Anti-infectives: can cellular screening deliver?

In an era of emerging and reemerging infectious diseases, and increasing multidrug resistance, the need to identify novel therapy is imperative. Unfortunately, the recent shift of the drug discovery paradigm from cellular screening to target-based approaches has not delivered the anticipated benefits. A recent renaissance of the traditional cell-based approach, on the other hand, has yielded several clinical candidates. Three successful examples are illustrated in this review, namely spiroindolone, thiazolidinone, and diarylquinoline for the treatment of malaria, hepatitis C virus, and tuberculosis, respectively. We describe in detail their identification, mechanism of action (MoA), and common features in the chemical structures. The challenges of the cell-based approach for anti-infective drug discovery are also discussed. We propose a shift from standard libraries to synthetic natural-product-like compound collections to improve the success of phenotypic lead finding and to facilitate the validation of hits.     

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4^th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure.     

Unravelling insect declines: can space replace time?

Temporal trends in insect numbers vary across studies and habitats, but drivers are poorly understood. Suitable long-term data are scant and biased, and interpretations of trends remain controversial. By contrast, there is substantial quantitative evidence for drivers of spatial variation. From observational and experimental studies, we have gained a profound understanding of where insect abundance and diversity is higher—and identified underlying environmental conditions, resource change and disturbances. We thus propose an increased consideration of spatial evidence in studying the causes of insect decline. This is because for most time series available today, the number of sites and thus statistical power strongly exceed the number of years studied. Comparisons across sites allow quantifying insect population risks, impacts of land use, habitat destruction, restoration or management, and stressors such as chemical and light pollution, pesticides, mowing or harvesting, climatic extremes or biological invasions. Notably, drivers may not have to change in intensity to have long-term effects on populations, e.g. annually repeated disturbances or mortality risks such as those arising from agricultural practices. Space-for-time substitution has been controversially debated. However, evidence from well-replicated spatial data can inform on urgent actions required to halt or reverse declines—to be implemented in space.     

What can surface chemistry do for cell biology?

Recent research has enhanced the development of substrates that serve as models of extracellular matrix and their use in studies of cell adhesion and migration. Advances include the development of methods to prepare substrates having ligands immobilized in controlled densities and patterns, and recent work that is developing dynamic substrates which can modulate, in real-time, the activities of ligands. These technologies are providing new opportunities for studies of cell-extracellular-matrix interactions.     

Is spinal neuromuscular function asymmetrical in adolescents with idiopathic scoliosis compared to those without scoliosis?: A narrative review of surface EMG studies

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity occurring between ages of 10–18 years. We aimed to present a reasoned synthesis of the published evidence for and against asymmetrical paraspinal muscle activation in AIS. PubMed and Embase databases were searched using terms: adolescent idiopathic scoliosis AND electromyogra* (EMG). Identified studies (n = 94) were screened for eligibility. We identified 16 studies, from which 136 EMG outcome measures contributed to the review.For EMG onset, one of two studies provided evidence of earlier muscle activation on the convex compared to concave side of the spine, particularly in those with progressive AIS. For EMG amplitude, 43 outcome measures provided evidence of convex > concave activation, 85 outcomes supported no difference between sides, and 8 outcomes supported concave > convex activation. Greater activity on the convex than concave side was more commonly demonstrated at the scoliosis curve apex level, in people with single right thoracic [progressive] curves, during postural tasks.Further research is needed to determine the relationships between muscle activity asymmetry and spinal curve parameters in a variety of motor tasks. Recommendations are provided to improve methodological quality for future studies of spinal neuromuscular function in AIS, as well as more comprehensive and transparent reporting of methods and results.     

Determinants of miniprotein stability: can anything replace a buried H-bonded Trp sidechain?

A novel 20-residue fold, designated the `Trp-cage' motif, hasbeen shown to be 98+% folded in both water and 30 vol-%trifluoroethanol solution. Folding is cooperative andhydrophobically driven, resulting in the burial of the Trpsidechain and a stable H-bond from the Trp-NH to a sequenceremote backbone carbonyl. In the present study the effects ofreplacing the Trp with His, Phe and both isomers of -naphthylalanine are examined. The results suggest that thehydrophobic cluster is a specific interaction of proline ringswith the indole ring which can be partially mimicked by anaphthalene ring. The His and Phe mutants are completelyunfolded in aqueous medium. The naphthylalanine mutants forma stable hydrophobic cluster in 30% trifluoroethanol, but areless stable in water than the native structure.     

How many deaths can be prevented by newborn screening for congenital adrenal hyperplasia?

BACKGROUND/AIMS: Congenital adrenal hyperplasia (CAH) is increasingly being included in newborn screening programs. Screening can prevent neonatal mortality in children with salt-wasting CAH, but the number of deaths prevented is not known. Cost-effectiveness analyses of screening require estimates of the probability of mortality in CAH. METHODS: We reviewed the literature to identify cohort studies of children with CAH ascertained clinically in the absence of screening. We abstracted the numbers of infant deaths attributable to CAH. We also addressed sex ratios among children with clinically detected CAH and the contribution of ascertainment bias to unbalanced ratios. RESULTS: The evidence suggests a probability of infant death due to adrenal crises in salt-wasting CAH of 4% or less in contemporary advanced economies without screening for CAH. This is lower than previous estimates, although the rate of mortality could be considerably higher in populations with limited clinical awareness or access. CONCLUSION: Although screening for CAH is conducted in a number of countries, further research is still needed to provide reliable estimates on the numbers of prevented deaths, along with evidence-based assessments of the potential benefits, harms, and costs of screening.     

