Review of Two Decades of Cholera Diagnostics – How Far Have We Really Come?

Background

Cholera, an ancient scourge, continues to inflict high rates of mortality today. The rising incidence of epidemics in areas of poor sanitation and crowding highlight the need for better epidemic prevention and early response. Such interventions require the availability of rapid and accurate diagnostic techniques to trigger timely response and mitigate the scale of the outbreak. The current gold standard of bacterial culture is inadequate for rapid diagnosis, highlighting the overarching neglect of field diagnostic needs. This paper was written to support the World Health Organisation''s Global Task Force on Cholera Control mandated Cholera and diarrhoeal disease laboratory Network (CholdiNet) in devising a protocol for the validation of Rapid Diagnostic Tests (RDTs) for Vibrio cholerae. The status of diagnostic tools for Vibrio cholerae is assessed, describing products that have been commercialised over the last two decades and discussing their peer-reviewed evaluation.

Method

Review of post-1990 peer-reviewed and grey literature on rapid diagnostic tests for Vibrio cholerae.

Results

Since 1990, twenty four diagnostic tests have been developed for the detection of Vibrio cholerae in human faecal samples. Fourteen of these have also been described in the literature, with rapid chromatographic-immuno assays (CIA) featuring strongly. Polymerase chain reaction (PCR) assays maintain the ability to detect the lowest amount of bacteria; however CIAs achieve both low detection thresholds and high sensitivity and specificity, making them possible candidates for use in field conditions. Field and laboratory studies were performed in a wide range of settings demonstrating variability in performance, however only a few of these studies were sufficiently stringent, highlighting five RDTs that showed promise in field conditions; COAT, IP cholera dipstick, SMART, IP dipstick and Medicos. In light of non-independent reporting, the authors would like to see these five products undergoing additional studies, with further technical improvements if needed and commercial production. The authors hope that public health use of such a RDT in limited-resource field conditions on stool samples may contribute to effective reduction in cholera epidemic spread.     

Two Decades of River Restoration in California: What Can We Learn?

As part of the National River Restoration Science Synthesis (NRRSS), we developed a summary database of 4,023 stream restoration projects built in California since 1980, from which we randomly selected 44 records for in‐depth interviews with project managers. Despite substantial difficulties in gathering the data, we were able to draw conclusions about current design, implementation, monitoring, and evaluation practices used in California projects and compare them with national trends. Although more than half of the projects for which we conducted interviews were located in watersheds for which a management or assessment plan had been prepared, these plans had a limited impact on site selection. We also found that the state lacks a consistent framework for design, monitoring, and reporting restoration projects, and that although monitoring is far more widespread than the information in the NRRSS summary database would suggest, there are still problems with the type, duration, and reporting of monitoring. The general lack of systematic, objective assessment of completed projects hinders the advance of restoration science.     

Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990-2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value, may become highly valuable in the ongoing search for new drugs from the sea.     

IRIS and Fungal Infections: What Have We Learned?

Restoration of pathogen-specific immunity as a result of highly active antiretroviral therapy or reduction of immunosuppression in solid-organ transplant recipients can result in a destructive inflammatory response known as the immune reconstitution inflammatory syndrome (IRIS). Though immune reconstitution disorders can occur in the context of a number of infectious and neoplastic processes, IRIS associated with invasive mycoses, in particular cryptococcosis, is a highly prevalent and morbid entity worldwide. Recent consensus definitions and prospective analyses of cryptococcal IRIS, with particular attention to baseline clinical features, serum and cerebrospinal fluid biomarkers, and the evolution of these over time in individual patients have provided critical insights into pathogenesis. This review focuses on the current understanding of IRIS in the context of opportunistic mycoses, with particular attention to Cryptococcus infection, and discusses the basis for this understanding, including biomarkers as clues to pathogenesis and aids in diagnosis and novel approaches to prevention and management.     

Domestication and Breeding of Tomatoes: What have We Gained and What Can We Gain in the Future?

Background

It has been shown that a large variation is present and exploitable from wild Solanum species but most of it is still untapped. Considering the thousands of Solanum accessions in different gene banks and probably even more that are still untouched in the Andes, it is a challenge to exploit the diversity of tomato. What have we gained from tomato domestication and breeding and what can we gain in the future?

