON A USER-FRIENDLY SYSTEM FOR TRANSFORMATION OF PROGRAMS IN ABSTRACTO

Transformational programming is a program development method which is usually applied using 'pen and paper'. Since this requires a lot of clerical work (copying expressions, con- sistent substitution) which is tiresome and prone to error, some form of machine support is desirable. In this paper a number of systems are described that have already been built to this aim. Some of their shortcomings and limitations are identified. Based on experience with program transformation and transformation systems, a long list of features is given that would be useful in an 'utopian' transformation system. This list is presented using an orthogonal division of the problem area. A number of problems with the realisation of some aspects of our 'utopian' system are identified, and some areas for further research are indicated

An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery

Background An investigation was undertaken to compare the effect of multi-component compression bandages and compression hosiery kits on individuals’ range of ankle motion whilst wearing typical and medical footwear, and barefoot. Methods A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. Results Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54° at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12° at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51° at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. Conclusions Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types

Apicotomy: a root apical fracture for surgical treatment of impacted upper canines

Impacted canines, due to systemic or local factors, represent a frequent problem in most populations. Surgical intervention usually involves exposure for spontaneous eruption, exposure for orthodontic traction or extraction. The author presents the apicotomy technique, which has been successfully used during the past twenty years for conservative intervention in cases of impacted upper canines with dilaceration or apical root-ankylosis. This original method involves surgical fracture of the root apex, followed by orthodontic traction of the corono-radicular region

Examination of the effects of a new compression garment on skin tissue oxygenation in healthy volunteers

Objective: Compression devices have been shown to reduce venous stasis, increase blood flow and skin tissue oxygenation (StO2), promoting healthy tissue. This study aimed to explore the efficacy of a new compression garment in three different positions in healthy adults. Methods: In this quantitative study, potential participants were screened and recruited using the Physical Activity Readiness Questionnaire (PAR-Q, Canada). Participants attended three separate, one-hour sessions to evaluate StO2 in supine-lying, chair-sitting and long-sitting positions. StO2 was recorded for 20 minutes pre-, during and post- a 20-minute intervention using a compression garment, TributeWrap (Lohmann-Rauscher, Germany). A repeated-measures analysis of variance (ANOVA) was followed by post-hoc pairwise comparisons. Results: A total of 28 healthy volunteers took part (aged 24.6 ±8.4years; 13 males, 15 females). A significant difference was seen between the three positions (p<0.001). Chair-sitting had the lowest StO2 pre-intervention, increasing StO2 significantly (32.25%, p<0.001) during wear of the compression garment (24.8% higher than baseline post-intervention). No significant difference was seen between long sitting and supine-lying (p=1.000). In contrast, long-sitting and supine-lying StO2 was higher pre-intervention compared with chair-sitting and only increased post-intervention (11% and 16.8% respectively, p<0.001) compared with baseline. Conclusion: The compression garment significantly increased StO2 levels in both seating positions. Further studies are required to determine if increasing StO2 through short intervention sessions with this device has the potential to improve self-management of tissue health in individuals with reduced mobility, oedema or venous insufficiency

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Earthworm and belowground competition effects on plant productivity in a plant diversity gradient

Diversity is one major factor driving plant productivity in temperate grasslands. Although decomposers like earthworms are known to affect plant productivity, interacting effects of plant diversity and earthworms on plant productivity have been neglected in field studies. We investigated in the field the effects of earthworms on plant productivity, their interaction with plant species and functional group richness, and their effects on belowground plant competition. In the framework of the Jena Experiment we determined plant community productivity (in 2004 and 2007) and performance of two phytometer plant species [Centaurea jacea (herb) and Lolium perenne (grass); in 2007 and 2008] in a plant species (from one to 16) and functional group richness gradient (from one to four). We sampled earthworm subplots and subplots with decreased earthworm density and reduced aboveground competition of phytometer plants by removing the shoot biomass of the resident plant community. Earthworms increased total plant community productivity (+11%), legume shoot biomass (+35%) and shoot biomass of the phytometer C. jacea (+21%). Further, phytometer performance decreased, i.e. belowground competition increased, with increasing plant species and functional group richness. Although single plant functional groups benefited from higher earthworm numbers, the effects did not vary with plant species and functional group richness. The present study indicates that earthworms indeed affect the productivity of semi-natural grasslands irrespective of the diversity of the plant community. Belowground competition increased with increasing plant species diversity. However, belowground competition was modified by earthworms as reflected by increased productivity of the phytometer C. jacea. Moreover, particularly legumes benefited from earthworm presence. Considering also previous studies, we suggest that earthworms and legumes form a loose mutualistic relationship affecting essential ecosystem functions in temperate grasslands, in particular decomposition and plant productivity. Further, earthworms likely alter competitive interactions among plants and the structure of plant communities by beneficially affecting certain plant functional groups

Pathological and Incidental Findings on Brain MRI in a Single-Center Study of 229 Consecutive Girls with Early or Precocious Puberty

Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and European girls, it has been suggested that only girls with CPP below 6 years of age should have brain MRI performed

Inconsistent impacts of decomposer diversity on the stability of aboveground and belowground ecosystem functions

The intensive discussion on the importance of biodiversity for the stability of essential processes in ecosystems has prompted a multitude of studies since the middle of the last century. Nevertheless, research has been extremely biased by focusing on the producer level, while studies on the impacts of decomposer diversity on the stability of ecosystem functions are lacking. Here, we investigate the impacts of decomposer diversity on the stability (reliability) of three important aboveground and belowground ecosystem functions: primary productivity (shoot and root biomass), litter decomposition, and herbivore infestation. For this, we analyzed the results of three laboratory experiments manipulating decomposer diversity (1–3 species) in comparison to decomposer-free treatments in terms of variability of the measured variables. Decomposer diversity often significantly but inconsistently affected the stability of all aboveground and belowground ecosystem functions investigated in the present study. While primary productivity was mainly destabilized, litter decomposition and aphid infestation were essentially stabilized by increasing decomposer diversity. However, impacts of decomposer diversity varied between plant community and fertility treatments. There was no general effect of the presence of decomposers on stability and no trend toward weaker effects in fertilized communities and legume communities. This indicates that impacts of decomposers are based on more than effects on nutrient availability. Although inconsistent impacts complicate the estimation of consequences of belowground diversity loss, underpinning mechanisms of the observed patterns are discussed. Impacts of decomposer diversity on the stability of essential ecosystem functions differed between plant communities of varying composition and fertility, implicating that human-induced changes of biodiversity and land-use management might have unpredictable effects on the processes mankind relies on. This study therefore points to the necessity of also considering soil feedback mechanisms in order to gain a comprehensive and holistic understanding of the impacts of current global change phenomena on the stability of essential ecosystem functions