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It is estimated that 10% of individuals with a myeloid malignancy carry a germline susceptibility. Using the genome-first approach, in which individuals were ascertained on genotype alone, rather than clinical phenotype, we quantified the prevalence and penetrance of pathogenic germline variants in eight myeloid malignancy predisposition (gMMP) genes. ANKRD26, CEBPA, DDX41, MECOM, SRP72, ETV6, RUNX1 and GATA2, were analyzed from the Geisinger MyCode DiscovEHR (n = 170,503) and the United Kingdom Biobank (UKBB, n = 469,595). We identified a high risk of myeloid malignancies (MM) (odds ratio[OR] all genes: DiscovEHR, 4.6 [95% confidential interval (CI) 2.1-9.7], p < 0.0001; UKBB, 6.0 [95% CI 4.3-8.2], p = 3.1 × 10 -27 ), and decreased overall survival (hazard ratio [HR] DiscovEHR, 1.8 [95% CI 1.3-2.6], p = 0.00049; UKBB, 1.4 [95% CI 1.2-1.8], p = 8.4 × 10 -5 ) amongst heterozygotes. Pathogenic DDX41 variants were the most commonly identified, and in UKBB showed a significantly increased risk of MM (OR 5.7 [95% CI 3.9-8.3], p = 6.0 × 10 -20 ) and increased all-cause mortality (HR 1.35 [95% CI 1.1-1.7], p = 0.0063). Through a genome-first approach, this study genetically ascertained individuals with a gMMP and determined their MM risk and survival., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The food industry uses indigo carmine (IC) extensively as a blue colorant to make processed food for young children and the general population more attractive. Given that IC can act as a ligand, this raises concerns about its interactions with essential metal ions in the human body. In view of this interest, in the present investigation, the copper(II)/indigo carmine system was thoroughly investigated in aqueous solution and in the solid state, and the detailed structural characterization of the complexes formed between copper(II) and the ligand was performed using spectroscopic methods, complemented with DFT and TD-DFT calculations. NMR and UV/Vis absorption spectroscopy studies of the ligand in the presence of copper(II) show changes that clearly reveal strong complexation. The results point to the formation of complexes of 1:1, 1:2 and 2:1 Cu(II)/IC stoichiometry in aqueous solution, favored in the pH range 6-10 and stable over time. DFT calculations indicate that the coordination of the ligand to the metal occurs through the adjacent carbonyl and amine groups and that the 1:1 and the 2:1 complexes have distorted tetrahedral metal centers, while the 1:2 structure is five-coordinate with a square pyramidal geometry. FTIR results, together with EDS data and DFT calculations, established that the complex obtained in the solid state likely consists of a polymeric arrangement involving repetition of the 1:2 complex unit. These results are relevant in the context of the study of the toxicity of IC and provide crucial data for future studies of its physiological effects. Although the general population does not normally exceed the maximum recommended daily intake, young children are highly exposed to products containing IC and can easily exceed the recommended dose. It is, therefore, extremely important to understand the interactions between the dye and the various metal ions present in the human body, copper(II) being one of the most relevant due to its essential nature and, as shown in this article, the high stability of the complexes it forms with IC at physiological pH.

Prior studies found hand preference trajectories predict preschool language outcomes. However, this approach has been limited to examining bimanual manipulation in toddlers. It is not known whether hand preference during infancy for acquiring objects (i.e., reach-to-grasp) similarly predicts childhood language ability. The current study explored this motor-language developmental cascade in 90 children. Hand preference for acquiring objects was assessed monthly from 6 to 14 months and language skill was assessed at 5 years. Latent class growth analysis identified three infant hand preference classes: left, early right, and late right. Infant hand preference classes predicted 5-year language skills. Children in the left and early right classes, who were categorized as having a consistent hand preference, had higher expressive and receptive language scores relative to children in the inconsistent late right class. Consistent classes did not differ from each other on language outcomes. Infant hand preference patterns explained more variance for expressive and receptive language relative to previously reported toddler hand preference patterns, above and beyond socioeconomic status (SES). Results suggest that hand preference, measured at different time points across development using a trajectory approach, is reliably linked to later language., Competing Interests: The authors have no conflicts of interest to declare.