Scope

This review summarizes progress on tomato domestication and breeding and current efforts in tomato genome research. Also, it points out potential challenges in exploiting tomato biodiversity and depicts future perspectives in tomato breeding with the emerging knowledge from tomato-omics.

Conclusions

From first domestication to modern breeding, the tomato has been continually subjected to human selection for a wide array of applications in both science and commerce. Current efforts in tomato breeding are focused on discovering and exploiting genes for the most important traits in tomato germplasm. In the future, breeders will design cultivars by a process named ‘breeding by design’ based on the combination of science and technologies from the genomic era as well as their practical skills.Key words: Breeding, domestication, genomics, Solanum lycopersicum     

Sixty Years from Segretain’s Description: What Have We Learned and Should Learn About the Basic Mycology of Talaromyces marneffei?

Mycopathologia - The fungus Talaromyces marneffei was described by Professor Gabriel Segretain in 1959, originally as a member of the genus Penicillium. As early as 60 years ago, its...     

Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke

Given small sample sizes, loss of animals in preclinical experiments can dramatically alter results. However, effects of attrition on distortion of results are unknown. We used a simulation study to analyze the effects of random and biased attrition. As expected, random loss of samples decreased statistical power, but biased removal, including that of outliers, dramatically increased probability of false positive results. Next, we performed a meta-analysis of animal reporting and attrition in stroke and cancer. Most papers did not adequately report attrition, and extrapolating from the results of the simulation data, we suggest that their effect sizes were likely overestimated.

Where have all the rodents gone?Ooh ooh, ooh ooh, oohTo non-random attrition, every oneWhen will they ever learn?—with apologies to Pete Seeger, 1955

     

Antibiotic Use in Animal Agriculture: What Have We Learned and Where are We Going?

Antibiotics are enormously important for the humane and efficient production of food animals. These benefits are somewhat offset by the human and animal health antibiotic resistance risks posed by their use in animals. This article provides an overview of what we have learned about antibiotic resistance as an issue in animal agriculture and where that knowledge could lead us in the future. To preserve the effectiveness of antibiotics, more action is needed to ensure their prudent use, particularly in the case of antibiotic growth promoters and antibiotics deemed critically important for human and animal health.     

Thirty Years of Studies of Qβ Replicase: What Have We Learned and What Is Yet to Be Learned?

Qβ replicase (RNA-directed RNA polymerase of bacteriophage Qβ) has an unsurpassed capacity to amplify polynucleotides in vitro. In 1986, the Group of Viral RNA Biochemistry was organized at the Institute of Protein Research in order to exploit this property for the synthesis of messenger RNAs to be used in cell-free translation systems. Although the task has not been implemented in full, this work has led to a number of unexpected important results including uncovering the nature of the “template-free” RNA synthesis by Qβ replicase, discovering the ability of RNA molecules for spontaneous recombination, revealing the unusual mechanism Qβ replicase uses to discriminate between its proper and improper templates, and discovering a new function of the largest ribosomal protein S1, that is also one of the replicase subunits. Finally, our work resulted in the invention of the molecular colonies technique that has become the basis for the next generation sequencing methods and provided a new insight into the origin of life. However, Qβ replicase has not yet revealed all its secrets, and its studies promise further interesting findings.     

Six Years of Criticality Assessments: What Have We Learned So Far?

The “criticality” of the various elements used in modern technologies is a topic of increasing interest, with groups from governments, consultancies, and academic institutions developing a variety of methodologies and using them to make assessments. Other groups from similar organizations are studying the methodologies that generate these assessments. Here, we analyze the different types of studies, review issues of methodology, and comment on features of nine different studies published between 2008 and mid‐2014. From these studies, we derive lists of problematic, debatable, and desirable aspects of criticality studies. We emphasize that the criticality of an element can vary depending on the target organization and that, because criticality is a dynamic state, it must be periodically re‐evaluated. There is substantial value to be derived if a more uniform methodology could be developed. We discuss how a harmonized methodological framework might be achieved and what its benefits could be. Putting into place such a structure for collaborative and publicly available criticality determinations would be very likely to better serve the present and future needs of corporations and governments than is the case at present, where different methodologies generate different results.     

