An overview of values for the threshold of toxicological concern

An overview of values for the threshold of toxicological concern (TTC) is presented. This comprises the more established TTC values, including those that have been endorsed by regulatory bodies, and those that have more recently been proposed and may still need further development. The overview is structured by use/exposure scenario and provides, in particular, key information on the underlying databases. It is aimed to support the application of the TTC approach in the risk assessment of chemicals whereby it is important to be aware under which circumstances a certain TTC value can be applied. Some recommendations for potential future developments to further improve the TTC approach are also being made.     

Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement

Objectives: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD).

Methods: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated.

Results: Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus).

Conclusions: The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided.     

The Trelleborg Project: A Process Evaluation of a Multi-Sector Community Intervention to Reduce Alcohol Consumption and Related Harm

The Trelleborg project ran between 1999 and 2002. This article describes and analyzes the processes relating to institutionalization and social change, and their consequences, within the project. The research, funded by the Swedish National Institute of Public Health, was based on qualitative data collected during the project, including focused interviews with 12 key individuals, five focus group interviews, two evaluation seminars, and a large number of meeting minutes. The article concludes that positive interaction between organization elites is a prerequisite for institutionalization. However, the elites within an organization also have to take external pressures into account when transforming an ad hoc initiation into sustained activity.     

Mutational effects on stability are largely conserved during protein evolution

Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.Most biological proteins stably fold to a well-defined native structure (1). Stable folding to the native structure is typically essential for a protein to perform its evolutionarily selected function. Stability and folding are the result of highly cooperative interactions among a protein’s constituent amino acids (1). Therefore, evolutionary selection at a site in a protein acts on properties that in principle are determined by interactions of that site with every other position in the sequence.However, phylogenetic approaches assume that protein sites evolve independently. This assumption has historically been justified primarily by pragmatic considerations. If substitution models are site independent, then the evolution of each site is mathematically described by a 20 × 20 matrix, with entries corresponding to all amino acid interchanges at that site. On the other hand, if each site depends upon all other sites, then the evolution of a protein of length L is mathematically described by a 20^L × 20^L matrix, with entries corresponding to all interchanges among the 20^L sequences. Even for a small protein of length L = 100, the number of entries in such a matrix vastly exceeds the number of atoms in the universe, which poses severe computational challenges.The fact that sites are not actually independent at the physicochemical level has provoked concern about the use of site-independent substitution models (2–5). Pollock et al. (2) have used computer simulations to suggest that there are widespread evolutionary shifts in mutational effects, where for instance a mutation is destabilizing in one homolog but stabilizing in another homolog due to interactions with other covarying sites. They have argued that such evolutionary shifts in mutational effects on stability have profound implications for phylogenetic modeling (2).However, are such evolutionary shifts really of sufficient prevalence and magnitude to require a radical rethinking of approaches used to model protein evolution? The standard way to address this question has been to simulate or analyze protein sequences, using some computational force field that predicts the stability of different variants (2–5). Unfortunately, there is no good a priori reason to believe that the force fields themselves authentically represent interactions among sites. Even state-of-the-art force fields are at best modestly accurate at predicting mutational effects (6, 7). Furthermore, all tractable force fields approximate the true multibody quantum–mechanical interactions among protein sites in terms of pairwise interactions (8–10).Here we experimentally assess the extent to which mutational effects on stability change during protein evolution. We introduce the same mutations into a series of homologs and measure the effects on stability. We find that the effects of individual mutations on stability are largely conserved even when homologs differ at as many as 28% of sites. Our results do not imply an absence of all forms of epistasis (interactions among sites) during protein evolution. Epistasis at the level of function and fitness can arise even if stability is fully site independent due to counterbalancing stabilizing and destabilizing mutations (11, 12), and stability is only one mechanism of epistasis (13, 14). However, for reasons that we discuss below, these other forms of epistasis seem less likely to cause pervasive shifts in substitution patterns that would seriously confound phylogenetic approaches. However, our experiments do highlight the existence of strong and largely conserved preferences for certain amino acids at specific sites. We therefore suggest that the use and further development of phylogenetic approaches (15–24) that account for these clearly observable site-specific but largely site-independent preferences is of far greater practical importance than accounting for rare evolutionary shifts in site preferences.     

Genome Characterization of Yellow Fever Virus Wild-Type Strain Asibi,Parent to Live-Attenuated 17D Vaccine,from Three Different Sources

The yellow fever virus vaccine, 17D, was derived through the serial passage of the wild-type (WT) strain Asibi virus in mouse and chicken tissue. Since its derivation, the mechanism of attenuation of 17D virus has been investigated using three 17D substrains and WT Asibi virus. Although all three substrains of 17D have been sequenced, only one isolate of Asibi has been examined genetically and all interpretation of attenuation is based on this one isolate. Here, we sequenced the genome of Asibi virus from three different laboratories and show that the WT strain is genetically homogenous at the amino acids that distinguish Asibi from 17D vaccine virus.     