The COVID-19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near-universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the current paper focused on BI examined prior to COVID, because of its developmental link to anxiety and ER, as difficulties may be associated with differences in anxiety. We examined a neurocognitive marker of ER processes, delta-beta coupling (DBC). The current paper had two goals: (1) to examine BI in relation to COVID-related worry and social anxiety experienced during the pandemic, and (2) to explore the role of individual differences in early DBC in the relationship between BI and anxiety outcomes 6 months apart during COVID-19 (n = 86; T1 M age  = 15.95, SD = 1.73; T6 M age  = 16.43, SD = 1.73). We found support for the moderating role of DBC in the relationship between BI levels and social anxiety disorder (SAD) symptom severity during the pandemic. Here, high BI was predictive of increased SAD symptom levels in adolescents with stronger DBC., (© 2024 Wiley Periodicals LLC.)

Purpose: This article presents a review of the main causes of inherited dual sensory impairment (DSI) with an emphasis on the multidisciplinary approach., Methods: A narrative review of English literature published before January 2023 was conducted using PubMed, Medline, and Scopus databases. The different causes of inherited DSI are discussed from a multidisciplinary perspective., Results: There are a wide range of dual sensory impairment (DSI), commonly referred to as blindness and deafness. While Usher syndrome is the most frequent genetic cause, other genetic syndromes such as Alport syndrome or Stickler syndrome can also lead to DSI. Various retinal phenotypes, including pigmentary retinopathy as seen in Usher syndrome, vitreoretinopathy as in Stickler syndrome, and macular dystrophy as in Alport syndrome, along with type of hearing loss (sensorineural or conductive) and additional systemic symptoms can aid in diagnostic suspicion. A thorough ophthalmologic and otorhinolaryngologic examination can help guide diagnosis, which can then be confirmed with genetic studies, crucial for determining prognosis. Effective hearing rehabilitation measures, such as hearing implants, and visual rehabilitation measures, such as low vision optical devices, are crucial for maintaining social interaction and proper development in these patients., Conclusions: While Usher syndrome is the primary cause of inherited dual sensory impairment (DSI), other genetic syndromes can also lead to this condition. A proper diagnostic approach based on retinal phenotypes and types of hearing loss can aid in ruling out alternative causes. Multidisciplinary approaches can assist in reaching a definitive diagnosis, which has significant prognostic implications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) <0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs) and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation., (© 2023 UICC.)

This study evaluated the antimicrobial efficacy of a new intracanal drug based on Pentaclethra macroloba extract, a plant of Amazonian origin, against Enterococcus faecalis using macrodilution test and intratubular evaluation with Confocal Laser Scanning Microscopy (CLSM). The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the pure extract of Pentaclethra macroloba andits association with calcium hydroxide and ultracall were determined. Then, thirty-three dentin cylinders were prepared and inoculated with E. faecalis, to evaluate the antimicrobial effect of the medications on the dentinal tubules with CLSM. The data was analyzed using the Kruskal-Wallis and Dunn tests. The extract in association with calcium hydroxide showed a lower CBM, and in the intratubular test all tested medications were effective against E. faecalis (P >0.05). The new intracanal drug based on P. macroloba extract has an antimicrobial effect against E. faecalis and further studies are needed for its clinical use.

