The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD

Bullying behaviour in schools, socioeconomic position and psychiatric morbidity: a cross-sectional study in late adolescents in Greece

<p>Abstract</p> <p>Background</p> <p>Bullying is quite prevalent in the school setting and has been associated with the socioeconomic position and psychiatric morbidity of the pupils. The aim of the study was to investigate the association between bullying and socioeconomic status in a sample of Greek adolescents and to examine whether this is confounded by the presence of psychiatric morbidity, including sub-threshold forms of illness.</p> <p>Methods</p> <p>5,614 adolescents aged 16-18 years old and attending 25 senior high schools were screened and a stratified random sample of 2,427 were selected for a detailed interview. Psychiatric morbidity was assessed with a fully structured psychiatric interview, the revised Clinical Interview Schedule (CIS-R), while bullying was assessed with the revised Olweus bully/victim questionnaire. The following socio-economic variables were assessed: parental educational level and employment status, financial difficulties of the family and adolescents' school performance. The associations were investigated using multinomial logit models.</p> <p>Results</p> <p>26.4% of the pupils were involved in bullying-related behaviours at least once monthly either as victims, perpetrators or both, while more frequent involvement (at least once weekly) was reported by 4.1%. Psychiatric morbidity was associated with all types of bullying-related behaviours. No socioeconomic associations were reported for victimization. A lower school performance and unemployment of the father were significantly more likely among perpetrators, while economic inactivity of the mother was more likely in pupils who were both victims and perpetrators. These results were largely confirmed when we focused on high frequency behaviours only. In addition, being overweight increased the risk of frequent victimization.</p> <p>Conclusions</p> <p>The prevalence of bullying among Greek pupils is substantial. Perpetration was associated with some dimensions of adolescents' socioeconomic status, while victimization showed no socioeconomic associations. Our findings may add to the understanding of possible risk factors for bullying behaviours in adolescence.</p

Biodiversity patterns of Arctic diatom assemblages in lakes and streams: Current reference conditions and historical context for biomonitoring

Comprehensive assessments of contemporary diatom distributions across the Arctic remain scarce. Furthermore, studies tracking species compositional differences across space and time, as well as diatom responses to climate warming, are mainly limited to paleolimnological studies due to a lack of routine monitoring in lakes and streams across vast areas of the Arctic. The study aims to provide a spatial assessment of contemporary species distributions across the circum-Arctic, establish contemporary biodiversity patterns of diatom assemblages to use as reference conditions for future biomonitoring assessments, and determine pre-industrial baseline conditions to provide historical context for modern diatom distributions. Diatom assemblages were assessed using information from ongoing regulatory monitoring programmes, individual research projects, and from surface sediment layers obtained from lake cores. Pre-industrial baseline conditions as well as the nature, direction and magnitude of changes in diatom assemblages over the pastc.200 years were determined by comparing surface sediment samples (i.e. containing modern assemblages) with a sediment interval deposited prior to the onset of significant anthropogenic activities (i.e. containing pre-1850 assemblages), together with an examination of diatoms preserved in contiguous samples from dated sediment cores. We identified several biotypes with distinct diatom assemblages using contemporary diatom data from both lakes and streams, including a biotype typical for High Arctic regions. Differences in diatom assemblage composition across circum-Arctic regions were gradual rather than abrupt. Species richness was lowest in High Arctic regions compared to Low Arctic and sub-Arctic regions, and higher in lakes than in streams. Dominant diatom taxa were not endemic to the Arctic. Species richness in both lakes and streams reached maximum values between 60 degrees N and 75 degrees N but was highly variable, probably reflecting differences in local and regional environmental factors and possibly sampling effort. We found clear taxon-specific differences between contemporary and pre-industrial samples that were often specific to both ecozone and lake depth. Regional patterns of species turnover (beta-diversity) in the pastc.200 years revealed that regions of the Canadian High Arctic and the Hudson Bay Lowlands to the south showed most compositional change, whereas the easternmost regions of the Canadian Arctic changed least. As shown in previous Arctic diatom studies, global warming has already affected these remote high latitude ecosystems. Our results provide reference conditions for future environmental monitoring programmes in the Arctic. Furthermore, diatom taxa identification and harmonisation require improvement, starting with circum-Arctic intercalibrations. Despite the challenges posed by the remoteness of the Arctic, our study shows the need for routine monitoring programmes that have a wide geographical coverage for both streams and lakes

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System

The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32?36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component

Connectivity and zebra mussel invasion offer short‐term buffering of eutrophication impacts on floodplain lake landscape biodiversity

