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    Evaluation of Posaconazole Serum Concentrations Achieved With Delayed-release Tablets and Oral Suspension in Patients Undergoing Intensive Chemotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome.

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    Data on posaconazole serum levels of patients on prophylaxis with delayed-release tablets or oral suspension during intensive chemotherapy for acute myeloid leukemia and myelodysplastic syndrome are scarce. In this analysis, the proportion of patients with acute myeloid leukemia/myelodysplastic syndrome achieving posaconazole target concentrations with delayed-release tablets was higher than with oral suspension

    Genetic architecture of disease resistance and tolerance in Douglas-fir trees.

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    Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes

    Challenging the Urologist of the Future: Time for a Change?

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    Physicians need both medical expertise and diverse skills for effective patient care. Adaptability is also key in embracing advances in technology and new techniques. We outline six thought-provoking points to guide the new generation of urologists

    Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

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    AIMS Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction

    Assessment of the knowledge, attitudes, and practices toward human tuberculosis amongst rural communities in Chad.

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    INTRODUCTION Tuberculosis (TB) is an infectious zoonotic disease caused by bacteria belonging to the Mycobacterium tuberculosis complex. In sub-Saharan African countries such as Chad, TB is endemic and causes a high burden on humans and animals through morbidity, mortality, and reduced productivity in livestock. To effectively prevent and control the disease, strong coordination between policymakers, health and veterinary services, civil society organizations, and communities is needed. It also requires an understanding of the knowledge the communities have regarding TB. However, such knowledge is under-investigated, especially in rural areas. How knowledge affects people's attitudes and practices is also unclear. The main objective of this study was to investigate the knowledge, attitudes, and practices (KAP) of Chadian rural communities to better involve them in TB surveillance programs. METHODS A survey was conducted in 2021 in five rural health centers. Face-to-face interviews were conducted with persons suspected of having TB, and data on KAP were recorded and analyzed. RESULTS In total, 139 participants were enrolled. Overall, the knowledge and attitude of the participants were found to be good to moderate, with 126 (90.6%) and 97 (69.7%) having good knowledge and attitude, respectively. However, their practices were found to be rather weak, with only 40 (28.7%) participants having good practices. Men were found to have good knowledge about the disease significantly more often than women. Poor attitude was significantly associated with a mobile lifestyle compared to settled lifestyles and with farmers (mainly engaged in agriculture) compared to breeders (livestock keepers). Poor health practices were associated more with men than women and with settled lifestyles compared to a mobile lifestyle. Good practices were found to be in line with good knowledge and good attitudes; however, in the analyses, the association was not significant [OR knowledge = 5.83 (95% C.I. 0.6842.83), p = 0.112; OR attitude = 2.09 (95% C.I. 0.875.04), p = 0.100]. Furthermore, attitude was not associated with knowledge [OR = 1.03 (95% C.I. 0.303.55), p = 0.964]. DISCUSSION AND CONCLUSION Our study highlights the need for targeted sensitization and awareness campaigns for communities with poor knowledge and attitudes regarding TB. These campaigns should also include practical training to increase the level of good practice rather than simply providing knowledge

    Effect of femtosecond laser induced surface patterns on the flexural strength of monolithic zirconia.

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    To investigate how patterns generated by femtosecond (fs) laser and femtosecond laser power affect the surface roughness (Ra) and biaxial flexural strength (BFS) of monolithic zirconia. Eighty disk-shaped zirconia specimens were divided into eight subgroups (n = 10): Control (C), airborne-particle abrasion (APA), 400 mW fs laser (spiral [SP(400)], square [SQ(400)], circular [CI(400)]), and 700 mW fs laser ([SP(700)], [SQ(700)], [CI(700)]). Ra values were calculated by using a surface profilometer. One additional specimen per group was analyzed with scanning electron microscopy and x-ray diffractometry. BFS values were obtained by using the piston-on-3-ball test. One-way ANOVA and either Tukey's HSD (BFS) or Tamhane's T2 (Ra) tests were used to evaluate data (α = 0.05). Regardless of the pattern and power, fs laser groups had higher Ra than C and APA, while SP groups had lower Ra than CI and SQ groups (p ≤ 0.004). For each pattern, Ra increased with higher laser power (p < 0.001), while the laser power did not affect the BFS (p ≥ 0.793). CI and SQ groups had lower BFS than the other groups (p ≤ 0.040), whereas SP groups had similar BFS to C and APA (p ≥ 0.430). Fs laser microstructuring with spiral surface pattern increased the Ra without jeopardizing the BFS of zirconia. Thus, this treatment might be an option to roughen tested zirconia

    Radiation doses received by major organs at risk in children and young adolescents treated for cancer with external beam radiation therapy: a large-scale study from 12 European countries.

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    BACKGROUND Childhood cancer survivors are at high risk of long-term iatrogenic events, in particular those treated with radiotherapy. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. PURPOSE We aimed to set up a standardised organ dose table in order to help former patients and clinician in charge of long term follow-up clinics. MATERIAL AND METHODS We performed whole body dosimetric reconstruction for 2646 patients from 12 European Countries treated between 1941 and 2006 (median: 1976). Most planning were 2D or 3D, 46% of patients were treated using Cobalt 60 and 41% using linear accelerator, the median prescribed dose being 27.2 Gy (IQ1-IQ3: 17.6-40.0 Gy), A patient specific voxel-based anthropomorphic phantom with more than 200 anatomical structures or sub-structures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system (TPS) based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the TPS dose calculation to the whole-body, by type and localisation of childhood cancer. RESULTS The integral dose and normal-tissue doses to most of the 23 considered organs increased between the 1950's and the 1970's and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability. CONCLUSION The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, gender, age and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics

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