Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.

Bovine Tuberculosis Risk Factors for British Herds Before and After the 2001 Foot-and-Mouth Epidemic: What have we Learned from the TB99 and CCS2005 Studies?

Over the last couple of decades, the UK experienced a substantial increase in the incidence and geographical spread of bovine tuberculosis (TB), in particular since the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the Randomized Badger Culling Trial (RBCT) in 1998 in south-west England provided an opportunity for an in-depth collection of questionnaire data (covering farming practices, herd management and husbandry, trading and wildlife activity) from herds having experienced a TB breakdown between 1998 and early 2006 and randomly selected control herds, both within and outside the RBCT (the so-called TB99 and CCS2005 case-control studies). The data collated were split into four separate and comparable substudies related to either the pre-FMD or post-FMD period, which are brought together and discussed here for the first time. The findings suggest that the risk factors associated with TB breakdowns may have changed. Higher Mycobacterium bovis prevalence in badgers following the FMD epidemic may have contributed to the identification of the presence of badgers on a farm as a prominent TB risk factor only post-FMD. The strong emergence of contact/trading TB risk factors post-FMD suggests that the purchasing and movement of cattle, which took place to restock FMD-affected areas after 2001, may have exacerbated the TB problem. Post-FMD analyses also highlighted the potential impact of environmental factors on TB risk. Although no unique and universal solution exists to reduce the transmission of TB to and among British cattle, there is an evidence to suggest that applying the broad principles of biosecurity on farms reduces the risk of infection. However, with trading remaining as an important route of local and long-distance TB transmission, improvements in the detection of infected animals during pre- and post-movement testing should further reduce the geographical spread of the disease.

The Spanish variety of Malaga: From real to mental to virtual speech

Internet has affected our lives and society in manifold ways, and partly, in fundamental ways. Therefore, it is no surprise that one of the affected areas is language and communication itself. Over the last few years, online social networks have become a widespread and continuously expanding medium of communication. Being a new medium of social interaction, online social networks produce their own communication style, which in many cases differs considerably from real speech and is also perceived differently. The focus of analysis of my PhD thesis is how social network users from the city of Malaga create this virtual style by means of phonic features typical of the Andalusian variety of Spanish and how the users’ language attitude has an influence on the use of these phonic features. The data collection was fourfold: 1) a main corpus was compiled from 240 informants’ utterances on Facebook and Tuenti; 2) a corpus constituted of broad transcriptions of recordings with 120 people from Malaga served as a comparison; 3) a survey in which 240 participants rated the use of said phonetic variants on the following axes: “good–bad”, “correct–incorrect” and “beautiful–ugly” was carried out; 4) a survey with 240 participants who estimated with which frequency the analysed features are used in Malaga was conducted. For the analysis, which is quantitative and qualitative, ten variables were chosen. Results show that the studied variants are employed differently in virtual and real speech depending on how people perceive these variants. In addition, the use of the features is constrained by social factors. In general, people from Malaga have a more positive attitude towards non-­‐standard features if they are used in virtual speech than in real speech. Thus, virtual communication is seen as a style serving to create social meaning and to express linguistic identity. These stylistic practices reflect an amalgam of social presuppositions about usage conventions and individual strategies for handling a new medium. In sum, the virtual style is an initiative deliberately taken by the users, to create their, real and virtual, identities, and to define their language attitudes towards the features of their variety of speech.

