Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Summary
Background
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline ...phosphatase ALP and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long‐term effectiveness of second‐line treatments remains uncertain.
Aims
To evaluate the long‐term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
Methods
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non‐responsive PBC patients (Paris‐II criteria) from Spain and Portugal who received OCA ± fibrates.
Results
Of 255 patients, median follow‐up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE‐PBC and 5‐year UK‐PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
Conclusion
Triple therapy was superior in achieving therapeutic goals in UDCA‐nonresponsive PBC. Decompensation was linked to pre‐existing portal hypertension.
Longitudinal, real‐world study on 255 UDCA‐nonresponsive PBC patients (Per Paris II criteria); median follow‐up of 35.1 months (IQR: 20–53). All patients received obeticholic acid (OCA), with 25% receiving later add‐on fibrate treatment (triple therapy). In multivariate analysis, triple therapy outperformed dual therapy across all surrogate biochemical endpoints of outcomes.
•How temperature and KOH concentration influence on the carotenoids extraction.•How different polarity solvents influence on the recovery.•To establish a standard method for all microalgae is not ...possible.
Microalgae are an interesting source of natural pigments that have valuable applications. However, further research is necessary to develop processes that allow us to achieve high levels of carotenoid recovery while avoiding degradation. This work presents a comprehensive study on the recovery of carotenoids from several microalgae genera, optimizing carotenoid extraction using alkaline saponification at various temperatures and KOH concentrations. Results show that I. galbana requires a temperature of 60 °C and <10% KOH, N. gaditana and K. veneficum require 60 °C and no saponification, P. reticulatum requires 40 °C and 10% KOH, T. suecica and H. pluvialis require 25 °C and 40% KOH while C. sp. and S. almeriensis require 80 °C and 40% KOH. The influence of the solvent on carotenoid recovery was also studied. In general terms, an ethanol:hexane:water (77:17:6 v/v/v) mixture results in good yields.
An intensive isolation program carried out in three replicated composting piles allowed the identification of the resident and transient components of the composting microbiome. More than 4000 ...bacterial strains were isolated, enzymatically characterized and identified by partial sequencing of their 16S rRNA gene. While microorganisms isolated under mesophilic conditions were prominent throughout the process, thermophilic stages gathered the highest total counts and spore-forming bacteria prevailed at the bio-oxidative phase of composting. Enzymatic capabilities related to the degradation of polymeric materials were exhibited by most of the isolates and as a result of these activities, more soluble compounds could be made available to the entire composting microbiota. A high proportion of isolates showed to be thermotolerant as they were detected at mesophilic and thermophilic phases. Isolated strains belonged to 187 bacterial species. Biodiversity was greater at the central stages of composting and mesophilic, thermophilic and cooling phases shared 50% of species.
Insulin resistance in hidradenitis suppurativa: a case–control study Vilanova, I.; Hernández, J.L.; Mata, C. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
20/May , Letnik:
32, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background
The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a ...chronic inflammatory cutaneous disease that affects the apocrine gland‐bearing areas of the body.
Objective
We aimed to determine the prevalence of IR in patients with HS.
Methods
This cross‐sectional, case–control study enrolled 137 subjects, 76 patients with HS and 61 age‐ and gender‐matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA‐IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels.
Results
The median (IQR) HOMA‐IR value in HS patients was significantly higher 2.0 (1.0–3.6) than in controls 1.5 (0.9–2.3) (P = 0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (P = 0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA‐IR 2.51 (0.18) vs 1.92(0.21); P = 0.04. The HOMA‐IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease.
Conclusion
Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly.
•NH3 removal using gas-permeable membrane improved anaerobic digestion of manure.•Both the quality and quantity of the biogas produced was positively impacted.•CH4 yield increased on average ...10-17%.•Higher percentages of CH4 in biogas were obtained.•A uniform TAN recovery rate of 6.7 g per m2 of membrane and per day was obtained.
In feedstocks containing high ammonia (NH3) concentration, removal of the NH3 during the anaerobic digestion (AD) process can improve AD process performance. In the present study, the effect of NH3 removal using gas-permeable membrane (GPM) technology on AD process performance and biogas production was investigated using swine manure feedstock. Batch and semi-continuous AD experiments were carried out under mesophilic conditions. In the reactor with NH3 recovery, total ammonia nitrogen (TAN) concentration was reduced 28% in batch experiments and 23% on average in the semicontinuous experiment compared with the reactor without NH3 recovery. Free ammonia (FA) concentrations were also decreased by 23% and 4% on average in batch and semicontinuous experiments, respectively. These reductions in TAN and FA by GPM system positively impacted both the quality and quantity of the biogas produced by AD of swine manure. Specifically, the specific methane yield increased 9% in the batch experiment and 17% on average in the semicontinuous experiment. Furthermore, higher percentages of methane in biogas were obtained during AD retrofitted with GPM system, 24% increase in the batch experiment and 11% on average in the semicontinuous experiment (range 8.3-13.6%). Simultaneously, a uniform TAN recovery rate of 6.7 g N TAN per m2 of membrane and per day was obtained for the 205 days of semicontinuous operation; ammonia nitrogen was recovered in the form of ammonium sulphate solution. Therefore, the AD-GPM configuration produces beneficial results on biogas quantity and quality while recovering ammonia nitrogen in form of ammonium sulphate.
