Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study.

BackgroundNiemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.MethodsClinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.ResultsThe shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4¿5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.ConclusionA neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

Evidence for catabolic pathway of propionate metabolism in CNS: expression pattern of methylmalonyl-CoA mutase and propionyl-CoA carboxylase alpha-subunit in developing and adult rat brain.

Methylmalonyl-CoA mutase (MCM) and propionyl-CoA carboxylase (PCC) are the key enzymes of the catabolic pathway of propionate metabolism and are mainly expressed in liver, kidney and heart. Deficiency of these enzymes leads to two classical organic acidurias: methylmalonic and propionic aciduria. Patients with these diseases suffer from a whole spectrum of neurological manifestations that are limiting their quality of life. Current treatment does not seem to effectively prevent neurological deterioration and pathophysiological mechanisms are poorly understood. In this article we show evidence for the expression of the catabolic pathway of propionate metabolism in the developing and adult rat CNS. Both, MCM and PCC enzymes are co-expressed in neurons and found in all regions of the CNS. Disease-specific metabolites such as methylmalonate, propionyl-CoA and 2-methylcitrate could thus be formed autonomously in the CNS and contribute to the pathophysiological mechanisms of neurotoxicity. In rat embryos (E15.5 and E18.5), MCM and PCC show a much higher expression level in the entire CNS than in the liver, suggesting a different, but important function of this pathway during brain development.

Serum glycodelin pattern during the menstrual cycle in healthy young women.

OBJECTIVE: Glycodelin (PP14) is produced by the epithelium of the endometrium and its determination in the serum is used for functional evaluation of this tissue. Given the complex regulation and the combined contraceptive and immunosuppressive roles of glycodelin, the current lack of normal values for its serum concentration in the physiological menstrual cycle, derived from a large sample number, is a problem. We have therefore established reference values from over 600 sera. DESIGN: Retrospective study using banked serum samples. SETTING: University hospital. METHODS: Measurement of blood samples daily or every second day during one full cycle. MAIN OUTCOME MEASURES: Serum concentrations of glycodelin and normal values for every such one- or two-day interval were calculated. Late luteal phase glycodelin levels were compared with ovarian hormones. Follicular phase levels were compared with stimulated cycles from patients undergoing in vitro fertilization. RESULTS: Glycodelin concentrations were low around ovulation. Highest levels were observed at the end of the luteal phase; the glycodelin serum peak was reached 6-8 days after the one for progesterone. Late luteal glycodelin levels correlated negatively with the body mass index and positively with the progesterone level earlier in the secretory (mid-luteal) phase in the same woman. No associations with other ovarian hormones were observed. Follicular phase glycodelin levels were higher in the spontaneous than in the in vitro fertilization cycles. CONCLUSIONS: Normal values taken at two- or one-day intervals demonstrate the very late appearance of high serum glycodelin levels during the physiological menstrual cycle and their correlation with progesterone occurring earlier in the cycle.

Male-pattern baldness susceptibility locus at 20p11.

We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)).

Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis.

BACKGROUND: MR tissue tagging allows the noninvasive assessment of the locally and temporally resolved motion pattern of the left ventricle. Alterations in cardiac torsion and diastolic relaxation of the left ventricle were studied in patients with aortic stenosis and were compared with those of healthy control subjects and championship rowers with physiological volume-overload hypertrophy. METHODS AND RESULTS: Twelve aortic stenosis patients, 11 healthy control subjects with normal left ventricular function, and 11 world-championship rowers were investigated for systolic and diastolic heart wall motion on a basal and an apical level of the myocardium. Systolic torsion and untwisting during diastole were examined by use of a novel tagging technique (CSPAMM) that provides access to systolic and diastolic motion data. In the healthy heart, the left ventricle performs a systolic wringing motion, with a counterclockwise rotation at the apex and a clockwise rotation at the base. Apical untwisting precedes diastolic filling. In the athlete's heart, torsion and untwisting remain unchanged compared with those of the control subjects. In aortic stenosis patients, torsion is significantly increased and diastolic apical untwisting is prolonged compared with those of control subjects or athletes. CONCLUSIONS: Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

Quality of life depends on the drinking pattern in alcohol-dependent patients.

AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns.