Neuropathology and pathogenesis of HIV encephalopathies

The nervous system is frequently affected in patients with the acquired immune deficiency syndrome (AIDS). In addition to opportunistic CNS infections and cerebral lymphomas, approx. 20% of the patients develop HIV-associated encephalopathies. Two major histopathological manifestations are observed. HIV leukoencephalopathy (progressive diffuse leukoencephalopathy) is characterized by a diffuse loss of myelin in the deep white matter of the cerebral and cerebellar hemispheres, with scattered multinucleated giant cells and microglia but scarce or absent inflammatory reaction. HIV encephalitis (multinucleated giant cell encephalitis) is associated with accumulations of multinucleated giant cells, inflammatory reaction and often focal necroses. In some patients, both patterns may overlap. In order to identify the HIV genome in the CNS, brain tissue from 27 patients was analyzed for the presence of HIV gag sequences using the polymerase chain reaction (PCR) and primers encoding a 109 base pair segment of the gag gene. Amplification of HIV gag succeeded in all 5 patients with clinical and histopathological evidence for HIV encephalopathy but was negative in the 20 AIDS patients with opportunistic bacterial, parasitic and/or viral infections or with cerebral lymphomas. These results strongly suggest that the evolution of histopathologically recognizable HIV-encephalopathies closely correlates with the presence and/or tissue concentration of HIV. Since there were no cases with amplified HIV DNA in the absence of HIV-associated tissue lesions, we conclude that harboring and replication of HIV in the CNS rapidly causes corresponding clinical and morphological changes of HIV-associated encephalopathies. In two children with severe HIV encephalomyelitis, large amounts of HIV gag and env transcripts were detected in affected areas of the brain and spinal cord by in situ hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)

Mass Movement-Induced Tsunami Hazard on Perialpine Lake Lucerne (Switzerland): Scenarios and Numerical Experiments

Previous studies of the sediments of Lake Lucerne have shown that massive subaqueous mass movements affecting unconsolidated sediments on lateral slopes are a common process in this lake, and, in view of historical reports describing damaging waves on the lake, it was suggested that tsunamis generated by mass movements represent a considerable natural hazard on the lakeshores. Newly performed numerical simulations combining two-dimensional, depth-averaged models for mass-movement propagation and for tsunami generation, propagation and inunda- tion reproduce a number of reported tsunami effects. Four analysed mass-movement scenarios—three based on documented slope failures involving volumes of 5.5 to 20.8 9 106 m3—show peak wave heights of several metres and maximum runup of 6 to [10 m in the directly affected basins, while effects in neighbouring basins are less drastic. The tsunamis cause large-scale inundation over distances of several hundred metres on flat alluvial plains close to the mass-movement source areas. Basins at the ends of the lake experience regular water-level oscillations with characteristic periods of several minutes. The vulnerability of potentially affected areas has increased dramatically since the times of the damaging historical events, recommending a thorough evaluation of the hazard.

Fluorescence lifetime imaging in retinal artery occlusion.

PURPOSE Fluorescence lifetime imaging ophthalmoscopy is a technique to measure decay times of endogenous retinal fluorophores. The purpose of this study was to investigate fluorescence lifetimes in eyes with central and branch retinal artery occlusion. METHODS Twenty-four patients with central or branch retinal artery occlusion were included in this study. The contralateral unaffected fellow eye was used as control. Measurements were performed using a fluorescence lifetime imaging ophthalmoscope based on a HRA Spectralis system. Fluorescence excitation wavelength was 473 nm, and mean lifetimes were measured in a short (498-560 nm) and in a long (560-720 nm) spectral channel. Fluorescence lifetimes in the area of retinal artery occlusion were measured and compared to corresponding areas in contralateral unaffected eyes. Additionally, findings were correlated to optical coherence tomography measurements. RESULTS Retinal lifetime images of 24 patients with retinal artery occlusion were analyzed. Mean retinal fluorescence lifetimes were prolonged by 50% in the short and 20% in the long spectral channel in ischemic retinal areas up to 3 days after retinal artery occlusion compared to the contralateral unaffected eyes. In the postacute disease stage there was no difference between the lifetimes of affected areas and unaffected fellow eyes. CONCLUSIONS Retinal artery occlusion leads to significantly longer fluorescence lifetimes of the retina in the acute phase and may serve as a useful indicator for acute ischemic retinal damage.

Bonding of simplified adhesive systems to caries-affected dentin of primary teeth.

