Mobility, balance and falls in persons with multiple sclerosis

Background

There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS).

Methods

52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery.

Results

Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS.

Conclusions

The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established.     

Field performance of a genetically engineered strain of pink bollworm

Pest insects harm crops, livestock and human health, either directly or by acting as vectors of disease. The Sterile Insect Technique (SIT)--mass-release of sterile insects to mate with, and thereby control, their wild counterparts--has been used successfully for decades to control several pest species, including pink bollworm, a lepidopteran pest of cotton. Although it has been suggested that genetic engineering of pest insects provides potential improvements, there is uncertainty regarding its impact on their field performance. Discrimination between released and wild moths caught in monitoring traps is essential for estimating wild population levels. To address concerns about the reliability of current marking methods, we developed a genetically engineered strain of pink bollworm with a heritable fluorescent marker, to improve discrimination of sterile from wild moths. Here, we report the results of field trials showing that this engineered strain performed well under field conditions. Our data show that attributes critical to SIT in the field--ability to find a mate and to initiate copulation, as well as dispersal and persistence in the release area--were comparable between the genetically engineered strain and a standard strain. To our knowledge, these represent the first open-field experiments with a genetically engineered insect. The results described here provide encouragement for the genetic control of insect pests.     

Migrants in the Mediterranean: Do's and Don’ts in Maritime Interdiction

Mediterranean European Union member states have to deal with thousands of migrants arriving by sea every year. Frontex (the EU external borders agency) organizes joint surveillance operations at sea to interdict these migrant boats, helping states to cope with the problem. This article discusses the legality of these maritime interdictions done by Frontex according to the international law of the sea as well as the conformity of the operations with the nonrefoulement principle.     

Agricultural intensification drives changes in hybrid network robustness by modifying network structure

Within ecological communities, species engage in myriad interaction types, yet empirical examples of hybrid species interaction networks composed of multiple types of interactions are still scarce. A key knowledge gap is understanding how the structure and stability of such hybrid networks are affected by anthropogenic disturbance. Using 15,169 interaction observations, we constructed 16 hybrid herbivore‐plant‐pollinator networks along an agricultural intensification gradient to explore changes in network structure and robustness to local extinctions. We found that agricultural intensification led to declines in modularity but increases in nestedness and connectance. Notably, network connectance, a structural feature typically thought to increase robustness, caused declines in hybrid network robustness, but the directionality of changes in robustness along the gradient depended on the order of local species extinctions. Our results not only demonstrate the impacts of anthropogenic disturbance on hybrid network structure, but they also provide unexpected insights into the structure‐stability relationship of hybrid networks.     

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large,Community Randomized Trial

Background

Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.

Methods and Findings

Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept.

Conclusions

In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.     

Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome

Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins.     

Modular,efficient synthesis of asymmetrically substituted piperazine scaffolds as potent calcium channel blockers

A novel approach to the synthesis of substituted piperazines and their investigation as N-type calcium channel blockers is presented. A common scaffold exhibiting high activity as N-type blockers is N-substituted piperazine. Using recently developed titanium and zirconium catalysts, we describe the efficient and modular synthesis of 2,5-asymmetrically disubstituted piperazines from simple amines and alkynes. The method requires only three isolation/purification protocols and no protection/deprotection steps for the diastereoselective synthesis of 2,5-dialkylated piperazines in moderate to high yield. Screening of the synthesized piperazines for N-type channel blocking activity and selectivity shows the highest activity for a compound with a benzhydryl group on the nitrogen (position 1) and an unprotected alcohol-functionalized side chain.     

Changes in cardiac troponins with gestational age explain changes in cardiac muscle contractility in the sheep fetus

The development of the adult cardiac troponin complex in conjunction with changes in cardiac function and cardiomyocyte binucleation has not been systematically characterized during fetal life in a species where maturation of the cardiomyocytes occurs prenatally as it does in the human. The aim of this study was to correlate the expression of each of the major adult troponin isoforms (T, I, and C) during late gestation (term of 150 days) to changes in both Ca(2+) sensitivity and maximum Ca(2+)-activated force of the contractile apparatus and the maturation of cardiomyocytes. The percentage of mononucleated cardiomyocytes in the right ventricle decreased with gestational age to 46% by 137-142 days of gestation. The length of binucleated cardiomyocytes did not change with gestational age, but the length of binucleated cardiomyocytes relative to heart weight decreased with gestational age. There was no change in the expression of adult cardiac troponin T with increasing gestation. The contractile apparatus was significantly more sensitive to Ca(2+) at 90 days compared with either 132 or 139 days of gestation, consistent with an ～30% increase in the expression of adult cardiac troponin I between 90 and 110 days of gestation. Maximum Ca(2+)-activated force significantly increased from 90 days compared with 130 days consistent with an increase of ～40% in cardiac troponin C protein expression. These data show that increased adult cardiac troponin I and C protein expression across late gestation is consistent with reduced Ca(2+) sensitivity and increased maximum Ca(2+)-activated force. Furthermore, changes in cardiac troponin C, not I, protein expression track with the timing of cardiomyocyte binucleation.