The aim of this study was to evaluate root canal preparation with nickel titanium rotary instruments and complementary preparation with ultrasonic tip in curved canals of mandibular molars with isthmus. Twenty-eight mesial roots of mandibular molars with curvature between 20° and 40° and presence of isthmus throughout the entire extension of the root canals were prepared using ProDesign Logic CM (PDL) up to size 40.05, or HyFlex EDM (HFEDM) up to size 40.04. Complementary preparation was performed in the isthmus region using the ultrasonic insert E18D (Helse, Istmo Diamantada). The root canals were scanned using micro-CT (SkyScan 1176) at 9 µm voxel size before and after each preparation step. Transportation, percentage of increase in volume, debris and uninstrumented surface (UNS) were evaluated. Mann Whitney, Wilcoxon, paired and non-paired t-tests were used for statistical analysis (α = 0.05). The canals prepared with PDL and HFEDM obtained similar results for all the variables assessed before using E18D (p > 0.05). E18D significantly decreased the percentage of debris and UNS values in both Groups (p < 0.05). The complementary preparations with E18D caused a smaller quantity of debris in the isthmus of the canals previously prepared with PDL in comparison with HFEDM (p < 0.05). PDL and HFEDM provided similar root canal preparation. PDL promoted a smaller quantity of Debris in the isthmus than HFEDM after using E18D. E18D significantly improved cleaning, and reduced Debris and UNS.

Background and Objective: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported., Material and Methods: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale., Results: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ± 16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ± 3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp β: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp β: 1.73; P = 0.006; CI (1.17-2.56)., Conclusions: A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival ( p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes ( p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.

We report the synthesis of a new conjugated polymer bearing crown ether moieties, poly[( N (1-aza-[18]crown-6)carbamido)thiophene-2,5-diyl- alt -1,4-phenylene] (BG2). In water, BG2 forms a dispersion with a slightly cloudy appearance. We have studied the effect of adding surfactants, with different polar head groups, on these polymer-polymer aggregates. Special attention is given to the system with the anionic surfactant, sodium dodecyl sulfate (SDS). The combination of photophysical techniques with electrical conductivity, NMR ( 1 H, 13 C, and 27 Na), DFT calculations, molecular dynamics simulations, and small-angle neutron scattering (SANS) provides a detailed picture on the behavior of the SDS/BG2 system in aqueous solution and in thin films. NMR, electric conductivity, and DFT results suggest that hydrophilic interactions occur between the polar headgroup of the surfactant (OSO 3 - Na + ) and the aza-[18]-crown-6 moiety. DFT calculations confirmed the capability of BG2 to form stable complexes with the Na + cations, where the cation can be either inside the azacrown cavity or sandwiched between the cavity and the polymer chain, which seem to determine the position of the surfactant hydrocarbon chain and, therefore, be responsible for the disruption of the BG2 aggregates and subsequent increase in the photoluminescence quantum yields. SANS measurements, made with hydrogenated and deuterated SDS in D 2 O, clearly show how micron-sized aggregates of BG2 are broken down by SDS and then how BG2 becomes preferentially incorporated within joint colloidal particles of BG2 and SDS with increasing [SDS]/[BG2] molar ratio.

Objective: The objective of this study is to compare the effectiveness of complex physical therapy combined with intermittent pneumatic compression (CPT + IPC) versus Kinesio taping (KT) for breast cancer-related lymphedema., Methods: A cross-over clinical trial was conducted in 43 women with lymphedema. All participants received two interventions: CPT + IPC and KT, both lasting 3 weeks and a washout period. The main outcome variable was the relative volume change (RVC). The secondary variables were Satisfaction Questionnaire about Textile Therapeutic Devices used for Breast Cancer-Related Lymphedema, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, motion range of upper limb and lymphedema-related symptoms., Results: The RVC reduction was greater with CPT + IPC (-2.2%, SD = 4.7) versus KT (-0.9%, SD = 1.7) (P = 0.002). KT was more satisfactory than multilayer bandaging (8.9 points difference, P < 0.001) and improved DASH score more than CPT + IPC (14.3 points difference, P = 0.002). Regarding motion ranges, only shoulder movements showed significant improvement with CPT + IPC compared with KT (differences between 5.6° and 11.4°). Of the symptoms assessed, only pain reduction showed a significant improvement with KT versus CPT + IPC (0.5 points, P = 0.035)., Conclusions: CPT + IPC achieved higher RVC and greater improvement in th shoulder motion range than KT. Conversely, KT was more satisfactory than multilayer bandaging, obtained better DASH scores and relieved pain more than CPT + IPC., Clinical Registration: ClinicalTrial registration number: NCT03051750 (date of registration 14 February 2017)., (© 2022 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