PURPOSE To evaluate the bonding of simplified adhesive systems to sound and caries-affected dentin of primary teeth with microtensile (µTBS) and nanoleakage (NL) tests. MATERIALS AND METHODS Occlusal cavities were prepared in 36 sound second primary molars. Half of the specimens were submitted to pH cycling to simulate caries-affected dentin. Teeth were randomly restored with one of three materials: the etch-and-rinse adhesive system Adper Single Bond 2 (SB), the two-step self-etching adhesive system Adper SE Plus (SE), and the one-step self-etching adhesive system Adper Easy One (EASY). After storage for 24 h, specimens with cross-sectional areas of 0.8 mm2 were prepared for microtensile testing (1 mm/min). One stick from each tooth was immersed in silver nitrate solution (24 h) and allowed to develop for 8 h in order to score the nano leakage with SEM. The fracture pattern was evaluated using a stereomicroscope (400X). The µTBS means were analyzed by two-way ANOVA and Tukey's post-hoc test. For NL, the Kruskal- Wallis and Mann-Whitney tests were used (α < 0.05). RESULTS SB (35.5 ± 3.5) showed the highest µTBS value to sound dentin, followed by EASY (26.3 ± 1.9) and SE (18.2 ± 6.5) (p < 0.05). No difference among materials was observed for caries-affected dentin (SB: 17.8 ± 4.2; SE: 13.9 ± 3.2; EASY: 14.4 ± 4.2, p > 0.05). For all groups, adhesive/mixed fracture prevailed. Caries affected dentin promoted silver nitrate uptake into the adhesive interface; however, with SE, the nano leakage was more pronounced than in the other adhesive systems, even in sound dentin. CONCLUSION Caries-affected dentin negatively influences the bond strength and nano leakage of the two-step etch-and-rinse and one-step self-etching adhesive systems tested in primary teeth.

Impacts of out-migration on land management in mountain areas

INTRODUCTION Out-migration from mountain areas is leaving behind half families and elderly to deal with managing the land alongside daily life challenges. A potential reduction of labour force as well as expertise on cropping practices, maintenance of terraces and irrigation canals, slope stabilization, grazing, forest and other land management practices are further challenged by changing climate conditions and increased environmental threats. An understanding of the resilience of managed land resources in order to enhance adaptation to environmental and socio-economic variability, and evidence of the impact of Sustainable Land Management (SLM) on the mitigation of environmental threats have so far not sufficiently been tackled. The study presented here aims to find out how land management in mountains is being affected by migration in the context of natural hazards and climate change in two study sites, namely Quillacollo District of Bolivia and Panchase area of Western Nepal, and which measures are needed to increase resilience of livelihoods and land management practices. The presentation includes draft results from first field work periods in both sites. A context of high vulnerability According to UNISDR, vulnerability is defined as “the characteristics and circumstances of a community, system or asset that make it susceptible to the damaging effects of a hazard”.Hazards are another threat affecting people’s livelihood in mountainous area. They can be either natural or human induced. Landslides, debris flow and flood are affecting peopleGood land management can significantly reduce occurrence of hazards. In the opposite bad land management or land abandonment can lead to negative consequences on the land, and thus again increase vulnerability of people’s livelihoods. METHODS The study integrates bio-physical and socio-economic data through a case study as well as a mapping approach. From the social sciences, well-tested participatory qualitative methodologies, typically used in Vulnerability and Capacity Analyses, such as semi-structured interviews with so-called ‘key informants’, transect walks, participatory risk and social resource mapping are applied. The bio-physical analysis of the current environmental conditions determining hazards and structural vulnerability are obtained from remote sensing analysis, field work studies, and GIS analysis The assessment of the consequences of migration in the area of origin is linked with a mapping and appraisal of land management practices (www.wocat.net, Schwilch et al., 2011). The WOCAT mapping tool (WOCAT/LADA/DESIRE 2008) allows capturing the major land management practices / technologies, their spread, effectiveness and impact within a selected area. Data drawn from a variety of sources are compiled and harmonised by a team of experts, consisting of land degradation and conservation specialists working in consultation with land users from various backgrounds. The specialists’ and land users’ knowledge is combined with existing datasets and documents (maps, GIS layers, high-resolution satellite images, etc.) in workshops that are designed to build consensus regarding the variables used to assess land degradation and SLM. This process is also referred to as participatory expert assessment or consensus mapping. The WOCAT mapping and SLM documentation methodologies are used together with participatory mapping and other socio-economic data collection (interviews, questionnaires, focus group discussions, expert consultation) to combine information about migration types and land management issues. GIS and other spatial visualization tools (e.g. Google maps) will help to represent and understand these links. FIRST RESULTS Nepal In Nepal, migration is a common strategy to improve the livelihoods. Migrants are mostly men and they migrate to other Asian countries, first to India and then to the Gulf countries. Only a few women are migrating abroad. Women migrate essentially to main Nepali cities when they can afford it. Remittances are used primarily for food and education; however they are hardly used for agricultural purposes. Besides traditional agriculture being maintained, only few new practices are emerging, such as vegetable farming or agroforestry. The land abandonment is a growing consequence of outmigration, resulting in the spreading of invasive species. However, most impacts of migration on land management are not yet clear. Moreover, education is a major concern for the respondents; they want their children having a better education and get better opportunities. Linked to this, unemployment is another major concern of the respondents, which in turn is “solved” through outmigration. Bolivia Migration is a common livelihood strategy in Bolivia. In the area of study, whole families are migrating downward to the cities of the valleys or to other departments of Bolivia, especially to Chapare (tropics) for the coca production and to Santa Cruz. Some young people are migrating abroad, mostly to Argentina. There are few remittances and if those are sent to the families in the mountain areas, then they are mainly used for agriculture purpose. The impacts of migration on land management practices are not clear although there are some important aspects to be underlined. The people who move downward are still using their land and coming back during part of the week to work on it. As a consequence of this multi-residency, there is a tendency to reduce land management work or to change the way the land is used. As in Nepal, education is a very important issue in this area. There is no secondary school, and only one community has a primary school. After the 6th grade students have therefore to go down into the valley towns to study. The lack of basic education is pushing more and more people to move down and to leave the mountains. CONCLUSIONS This study is on-going, more data have to be collected to clearly assess the impacts of out-migration on land management in mountain areas. The first results of the study allow us to present a few interesting findings. The two case studies are very different, however in both areas, young people are not staying anymore in the mountains and leave behind half families and elderly to manage the land. Additionally in both cases education is a major reason for moving out, even though the causes are not always the same. More specifically, in the case of Nepal, the use of remittances underlines the fact that investment in agriculture is not the first choice of a family. In the case of Bolivia, some interesting findings showed that people continue to work on their lands even if they move downward. The further steps of the study will help to explore these interesting issues in more detail. REFERENCES Schwilch G., Bestelmeyer B., Bunning S., Critchley W., Herrick J., Kellner K., Liniger H.P., Nachtergaele F., Ritsema C.J., Schuster B., Tabo R., van Lynden G., Winslow M. 2011. Experiences in Monitoring and Assessment of Sustainable Land Management. Land Degradation & Development 22 (2), 214-225. Doi 10.1002/ldr.1040 WOCAT/LADA/DESIRE 2008. A Questionnaire for Mapping Land Degradation and Sustainable Land Management. Liniger H.P., van Lynden G., Nachtergaele F., Schwilch G. (eds), Centre for Development and Environment, Institute of Geography, University of Berne, Berne

