Experimental endocarditis following dental extractions in rats with periodontitis.

This study analyzed the development of bacterial endocarditis following dental extraction in rats with periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars, and placing the animals on a high sucrose diet. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hours later the maxillary first molars were extracted. The animals were killed 72 hours after the extractions. In rats with periodontal disease induced for 10 and 14 weeks, extractions resulted in an incidence of bacterial endocarditis of 24% and 50%, respectively, most of which were due to streptococcal species (two were caused by Staphylococcus [corrected] aureus). The difference, though not statistically significant (p = 0.10, chi 2 with Yates correction), shows a trend toward increased incidence of endocarditis with increasing severity of periodontal disease. This model demonstrates that one can reliably induce bacterial endocarditis after dental extractions in rats with periodontal disease.

Longer survival for patients with alternative lengthening of telomeres (ALT) glioblastoma multiforme is due to a less aggressive phenotype and not to improved response to adjuvant therapy

Introduction: The Alternative Lengthening of Telomeres (ALT) mechanism is a significant prognostic factor for longer survival in patients with GBM, irrespective of age. The reasons for this are unknown. We considered two possibilities; firstly that ALT identifies a subset of less aggressive GBMs, or alternatively, a group of tumours that respond more favourably to adjuvant therapy. Methods: ALT was determined by staining for ALT Associated PML Bodies (APBs) in archival tissue in a retrospective analysis of 573 GBM patients. IDH1 mutation was determined by immunohistochemistry in a subset of these. Results: We identified the presence of the telomerase-independent ALT in 15% of GBM patients and found that it correlated with survival (22% of ALT patients survive more than 2 years compared to 9% for non-ALT). This survival advantage was independent of surgery type (biopsy or full resection) and treatment (radiotherapy and chemotherapy). Interestingly ALT conferred a significant survival advantage for patients who only received surgery (13.3 months compared to 5.5 months) (19% vs 1% .2 year survival). This survival benefit was also observed in GBM patients who received surgery and radiotherapy (18.5% vs 2.4%. 2 year survival), but less so for chemotherapy (21% vs 17% . 2 year survival). For the ALT patients the fraction surviving more than 2 years did not improve significantly with adjuvant therapy. IDH1 mutation also associated with ALT. Conclusions: These data indicate ALT+ tumours are biologically distinct and associated with improved patient survival, probably due to less aggressive/invasive growth. However they respond poorly to current adjuvant treatment and therefore new therapies are urgently needed for this group.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial.

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Periodontitis crónica del adulto y alteraciones inmunitarias

El hecho de que las alteraciones inmunitarias están implicadas en la enfermedad periodontal está ampliamente recogido en la literatura. No obstante la naturaleza exacta y la implicación de las mismas no está clara. Por otro lado el empleo de la citometría de flujo ha posibilitado un avance importante en las técnicas de investigación biomédica y en el caso concreto que nos ocupa la posibilidad de determinar diferentes marcadores monoclonales en la línea celular linfocítica. Estudiamos los marcadores monoclonales (CD4, CDB, CD3 y CD19) en 15 pacientes afectados de enfermedad periodontal avanzada. Los resultados obtenidos se encuentran dentro de los límites de normalidad. Si bien no hemos obtenido datos significativos creemos que la muestra es pequeña y sería útil realizar estudios más amplios y a ser posible a nivel local. No obstante pensamos que lo novedoso es el estudio de anticuerpos monoclonales en relacióncon la enfermedad periodontal, datos que no hemos encontrado en la literatura.

Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.

