Review: leucocyte-endothelial cell crosstalk at the blood-brain barrier: a prerequisite for successful immune cell entry to the brain

Leucocyte migration into the central nervous system is a key stage in the development of multiple sclerosis. While much has been learnt regarding the sequential steps of leucocyte capture, adhesion and migration across the vasculature, the molecular basis of leucocyte extravasation is only just being unravelled. It is now recognized that bidirectional crosstalk between the immune cell and endothelium is an essential element in mediating diapedesis during both normal immune surveillance and under inflammatory conditions. The induction of various signalling networks, through engagement of cell surface molecules such as integrins on the leucocyte and immunoglobulin superfamily cell adhesion molecules on the endothelial cell, play a major role in determining the pattern and route of leucocyte emigration. In this review we discuss the extent of our knowledge regarding leucocyte migration across the blood-brain barrier and in particular the endothelial cell signalling pathways contributing to this process.

Peer Review Processes for Transdisciplinary Articles: A Reflection on Journal's Practices

Publishing is an essential means of validation and communication of research. This is no different in transdisciplinary research, where publishing also aims at contributing to the development of society through sharing of knowledge. In the scientific world, authors need to disseminate and validate results, reflect on issues, and participate in debates. On the other hand, institutions and individuals are assessed according to their publication record – as probably the most influential of all current evaluation criteria. Occupying the space between article production and counting impact factors, journal editors and reviewers play an important role in defining and using rules to assess and improve the work submitted to them. Publishing transdisciplinary research poses specific challenges, in particular with regard to peer-review processes, as it addresses different knowledge communities with different value systems and purposes.

The precipitous decline of the ortolan bunting Emberiza hortulana: time to build on scientific evidence to inform conservation management

In recent decades there has been a marked decline in most ortolan bunting Emberiza hortulana populations in temperate Europe, with many regional populations now extinct or on the brink of extinction. In contrast, Mediterranean and, as far as we know, eastern European popula-tions seem to have remained relatively stable. The causes of decline remain unclear but include: habitat loss and degradation, and related reduction in prey availability; climate change on the breeding grounds; altered population dynamics; illegal captures during migration; and environmental change in wintering areas. We review the current knowledge of the biology of the ortolan bunting and discuss the proposed causes of decline in relation to the different population trends in temperate and Mediterranean Europe. We suggest new avenues of research to identify the factors limiting ortolan bunting populations. The main evidence-based conservation measure that is likely to enhance habitat quality is the creation of patches of bare ground to produce sparsely vegetated foraging grounds in invertebrate-rich grassy habitats close to breeding areas.

Stability after bilateral sagittal split osteotomy setback surgery with rigid internal fixation: a systematic review

PURPOSE: The purpose of this systematic review was to evaluate relapse and its causes in bilateral sagittal split setback osteotomy with rigid internal fixation. MATERIALS AND METHODS: Literature research was done in databases such as PubMed, Ovid, the Cochrane Library, and Google Scholar Beta. From the original 488 articles identified, 14 articles were finally included. Only 5 studies were prospective and 9 retrospective. The range of postoperative study records was from 6 weeks to 12.7 years. RESULTS: The horizontal short-term relapse was between 9.9% and 62.1% at point B and between 15.7% and 91.3% at pogonion. Long-term relapse was between 14.9% and 28.0% at point B and between 11.5% and 25.4% at pogonion. CONCLUSIONS: Neither large increase nor decrease of relapse was seen when short-term values were compared with long-term. Bilateral sagittal split osteotomy for mandibular setback in combination with orthodontics is an effective treatment of skeletal Class III and a stable procedure in the short- and long-term. The etiology of relapse is multifactorial: the proper seating of the condyles, the amount of setback, the soft tissue and muscles, remaining growth and remodeling, and gender were identified. Age did not show any correlations. To obtain reliable scientific evidence, further short- and long-term research of bilateral sagittal split osteotomy setback with rigid internal fixation should exclude additional surgery, ie, genioplasty or maxillary surgery, and include correlation statistics.