The error-related negativity (ERN), a well-established neural marker of anxiety, reflects enhanced attention to internal threat signals. While attention to threat plays a crucial role in the development and maintenance of anxiety, it is unclear how attentional control influences the ERN-anxiety association. To address this, 37 youths (M age  = 10.89 years) completed self-report measures of attentional control and anxiety symptoms. To obtain ERN amplitude, youth completed a flanker task while simultaneous EEG was collected. Attentional control, specifically attentional shifting rather than focusing, moderated the relation between ERN amplitude and anxiety. Youth who displayed smaller neural responses to making an error and higher ability to shift attention experienced lower levels of anxiety, relative to those who exhibited larger neural responses to making an error or lower attention-shifting ability. These findings highlight that response magnitude to internal threat and ability to flexibly shift attention may jointly contribute to anxiety in youth., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: Undetectable measurable residual disease (MRD) is a surrogate of prolonged survival in multiple myeloma. Thus, treatment individualization based on the probability of a patient achieving undetectable MRD with a singular regimen could represent a new concept toward personalized treatment, with fast assessment of its success. This has never been investigated; therefore, we sought to define a machine learning model to predict undetectable MRD at the onset of multiple myeloma., Experimental Design: This study included 487 newly diagnosed patients with multiple myeloma. The training (n = 152) and internal validation cohorts (n = 149) consisted of 301 transplant-eligible patients with active multiple myeloma enrolled in the GEM2012MENOS65 trial. Two external validation cohorts were defined by 76 high-risk transplant-eligible patients with smoldering multiple myeloma enrolled in the Grupo Español de Mieloma(GEM)-CESAR trial, and 110 transplant-ineligible elderly patients enrolled in the GEM-CLARIDEX trial., Results: The most effective model to predict MRD status resulted from integrating cytogenetic [t(4;14) and/or del(17p13)], tumor burden (bone marrow plasma cell clonality and circulating tumor cells), and immune-related biomarkers. Accurate predictions of MRD outcomes were achieved in 71% of cases in the GEM2012MENOS65 trial (n = 214/301) and 72% in the external validation cohorts (n = 134/186). The model also predicted sustained MRD negativity from consolidation onto 2 years maintenance (GEM2014MAIN). High-confidence prediction of undetectable MRD at diagnosis identified a subgroup of patients with active multiple myeloma with 80% and 93% progression-free and overall survival rates at 5 years., Conclusions: It is possible to accurately predict MRD outcomes using an integrative, weighted model defined by machine learning algorithms. This is a new concept toward individualized treatment in multiple myeloma. See related commentary by Pawlyn and Davies, p. 2482., (©2022 American Association for Cancer Research.)

Purpose: The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort., Materials/methods: Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors., Results: A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age <50 remained to be a significant prognostic factor for local recurrence (HR 0.19, 95% CI 0.08-0.47; p < 0.05). The 10-year estimated OS was 81.2%., Conclusion: Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings., Competing Interests: GS: personal fees and travel costs from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Trials, travel costs from Guerbet SA, not related to this work. FW: reports personal fees from Celgene GmbH, fees Roche Pharma AG, fees Eli Lilly and Company, fees from Ipsen Pharma GmbH and grants and other from Carl Zeiss Meditec AG and Elekta AB, patent by Carl Zeiss Meditec AG, not related to this work, outside the submitted work. FG: grants and personal fees from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, grants and personal fees from Elekta AB, grants and personal fees from NOXXON Pharma AG, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from MSD Sharp and Dome GmbH, grants and personal fees from AstraZeneca GmbH, non-financial support from ONCARE GmbH, non-financial support from OPASCA GmbH, outside the submitted work. GS: personal fees and travel costs from Carl Zeiss Meditec AG, not related to this work. ES: grants from the Ministry for Science and Arts and others from Carl Zeiss Meditec, outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sarria, Ramos, Palacios, Del Castillo, Castro, Calvo, Cotrina, Heredia, Galarreta, Fuentes-Rivera, Avalos, Martinez, Colqui, Ziegler, Schmeel, Pinillos, Wenz, Giordano, Sarria and Sperk.)