Workplace Aggressive Behaviors: Three Essays

Abstract¦This thesis examines through three essays the role of the social context and of people concern for justice in explaining workplace aggressive behaviors.¦In the first essay, I argue that a work group instrumental climate - a climate emphasizing respect of organizational procedures -deters employees to manifest counterproductive work behaviors through informal sanctions (i.e., socio-emotional disapproval) they anticipate from it for misbehaving. A contrario, a work group affective climate - a climate concerned about others' well-being - leads employees to infer less informal sanctions and thus indirectly facilitates counterproductive work behaviors. I additionally expect these indirect effects to be conditional on employees' level of conscientiousness and agreeableness. Cross-level structural equations on cross-sectional data obtained from 158 employees in 26 work groups supported my expectations. By promoting collective responsibility for the respect of organizational rules and by knowing what their work group considers threatening their well-being, leaders may be able to prevent counterproductive work behaviors.¦Adopting an organizational justice perspective, the second essay provides a theoretical explanation of why and how collective deviance can emerge in a collective. In interdependent situations, employees use justice perceptions to infer others' cooperative intent. Even if moral transgressions (e.g., injustice) are ambiguous, their repetition and configuration within a team can lead employees to assign blame and develop collective cynicism toward the transgressor. Over time, collective cynicism - a shared belief about the transgressor's intentional lack of integrity - progressively constrains the diversity of employees' response to blame and leads collective deviance to emerge. This essay contributes to workplace deviance research by offering a theoretical framework for investigations of the phenomenon at the collective level. It organizations effort to manage and prevent deviance should consider.¦In the third essay, I solve an apparent contradiction in the literature showing that justice concerns sometimes lead employees to react aggressively to injustice and sometimes to refrain from it. Drawing from just-world theory, a cross-sectional field study and an experiment provide evidence that retaliatory tendencies following injustice are moderated by personal and general just-world beliefs. Whereas a high personal just-world belief facilitates retaliatory reactions to injustice, a high general just-world belief attenuates such reactions. This essay uncovers a dark side of personal just-world belief and a bright one of general just-world belief, and participates to extend just-world theory to the working context.

Melanin-based colour polymorphism signals aggressive personality in nest and territory defence in the tawny owl (Strix aluco)

Nest and territory defence are risky and potentially dangerous behaviours. If the resolution of life history trade-offs differs between individuals, the level of defence may also vary among individuals. Because melanin-based colour traits can be associated with life history strategies, differently coloured individuals may display different nest and territory defence strategies. We investigated this issue in the colour polymorphic tawny owl (Strix aluco) for which plumage varies from dark to light reddish melanic. Accordingly, we found that (1) our presence induced a greater response (flying around) from dark-coloured than light-coloured females and (2) dark reddish males suffered lower nest predation rates than light-coloured males. In experimentally enlarged broods, the probability that females reacted after we played back the hoot calls of a stranger male was higher if these females were lighter reddish; the opposite pattern was found in experimentally reduced broods with dark parents being more reactive than light parents. Finally, darker females alarmed more frequently when paired with a light than with a dark male, suggesting that partners adjust their behaviour to each other. We also tested whether colouration is used as a signal by conspecifics to adjust the level of their defensive behaviour. Accordingly, breeding females responded more vigorously to a dark than a light reddish stuffed tawny owl placed beside their nest. We conclude that melanin-based colouration is a signal of alternative nest and territory defence behaviour that depends on ecological factors.

Systematic evaluation of clinical predictors of aggressive ulcerative colitis

Background: Studies evaluating risk factors associated with an "aggressive" disease course in ulcerative colitis (UC) are scarce. A recent definition of "aggressive" UC incorporated the following characteristics: 1) high relapse rate, 2) need for surgery, 3) development of colorectal cancer, and 4) presence of extraintestinal manifestations (EIM). The following factors for an aggressive / disabling disease course in UC have been identified so far: age < 40 years at S140 Poster presentations UC diagnosis, pancolitis, concomitant primary sclerosing cholangitis, and deep ulcerations of the colonic mucosa. We aimed to evaluate risk factors for an "aggressive" disease course in UC patients. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (80%), regional hospitals (19%), and private practices (1%). We applied the following definition for "aggressive" UC: 1) patients ever treated with TNFantagonists or calcineurin inhibitors (tacrolimus / cyclosporine), and 2) need for (procto)-colectomy. Non-normal data are presented as median and interquartile range [IQR].

Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.

