Use of antibiotic spacers for knee endoprosthesis infections treatment

OBJCTIVE: The aim of this study is to evaluate the use of cement spacers impregnated with antibiotics for the treatment of infections in the nonconventional endoprostheses of the knee. METHODOLOGY: We have treated seven patients since 2004 (of which six were submitted to surgery in our service and one patient had been submitted to a primary tumor surgery in another removal service) with deep infection in knee tumor prosthesis. All patients were submitted to endoprosthesis removal and reconstructed with antibiotic cement spacer. All patients were monitored both clinically and by lab tests as for monitoring the evolution, being considered able for reviews after 6 (six) months without infections signs. RESULTS: We have noted a small predominance of infectious processes on the prosthesis inserted on proximal tibia as compared with distal femur (57.1% x 42.9%). The mean follow-up time of patients was 68.2 months. During the follow up, one patient died as a result of the root disease. Six patients out of seven were regarded as cured and one persisted with infection signs and symptoms. CONCLUSION: The results obtained up to date have motivated us to continue using this method of treatment.OBJETIVO: O objetivo do estudo é avaliar a utilização dos espaçadores de cimento acrílico com antibiótico no tratamento das infecções em endopróteses não convencionais de joelho. MÉTODO: Desde de 2004 foram tratados sete pacientes (seis pacientes operados no nosso serviço e um paciente que havia sido submetido a cirurgia primária do tumor em outro serviço) com infecção peri-endoprótese não convencional de joelho. Todos pacientes foram submetidos a retirada da endoprótese e reconstrução com espaçador com cimento acrílico com antibiótico. Todos os pacientes foram monitorados clínica e laboratorialmente quanto ao controle da evolução, sendo considerados aptos para a revisão e recolocação de endoprótese após 06 (seis) meses sem sinais infecciosos RESULTADOS: Notamos um discreto predomínio do do processo infeccioso nas próteses realizadas na tíbia proximal em comparação com o fêmur distal (57,1% x 42,9%). O seguimento médio dos pacientes foi 68,2 meses. Durante o seguimento, um paciente faleceu devido a doença de base. Dos sete pacientes, 6 foram considerados curados e um persistiu com sinais e sintomas de infecção. CONCLUSÃO: Os resultados obtidos até o momento tem motivado a continuidade deste método de tratamento.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaSciEL

TRIM16 Acts as an E3 Ubiquitin Ligase and Can Heterodimerize with Other TRIM Family Members

The TRIM family of proteins is distinguished by its tripartite motif (TRIM). Typically, TRIM proteins contain a RING finger domain, one or two B-box domains, a coiled-coil domain and the more variable C-terminal domains. TRIM16 does not have a RING domain but does harbour two B-box domains. Here we showed that TRIM16 homodimerized through its coiled-coil domain and heterodimerized with other TRIM family members; TRIM24, Promyelocytic leukaemia (PML) protein and Midline-1 (MID1). Although, TRIM16 has no classic RING domain, three-dimensional modelling of TRIM16 suggested that its B-box domains adopts RING-like folds leading to the hypothesis that TRIM16 acts as an ubiquitin ligase. Consistent with this hypothesis, we demonstrated that TRIM16, devoid of a classical RING domain had auto-polyubiquitination activity and acted as an E3 ubiquitin ligase in vivo and in vitro assays. Thus via its unique structure, TRIM16 possesses both heterodimerization function with other TRIM proteins and also has E3 ubiquitin ligase activity

Social interaction style of children and adolescents with high-functioning autism spectrum disorder

Qualitative differences in social interaction style exist within the autism spectrum. In this study we examined whether these differences are associated with (1) the severity of autistic symptoms and comorbid disruptive behavior problems, (2) the child's psycho-social health, and (3) executive functioning and perspective taking skills. The social interaction style of 156 children and adolescents (6-19 years) with high-functioning autism spectrum disorder (HFASD) was determined with the Wing Subgroups Questionnaire. An active-but-odd social interaction style was positively associated with symptoms of autism, attention deficit and hyperactivity. Furthermore, an active-but-odd social interaction style was negatively associated with children's psycho-social health and positively with executive functioning problems. Social interaction style explains part of the heterogeneity among children with HFASD