Aim To investigate if connectivity and zebra mussel (Dreissena polymorpha) occurrence can mitigate effects of eutrophication in a lowland lake landscape. Location Upper Lough Erne, Northern Ireland, UK. Methods Data on environment, macrophytes and invertebrates were assembled for three basins of a large central lake and its satellite floodplain lakes via field surveys and palaeolimnological analyses. Space–time interaction analyses of palaeoecological data were compared pre‐1950 and post‐1950. Multivariate analyses examined how connectivity, environment and zebra mussels influenced contemporary lake communities, and explain their divergence from historical communities in the past. Results Pre‐1950, we found high community variation across sites and low within‐lake variation in macrophytes, but progressive eutrophication accentuated within‐lake community variation after 1950. Partitioning analysis showed larger effects of connectivity than nutrient enrichment on contemporary macrophyte composition, while local effects structured invertebrate communities. Three clusters of lakes were revealed according to variation in macrophyte composition, isolation from the central lake and nutrient enrichment: Group 1– the central lake and six nearby lakes were meso‐eutrophic (TP = 66.7 ± 47.6 μg/L; TN = 0.79 ± 0.41 mg/L) and had the highest zebra mussel abundances and organismal biodiversity; Group 2– Eight eutrophic (TP = 112±36.6 μg/L; TN = 1.25 ± 0.5 mg/L) and connected lakes; Group 3– Seven isolated and hypertrophic (TP = 163.2 ± 101.5 μg/L; TN = 1.55 ± 0.3 mg/L) lakes. Pre‐1950 palaeolimnological data for macrophytes and invertebrates for 5 lakes and a basin in the central lake most resembled extant lake communities of Group 1. However, palaeo‐records revealed that macrophytes and invertebrates subsequently converged towards those of Groups 2 and 3. Main conclusions Our study reveals that the central “mother” lake acts as a hub for preserving biodiversity via shared hydrological connectivity with satellite lakes and high zebra mussel abundances. These may buffer the impoverishing effects of eutrophication and sustain unexpectedly high biodiversity in the short term. Such protective buffering, however, cannot be relied upon indefinitely to conserve biodiversity

HIV testing within general practices in Europe : A mixed-methods systematic review

Funding Information: This work was supported by IWT (Belgium) and the ANRS (France) through the framework of HIVERA JTC 2014. Publisher Copyright: © 2018 The Author(s).Background: Late diagnosis of HIV infection remains a key challenge in Europe. It is acknowledged that general practitioners (GPs) may contribute greatly to early case finding, yet there is evidence that many diagnostic opportunities are being missed. To further promote HIV testing in primary care and to increase the utility of available research, the existing evidence has been synthesised in a systematic review adhering to the PRISMA guidelines. Methods: The databases PubMed, Scopus and Embase were searched for the period 2006-2017. Two authors judged independently on the eligibility of studies. Through a mixed-methods systematic review of 29 studies, we provide a description of HIV testing in general practices in Europe, including barriers and facilitators. Results: The findings of the study show that although various approaches to target patients are used by GPs, most tests are still carried out based on the patient's request. Several barriers obstruct HIV testing in general practice. Included are a lack of communication skills on sexual health, lack of knowledge about HIV testing recommendations and epidemic specificities, difficulties with using the complete list of clinical HIV indicator diseases and lack of experience in delivering and communicating test results. The findings also suggest that the provision of specific training, practical tools and promotion programmes has an impact on the testing performance of GPs. Conclusions: GPs could have an increased role in provider-initiated HIV-testing for early case finding. To achieve this objective, solutions to the reported barriers should be identified and testing criteria adapted to primary healthcare defined. Providing guidance and training to better identify priority groups for HIV testing, as well as information on the HIV epidemic's characteristics, will be fundamental to increasing awareness and testing by GPs.publishersversionPeer reviewe

Comparative Geno-Plasticity Analysis of Mycoplasma bovis HB0801 (Chinese Isolate)

Mycoplasma bovis pneumonia in cattle has been epidemic in China since 2008. To investigate M. bovis pathogenesis, we completed genome sequencing of strain HB0801 isolated from a lesioned bovine lung from Hubei, China. The genomic plasticity was determined by comparing HB0801 with M. bovis strain ATCC® 25523™/PG45 from cow mastitis milk, Chinese strain Hubei-1 from lesioned lung tissue, and 16 other Mycoplasmas species. Compared to PG45, the genome size of HB0801 was reduced by 11.7 kb. Furthermore, a large chromosome inversion (580 kb) was confirmed in all Chinese isolates including HB0801, HB1007, a strain from cow mastitis milk, and Hubei-1. In addition, the variable surface lipoproteins (vsp) gene cluster existed in HB0801, but contained less than half of the genes, and had poor identity to that in PG45, but they had conserved structures. Further inter-strain comparisons revealed other mechanisms of gene acquisition and loss in HB0801 that primarily involved insertion sequence (IS) elements, integrative conjugative element, restriction and modification systems, and some lipoproteins and transmembrane proteins. Subsequently, PG45 and HB0801 virulence in cattle was compared. Results indicated that both strains were pathogenic to cattle. The scores of gross pathological assessment for the control group, and the PG45- and HB0801-infected groups were 3, 13 and 9, respectively. Meanwhile the scores of lung lesion for these three groups were 36, 70, and 69, respectively. In addition, immunohistochemistry detection demonstrated that both strains were similarly distributed in lungs and lymph nodes. Although PG45 showed slightly higher virulence in calves than HB0801, there was no statistical difference between the strains (P>0.05). Compared to Hubei-1, a total of 122 SNP loci were disclosed in HB0801. In conclusion, although genomic plasticity was thought to be an evolutionary advantage, it did not apparently affect virulence of M. bovis strains in cattle

Identification of epitopes recognised by mucosal CD4+ T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7

Additional file 5. Sequence alignment of Intimin epitopes against Intimin sequences from non-O157 EHEC serotypes. Alignment of Intimin CD4+ T-cell epitope sequences with representative Intimin sequences from EHEC serotypes O145, O127, O26, O103, O121, O45 and O111. Percentage values indicate % similarity to the EHEC O157:H7 reference sequence