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 Δ mutant dataset) compared to the wild-type yeast cells. The Set4 Δ mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 Δ mutant dataset., (© 2021 Wiley-VCH GmbH.)

Following previous studies on the complexation in aqueous solutions of 8-hydroxyquinoline-5-sulfonate (8-HQS) with the trivalent metal ions, Al(III) and Ga(III) and various other metal ions, using multinuclear NMR, DFT calculations, UV-vis absorption and luminescence techniques, we have extended our studies on 8-HQS complexation to the trivalent metal ion In(III). The study combines the high sensitivity of luminescence techniques and the selectivity of multinuclear NMR spectroscopy with the structural details accessible through DFT calculations, and aims to obtain a complete understanding of the complexation between the In 3+ metal ion and 8-HQS, and how this influences the luminescence behaviour. A full speciation study has been performed and, as has been reported for the complexes of 8-hydroxyquinoline (8-HQ), the dominant complexes of 8-HQS with In(III) show marked differences in the complexation behaviour when compared with the equivalent complexes with the other group 13 cations Al(III) and Ga(III). While all three complexes have a 1 : 3 (metal : ligand) stoichiometry, those with Al(III) and Ga(III) show a mer -geometry of the ligands around the metal centre, whereas the fac -geometry is observed for the complexes with In(III). On binding to metal ions, 8-HQS shows a marked increase in the intensity of the fluorescence emission band compared to that of the virtually non-luminescent free ligand. However, the increase for In(III) is less pronounced than with Al(III) or Ga(III). These observations have important implications for the application of the complexes in sensing, light emitting devices ( e.g. OLEDs), or as electron transport layers in photovoltaics for solar energy conversion. Furthermore, surfactant complexation is known to improve the fluorescence intensity in metal complexes with 8-HQS, by inhibiting the ligand exchange, as we have reported for complexes of HQS with Al(III) and Ga(III). Accordingly, in view of the development of applications in either sensing or optoelectronics, our interest also includes the study of HQS complexes of In(III) in the presence of cationic surfactants, in comparison with previous results with Al(III) and Ga(III).

Purpose: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG)., Patients and Methods: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10 -6 . Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial., Results: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%., Conclusion: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.

Background: Aging should not be seen as a hindrance to the continuity of work, while including older adults in the labor market contributes to national economies., Objective: To analyze the association between subjective quality of life (QoL) assessment, sociodemographic variables and self-reported morbidity among working older adults., Methods: The present study was conducted at farmers' markets in Presidente Prudente, Sao Paulo, Brazil. Participants were 24 older adults aged 68.69±6.5 years old. We administered the World Health Organization Quality of Life (WHOQOL-bref) questionnaire, a sociodemographic questionnaire including working conditions and a questionnaire to survey the participants' medical history. The normality assumption was assessed with the Shapiro-Wilk test. Pearson's and Spearman's tests were used for correlation analysis., Results: The sample exhibited average QoL. Most participants were female, with 1 to 8 years of formal schooling, married, with family income 1 to 3 times the equivalent of the minimum wage and sought healthcare within the national health system. All the participants lived in their own house. Hypertension was the most prevalent disease., Conclusion: QoL and morbidity exhibited moderate negative correlation. There was negative correlation between the QoL physical and psychological domains and variables years in the job, daily working hours, meal/rest breaks and number of meals/day. There was moderate negative correlation between the QoL environment domain and meal/rest breaks.