What Comes First,Job Burnout or Secondary Traumatic Stress? Findings from Two Longitudinal Studies from the U.S. and Poland

This longitudinal research examined the directions of the relationships between job burnout and secondary traumatic stress (STS) among human services workers. In particular, using cross-lagged panel design, we investigated whether job burnout predicts STS at 6-month follow up or whether the level of STS symptoms explains job burnout at 6-month follow-up. Participants in Study 1 were behavioral or mental healthcare providers (N = 135) working with U.S. military personnel suffering from trauma. Participants in Study 2 were healthcare providers, social workers, and other human services professions (N = 194) providing various types of services for civilian trauma survivors in Poland. The cross-lagged analyses showed consistent results for both longitudinal studies; job burnout measured at Time 1 led to STS at Time 2, but STS assessed at Time 1 did not lead to job burnout at Time 2. These results contribute to a discussion on the origins of STS and job burnout among human services personnel working in highly demanding context of work-related secondary exposure to traumatic events and confirm that job burnout contributes to the development of STS.     

What Can We Learn from the Evolution of Protein-Ligand Interactions to Aid the Design of New Therapeutics?

Efforts to increase affinity in the design of new therapeutic molecules have tended to lead to greater lipophilicity, a factor that is generally agreed to be contributing to the low success rate of new drug candidates. Our aim is to provide a structural perspective to the study of lipophilic efficiency and to compare molecular interactions created over evolutionary time with those designed by humans. We show that natural complexes typically engage in more polar contacts than synthetic molecules bound to proteins. The synthetic molecules also have a higher proportion of unmatched heteroatoms at the interface than the natural sets. These observations suggest that there are lessons to be learnt from Nature, which could help us to improve the characteristics of man-made molecules. In particular, it is possible to increase the density of polar contacts without increasing lipophilicity and this is best achieved early in discovery while molecules remain relatively small.     

What Have Stable Isotope Studies Revealed About the Nature and Mechanisms of N Saturation and Nitrate Leaching from Semi-Natural Catchments?

Various studies over the last 15 years have attempted to describe the processes of N retention, saturation and NO₃ ⁻ leaching in semi-natural ecosystems based on stable isotope studies. Forest ecologists and terrestrial biogeochemists have used ¹⁵N labelled NO₃ ⁻ and NH₄ ⁺ tracers to determine the fate of atmospheric deposition inputs of N to terrestrial ecosystems, with NO₃ ⁻ leaching to surface waters being a key output flux. Separate studies by aquatic ecologists have used similar isotope tracer methods to determine the fate and impacts of inorganic N species, leached from terrestrial ecosystems, on aquatic ecosystems, usually without reference to comparable terrestrial studies. A third group of isotopic studies has employed natural abundances of ¹⁵N and ¹⁸O in precipitation and surface water NO₃ ⁻ to determine the relative contributions of atmospheric and microbial sources. These three sets of results often appear to conflict with one another. Here we attempt to synthesize and reconcile the results of these differing approaches to identifying both the source and the fate of inorganic N in natural or semi-natural ecosystems, and identify future research priorities. We conclude that the results of different studies conform to a consistent conceptual model comprising: (1) rapid microbial turnover of atmospherically deposited NO₃ ⁻ at multiple biologically active locations within both terrestrial and aquatic ecosystems; (2) maximum retention and accumulation of N in carbon-rich ecosystems and (3) maximum leaching of NO₃ ⁻, most of which has been microbially cycled, from carbon-poor ecosystems exposed to elevated atmospheric N inputs.     

Have We Neglected the Role of Fetal Endothelium in Transplacental Transport?

Maternal‐to‐fetal transfer of nutrient and other substances occurs across the placental barrier (PB) which is made up of endothelial cells (EC) on the fetal side and the syncytiotrophoblast (STB) on the maternal side. Numerous studies were conducted to explore the transport characteristics across the STB layer, which is also considered as the major resistance for maternal‐to‐fetal exchange of materials. In contrast the layer of EC has received very little attention if at all. A recently developed viable co‐culture model of the PB revealed significant resistance of the EC layer for maternal‐to‐fetal transfer of glucose. This argues for a major contribution of the EC to overall transplacental transfer of nutrients. Accordingly, it is recommended to fill the void of knowledge and expand our understanding on the role of the feto‐placental endothelium for transplacental transport characteristics.