Stability after bilateral sagittal split osteotomy advancement surgery with rigid internal fixation: a systematic review

PURPOSE: The purpose of this systematic review was to evaluate horizontal relapse and its causes in bilateral sagittal split advancement osteotomy (BSSO) with rigid internal fixation of different types. MATERIALS AND METHODS: A search of the literature was performed in the databases PubMed, Ovid, Cochrane Library, and Google Scholar Beta. From 488 articles identified, 24 articles were finally included. Six studies were prospective, and 18 were retrospective. The range of postoperative study records was 6 months to 12.7 years. RESULTS: The short-term relapse for bicortical screws was between 1.5% and 32.7%, for miniplates between 1.5% and 18.0%, and for bioresorbable bicortical screws between 10.4% and 17.4%, at point B. The long-term relapse for bicortical screws was between 2.0% and 50.3%, and for miniplates between 1.5% and 8.9%, at point B. CONCLUSIONS: BSSO for mandibular advancement is a good treatment option for skeletal Class II, but seems less stable than BSSO setback in the short and long terms. Bicortical screws of titanium, stainless steel, or bioresorbable material show little difference regarding skeletal stability compared with miniplates in the short term. A greater number of studies with larger skeletal long-term relapse rates were evident in patients treated with bicortical screws instead of miniplates. The etiology of relapse is multifactorial, involving the proper seating of the condyles, the amount of advancement, the soft tissue and muscles, the mandibular plane angle, the remaining growth and remodeling, the skill of the surgeon, and preoperative age. Patients with a low mandibular plane angle have increased vertical relapse, whereas patients with a high mandibular plane angle have more horizontal relapse. Advancements in the range of 6 to 7 mm or more predispose to horizontal relapse. To obtain reliable scientific evidence, further short-term and long-term research into BSSO advancement with rigid internal fixation should exclude additional surgery, ie, genioplasty or maxillary surgery, and include a prospective study or randomized clinical trial design with correlation statistics.

Clinical outcome of single porcelain-fused-to-zirconium dioxide crowns: a systematic review

STATEMENT OF PROBLEM The increasing demand by patients for esthetic and metal-free restorations has driven the development of ceramic restorations with good esthetic and mechanical stability. Recent clinical studies have investigated the use of zirconium dioxide as a core material for complete crowns and computer-aided-design/computer-aided-manufacturing fabricated restorations. PURPOSE The aim of this systematic review was to evaluate the clinical survival rates of porcelain-fused-to-zirconia (PFZ) single crowns on anterior and posterior teeth and to compare them with metal ceramic (MC) crowns. MATERIAL AND METHODS A systematic search was conducted with PubMed and manual research to identify literature written in English that refers to in vivo studies published from January 1, 1950 through July 1, 2011. Clinical trials that evaluated PFZ and MC single crowns on natural teeth were selected for further analysis. Titles and/or abstracts of articles identified through the electronic searches were reviewed and evaluated for appropriateness. In addition, a hand search of relevant dental journals was peformed, and reference lists of culled articles were screened to identify publications. RESULTS The search resulted in a total of 488 initial matches. Nineteen studies with a total of 3621 crowns met the inclusion criteria. The survival rates of PFZ crowns (total 300) ranged from 92.7% to 100% for a follow-up time of 24 to 39 months, whereas those of MC crowns (total 3321) ranged from 70% to 100% for a follow-up time of 12 to 298 months. Studies that reported long-term results were found only for the MC crown group. CONCLUSIONS The scientific clinical data available to compare PFZ and MC crowns are limited. The survival rates may well be influenced by the selection and appropriate use of the veneering ceramic, and, therefore, additional prospective long-term clinical trials are necessary to draw reliable conclusions.

STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases

OBJECTIVE The steroidogenic acute regulatory protein (StAR) transports cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY disorder of sex development (DSD) and failure of pubertal development. Partial loss of StAR activity may cause adrenal insufficiency only. PATIENT A newborn girl was admitted for mild dehydration, hyponatremia, hyperkalemia and hypoglycaemia and had normal external female genitalia without hyperpigmentation. Plasma cortisol, 17OH-progesterone, DHEA-S, androstendione and aldosterone were low, while ACTH and plasma renin activity were elevated, consistent with the diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and cytogenetics revealed a 46,XX karyotype. She was treated with fluids, hydrocortisone and fludrocortisone. DESIGN, METHODS AND RESULTS Genetic studies revealed a novel homozygous STAR mutation in the 3' acceptor splice site of intron 4, c.466-1G>A (IVS4-1G>A). To test whether this mutation would affect splicing, we performed a minigene experiment with a plasmid construct containing wild-type or mutant StAR gDNA of exons-introns 4-6 in COS-1 cells. The splicing was assessed on total RNA using RT-PCR for STAR cDNAs. The mutant STAR minigene skipped exon 5 completely and changed the reading frame. Thus, it is predicted to produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis revealed that this mutant protein lacks wild-type exons 5-7 which are essential for StAR-cholesterol interaction. CONCLUSIONS STAR c.466-1A skips exon 5 and causes a dramatic change in the C-terminal sequence of the protein, which is essential for StAR-cholesterol interaction. This splicing mutation is a loss-of-function mutation explaining the severe phenotype of our patient. Thus far, all reported splicing mutations of STAR cause a severe impairment of protein function and phenotype.