The whale shark ( Rhincodon typus ) is an endangered marine fish species which can be adversely affected by the fishing activities of the industrial purse seine fleet targeting tropical tuna. Tuna tend to aggregate around all types of floating objects, including whale sharks. We analyzed and modeled the spatial distribution and environmental preferences of whale sharks based on the presence and absence data from fishing observations in the Atlantic Ocean. We used a thorough multialgorithm analysis, based on a new presence-absence dataset, and endeavored to follow the most recent recommendations on best practices in species distribution modeling. First, we selected a subset of relevant variables using a generalized linear model that addressed multicollinearity, statistical errors, and information criteria. We then used the selected variables to build a model ensemble including 19 different algorithms. After eliminating models with insufficient performance, we assessed the potential distribution of whale sharks using the mean of the predictions of the selected models. We also assessed the variance among the predictions of different algorithms, in order to identify areas with the highest model consensus. The results show that several coastal regions and warm shallow currents, such as the Gulf Stream and the Canary and Benguela currents, are the most suitable areas for whale sharks under current environmental conditions. Future environmental projections for the Atlantic Ocean suggest that some of the suitable regions will shift northward, but current concentration areas will continue to be suitable for whale shark, although with less productivity, which could have negative consequences for conservation of the species. We discuss the implications of these predictions for the conservation and management of this charismatic marine species., Competing Interests: All authors declare they have no conflict of interest., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Transport properties of model compounds in aqueous solutions such as amino acids can provide valuable information in order to understand the complex interactions in aqueous solutions as well as the protein stability in water and the relevant factors involved. Informations about the diffusion of amino acids in water and in aqueous solutions of sodium chloride are very scarce, especially for the 5-aminopentanoic acid and 6-aminohexanoic acid. In this study, limiting binary mutual diffusion coefficients at 298.15 K of 5-aminopentanoic and 6-aminohexanoic acids in aqueous solutions of NaCl 0.15 mol kg -1 , using the Taylor dispersion technique, were determined and the results compared with the limiting binary mutual diffusion coefficients for 2-aminopentanoic acid, and 2-aminohexanoic acid, obtained in the same experimental conditions. The discussion of the properties of the selected amino acids is centered on the positions of the ionic groups in the hydrocarbon chain and, in addition, we have discussed the effects of NaCl on their structures and properties. The data on diffusion properties are supported by 1 H, 13 C and 23 Na NMR experiments, which we have obtained for 5-aminopentanoic and 6-aminohexanoic acids, in aqueous solution, also in the presence of NaCl.

Late-stage attentional processing of threatening stimuli, quantified through event-related potentials (ERPs), differentiates youth with and without anxiety disorders. It is unknown whether early-stage attentional processing of threatening stimuli differentiates these groups. Examining both early and late stage attentional processes in youth may advance knowledge and enhance efforts to identify biomarkers for translational prevention and treatment research. Twenty-one youth with primary DSM-IV-TR anxiety disorders (10 males, ages 8-15 years) and 21 typically developing Controls (15 males, ages 8-16 years) completed a dot probe task while electroencephalography (EEG) was recorded, and ERPs were examined. Youth with anxiety disorders showed significantly larger (more positive) P1 amplitudes for threatening stimuli than for neutral stimuli, and Controls showed the opposite pattern. Youth with anxiety showed larger (more negative) N170 amplitudes compared with Controls. Controls showed significantly larger (more positive) P2 and P3 amplitudes, regardless of stimuli valence, compared with youth with anxiety disorders. ERPs observed during the dot probe task indicate youth with anxiety disorders display distinct neural processing during early stage attentional orienting and processing of faces; this was not the case for Controls. Such results suggest these ERP components may have potential as biomarkers of anxiety disorders in youth.

