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  • Patel posted an update 9 months ago

    We discuss the crucial roles of nanoscale actin dynamics in both nascent and mature spines, which may differ fundamentally in the organization of actin filaments. Combined with the progress in the mathematical simulation of spine actin dynamics, realistic modeling of spine nanostructure based on the dynamic organization of actin filaments will become possible. The models will promote our understanding of the complex interaction between the structure, function, and signaling of dendritic spines.Hyaluronic acid (HA) dermal fillers are produced by crosslinking HA with agents, such as 1,4-butanediol diglycidyl ether (BDDE) and poly (ethylene glycol) diglycidyl ether (PEGDE) to acquire desired properties. Thus, the safety evaluation of these crosslinkers is needed at the cellular level. In the present study, cell viability, cytotoxicity, membrane integrity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory responses were evaluated in the human keratinocyte cell line, HaCaT and human dermal fibroblast cell line, HDF in response to treatment with the crosslinkers. In both the cell lines, BDDE significantly decreased cell viability at 100-1000 ppm, while PEGDE showed a decrease at 500-1000 ppm. In HaCaT cells, BDDE markedly increased cytotoxicity (lactate dehydrogenase release) at 100-1000 ppm, but PEGDE showed an increase at 500-1000 ppm. Cells treated with BDDE (100 ppm) caused alteration in the integrity of cell membrane and shape. In both the cell lines, BDDE-treated cells showed significantly higher ROS levels and MMP loss than PEGDE-treated cells. Also, BDDE-treated cells exhibited higher COX-2 expression at 100 ppm. Expression of inflammatory cytokines (TNF-α, and IL-1 β) was higher in BDDE-treated cells. Taken together, PEGDE-treated cells showed markedly lower cytotoxicity, ROS production, and inflammatory responses than BDDE-treated cells. Our data suggest that PEGDE is safer than BDDE as a crosslinker in HA dermal fillers.Tendons have a uniaxially aligned structure with a hierarchical organization of collagen fibrils crucial for tendon function. Collagen XII is expressed in tendons and has been implicated in the regulation of fibrillogenesis. It is a non-fibrillar collagen belonging to the Fibril-Associated Collagens with Interrupted Triple Helices (FACIT) family. Mutations in COL12A1 cause myopathic Ehlers Danlos Syndrome with a clinical phenotype involving both joints and tendons supporting critical role(s) for collagen XII in tendon development and function. Here we demonstrate the molecular function of collagen XII during tendon development using a Col12a1 null mouse model. Col12a1 deficiency altered tenocyte shape, formation of interacting cell processes, and organization resulting in impaired cell-cell communication and disruption of hierarchal structure as well as decreased tissue stiffness. Immuno-localization revealed that collagen XII accumulated on the tenocyte surface and connected adjacent tenocytes by building matrix bridges between the cells, suggesting that collagen XII regulates intercellular communication. In addition, there was a decrease in fibrillar collagen I in collagen XII deficient tenocyte cultures compared with controls suggesting collagen XII signaling specifically alters tenocyte biosynthesis. This suggests that collagen XII provides feedback to tenocytes regulating extracellular collagen I. Together, the data indicate dual roles for collagen XII in determination of tendon structure and function. Through association with fibrils it functions in fibril packing, fiber assembly and stability. In addition, collagen XII influences tenocyte organization required for assembly of higher order structure; intercellular communication necessary to coordinate long range order and feedback on tenocytes influencing collagen synthesis. Integration of both regulatory roles is required for the acquisition of hierarchal structure and mechanical properties.

    The management of prosthetic joint infection requires a complex treatment procedure and can be associated with complications. However, the occurrence of severe adverse events during this intervention has been poorly evaluated.

    A 5-year multicentric retrospective study including patients from 3 hospitals in the South-Western France referral center for complex bone and joint infections (Crioac GSO) and treated for hip or knee prosthetic joint infection with 1 or 2-stage implant exchanges. The objective was to describe grade≥3 adverse events, according to the CTCAE classification, occurring within 6 weeks after surgery and to identify their associated factors.

    One hundred and eighteen patients were identified. We observed 71 severe events in 50 patients (42.3%; 95% confidence interval [CI95%] 33.8-51.4%). Sixteen severe events were an evolution of the infection. The remaining 55 others (47 grade 3 and 8 grade 4) occurred in 41 patients (34.7%; CI95% 26.8-43.7%). They were distributed as follows 27 (49.1%) medical complications, 21 (38.2%) surgical complications and 7 (12.7%) antibiotic-related complications. The main identified risk factor was a two-stage prosthetic exchange with OR=3.6 (CI95% [1.11-11.94], P=0.032). Obesity was limit of significance with OR=3.3 (CI95% [0.9-12.51], P=0.071). Infection with coagulase negative Staphylococcus was a protective factor with OR=0.3 (CI95% [0.12-0.99], P=0.047).

    Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange.

    Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange.

    Microbiological tests are required for individuals on HIV Pre-Exposure Prophylaxis (PrEP), but their real-life numbers, types and cost are poorly described.

    Number, type, and results of microbiological tests performed in a Besançon Hospital-associated laboratory, France, from 2016 to 2019, in the setting of PrEP consultations were retrospectively collected. (R,S)-3,5-DHPG price Costs were estimated by the current reimbursement rate set by the French national protection system.

    756 consultations for PrEP initiation or follow-up of 135 persons were performed over 4 years. Among 3434 tests performed in the institution-associated laboratory, 1083 and 2351 were virological and bacteriological tests, respectively. Serology was predominant in virology (98% of virological tests), with HIV, HCV, and HBV screening as the 3 more frequent assays, whereas molecular biology was predominant in bacteriology (63.1% of bacteriological tests) with N.gonorrhoeae and C.trachomatis screening as leader assays. Agar-based culture accounted for 1% of bacterial tests.

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