Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens

We explored the host-pathogen interactions of the human opportunistic fungus Candida albicans using Drosophila melanogaster. We established that a Drosophila strain devoid of functional Toll receptor is highly susceptible to the human pathogen C. albicans. Using this sensitive strain, we have been able to show that a set of specific C. albicans mutants of different virulence in mammalian infection models are also impaired in virulence in Drosophila and remarkably display the same rank order of virulence. This immunodeficient insect model also revealed virulence properties undetected in an immunocompetent murine model of infection. The genetic systems available in both host and pathogen will enable the identification of host-specific components and C. albicans genes involved in the host-fungal interplay.

The role of self-monitoring of blood glucose in patients treated with SGLT-2 inhibitors: a European expert recommendation.

The role for the novel treatment approach of sodium-glucose cotransporter-2 (SGLT-2) in type 2 diabetes is increasing. Structured self-monitoring of blood glucose (SMBG), based on a less intensive and a more intensive scheme, may contribute to an optimization of SGLT-2 inhibitor based treatment. The current expert recommendation suggests individualized approaches of SMBG, using simple and clinically applicable schemes. Potential benefits of SMBG in SGLT-2 inhibitor based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and education. The length and frequency of SMBG should depend on the clinical setting and the quality of metabolic control.

Perceptions of critical situations involving football fans: the dynamics of conflict escalation or de-escalation

Fan violence in the context of football matches has drawn the attention of stakeholders and the media. This phenomenon has also attracted the scientific community’s attention, where research mostly focused on reasons for violence escalation. The Elaborated Social Identity Model (ESIM; Drury & Reicher, 2000) for example focuses on group-interactions and social identities, while the Aggravation Mitigation Model (AM model; Hylander & Guvå, 2010) concentrates on factors contributing to an escalation or a non-escalation of group-violence. However individual perceptions of the different persons involved in potential conflicts have not been sufficiently examined. Beside of that research in domestic football or involving ultrafans is scarce. Especially in Switzerland, there is a lack of research concerning the dynamics of the development or non-development of fan violence. This exploratory study included eight critical situations from the season 2012/2013 of the Swiss premier league to gather data about the perceptions of various persons involved (fans, police officers or security) and the dynamics contributing towards escalation or de-escalation. Fifty-nine narrative interviews were conducted and analysed with interpretative phenomenological analysis (Smith, Flowers, & Larkin, 2009). The individuals involved (fans, police and security personnel) showed groupspecific perceptions and a tendency to stereotype the opponent group. Provocative symbols (balaclavas or riot-gear uniforms) were important for the interpretation of the situation. No escalation occurred when successful communication and sufficient distance between the groups was established. Knowledge about the local fan culture is important, because it influences the perception of legitimacy on the side of the fans. This study improves the understanding of fan violence and is congruent with the ESIM and the AM model. It is suggested to deploy police dialogue teams without riot gear. Their task is to establish direct communication with the fans to facilitate a peaceful ending of a critical situation.

Identifying observable criteria defining a critical situation involving football fans: an expert focus group study

Critical situations (CSs) involving football fans is a well-researched phenomenon with most studies examining factors leading to an escalation of violence (e.g. Braun & Vliegenthart, 2008). However, research so far has fallen short of analysing CSs that do not escalate (e.g. Hylander & Guvå, 2010) as well as establishing observable criteria that constitute such CSs. Granström et al. (2009), for instance, put forward a definition of a CS describing such situations as characterised by a discrepancy between peace and war-making behaviours between police and demonstrators. Still, this definition remains vague and does not provide concrete, defining criteria that can be identified on site. The present study looks beyond fans’ violent acts per se and focuses on these situations with a potentially – but not necessarily - violent outcome. The aim of this preliminary study is to identify observable criteria defining such a CS involving football fans. This focus group comprised of five experts working with football fans in the German-speaking area of Switzerland who discussed observable characteristics of a CS. Inductive content analysis led to the identification of specific criteria such as, “arrest of a fan”, “insufficient distance (<30m) between fans and police” and “fans mask themselves”. These criteria were then assigned to four phases of a CS highlighting the dynamic aspect of this phenomenon: Antecedents, Causes, Reactions, Consequence. Specifically, Causes, Reactions and Consequences are observable on site, while Antecedents include relevant, background information directly influencing a CS. This study puts forward a working definition of a CS that can facilitate the assessment of actual situations in the football context as well as for further research on fan violence prevention and control. These results also highlight similarities with studies investigating fan violence in other European countries while acknowledging unique characteristics of the Swiss German fan culture.

