Balance control in stepping down expected and unexpected level changes

Stepping down an elevation in ongoing gait is a common task that can cause falls when the level change is unexpected. The aim of this study was to compare expected and unexpected stepping down. We hypothesized that unexpected stepping would lead to loss of control over the movement and potentially falls due to buckling of the leading leg at landing. Ten male subjects repeatedly walked over a platform on which they stepped down an expected 10-cm height difference. In 5 out of 50 trials, the height difference was encountered unexpectedly early. Kinematics and ground reaction forces under both feet were measured during the stride in which the height difference was negotiated. Stepping down involved a substantial increase in forward horizontal and angular momenta (approximately 40 N s and 20 N ms). In expected stepping down, step length was significantly increased (17%), which allowed control of these forward horizontal and angular momenta immediately following landing. In unexpected stepping down, the time between expected ground contact and actual ground contact (110 ms) appeared too short to substantially adjust leg movement and increase step length. Although buckling of the leg did not occur, presumably due to its more vertical orientation at landing, momentum could not be sufficiently attenuated at landing, but a fall was prevented by a rapid step of the trailing limb. The lack of control of momentum might cause a fall, when the capacity to make such a rapid step falls short, as in the elderly, or when the height difference is larger.     

Dental anxiety in relation to emotional and behavioral problems in Croatian adolescents

The investigation was performed on 113 adolescents in the age between 15 and 18 years (63 boys, 50 girls). Corah Dental Anxiety Scale (CDAS) and Children's Fear Survey Schedule - Dental Subscale (CFSS-DS) were used for evaluation of dental fear and Child Medical Fear Questionnaire (CMFQ) for evaluation of the fear of medical treatment. Achenbach Youth Self Report questionnaire (YSR) was used for evaluation of emotional and behavioral problems. The tests were filled in by children. The aim of the study was to evaluate the level of dental anxiety in adolescents and to assess a cause--consequence relationship between dental anxiety and emotional and behavioral problems in adolescents. The results of CDAS, CFSS-DS and CMFQ tests showed that dental anxiety scores and the total internalizing problems were higher in girls. Girls displayed more physical problems (p < 0.001) and were more prone to anxiety/depression disorders (p < 0.05). Both boys and girls were more aggressive, more prone to delinquent behaviour and had more externalizing problems in comparison with the average values obtained for the Croatian population. Significant correlation coefficients for boys were calculated for age and anxiety/depression, and delinquent behaviour and aggression (p < 0.05). Significant correlations were observed between physical problems and dental anxiety measured by the CFSS-DS test (p < 0.01), and between physical problems and the total internalizing problems (p < 0.05). In girls, the CMFQ scores showed significant correlations between dental anxiety and physical problems (p < 0.05), and anxiety/ depression (p < 0.01) and the total internalizing and externalizing problems (p < 0.05). Significant correlations were calculated for age and the total internalizing and externalizing problems for boys (p < 0.05). According to the results of both CDAS and CMFQ tests, anxiety in girls showed significant correlations with delinquent behaviour (p < 0.01). CDAS scores for girls showed significant correlations with aggression (p < 0.05) and the total externalizing problems (p < 0.01).     

Abundant Trimethylornithine Lipids and Specific Gene Sequences Are Indicative of Planctomycete Importance at the Oxic/Anoxic Interface in Sphagnum-Dominated Northern Wetlands

Northern wetlands make up a substantial terrestrial carbon sink and are often dominated by decay-resistant Sphagnum mosses. Recent studies have shown that planctomycetes appear to be involved in degradation of Sphagnum-derived debris. Novel trimethylornithine (TMO) lipids have recently been characterized as abundant lipids in various Sphagnum wetland planctomycete isolates, but their occurrence in the environment has not yet been confirmed. We applied a combined intact polar lipid (IPL) and molecular analysis of peat cores collected from two northern wetlands (Saxnäs Mosse [Sweden] and Obukhovskoye [Russia]) in order to investigate the preferred niche and abundance of TMO-producing planctomycetes. TMOs were present throughout the profiles of Sphagnum bogs, but their concentration peaked at the oxic/anoxic interface, which coincided with a maximum abundance of planctomycete-specific 16S rRNA gene sequences. The sequences detected at the oxic/anoxic interface were affiliated with the Isosphaera group, while sequences present in the anoxic peat layers were related to an uncultured planctomycete group. Pyrosequencing-based analysis identified Planctomycetes as the major bacterial group at the oxic/anoxic interface at the Obukhovskoye peat (54% of total 16S rRNA gene sequence reads), followed by Acidobacteria (19% reads), while in the Saxnäs Mosse peat, Acidobacteria were dominant (46%), and Planctomycetes contributed to 6% of the total reads. The detection of abundant TMO lipids in planctomycetes isolated from peat bogs and the lack of TMO production by cultures of acidobacteria suggest that planctomycetes are the producers of TMOs in peat bogs. The higher accumulation of TMOs at the oxic/anoxic interface and the change in the planctomycete community with depth suggest that these IPLs could be synthesized as a response to changing redox conditions at the oxic/anoxic interface.     