Homicide-suicides compared to homicides and suicides: systematic review and meta-analysis.

Homicide-suicides, the murder of one or several individuals followed by the suicide of the perpetrator, are rare but have devastating effects on families and communities. We did a systematic review and meta-analysis of studies comparing perpetrators of homicide-suicides with perpetrators of simple homicides and suicides and examined the proportion of firearm use and its correlation with firearm availability. We searched Medline and Embase from inception to July 2012 and identified 27 eligible studies. Perpetrators of homicide-suicides were older and more likely to be male and married to or separated from their victims than perpetrator of simple homicides or suicides. Influence of alcohol and a history of domestic violence or unemployment were less prevalent in homicide-suicides than in homicides. The proportion of firearm use in homicide-suicides varied across countries and was highest in the USA, Switzerland and South Africa, followed by Australia, Canada, The Netherlands and England and Wales, with a strong correlation between the use of firearms and the level of civilian gun ownership in the country. Our results indicate that homicide-suicides represent a distinct entity, with characteristics distinguishing them both from homicides and suicides.

REVIEW ON THE DETERMINATION OF α s FROM THE QCD STATIC ENERGY

We review the determination of the strong coupling αs from the comparison of the perturbative expression for the Quantum Chromodynamics static energy with lattice data. Here, we collect all the perturbative expressions needed to evaluate the static energy at the currently known accuracy.

Social networking sites and older users - a systematic review

BACKGROUND Social networking sites can be beneficial for senior citizens to promote social participation and to enhance intergenerational communication. Particularly for older adults with impaired mobility, social networking sites can help them to connect with family members and other active social networking users. The aim of this systematic review is to give an overview of existing scientific literature on social networking in older users. METHODS Computerized databases were searched and 105 articles were identified and screened using exclusion criteria. After exclusion of 87 articles, 18 articles were included, reviewed, classified, and the key findings were extracted. Common findings are identified and critically discussed and possible future research directions are outlined. RESULTS The main benefit of using social networking sites for older adults is to enter in an intergenerational communication with younger family members (children and grandchildren) that is appreciated by both sides. Identified barriers are privacy concerns, technical difficulties and the fact that current Web design does not take the needs of older users into account. CONCLUSIONS Under the conditions that these problems are carefully addressed, social networking sites have the potential to support today's and tomorrow's communication between older and younger family members.

Differences in primary sites of infection between zoonotic and human tuberculosis: results from a worldwide systematic review.

Tuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

Indication and timing of soft tissue augmentation at maxillary and mandibular incisors in orthodontic patients. A systematic review.

OBJECTIVE To assess the indication and timing of soft tissue augmentation for prevention or treatment of gingival recession when a change in the inclination of the incisors is planned during orthodontic treatment. MATERIALS AND METHODS Electronic database searches of literature were performed. The following electronic databases with no restrictions were searched: MEDLINE, EMBASE, Cochrane, and CENTRAL. Two authors performed data extraction independently using data collection forms. RESULTS No randomized controlled trial was identified. Two studies of low-to-moderate level of evidence were included: one of prospective and retrospective data collection and one retrospective study. Both implemented a periodontal intervention before orthodontics. Thus, best timing of soft tissue augmentation could not be assessed. The limited available data from these studies appear to suggest that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontics may yield satisfactory results with respect to the development or progression of gingival recessions. However, the strength of the available evidence is not adequate in order to change or suggest a possible treatment approach in the daily practice based on solid scientific evidence. CONCLUSIONS Despite the clinical experience that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontic treatment may be a clinically viable treatment option in patients considered at risk, this treatment approach is not based on solid scientific evidence. Moreover, the present data do not allow to draw conclusions on the best timing of soft tissue augmentation when a change in the inclination of the incisors is planned during orthodontic treatment and thus, there is a stringent need for randomized controlled trials to clarify these open issues.

The canine neuronal ceroid-lipofuscinosis: a review.

The present article gives a survey over the current scientific knowledge of the canine neuronal ceroid-lipofuscinosis (NCL). NCL is a heterogenous group of lysosomal storage diseases in humans and animals. In consequence of a gene mutation, there is an accumulation of ceroid-lipofuscin in neurons, cells of the retina and the skin and other cells. The stored ceroid-lipofuscin in neurons leads to an impaired cell function and subsequently to cell death. Recently, the underlying genetic defect was discovered in several dog breeds. Genetic testing permits an ante mortem diagnosis of the disease, which up to now was only possible with a positive biopsy result. Another advantage is the identification of carrier animals to eliminate the deleterious alleles.