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We evaluated the MYD88 L265P mutation in Waldenström's macroglobulinemia (WM) and B-cell lymphoproliferative disorders by specific polymerase chain reaction (PCR) (sensitivity ∼10(-3)). No mutation ...was seen in normal donors, while it was present in 101/117 (86%) WM patients, 27/31 (87%) IgM monoclonal gammapathies of uncertain significance (MGUS), 3/14 (21%) splenic marginal zone lymphomas and 9/48 (19%) non-germinal center (GC) diffuse large B-cell lymphomas (DLBCLs). The mutation was absent in all 28 GC-DLBCLs, 13 DLBCLs not subclassified, 35 hairy cell leukemias, 39 chronic lymphocytic leukemias (16 with M-component), 25 IgA or IgG-MGUS, 24 multiple myeloma (3 with an IgM isotype), 6 amyloidosis, 9 lymphoplasmacytic lymphomas and 1 IgM-related neuropathy. Among WM and IgM-MGUS, MYD88 L265P mutation was associated with some differences in clinical and biological characteristics, although usually minor; wild-type MYD88 cases had smaller M-component (1.77 vs 2.72 g/dl, P=0.022), more lymphocytosis (24 vs 5%, P=0.006), higher lactate dehydrogenase level (371 vs 265 UI/L, P=0.002), atypical immunophenotype (CD23-CD27+ +FMC7+ +), less Immunoglobulin Heavy Chain Variable gene (IGHV) somatic hypermutation (57 vs 97%, P=0.012) and less IGHV3-23 gene selection (9 vs 27%, P=0.014). These small differences did not lead to different time to first therapy, response to treatment or progression-free or overall survival.
Gas-permeable membrane technology is useful to recover ammonia (NH3) from liquid manures. In this study, phosphorus (P) recovery via MgCl2 precipitation was enhanced by combining it with NH3 recovery ...through gas-permeable membranes. Anaerobically digested swine wastewater containing approximately 2300 mg NH4+-N L−1 and 450 mg P L−1 was treated using submerged membranes plus low-rate aeration to recover the NH3 from within the liquid and MgCl2 to precipitate the P. The experiments included a first configuration where N and P were recovered sequentially and a second configuration with simultaneous recovery. The low-rate aeration reduced the natural carbonate, increased pH and accelerated NH3 uptake by the gas-permeable membrane system, which in turn benefited P recovery. Phosphorus removal efficiency was >90% and P recovery efficiency was about 100%. With higher NH3 capture, the recovered P contained higher P2O5 content (37–46%, >98% available), similar to the composition of the biomineral newberyite (MgHPO4·3H2O).
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•Phosphorus recovery was combined with ammonia recovery using gas-permeable membranes.•Aeration stripped carbonates, increased pH, and enhanced ammonia capture.•The process provided approximately 100% phosphorus recovery efficiencies.•With active ammonia capture, the recovered phosphate minerals contained higher phosphate grade.•The recovered phosphate minerals were similar to the composition of the biomineral newberyite.
•PLE is a more sustainable and efficient technique for the extraction of proteins from BSG than conventional alkaline extraction.•Tuning of PLE conditions enables to tailor composition and ...bioactivity of extracts.•Extraction technique and conditions affect the kind of extracted proteins observing more hordeins in PLE extracts.•Hydrolysates from PLE extracts show more hydrophobic peptides and higher bioactivity than the hydrolysate from the alkaline extract.
A green methodology based on pressurized liquids (PLE) to extract proteins and obtain highly active extracts from brewer’s spent grain (BSG) is proposed. Box-Behnken experimental design was employed to study the effect of extraction parameters on the protein content (PC), the total phenolic content (TPC), and the antioxidant activity of extracts. Results were compared with those obtained by conventional alkaline extraction assisted with ultrasounds (UAE). The selection of PLE conditions enabled to tailor the PC and TPC of extracts. PLE extracted 36 % more proteins than UAE. PLE extracts showed higher antioxidant, cholesterol esterase inhibition, and ACE inhibitory activities than UAE extract. HPLC-MS/MS enabled to observe that the extraction technique and experimental conditions significantly affected to the kind and amount of extracted proteins, and released peptides, and phenolic compounds. A higher ratio of hydrophobic peptides was observed in PLE extracts, which justified their higher bioactivity.
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•Intense turnover of organic matter was induced by inoculation of composting piles.•More simple compounds were released from polymeric fractions in inoculated piles.•Humification was ...more intense and earlier achieved in inoculated piles.•Inoculation clearly stimulated growth and activity of the composting microbiota.•Inoculation affected microbiota structure but its functionality remained unaltered.
Enhanced organic matter turnover was detected in lignocellulosic composting piles inoculated with microorganisms specifically capable of decomposing polymeric compounds. In comparison to uninoculated piles, the following results were obtained in the inoculated piles: degradation of hemicellulose, cellulose and lignin were 28%, 21% and 25% respectively higher. Total organic matter, total sugars and phenolic compounds also decreased more intensely. Greater amounts of soluble organic carbon, reducing sugars and soluble proteins were available to the composting microbiota. Recycling of organic to inorganic nitrogen was improved and humification was more intense and earlier attained. Microbial community structure was also affected by inoculation. It was initially thought that these effects were due to enzymatic capabilities of inoculants, however, microbial counts, especially those corresponding to functional groups, revealed that inoculation induced a true stimulation of microbial growth and activity in the entire composting microbiota which was actually responsible for all the beneficial effects reported here.
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