Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been ...initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx‐markers into routine care, because the evidence base is currently limited to specific, individual drug‐gene pairs. The Ubiquitous Pharmacogenomics (U‐PGx) Consortium, which has been funded by the European Commission's Horizon‐2020 program, aims to address this unmet need. In a prospective, block‐randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions PREPARE), pre‐emptive genotyping of a panel of clinically relevant PGx‐markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost‐effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi‐ethnic, and multihealthcare system approach.
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•Composite films based on chitosan and waste coffee grounds (WCG) were developed.•WCG-containing composites enhanced the adsorption of pharmaceuticals from water.•Maximum removal of ...pharmaceuticals was verified under mild experimental conditions.•The composite shows acceptable reusability in consecutive adsorption processes.
Waste coffee-grounds (WCG), a poorly explored source of biocompounds, were combined with chitosan (Cs) and poly(vinyl alcohol) (PVA) in order to obtain composites. Overall, WCG showed a good interaction with the polymeric matrix and good dispersibility up to 10 wt-%. At 5 wt-% WCG, the composite exhibited a noticeable enhancement (from 10 to 44%) of the adsorption of pharmaceuticals (metamizol (MET), acetylsalicylic acid (ASA), acetaminophen (ACE), and caffeine (CAF)) as compared to the pristine sample. The highest removal efficiency was registered at pH 6 and the removal followed the order ASA > CAF > ACE > MET. For all pharmaceuticals, the adsorption kinetics was found to follow the pseudo-second order model, while the adsorption mechanism was explained by the Freundlich isotherm. Reuse experiments indicated that the WCG-containing composite has an attractive cost-effectiveness since it presented a remarkable reusability in at least five consecutive adsorption/desorption cycles.
Erucic acid (cis-docosa-13-enoic acid, C22:1∆13) and nervonic acid (cis-tetracosa-15-enoic acid, C24:1 ∆15) are important renewable feedstocks in plastic, cosmetic, nylon, and lubricant industries. ...Furthermore, nervonic acid is also applied to the treatment of some neurological diseases. However, the production of these two very long-chain fatty acids (VLCFA) is very limited as both are not present in the main vegetable oils (e.g., soybean, rapeseed, sunflower, and palm). Ectopic integration and heterologous expression of fatty acid elongases (3-ketoacyl-CoA synthases, KCS) from different plants in
Rhodosporidium toruloides
resulted in the de novo synthesis of erucic acid and nervonic acid in this oleaginous yeast. Increasing
KCS
gene copy number or the use of a push/pull strategy based on the expression of elongases with complementary substrate preferences increased significantly the amount of these two fatty acids in the microbial oils. Oil titers in 7-L bioreactors were above 50 g/L, and these two VLCFA represented 20–30% of the total fatty acids. This is the first time that microbial production of these types of oils is reported.
Film mammography has limited sensitivity for the detection of breast cancer in women with radiographically dense breasts. We assessed whether the use of digital mammography would avoid some of these ...limitations.
A total of 49,528 asymptomatic women presenting for screening mammography at 33 sites in the United States and Canada underwent both digital and film mammography. All relevant information was available for 42,760 of these women (86.3 percent). Mammograms were interpreted independently by two radiologists. Breast-cancer status was ascertained on the basis of a breast biopsy done within 15 months after study entry or a follow-up mammogram obtained at least 10 months after study entry. Receiver-operating-characteristic (ROC) analysis was used to evaluate the results.
In the entire population, the diagnostic accuracy of digital and film mammography was similar (difference between methods in the area under the ROC curve, 0.03; 95 percent confidence interval, -0.02 to 0.08; P=0.18). However, the accuracy of digital mammography was significantly higher than that of film mammography among women under the age of 50 years (difference in the area under the curve, 0.15; 95 percent confidence interval, 0.05 to 0.25; P=0.002), women with heterogeneously dense or extremely dense breasts on mammography (difference, 0.11; 95 percent confidence interval, 0.04 to 0.18; P=0.003), and premenopausal or perimenopausal women (difference, 0.15; 95 percent confidence interval, 0.05 to 0.24; P=0.002).
The overall diagnostic accuracy of digital and film mammography as a means of screening for breast cancer is similar, but digital mammography is more accurate in women under the age of 50 years, women with radiographically dense breasts, and premenopausal or perimenopausal women. (ClinicalTrials.gov number, NCT00008346.)
Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly ...characteristics over time. The
, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years;
< 0.001). The median delay from first symptoms to diagnosis was 2 years longer in females (
= 0.015). Ages at diagnosis and first symptoms increased significantly over time (
< 0.001). Tumors were larger in males than females (
< 0.001); tumor size and invasion were inversely related to patient age (
< 0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (
< 0.001). GH was inversely related to age in both sexes (
< 0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6-4.4% had experienced a fracture. In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis.
► NZVI efficiently immobilised Pb and Zn in polluted soils. ► NZVI had little impact on cellular viability and functionality in soil microbiota. ► Three selected treatment-related genes showed no ...changes in their expression ratios. ► NZVI caused changes in structure and composition of the soil bacteria population.
In this work, nanoscale zero-valent iron (NZVI) particles have been used as an immobilisation strategy to reduce Pb and Zn availability and mobility in polluted soils. The application of NZVI to two soil microcosms (MPb and MZn) at a dose of 34mgg−1 soil efficiently immobilised Pb (25%) and zinc (20%). Exposure to NZVI had little impact on the microbial cellular viability and biological activity in the soils. Three bacterial genes (narG, nirS and gyrA) were used as treatment-related biomarkers. These biomarkers ruled out a broad bactericidal effect on the bulk soil microbial community. A transcriptome analysis of the genes did not reveal any changes in their expression ratios after the NZVI treatment: 1.6 (narG), 0.8 (nirS) and 0.7 (gyrA) in the MPb microcosm and 0.6 (narG), 1.2 (nirS) and 0.5 (gyrA) in the MZn microcosm. However, significant changes in the structure and composition of the soil bacteria population were detected by fluorescence insitu hybridisation. Thus, our results showed that NZVI toxicity could be highly dose and species dependent, and the effective applicability of the proposed molecular approach in assessing the impact of this immobilisation strategy on soil microbial population.
Tumor-resident lymphocytes can mount a response against neoantigens expressed in microsatellite-stable gastrointestinal (GI) cancers, and adoptive transfer of neoantigen-specific lymphocytes has ...demonstrated antitumor activity in selected patients. However, whether peripheral blood could be used as an alternative minimally invasive source to identify lymphocytes targeting neoantigens in patients with GI cancer with relatively low mutation burden is unclear. We used a personalized high-throughput screening strategy to investigate whether PD-1 expression in peripheral blood could be used to identify CD8+ or CD4+ lymphocytes recognizing neoantigens identified by whole-exome sequencing in 7 patients with GI cancer. We found that neoantigen-specific lymphocytes were preferentially enriched in the CD8+PD-1+/hi or CD4+PD-1+/hi subsets, but not in the corresponding bulk or PD-1- fractions. In 6 of 7 individuals analyzed we identified circulating CD8+ and CD4+ lymphocytes targeting 6 and 4 neoantigens, respectively. Moreover, neoantigen-reactive T cells and a T cell receptor (TCR) isolated from the CD8+PD-1+ subsets recognized autologous tumor, albeit at reduced levels, in 2 patients with available cell lines. These data demonstrate the existence of circulating T cells targeting neoantigens in GI cancer patients and provide an approach to generate enriched populations of personalized neoantigen-specific lymphocytes and isolate TCRs that could be exploited therapeutically to treat cancer.
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