Az onkokardiológiai ellátás új irányelvei

K

Natterin-Induced Neutrophilia Is Dependent on cGAS/STING Activation via Type I IFN Signaling Pathway

Natterin is a potent pro-inflammatory fish molecule, inducing local and systemic IL-1β/IL-1R1-dependent neutrophilia mediated by non-canonical NLRP6 and NLRC4 inflammasome activation in mice, independent of NLRP3. In this work, we investigated whether Natterin activates mitochondrial damage, resulting in self-DNA leaks into the cytosol, and whether the DNA sensor cGAS and STING pathway participate in triggering the innate immune response. Employing a peritonitis mouse model, we found that the deficiency of the tlr2/tlr4, myd88 and trif results in decreased neutrophil influx to peritoneal cavities of mice, indicative that in addition to MyD88, TRIF contributes to neutrophilia triggered by TLR4 engagement by Natterin. Next, we demonstrated that gpcr91 deficiency in mice abolished the neutrophil recruitment after Natterin injection, but mice pre-treated with 2-deoxy-d-glucose that blocks glycolysis presented similar infiltration than WT Natterin-injected mice. In addition, we observed that, compared with the WT Natterin-injected mice, DPI and cyclosporin A treated mice had a lower number of neutrophils in the peritoneal exudate. The levels of dsDNA in the supernatant of the peritoneal exudate and processed IL-33 in the supernatant of the peritoneal exudate or cytoplasmic supernatant of the peritoneal cell lysate of WT Natterin-injected mice were several folds higher than those of the control mice. The recruitment of neutrophils to peritoneal cavity 2 h post-Natterin injection was intensely impaired in ifnar KO mice and partially in il-28r KO mice, but not in ifnγr KO mice. Finally, using cgas KO, sting KO, or irf3 KO mice we found that recruitment of neutrophils to peritoneal cavities was virtually abolished in response to Natterin. These findings reveal cytosolic DNA sensors as critical regulators for Natterin-induced neutrophilia

Laser capture microdissection (LCM) and whole genome amplification (WGA) of DNA from normal breast tissue --- optimization for genome wide array analyses

<p>Abstract</p> <p>Background</p> <p>Laser capture microdissection (LCM) can be applied to tissues where cells of interest are distinguishable from surrounding cell populations. Here, we have optimized LCM for fresh frozen normal breast tissue where large amounts of fat can cause problems during microdissection. Since the amount of DNA needed for genome wide analyses, such as single nucleotide polymorphism (SNP) arrays, is often greater than what can be obtained from the dissected tissue, we have compared three different whole genome amplification (WGA) kits for amplification of DNA from LCM material. In addition, the genome wide profiling methods commonly used today require extremely high DNA quality compared to PCR based techniques and DNA quality is thus critical for successful downstream analyses.</p> <p>Findings</p> <p>We found that by using FrameSlides without glass backing for LCM and treating the slides with acetone after staining, the problems caused by excessive fat could be significantly decreased. The amount of DNA obtained after extraction from LCM tissue was not sufficient for direct SNP array analysis in our material. However, the two WGA kits based on Phi29 polymerase technology (Repli-g^®(Qiagen) and GenomiPhi (GE Healthcare)) gave relatively long amplification products, and amplified DNA from Repli-g^®gave call rates in the subsequent SNP analysis close to those from non-amplified DNA. Furthermore, the quality of the input DNA for WGA was found to be essential for successful SNP array results and initial DNA fragmentation problems could be reduced by switching from a regular halogen lamp to a VIS-LED lamp during LCM.</p> <p>Conclusions</p> <p>LCM must be optimized to work satisfactorily in difficult tissues. We describe a work flow for fresh frozen normal breast tissue where fat is inclined to cause problems if sample treatment is not adapted to this tissue. We also show that the Phi29-based Repli-g^®WGA kit (Qiagen) is a feasible approach to amplify DNA of high quality prior to genome wide analyses such as SNP profiling.</p

Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy

Self-reported and measured time of vibration exposure at ultrasonic scaling in dental hygienists

In the present study, our objective was to quantify the daily duration of vibration exposure from ultrasonic scaling in dental hygienists and to compare different methods of self-estimates to time-recorded measurements. The exposure time was self-estimated by use of diary and interview methods in 10 subjects. We found that the measured total daily exposure time was limited, only on average 12 min, with a great variation, however, between and within the subjects. Self-assessed duration of exposure was overestimated, on average three times higher with a diary and even more at an interview (8 times). In conclusion, the objectively measured exposure time was short and clearly overestimated in self-reports

Physical workload in neck, shoulders and wrists/hands in dental hygienists during a work-day.

Physical workload was recorded by electromyography, inclinometry and goniometry for twelve female dental hygienists during authentic work. Their work was, in relation to other types of work, characterised by pronounced head flexion (90th percentile 46°), high loads on the forearm extensor muscles (90th percentile 23% and 18% of maximal EMG (MVE), for the right and left sides, respectively), average loads on trapezius muscles (90th percentile 15% and 14% MVE), average arm elevation (99th percentile 83° and 72°) and average wrist flexion and velocities (50th percentiles 17° of extension and 7.3°/s, for the right side). Manual scaling and machinery (use of ultrasonic scaling and hand-pieces) showed higher loads on the trapezius muscles, regarding muscular rest, as well as the 10th and 50th percentiles, than the other tasks, and for the forearm extensor muscles, an almost complete lack of muscular rest (0.1% time), and much higher loads regarding the 10th and 50th percentiles. Further, more pronounced head flexion and lower head and upper arm velocities were found, indicating more constrained postures for the neck and shoulders for the manual scaling and machinery. Use of ultrasonic scaler reduced the 50th percentile loads on the right forearm extensor muscles, but had no effect on the fraction of muscular rest and on the 10th percentile load. These findings are consistent with the high prevalences of musculoskeletal disorders among dental hygienists

Sick Leave Before and After Diagnosis of Rheumatoid Arthritis - A Report from the Swedish TIRA Project

Objective. Our study describes sick leave during 3 years before and 3 years after diagnosis of rheumatoid arthritis (RA) in relation to referents and identifies predictors for sick leave during the third year after diagnosis of RA. Methods. One hundred twenty patients (76% women) from the Swedish early RA study TIRA were included. Disease activity and disability were registered regularly during 3 years in TIRA. Referents were matched for sex, age, and home town. Sick leave data were obtained for patients 3 years before and 3 years after diagnosis and for the referents for the corresponding 6 years. Results. No differences were seen between patients and referents regarding sick leave during the first 2 years, whereas sick leave increased in patients 6 months before diagnosis, from 30% to 53%. During the 3 years after diagnosis, sick leave among patients was rather stable, varying between 50% and 60%, even though disability pension increased and sickness benefit decreased. Sick leave before diagnosis, disability I year after diagnosis, and type of work were identified as predictors for sick leave during the third year after diagnosis. Conclusion. Not surprisingly, sick leave in patients increased the year before diagnosis. Although disease activity and disability diminished after diagnosis, the patients' sick leave remained essentially unchanged. Sick leave 3 years after diagnosis was foremost predicted by earlier sick leave, disability, and type of work. (First Release May 1 2009; J Rheumatol 2009:36:1170-9; doi:10.3899/jrheum.080523