Moral Disengagement in the Legitimation and Realization of Aggressive Behaviors in Soccer and Ice Hockey

The aim of the present study was to test the effect of moral disengagement on the tolerance and realization of aggressive acts in male soccer and ice hockey players in Switzerland. One hundred and four soccer and 98 ice hockey players evaluated the legitimacy of four videotaped aggressive behaviors and completed a questionnaire that included a moral disengagement scale and self-reported aggression. The level of moral disengagement, which mediates the effects of perceived coach and ego attitudes toward transgressions, largely explains the tolerance of hostile aggression within teams, as well as the level of high aggressive acts reported by the participants.

The role of executive functions in the control of aggressive behavior

An extensive literature suggests a link between executive functions and aggressive behavior in humans, pointing mostly to an inverse relationship, i.e., increased tendencies toward aggression in individuals scoring low on executive function tests. This literature is limited, though, in terms of the groups studied and the measures of executive functions. In this paper, we present data from two studies addressing these issues. In a first behavioral study, we asked whether high trait aggressiveness is related to reduced executive functions. A sample of over 600 students performed in an extensive behavioral test battery including paradigms addressing executive functions such as the Eriksen Flanker task, Stroop task, n-back task, and Tower of London (TOL). High trait aggressive participants were found to have a significantly reduced latency score in the TOL, indicating more impulsive behavior compared to low trait aggressive participants. No other differences were detected. In an EEG-study, we assessed neural and behavioral correlates of error monitoring and response inhibition in participants who were characterized based on their laboratory-induced aggressive behavior in a competitive reaction time task. Participants who retaliated more in the aggression paradigm and had reduced frontal activity when being provoked did not, however, show any reduction in behavioral or neural correlates of executive control compared to the less aggressive participants. Our results question a strong relationship between aggression and executive functions at least for healthy, high-functioning people.

Interactions between genes and alcohol on aggressive behavior and anger related traits : the oxytocin receptor gene as a candidate

Alkoholberusning är en av de starkaste riskfaktorerna för aggressivt beteende. Alla individer blir dock inte aggressiva under alkoholberusning. I sin doktorsavhandling undersökte Johansson ifall individens genetiska uppsättning kan förklara skillnader i vem som reagerar på alkohol med ökat aggressivt beteende och ilska och vem som inte gör det. Resultaten visade att individer som är bärare av en viss variant av genen som kodar för oxytocinets receptorer är i högre grad benägna att uppvisa aggressivt beteende än andra när de är alkoholberusade. Sambandet mellan alkohol och ilska påverkades även av individens genetiska uppsättning av två oxytocinreceptorgenvarianter, vilket antyder att dessa genvarianter även påverkar benägenheten att känna ilska under alkoholberusning. Oxytocinet, som fungerar både som ett hormon och en neurotransmittor, har i tidigare studier visats ha breda effekter på sociala förmågor hos människan, såsom förmåga till igenkännande av andras känslouttryck. Resultaten är de första att hos människan experimentellt påvisa att vissa individer beter sig mer aggressivt än andra när de är berusade, beroende på individens genetiska uppsättning. ”Det är viktigt att komma ihåg att genens effekt i det här fallet inte är av en sådan natur att den direkt och ofrånkomligen orsakar aggressivt beteende. Med andra ord är det orimligt i detta fall att tänka att en individ skulle tillmätas ansvarsfrihet i exempelvis ett våldsbrottmål om hon bär på en viss variant av denna gen”, påpekar Johansson. Oxytocinreceptorgenens effekter analyserades i två olika urval. I ett experimentellt upplägg indelades 116 män slumpässigt i två grupper: en grupp som tilldelades alkoholhaltiga drycker, och en kontrollgrupp som tilldelades alkoholfria drycker. Aggressivt beteende mättes med ett laboratorietest där försökspersonerna fick bestraffa en fiktiv motspelare genom att spela upp motbjudande ljud för denne. Resultaten replikerades i ett populationsbaserat urval av män och kvinnor (n = 3755) vilka besvarat frågor om deras aggressiva beteenden, ilska, och alkoholanvändning.