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America.

OBJECTIVES Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). DESIGN AND METHODS Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. RESULTS Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). CONCLUSIONS In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.

Visualization of cell microtubules in their native state.

BACKGROUND INFORMATION Over the past decades, cryo-electron microscopy of vitrified specimens has yielded a detailed understanding of the tubulin and microtubule structures of samples reassembled in vitro from purified components. However, our knowledge of microtubule structure in vivo remains limited by the chemical treatments commonly used to observe cellular architecture using electron microscopy. RESULTS We used cryo-electron microscopy and cryo-electron tomography of vitreous sections to investigate the ultrastructure of microtubules in their cellular context. Vitreous sections were obtained from organotypic slices of rat hippocampus and from Chinese-hamster ovary cells in culture. Microtubules revealed their protofilament ultrastructure, polarity and, in the most favourable cases, molecular details comparable with those visualized in three-dimensional reconstructions of microtubules reassembled in vitro from purified tubulin. The resolution of the tomograms was estimated to be approx. 4 nm, which enabled the detection of luminal particles of approx. 6 nm in diameter inside microtubules. CONCLUSIONS The present study provides a first step towards a description of microtubules, in addition to other macromolecular assemblies, in an unperturbed cellular context at the molecular level. As the resolution appears to be similar to that obtainable with plunge-frozen samples, it should allow for the in vivo identification of larger macromolecular assemblies in vitreous sections of whole cells and tissues.

Nasolabial symmetry and esthetics in cleft lip and palate: analysis of 3D facial images

OBJECTIVES To determine the relationship between nasolabial symmetry and esthetics in subjects with orofacial clefts. MATERIAL AND METHODS Eighty-four subjects (mean age 10 years, standard deviation 1.5) with various types of nonsyndromic clefts were included: 11 had unilateral cleft lip (UCL); 30 had unilateral cleft lip and alveolus (UCLA); and 43 had unilateral cleft lip, alveolus, and palate (UCLAP). A 3D stereophotogrammetric image of the face was taken for each subject. Symmetry and esthetics were evaluated on cropped 3D facial images. The degree of asymmetry of the nasolabial area was calculated based on all 3D data points using a surface registration algorithm. Esthetic ratings of various elements of nasal morphology were performed by eight lay raters on a 100 mm visual analog scale. Statistical analysis included ANOVA tests and regression models. RESULTS Nasolabial asymmetry increased with growing severity of the cleft (p = 0.029). Overall, nasolabial appearance was affected by nasolabial asymmetry; subjects with more nasolabial asymmetry were judged as having a less esthetically pleasing nasolabial area (p < 0.001). However, the relationship between nasolabial symmetry and esthetics was relatively weak in subjects with UCLAP, in whom only vermilion border esthetics was associated with asymmetry. CONCLUSIONS Nasolabial symmetry assessed with 3D facial imaging can be used as an objective measure of treatment outcome in subjects with less severe cleft deformity. In subjects with more severe cleft types, other factors may play a decisive role. CLINICAL SIGNIFICANCE Assessment of nasolabial symmetry is a useful measure of treatment success in less severe cleft types.

Gingival labial recessions and the post-treatment proclination of mandibular incisors