Differential Sensitivities of Fast- and Slow-Cycling Cancer Cells to Inosine Monophosphate Dehydrogenase 2 Inhibition by Mycophenolic Acid

As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA.     

The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid and neurodevelopment were studied. An age-specific, standardized neurological assessment for the evaluation of minor neurological dysfunction (MND), and the Bayley Scales of Infant Development (BSID) were used. The intervention did not influence any of the outcomes. Umbilical venous (UV) Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index. Children with simple MND had lower UV DHA compared to normally classified children. We conclude that relatively short-term maternal DHA or DHA+AA supplementation does not influence neurodevelopment at toddler age, although some parameters of brain development are related to perinatal DHA and AA status.     

The discovery of novel indole-2-carboxamides as cannabinoid CB(1) receptor antagonists

The discovery and structure-activity relationship of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound 26i was found to be a high potency, selective cannabinoid CB(1) antagonist.     

Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008

Objectives

To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI).

Methods

All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985–1990, 1990–2000, and 2000–2008.

Results

We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985–1990 to 13% in 1990–2000, and to 6% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985–1990 to 4% in 1990–2000, and to 2% in 2000–2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively.

Conclusions

Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future.     

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study

Background

Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.

Method

We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.

Results

Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.

Conclusions

We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.

Trial Registration

Trialregitser.nl NTR1040     

Sharing roosts but not ectoparasites: high host-specificity in bat flies and wing mites of Miniopterus schreibersii and Rhinolophus ferrumequinum (Mammalia: Chiroptera)

Schreiber’s bent-winged bat Miniopterus schreibersii and the greater horseshoe bat Rhinolophus ferrumequinum are widespread and common cavernicolous species across southern Europe that host numerous specialized ectoparasite species. The objective of this study was to characterize the species assemblage, genetic diversity, and host specificity of bat flies (Nycteribiidae, Diptera) and wing mites (Spinturnicidae, Acari) found on these bat hosts in Serbia and Bosnia and Herzegovina. Notably, while bat flies lay puparia on the cave walls and can thus be transmitted indirectly, wing mites require direct body contact for transmission. Morphological identification and sequencing of a 710-bp fragment of cytochrome oxidase I gene of 207 bat flies yielded 4 species, 3 on M. schreibersii and 1 on R. ferrumequinum. Sequencing of a 460-bp small subunit ribosomal RNA fragment, in all 190 collected wing mites revealed 2 species, 1 per host. In no case was a parasite associated with 1 host found on the other host. Species and genetic diversity of flies were higher in M. schreibersii, likely reflecting their host’s larger colony sizes and migratory potential. Mite species of both hosts showed similarly low diversity, likely due to their faster life history and lower winter survival. Our findings highlight a remarkably high host-specificity and segregation of ectoparasite species despite direct contact among their hosts in the roost, suggesting a defined host preference in the investigated ectoparasite species. Furthermore, the differences in ectoparasite genetic diversity exemplify the interplay between host and parasite life histories in shaping parasite population genetic structure.     

Influence of temperature on the δ13C values and distribution of methanotroph‐related hopanoids in Sphagnum‐dominated peat bogs

Methane emissions from peat bogs are mitigated by methanotrophs, which live in symbiosis with peat moss (e.g. Sphagnum). Here, we investigate the influence of temperature and resultant changes in methane fluxes on Sphagnum and methanotroph‐related biomarkers, evaluating their potential as proxies in ancient bogs. A pulse‐chase experiment using ¹³C‐labelled methane in the field clearly showed label uptake in diploptene, a biomarker for methanotrophs, demonstrating in situ methanotrophic activity in Sphagnum under natural conditions. Peat cores containing live Sphagnum were incubated at 5, 10, 15, 20 and 25°C for two months, causing differences in net methane fluxes. The natural δ¹³C values of diploptene extracted from Sphagnum showed a strong correlation with temperature and methane production. The δ¹³C values ranged from ?34‰ at 5°C to ?41‰ at 25°C. These results are best explained by enhanced expression of the methanotrophic enzymatic isotope effect at higher methane concentrations. Hence, δ¹³C values of diploptene, or its diagenetic products, potentially provide a useful tool to assess methanotrophic activity in past environments. Increased methane fluxes towards Sphagnum did not affect δ¹³C values of bulk Sphagnum and its specific marker, the C₂₃ n‐alkane. The concentration of methanotroph‐specific bacteriohopanepolyols (BHPs), aminobacteriohopanetetrol (aminotetrol, characteristic for type II and to a lesser extent type I methanotrophs) and aminobacteriohopanepentol (aminopentol, a marker for type I methanotrophs) showed a non‐linear response to increased methane fluxes, with relatively high abundances at 25°C compared to those at 20°C or below. Aminotetrol was more abundant than aminopentol, in contrast to similar abundances of aminotetrol and aminopentol in fresh Sphagnum. This probably indicates that type II methanotrophs became prevalent under the experimental conditions relative to type I methanotrophs. Even though BHP concentrations may not directly reflect bacterial activity, they may provide insight into the presence of different types of methanotrophs.