Training text chunkers on a silver standard corpus: can silver replace gold?

Background  

To train chunkers in recognizing noun phrases and verb phrases in biomedical text, an annotated corpus is required. The creation of gold standard corpora (GSCs), however, is expensive and time-consuming. GSCs therefore tend to be small and to focus on specific subdomains, which limits their usefulness. We investigated the use of a silver standard corpus (SSC) that is automatically generated by combining the outputs of multiple chunking systems. We explored two use scenarios: one in which chunkers are trained on an SSC in a new domain for which a GSC is not available, and one in which chunkers are trained on an available, although small GSC but supplemented with an SSC.     

Reaching new heights: can drones replace current methods to study plant population dynamics?

Spatially explicit data on heterogeneously distributed plant populations are difficult to quantify using either traditional field-based methods or remote sensing techniques alone. Unmanned Aerial Vehicles (UAVs) offer new means and tools for baseline monitoring of such populations. We tested the use of vegetation classification of UAV-acquired photographs as a method to capture heterogeneously distributed plant populations, using Jacobaea vulgaris as a model species. Five sites, each containing 1–4 pastures with varying J. vulgaris abundance, were selected across Schleswig–Holstein, Germany. Surveys were conducted in July 2017 when J. vulgaris was at its flowering peak. We took aerial photographs at a 50 m altitude using three digital cameras (RGB, red-edge and near-infrared). Orthomosaics were created before a pixel-based supervised classification. Classification results were evaluated for accuracy; reliability was assessed with field data collected for ground verification. An ANOVA tested the relationship between field-based abundance estimations and the supervised classifications. Overall accuracy of the classification was very high (90.6%,?±?1.76 s.e.). Kappa coefficients indicated substantial agreement between field data and image classification (≥?0.65). Field-based estimations were a good predictor of the supervised classifications (F?=?7.91, df?=?4, P?=?0.007), resulting in similar rankings of J. vulgaris abundance. UAV-acquired images demonstrated the potential as an objective method for data collection and species monitoring. However, our method was more time consuming than field-based estimations due to challenges in image processing. Nonetheless, the increasing availability of low-cost consumer-grade UAVs is likely to increase the use of UAVs in plant ecological studies.     

Surgical and conservative treatment of patients with congenital scoliosis: α search for long-term results

Background

In view of the limited data available on the conservative treatment of patients with congenital scoliosis (CS), early surgery is suggested in mild cases with formation failures. Patients with segmentation failures will not benefit from conservative treatment. The purpose of this review is to identify the mid- or long-term results of spinal fusion surgery in patients with congenital scoliosis.

Methods

Retrospective and prospective studies were included, reporting on the outcome of surgery in patients with congenital scoliosis. Studies concerning a small numbers of cases treated conservatively were included too. We analyzed mid-term (5 to 7 years) and long-term results (7 years or more), both as regards the maintenance of the correction of scoliosis and the safety of instrumentation, the early and late complications of surgery and their effect on quality of life.

Results

A small number of studies of surgically treated patients were found, contained follow-up periods of 4-6 years that in the most cases, skeletal maturity was not yet reached, and few with follow-up of 36-44 years. The results of bracing in children with congenital scoliosis, mainly in cases with failure of formation, were also studied.

Discussion

Spinal surgery in patients with congenital scoliosis is regarded in short as a safe procedure and should be performed. On the other hand, early and late complications are also described, concerning not only intraoperative and immediate postoperative problems, but also the safety and efficacy of the spinal instrumentation and the possibility of developing neurological disorders and the long-term effect these may have on both lung function and the quality of life of children.

Conclusions

Few cases indicate the long-term results of surgical techniques, in the natural progression of scoliosis. Similarly, few cases have been reported on the influence of conservative treatment. In conclusion, patients with segmentation failures should be treated surgically early, according to the rate of deformity formation and certainly before the pubertal growth spurt to try to avoid cor- pulmonale, even though there is lack of evidence for that in the long-term. Furthermore, in patients with formation failures, further investigation is needed to document where a conservative approach would be necessary.     

What can neurons do for their brain? Communicate selectivity with bursts

Neurons deep in cortex interact with the environment extremely indirectly; the spikes they receive and produce are pre- and post-processed by millions of other neurons. This paper proposes two information-theoretic constraints guiding the production of spikes, that help ensure bursting activity deep in cortex relates meaningfully to events in the environment. First, neurons should emphasize selective responses with bursts. Second, neurons should propagate selective inputs by burst-firing in response to them. We show the constraints are necessary for bursts to dominate information-transfer within cortex, thereby providing a substrate allowing neurons to distribute credit amongst themselves. Finally, since synaptic plasticity degrades the ability of neurons to burst selectively, we argue that homeostatic regulation of synaptic weights is necessary, and that it is best performed offline during sleep.     

Angiogenesis: What can it offer for future medicine?

Modulation of angiogenesis for disease therapy was proposed nearly 40 years ago and today various protein and chemical molecules are available for the treatment of human malignant and ophthalmological disorders. Angiogenesis research has emerged, as one of the most comprehensive research areas, in biomedicine and development of novel drugs by targeting angiogenesis has become one of the main focuses among pharmaceutical giants. If 30% of annually 12 million new cancer cases worldwide receive antiangiogenic therapy, over 60 million cancer patients would be treated by the end of 2060. In this mini-review, I discuss current available antiangiogenic drugs and future therapeutic options based on the angiogenesis principle.