Peripheral snap-fit locking mechanisms and smooth surface finish of tibial trays reduce backside wear in fixed-bearing total knee arthroplasty

Background and purpose — Severe backside wear, observed in older generations of total knee replacements (TKRs), led to redesign of locking mechanisms to reduce micromotions between tibial tray and inlay. Since little is known about whether this effectively reduces backside wear in modern designs, we examined backside damage in retrievals of various contemporary fixed-bearing TKRs.

Patients and methods — A consecutive series of 102 inlays with a peripheral (Stryker Triathlon, Stryker Scorpio, DePuy PFC Sigma, Aesculap Search Evolution) or dovetail locking mechanism (Zimmer NexGen, Smith and Nephew Genesis II) was examined. Articular and backside surface damage was evaluated using the semiquantitative Hood scale. Inlays were examined using scanning electron microscopy (SEM) to determine backside wear mechanisms.

Results — Mean Hood scores for articular (A) and backside (B) surfaces were similar in most implants—Triathlon (A: 46, B: 22), Genesis II (A: 55, B: 24), Scorpio (A: 57, B: 24), PFC (A: 52, B: 20); Search (A: 56, B: 24)—except the NexGen knee (A: 57, B: 60), which had statistically significantly higher backside wear scores. SEM studies showed backside damage caused by abrasion related to micromotion in designs with dovetail locking mechanisms, especially in the unpolished NexGen trays. In implants with peripheral liner locking mechanism, there were no signs of micromotion or abrasion. Instead, “tray transfer” of polyethylene and flattening of machining was observed.

Interpretation — Although this retrieval study may not represent well-functioning TKRs, we found that a smooth surface finish and a peripheral locking mechanism reduce backside wear in vivo, but further studies are required to determine whether this actually leads to reduced osteolysis and lower failure rates.     

Genotoxicity and mutagenicity induced by acute crack cocaine exposure in mice

Context: Crack cocaine is an illicit drug derived from cocaine, in which use and abuse have increased around the world, especially in developing countries. Objectives: The aim of this study was to evaluate genomic damage in multiple organs of mice following acute exposure to crack cocaine. For this purpose, single cell gel (comet) assay in peripheral blood, liver, kidney, and brain cells was performed and micronucleus test for bone narrow and liver cells was also made in this setting. Material and methods: A total of 20 C57BL/10 male mice were distributed into four groups, as follows: 0, 4.5, 9, and 18?mg/kg b.w. of crack cocaine dissolved to 1% dimethyl sulfoxide by intraperitoneal (i.p.) route. All animals were sacrificed 24?h after i.p. injection. Results: The results showed that crack cocaine induced DNA damage in peripheral blood, and brain cells for higher doses used as depicted by single cell gel (comet) assay data. Analysis of kidney cells showed no genetic damage for all groups tested. The number of micronucleated cells did not increase after crack cocaine exposure in bone narrow or liver cells. Conclusion: In summary, crack cocaine is a genotoxic agent in peripheral blood, liver, and brain cells but not mutagenic in multiple organs of mice.     

Patterns and Motives for Electronic Cigarette Use in a Sample of Community-Recruited Gamblers

Many smokers are replacing tobacco with electronic cigarettes (e-cigarettes) or are engaging in dual-use. Evidence indicates that smoking rates are higher amongst gamblers; however, the extent to which gamblers use e-cigarettes is unknown. The current study examined rates of e-cigarette use in gamblers, identified associations between e-cigarette use and gambling, and assessed motives for e-cigarette use during gambling. A community-recruited sample of gamblers (N = 564) completed questionnaires on e-cigarettes, smoking, and gambling. ‘Ever use’ of e-cigarettes was 38.7% with 17.6% reporting ‘past 30-day use’. Furthermore, 11.9% used e-cigarettes while gambling in the past 12 months. Regression analyses for ‘past 30-day use’ revealed that occasional smoking, gambling severity, and number of gambling activities were associated with the highest odds of use. Reasons for use while gambling included: relaxation/stress, nicotine dependence and legal in casinos. These findings suggest e-cigarette use is common in gamblers and may be used to circumvent casino smoking bans.     

The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL‐12/23. The aim of this paper was to evaluate the efficacy of the anti‐IL12/23 therapy in seven psoriatic patients by assessing changes in the values of psoriasis area and severity index (PASI), dermatology life quality index (DLQI), body surface area (BSA) indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40‐week long observation periods. The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during Stage I for values of PASI (p = 0.0134), DLQI (p = 0.01299), BSA (p = 0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B. In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy.     

Assessment of transcriptional activity genes associated with the IL‐17 signaling pathway in skin fibroblasts under the influence of adalimumab

It is believed that IL‐17 is involved in the signaling pathways of nuclear factor κB (NFκB) and mitogen‐activated kinases (MAPKs). Adalimumab, a full anti‐TNF‐α monoclonal antibody, was used for treatment of moderate to severe psoriasis. This study aimed to investigate the effect of adalimumab on changes in the expression of genes associated with IL‐17 signaling pathways in normal human dermal fibroblast (NHDF) culture. NHDFs treated with adalimumab at 2, 8, and 24 hr were compared with those of control. Microarray technique and PANTHER program were used to determine the expression of genes. The number of mRNA IDs differentiating the culture displayed on adalimumab in comparison with the control culture (?3.0 < FC > + 3.0) was as follows: H‐2—32 mRNA ID, H‐8—3 mRNA ID, H‐2 and H‐8—47 mRNA ID, H‐8 and H‐24—1 mRNA ID. Analysis by the PANTHER program indicated that adalimumab significantly affects the six signaling pathways and 19 biological processes associated with IL‐17. The strongest changes in the expression profile concerned pathway genes associated with the chemokine and cytokine signaling pathway, the gonadotropin‐releasing hormone receptor pathway, and the CCKR signaling map.     

Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks

We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow-derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC-CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow-derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population.     

Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate

OBJECTIVES:

To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of São Paulo Medical School, Brazil.

METHODS:

Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of São Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients'' sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1.

RESULTS:

No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25%) and 4 of 9 patients with pemphigus foliaceus (44%) had positive indirect immunofluorescence using rat bladder epithelium as a substrate.

CONCLUSION:

Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.