Background: Maize technologies expressing Bacillus thuringiensis (Bt) insecticidal proteins are widely used in Argentina to control sugarcane borer (Diatraea saccharalis Fabricius). Unexpected D. saccharalis damage was observed to Bt maize events TC1507 (expressing Cry1F) and MON 89034 × MON 88017 (expressing Cry1A.105 and Cry2Ab2) in an isolated area of San Luis Province. Diatraea saccharalis larvae were sampled from MON 89034 × MON 88017 fields in the area to generate a resistant strain (RR), which was subsequently characterized in plant and diet bioassays., Results: Survivorship of the RR strain was high on TC1507 leaf tissue, intermediate on MON 89034 × MON 88017, and low on MON 810 (expressing Cry1Ab). The RR strain had high resistance to Cry1A.105 (186.74-fold) and no resistance to Cry2Ab2 in diet bioassays. These results indicate resistance to Cry1F and Cry1A.105 (and likely cross-resistance between them) but not to Cry1Ab or Cry2Ab2. Resistance to MON 89034 × MON 88017 was functionally recessive. Reviews of grower records suggest that resistance initially evolved to Cry1F, conferring cross-resistance to Cry1A.105, with low refuge compliance as the primary cause. A mitigation plan was implemented in San Luis that included technology rotation, field monitoring, and grower education on best management practices (BMPs) including refuges., Conclusion: In the affected area, the resistance to Cry1F and Cry1A.105 is being managed effectively through use of MON 89034 × MON 88017 and MON 810 in combination with BMPs, and no spread of resistance to other regions has been observed. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Objective We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid. Patients and methods CM women, aged 40-69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire. Results We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40-49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50-59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60-69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence. Conclusion In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Protein based hydrogels are a very interesting type of biomaterials with many probed strengths related to their source and chemical structure. Biocompatibility and biodegradability are accompanied by affordability when it comes to low cost sources. The main keratin source is agroindustrial waste, such as feathers, horns, hooves, hair and wool. Thus, the main cost of keratin hydrogels derives from their processing. Here is presented a new strategy for the obtaining of a keratin hydrogel with enhanced mechanical properties using low cost reagents. This keratin hydrogel is stiff enough to allow handling without special cares and also presenting a reversible pH-responsive behavior. The minimum swelling is observed at low pH due to a collapsed and disordered protein network with water tightly adsorbed to the hydrophilic sites. The swelling rises significantly above pH6 and the maximum swelling appears above pH8 where an expanded network allows water to enter to the pores., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.

Multinuclear ( 1 H and 13 C) NMR, and Raman spectroscopy, combined with DFT calculations, provide detailed information on the complexation between U(vi) oxoions and 8-hydroxyquinoline-5-sulfonate (8-HQS) in aqueous solution. Over the concentration region studied, U(vi) oxoions (uranyl ions) form one dominant complex with 8-HQS in water in the pH range 3-6, a mononuclear 1 : 2 (metal : ligand) complex, with the metal centre (UO 2 2+ ) coordinated to two 8-HQS ligands, together with one or more water molecules. An additional minor 1 : 1 complex has also been detected for solutions with a 1 : 1 metal : ligand molar ratio. The geometry of the dominant complex is proposed based on the combination of the NMR and Raman results with DFT calculations. Further information on the electronic structure of the complex has been obtained from UV/visible absorption and luminescence spectra. The complex of U(vi) and 8-HQS is non-luminescent, in contrast to what has been observed with this ligand and many other metal ions. We suggest that this is due to the presence of low-lying ligand-to-metal charge transfer (LMCT) states below the emitting ligand-based and uranyl-based levels which quench their emission. These studies have fundamental importance and are also relevant in the context of environmental studies, and the water soluble ligand 8-HQS has been chosen for application in uranium remediation of aqueous environments.