Influence of bedrock structures on the spatial pattern of erosional landforms in small alpine catchments

Structural settings and lithological characteristics are traditionally assumed to influence the development of erosional landforms, such as gully networks and rock couloirs, in steep mountain rock basins. The structural control of erosion of two small alpine catchments of distinctive rock types is evaluated by comparing the correspondences between the orientations of their gullies and rock couloirs with (1) the sliding orientations of potential slope failures mechanisms, and (2) the orientation of the maximum joint frequency, this latter being considered as the direction exploited primarily by erosion and mass wasting processes. These characteristic orientations can be interpreted as structural weaknesses contributing to the initiation and propagation of erosion. The morphostructural analysis was performed using digital elevation models and field observations. The catchment comprised of magmatic intrusive rocks shows a clear structural control, mostly expressed through potential wedges failure. Such joint configurations have a particular geometry that encourages the development of gullies in hard rock, e.g. through enhanced gravitational and hydrological erosional processes. In the catchment underlain by sedimentary rocks, penetrative joints that act as structural weaknesses seem to be exploited by gullies and rock couloirs. However, the lithological setting and bedding configuration prominently control the development of erosional landforms, and influence not only the local pattern of geomorphic features, but the general morphology of the catchment. The orientations of the maximum joint frequency are clearly associated with the gully network, suggesting that its development is governed by anisotropy in rock strength. These two catchments are typical of bedrock-dominated basins prone to intense processes of debris supply. This study suggests a quantitative approach for describing the relationship between bedrock jointing and geomorphic features geometry. Incorporation of bedrock structure can be relevant when studying processes governing the transfer of clastic material, for the assessment of sediment yields and in landforms evolution models.

The influence of drinking pattern, at individual and aggregate levels, on alcohol-related negative consequences.

AIM: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. METHODS: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. RESULTS: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country's drinking pattern, the less steep the association between the volume of drinking and its consequences. CONCLUSION: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences.

Melanic color-dependent anti-predator behavior strategies in barn owl nestlings

The arms race between predators and prey has led to morphological and behavioral adaptations. Different antipredator strategies can coexist within a population if each strategy is the result of a trade-off with competing demands. Antipredator behavior can be associated with morphological traits, like color patterns, either because in the context of sexual selection, coloration signals the ability to avoid predators or because coloration is a naturally selected trait useful in avoiding predators. Because in the barn owl (Tyto alba), heritable eumelanic plumage coloration is associated with the glucocorticoid-dependent response to stress, we tested whether antipredator behavior is also related to this trait. Compared with small-spotted nestlings, individuals displaying larger black spots hissed more intensely in the presence of humans, feigned death longer, had a lower breathing rate under stress, and were more docile when handled. Cross-fostering experiments showed that the covariation between the spot size and the duration of feigning death was inherited from the biological mother, whereas covariation between spot size and docility was inherited from the biological father. Our results confirm that melanin-based coloration is associated with suites of behavioral traits, which are under both genetic and environmental influence. Coloration can thus evolve as a direct or indirect response to predation, but it can also be a signal of antipredator strategies to potential mates.

A conserved transcript pattern in response to a specialist and a generalist herbivore.

Transcript patterns elicited in response to attack reveal, at the molecular level, how plants respond to aggressors. These patterns are fashioned both by inflicted physical damage as well as by biological components displayed or released by the attacker. Different types of attacking organisms might therefore be expected to elicit different transcription programs in the host. Using a large-scale DNA microarray, we characterized gene expression in damaged as well as in distal Arabidopsis thaliana leaves in response to the specialist insect, Pieris rapae. More than 100 insect-responsive genes potentially involved in defense were identified, including genes involved in pathogenesis, indole glucosinolate metabolism, detoxification and cell survival, and signal transduction. Of these 114 genes, 111 were induced in Pieris feeding, and only three were repressed. Expression patterns in distal leaves were markedly similar to those of local leaves. Analysis of wild-type and jasmonate mutant plants, coupled with jasmonate treatment, showed that between 67 and 84% of Pieris-regulated gene expression was controlled, totally or in part, by the jasmonate pathway. This was correlated with increased larval performance on the coronatine insensitive1 glabrous1 (coi1-1 gl1) mutant. Independent mutations in COI1 and GL1 led to a faster larval weight gain, but the gl1 mutation had relatively little effect on the expression of the insect-responsive genes examined. Finally, we compared transcript patterns in Arabidopis in response to larvae of the specialist P. rapae and to a generalist insect, Spodoptera littoralis. Surprisingly, given the complex nature of insect salivary components and reported differences between species, almost identical transcript profiles were observed. This study also provides a robustly characterized gene set for the further investigation of plant-insect interaction.

Spatial pattern and process at the plant neighbourhood scale: insights from communities dominated by the clonal grass Elymus repens (L.) Gould.