第四次全国幽门螺杆菌感染处理共识报告解读

为不断规范我国幽门螺杆菌(Helicobacter pylori,Hp)感染相关疾病的治疗,自1999年以来,我国先后制定了3份共识意见.近年来国际上先后举行的Hp感染处理的共识会议也为我国进一步规范Hp感染处理提供了相关依据.2012年4月26～27日,我国在江西井冈山召开了第四次Hp处理共识会议,2012年9月的中国消化病大会上推出了相关共识意见.现将新共识的变化及亮点进行解读.     

Folk medicinal use of fauna in Mapimi, Durango, México

Aim of the study

To document the use of animal species in traditional medicine from the municipality of Mapimi, Durango, México.

Materials and methods

Direct interviews were performed in several short visits with inhabitants from the municipality of Mapimi, Durango. The interviews were analyzed with two quantitative tools. The informant consensus factor that estimates the level of agreement between interviewees over which animals to use for each category and the fidelity level which indicates the percentage of informants claiming the use of a certain animal species for the same medicinal purpose.

Results

A total of 18 animal species, belonging to 17 families and four taxonomic categories, were reported by interviewees as used for medicinal purposes. Thirteen medicinal species were identified not previously reported. The results of the informant consensus factor showed that the dermatological, diabetes and reproductive categories had the greatest agreement. The most important species according to their fidelity level are: Mephitis macroura and Crotalus atrox.

Conclusion

This study demonstrates that many animal species play an important role in healing practices among inhabitants from Mapimi, Durango. Further experiments with medicinal fauna from Mapimi are needed to be carried out to obtain experimental information about their traditional uses, especially with C. atrox.     

Ethnomedicinal application of plants in the western plain region of North Jeolla Province in Korea

Ethnopharmacological relevance

This study aims to record and conserve oral traditional knowledge of medicinal plants from the indigenous people living in the western plain region of North Jeolla Province, Korea.

Materials and methods

Our research team interviewed 46 key informants (20 men and 26 women) who have lived over 50 years in the area. The average age of the informants was 74 (with a minimum age of 56 to maximum 84). Data was collected through the participatory rural appraisal method involving interviews, informal meetings, open and group discussions, and overt observation using semi-structured questionnaires.

Results

Ethnobotanical inventory possessed by the residents included 183 species of plants distributed in 156 genera belonging to 68 families and were used in 626 use-reports. Among them, the medicinal plants were comprised as 42 families, 75 genera, and 83 species in usage in 195 ways. A total of 71 ailments were treated with 222 kinds of remedies using medicinal plants. Parts of plant that were used as treatments total up to 17 and the methods of preparation for medicinal materials add up to 28. Informant consensus factor (ICF) showed that the muscular-skeletal disorders had the highest agreement measure (1.0) followed by cuts and wounds (0.87) and respiratory system disorders (0.77). Overall, 29 plant species showed fidelity level of 100%.

Conclusions

This study is noteworthy in that it records rapidly disappearing traditional knowledge of medicinal plants in a time period of pressing environmental changes with regard to the newly built sea wall, eventually leading more or less to the immigration of the seaside inhabitants and the familiarization of the modern medical systems to the farmland inhabitants.     

Herbal medicine used by the community of Koneba district in Afar Regional State,Northeastern Ethiopia

BackgroundPastoral communities of the Afar people in northeastern Ethiopia use medicinal plants for various health problems. However, very limited scientific documents are found addressing ethnomedicinal knowledge of the community.ObjectiveThis study aimed at documenting herbal medicine and the associated knowledge from Koneba district of Afar Regional State, Ethiopia.MethodsPurposive sampling method was used to select study sites and key informants. General informants were selected through simple random sampling methods. Semi-structured interviews and guided field walk were used to collect data while Informant Consensus Factor (ICF), Fidelity Level (FL) and Preference Ranking were used to analyze and verify data.ResultsA total of 67 medicinal plant species used to treat humans and livestock ailments were recorded and collected. Thirteen medicinal plant species were mentioned as effective medicine against snake bite (ICF; 0.68) while nine species used to treat malaria, common cold and fever (ICF: 0.67). Cyphostemma adenocaule (Steud. ex A.Rich.) Desc. ex Wild & R.B.Drumm. was the most preferred species used to combat snakebite, which was prevalent in the area.ConclusionSnake bite, malaria, common cold and fever are common health problems in the study area. Efficient use of herbal medicine has minimized the impact of these diseases.