INTRODUCTION A prerequisite for development of gingival recession is the presence of alveolar bone dehiscence. Proclination of mandibular incisors can result in thinning of the alveolus and dehiscence formation. OBJECTIVE To assess an association between proclination of mandibular incisor and development of gingival recession. METHODS One hundred and seventeen subjects who met the following inclusion criteria were selected: 1. age 11-14 years at start of orthodontic treatment (TS), 2. bonded retainer placed immediately after treatment (T0), 3. dental casts and lateral cephalograms available pre-treatment (TS), post-treatment (T0), and 5 years post-treatment (T5), and 4. post-treatment (T0) lower incisor inclination (Inc_Incl) <95° or >100.5°. Two groups were formed: non-proclined (N = 57; mean Inc_Incl = 90.8°) and proclined (N = 60; mean Inc_Incl = 105.2°). Clinical crown heights of mandibular incisors and the presence of gingival recession sites in this region were assessed on plaster models. Fisher's exact tests, t-tests, and regression models were computed for analysis of inter-group differences. RESULTS The mean increase of clinical crown heights (from T0 to T5) of mandibular incisors ranged from 0.75 to 0.83mm in the non-proclined and proclined groups, respectively (P = 0.273). At T5, gingival recession sites were present in 12.3% and 11.7% patients from the non-proclined and proclined groups, respectively. The difference was also not significant (P = 0.851). CONCLUSIONS The proclination of mandibular incisors did not increase a risk of development of gingival recession during five-year observation in comparison non-proclined teeth.

Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases.

Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology.

Dynamics of critical incidents with potentially violent outcomes involving ultra fans: an explorative study

This study examines incidents involving a tense atmosphere combined with higher risk of football fan violence. A systematic description of such critical incidents (CIs) identifying their risk factors and warning signs is yet lacking. This study looks beyond fans’ violent acts per se and focuses on CIs involving ultra fans with a potentially – but not necessarily – violent outcome. A preliminary study involving a focus group was conducted followed by a main study including eight case studies. The focus group comprised five professionals working with football fans who discussed CIs’ observable characteristics. Risk factors and warning signs were coded using content analysis, such as, ‘arrest of a fan’. In the main study, people involved in actual CIs were interviewed to explore these phenomena in more depth. An integrated model of CIs’ dynamics, risk factors and warning signs was compiled using data gathered in both studies.

Evaluation of an inventory for the assessment of critical incidents involving football fans

Introduction: Fan violence is a frequent occurrence in Swiss football (Bundesamt für Polizei, 2015) leading to high costs for prevention and control (Mensch & Maurer, 2014). Various theories put forward an explanation of fan violence, such as the Elaborated Social Identity Model (Drury & Reicher, 2000)and the Aggravation Mitigation Model (Hylander & Guvå, 2010). Important observations from these theories are the multi-dimensional understanding of fan violence and the Dynamics occurring in the fan group. Nevertheless, none of them deal with critical incidents (CIs) which involve a tense atmosphere combined with a higher risk of fan violence. Schumacher Dimech, Brechbühl and Seiler (2015) tackled this gap in research and explored CIs where 43 defining criteria were identified and compiled in an integrated model of CIs. The defining criteria were categorised in four higher-order themes “antecedents” (e.g. a documented history of fan rivalry), “triggers” (e.g. the arrest of a fan), “reactions” (e.g. fans masking themselves) and “consequences” (e.g. fans avoiding communication with fan social workers). Methods: An inventory based on this model is being developed including these 43 criteria. In an exploratory phase, this inventory was presented as an online questionnaire and was completed by 143 individuals. Three main questions are examined: Firstly, the individual items are tested using descriptive analyses. An item analysis is conducted to test reliability, item difficulty and discriminatory power. Secondly, the model’s four higher-order themes are tested using exploratory factor analysis (EFA). Thirdly, differences between sub -groups are explored, such as gender and age-related differences. Results: Respondents rated the items’ importance as high and the quota of incomplete responses was not systematic. Two items were removed from the inventory because of low mean or a high rate of “don’t know”-responses. EFA produced a six-factor solution grouping items into match-related factors, repressive measures, fans’ delinquent behaviour, intra-group behaviour, communication and control and inter-group factors. The item “fans consume alcohol” could not be ordered into any category but was retained since literature accentuates this factor’s influence on fan violence. Analyses examining possible differences between groups are underway. Discussion: Results exploring the adequacy of this inventory assessing defining criteria of CIs in football are promising and thus further evaluative investigation is recommended. This inventory can be used in two ways: as a standardised instrument of assessment for experts evaluating specific CIs and as an instrument for exploring differences in perception and assessment of a CI e.g. gender and age differences, differences between interest groups and stakeholders.

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study

BACKGROUND Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. METHODS Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. FINDINGS Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). INTERPRETATION Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. FUNDING EU Seventh Framework Programme.