Prevalence of antibodies against bluetongue virus serotype 8 in bulk-tank milk samples from dairy cattle herds located in risk areas for bluetongue virus transmission after a vaccination programme in Switzerland.

Switzerland had been affected by the bluetongue virus serotype 8 (BTV-8) epidemic in Europe in the years 2007 to 2009. After three years of mandatory vaccination and comprehensive surveillance, Switzerland showed to be free of BTV-8 in 2012. In the future Elisa testing of bulk-tank milk (BTM) samples as a very sensitive and cost-effective method should be used for the surveillance of all serotypes of BTV. To determine the prevalence of seropositive herds, BTM from 240 cattle herds was sampled in July 2012. The results showed an apparent seroprevalence of 98.7% in the investigated dairy herds. Most plausible, the high prevalence was caused by the vaccination campaigns rather than by infections with BTV-8. In the outbreak the cumulative number of BTV-8 cases in Switzerland had been 75.Thus it is very likely that the used inactivated vaccines induced long-term antibody titres. Due to the high seroprevalence, investigating for BT-antibodies cannot be used for early recognition of a new introduction of BTV at the moment. Nonetheless, testing of BTM samples is appropriate for an annual evaluation of the seroprevalence and especially as an instrument for early recognition for incursions as soon as the antibody prevalence declines.To determine this decline the BTM testing scheme should be conducted each year as described in this work.