Background: Periodontal disease is a highly prevalent illness that affects many dogs, reaching up to 85 % prevalence in individuals over the age of 4 years. Currently the drug of choice for combating the formation of dental plaque in these animals, the etiologic agent of the disease, is chlorhexidine, which has several side effects reported. Thus, surveys are conducted throughout the world in order to identify potential substitutes for antimicrobial therapy and prevention of periodontal disease. The objective of the work was to evaluate the antimicrobial activity of β-caryophyllene against bacteria from dog's dental plaque in vitro and in vivo. The minimum inhibitory concentration was evaluated by agar microdilution assay, the induction or inhibition of bacterial adherence by sub-inhibitory concentrations in 96-well plates, and reduction of dental plaque formation in mongrel dogs subjected to topical solution with β-caryophyllene for 15 days., Results: Results showed minimum inhibitory concentrations above 100 mg/mL for 25 % of the isolates, 100 mg/mL for 3 %, 50 mg/mL for 25 %, 25 mg/mL for 12 %, 12.5 mg/mL for 19 % and 6.25 mg/mL for 16 %. Bacterial adherences of three Enterococcus sp., one Streptococcus sp., one Haemophilus sp., one Aerococcus sp., one Bacillus sp. and one Lactococcus sp. isolates were inhibited by subinhibitory concentration. One Lactococcus sp., one Bacillus sp. and one Streptococcus sp. were stimulated to adhere by concentrations of 0.19, 1.56 and 0.78 mg/mL, respectively. In vivo assay showed reduction in dental plaque formation by β-caryophyllene, with final plaque coverage of 23.3 ± 2.6 % of the total area of the teeth, with significant difference compared with chlorhexidine group (37.5 ± 3.7 % - p < 0.05) and negative control group (65.5 ± 2.5 % - p < 0.001)., Conclusions: The results showed that β-caryophyllene has antimicrobial activity against the proliferation of dog's dental plaque-forming bacteria representing a suitable alternative to the use of chlorhexidine in prophylaxis and treatment of periodontal disease of dogs.

The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10(-5); n = 54, 34%), MRD positive (between <10(-4) and ≥10(-5); n = 20, 12%), and MRD positive (≥10(-4); n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10(-4) and ≥10(-5) vs ≥10(-4) (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249., (© 2016 by The American Society of Hematology.)

We have studied the interaction of 8-hydroxyquinoline-5-sulfonate (8-HQS) with the metal ions Al(iii) and Zn(ii) in aqueous solution in the presence of tetraalkylammonium surfactants using UV/vis absorption, fluorescence, NMR spectroscopy and electrical conductivity measurements, complemented by DFT calculations and molecular dynamics (MD) simulations. Under appropriate conditions, complexes between 8-HQS and metal ions form rapidly, and have similar electronic, spectroscopic and photophysical properties to the corresponding metal quinolates, such as Alq3. These interact with the cationic surfactants, leading to marked increases in fluorescence intensity. However, significant differences are seen in the behavior of the two metal ions. With aluminium, a stable [Al(8-QS)3](3-) anion is formed, and interacts, predominantly through electrostatic interactions, with the surfactant, without disrupting the metal ion coordination sphere. In contrast, with Zn(ii), there is a competition between the metal ion and surfactants in the interaction with 8-HQS, although the [Zn(8-QS)2(H2O)2](2-) species is stable at appropriate pH and surfactant concentration. The studies are extended to systems with the conjugated polyelectrolyte (CPE) poly-(9,9-bis(6-N,N,N-trimethylammonium)hexyl)-fluorene-phenylene bromide (HTMA-PFP), which has a similar alkylammonium chain to the surfactants. Mixing metal salt, 8-HQS and HTMA-PFP in the presence of a nonionic surfactant leads to the formation of a metal complex/CPE supramolecular assembly between the conjugated polyelectrolyte and the metal/8-HQS complex, as demonstrated by electronic energy transfer. The potential of these systems in sensing, light harvesting, and electron injection/transport layers in organic semiconductor devices is discussed.