Monoterpene Variation Mediated Attack Preference Evolution of the Bark Beetle Dendroctonus valens

Several studies suggest that some bark beetle like to attack large trees. The invasive red turpentine beetle (RTB), Dendroctonus valens LeConte, one of the most destructive forest pests in China, is known to exhibit this behavior. Our previous study demonstrated that RTBs preferred to attack large-diameter trees (diameter at breast height, DBH ≥30 cm) over small-diameter trees (DBH ≤10 cm) in the field. In the current study, we studied the attacking behavior and the underlying mechanisms in the laboratory. Behavioral assays showed that RTBs preferred the bark of large-DBH trees and had a higher attack rate on the bolts of these trees. Y-tube assays showed that RTBs preferred the volatiles released by large-DBH trees to those released by small-DBH trees. Subsequent analysis revealed that both large- and small-DBH trees had the same composition of monoterpenes, but the concentration of each component differed; thus it appeared that the concentrations acted as cues for RTBs to locate the right-sized host which was confirmed by further behavioral assays. Moreover, large-DBH pine trees provided more spacious habitat and contained more nutrients, such as nitrogen, than did small-DBH pine trees, which benefited RTBs' fecundity and larval development. RTBs seem to have evolved mechanisms to locate those large hosts that will allow them to maximize their fitness. Monoterpene variation mediated attack preference implies the potential for the management of RTB

Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection

Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection

Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease

Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling synaptic exocytosis. Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes, leading to the formation of a protein-conducting channel. The ∼50 kDa light chain (LC) protease is translocated into the cytosol by the ∼100 kDa heavy chain (HC), which consists of two modules: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD). Here we exploited the BoNT modular design to identify the minimal requirements for channel activity and LC translocation in neurons. Using the combined detection of substrate proteolysis and single-channel currents, we showed that a di-modular protein consisting only of LC and TD was sufficient to translocate active protease into the cytosol of target cells. The RBD is dispensable for cell entry, channel activity, or LC translocation; however, it determined a pH threshold for channel formation. These findings indicate that, in addition to its individual functions, each module acts as a chaperone for the others, working in concert to achieve productive intoxication

Group II Intron-Anchored Gene Deletion in Clostridium

Clostridium plays an important role in commercial and medical use, for which targeted gene deletion is difficult. We proposed an intron-anchored gene deletion approach for Clostridium, which combines the advantage of the group II intron “ClosTron” system and homologous recombination. In this approach, an intron carrying a fragment homologous to upstream or downstream of the target site was first inserted into the genome by retrotransposition, followed by homologous recombination, resulting in gene deletion. A functional unknown operon CAC1493–1494 located in the chromosome, and an operon ctfAB located in the megaplasmid of C. acetobutylicum DSM1731 were successfully deleted by using this approach, without leaving antibiotic marker in the genome. We therefore propose this approach can be used for targeted gene deletion in Clostridium. This approach might also be applicable for gene deletion in other bacterial species if group II intron retrotransposition system is established

The direction of effects between perceived parental behavioral control and psychological control and adolescents’ self-reported GAD and SAD symptoms

This study examined the direction of effects and age and sex differences between adolescents’ perceptions of parental behavioral and psychological control and adolescents’ self-reports of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) symptoms. The study focused on 1,313 Dutch adolescents (early-to-middle cohort n = 923, 70.3%; middle-to-late cohort n = 390, 29.7%) from the general population. A multi-group, structural equation model was employed to analyze the direction of the effects between behavioral control, psychological control and GAD and SAD symptoms for the adolescent cohorts. The current study demonstrated that a unidirectional child effect model of the adolescents’ GAD and SAD symptoms predicting parental control best described the data. Additionally, adolescent GAD and SAD symptoms were stronger and more systematically related to psychological control than to behavioral control. With regard to age–sex differences, anxiety symptoms almost systematically predicted parental control over time for the early adolescent boys, whereas no significant differences were found between the late adolescent boys and girls