Question: How do clonal traits of a locally dominant grass (Elymus repens (L.) Gould.) respond to soil heterogeneity and shape spatial patterns of its tillers? How do tiller spatial patterns constrain seedling recruitment within the community?Locations: Artificial banks of the River Rhone, France.Material and Methods: We examined 45 vegetation patches dominated by Elymus repens. During a first phase we tested relationships between soil variables and three clonal traits (spacer length, number of clumping tillers and branching rate), and between the same clonal traits and spatial patterns (i.e. density and degree of spatial aggregation) of tillers at a very fine scale. During a second phase, we performed a sowing experiment to investigate effects of density and spatial patterns of E. repens on recruitment of eight species selected from the regional species pool.Results: Clonal traits had clear effects - especially spacer length - on densification and aggregation of E. repens tillers and, at the same time, a clear response of these same clonal traits as soil granulometry changed. The density and degree of aggregation of E. repens tillers was positively correlated to total seedling cover and diversity at the finest spatial scales.Conclusions: Spatial patterning of a dominant perennial grass responds to soil heterogeneity through modifications of its clonal morphology as a trade-off between phalanx and guerrilla forms. In turn, spatial patterns have strong effects on abundance and diversity of seedlings. Spatial patterns of tillers most probably led to formation of endogenous gaps in which the recruitment of new plant individuals was enhanced. Interestingly, we also observed more idiosyncratic effects of tiller spatial patterns on seedling cover and diversity when focusing on different growth forms of the sown species.

Measuring the diurnal pattern of leaf hyponasty and growth in Arabidopsis - a novel phenotyping approach using laser scanning

Plants forming a rosette during their juvenile growth phase, such as Arabidopsis thaliana (L.) Heynh., are able to adjust the size, position and orientation of their leaves. These growth responses are under the control of the plants circadian clock and follow a characteristic diurnal rhythm. For instance, increased leaf elongation and hyponasty - defined here as the increase in leaf elevation angle - can be observed when plants are shaded. Shading can either be caused by a decrease in the fluence rate of photosynthetically active radiation (direct shade) or a decrease in the fluence rate of red compared with far-red radiation (neighbour detection). In this paper we report on a phenotyping approach based on laser scanning to measure the diurnal pattern of leaf hyponasty and increase in rosette size. In short days, leaves showed constitutively increased leaf elevation angles compared with long days, but the overall diurnal pattern and the magnitude of up and downward leaf movement was independent of daylength. Shade treatment led to elevated leaf angles during the first day of application, but did not affect the magnitude of up and downward leaf movement in the following day. Using our phenotyping device, individual plants can be non-invasively monitored during several days under different light conditions. Hence, it represents a proper tool to phenotype light- and circadian clock-mediated growth responses in order to better understand the underlying regulatory genetic network.

Letter to the Editor : on the value of probability for evaluating results of comparative pattern analyses

This letter to the Editor comments on the article Practical relevance of pattern uniqueness in forensic science by P.T. Jayaprakash (Forensic Science International, in press).

Evaluating fear of falling among community-dwelling older people: A qualitative pattern model based on the experience of falls

This research was conducted in the context of the project IRIS 8A Health and Society (2002-2008) and financially supported by the University of Lausanne. It was aomed at developping a model based on the elder people's experience and allowed us to develop a "Portrait evaluation" of fear of falling using their examples and words. It is a very simple evaluation, which can be used by professionals, but by the elder people themselves. The "Portrait evaluation" and the user's guide are on free access, but we would very much approciate to know whether other people or scientists have used it and collect their comments. (contact: Chantal.Piot-Ziegler@unil.ch)The purpose of this study is to create a model grounded in the elderly people's experience allowing the development of an original instrument to evaluate FOF.In a previous study, 58 semi-structured interviews were conducted with community-dwelling elderly people. The qualitative thematic analysis showed that fear of falling was defined through the functional, social and psychological long-term consequences of falls (Piot-Ziegler et al., 2007).In order to reveal patterns in the expression of fear of falling, an original qualitative thematic pattern analysis (QUAlitative Pattern Analysis - QUAPA) is developed and applied on these interviews.The results of this analysis show an internal coherence across the three dimensions (functional, social and psychological). Four different patterns are found, corresponding to four degrees of fear of falling. They are formalized in a fear of falling intensity model.This model leads to a portrait-evaluation for fallers and non-fallers. The evaluation must be confronted to large samples of elderly people, living in different environments. It presents an original alternative to the concept of self-efficacy to evaluate fear of falling in older people.The model of FOF presented in this article is grounded on elderly people's experience. It gives an experiential description of the three dimensions constitutive of FOF and of their evolution as fear increases, and defines an evaluation tool using situations and wordings based on the elderly people's discourse.