The main goal of this study was to accurately detect azole resistance in species of the Aspergillus fumigatus complex by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ...(MALDI-TOF MS).
Identification of isolates (n = 868) was done with MALDI-TOF MS using both commercial and in-house libraries. To determine azole susceptibility, the EUCAST E.Def. 9.3.2 method was applied as the reference standard. Identification of resistant isolates was confirmed by DNA sequence analysis. Protein spectra obtained by MALDI-TOF MS were analysed to differentiate species within the A. fumigatus complex and to detect azole-resistant A. fumigatus sensu stricto isolates.
Correct discrimination of A. fumigatus sensu stricto from cryptic species was accomplished in 100% of the cases applying principal component analysis (PCA) to protein spectra generated by MALDI-TOF MS. Furthermore, a specific peak (4586 m/z) was found to be present only in cryptic species. The application of partial least squares (PLS) discriminant analysis allowed 98.43% (±0.038) discrimination between susceptible and azole-resistant A. fumigatus sensu stricto isolates. Finally, based on PLS and SVM, A. fumigatus sensu stricto isolates with different cyp51A gene mutations were correctly clustered in 91.5% of the cases.
MALDI-TOF MS combined with peak analysis is a novel tool that allows the differentiation of A. fumigatus sensu stricto from other species within the A. fumigatus complex, as well as the detection of azole-resistant A. fumigatus sensu stricto. Although further studies are still needed, the results reported here show the great potential of MALDI-TOF and machine learning for the rapid detection of azole-resistant Aspergillus fumigatus isolates from clinical origins.
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Left atrium (LA) size has an important role in determining prognosis and risk stratification in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance myocardial feature tracking ...(CMR-FT) is a novel technique for the quantification of LA function. Our aim was first to evaluate LA function by CMR-FT and volumetric analysis in patients with HCM; and secondly we sought to determine the association of LA-longitudinal strain (LA-LS) with major cardiovascular outcomes, particularly all cause mortality and heart failure. 75 patients with HCM and 75 control subjects underwent a conventional CMR study including assessment of LA function by CMR-FT (LA-LS) and volumetric analysis. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Compared to controls, LA-LS and all volumetric indices of LA function were significantly impaired in HCM even in patients with normal LA volume and normal LV filling pressures. LA-LS showed moderate-high correlation with LA-emptying fraction (total, active and passive LA-EF, r = 0.68, r = 0.67, r = 0.31, p < 0.001 for all) and with parameters of diastolic function (E/é, r = 0.4, p < 0.001). The age, minimum LA volume and % of LGE were independent predictors of LA-LS (p < 0.01 for all). During a mean follow-up of 3.3 ± 1.2 years LA-LS was associated with the primary (HR: 0.85 (0.73–0.98), p = 0.02) and the secondary end-point (HR: 0.88 (0.82–0.96), p = 0.003). LA-LS by CMR-FT provides accurate measurements of LA function in HCM patients. LA-LS may become a novel potential predictor of poor cardiac outcomes, particularly cardiovascular mortality and HF.
Right ventricle (RV) dilatation and dysfunction are established criteria for intervention in severe tricuspid regurgitation (TR); however thresholds to support intervention are lacking. New measures ...of RV function such as RV shortening (RVS) and effective RV ejection fraction (eRVEF) may be earlier markers of RV dysfunction.
to compare the prognostic impact of different parameters of RV function and to describe cut-off values of RV size/function and TR severity of poor prognosis.
Consecutive patients evaluated in the Heart Valve Clinic with significant TR (severe, massive or torrential TR) undergoing a CMR study were included. In addition to parameters of biventricular volume and function, RVS and eRVEF were assessed. A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined.
75 patients were included (age 75 ± 8 years, female 75%). During a median follow-up of 3 years (IQR: 1.4–3.9 years), 39% experienced the endpoint. Cut-off values of worse prognosis were: RVS ≥ −14%, eRVEF ≤34%, RVEF ≤58%, RV-EDV ≥100 ml/m2, TR regurgitant fraction (TRF) ≥40% and TR volume ≥ 42 ml. RVS and eRVEF identified higher rates of RV dysfunction than RVEF. After adjustment for age and LVEF, both eRVEF ≤34% (HR: 5.29 2.25–12.4) and RVS ≥ −14% (HR: 3.46 1.13–9.17) were significantly associated with outcomes. Among all parameters of RV function, eRVEF was the strongest predictor of outcomes, incremental to RVEF (ΔC-statistic 0.139 0.040–0.237, p = 0.005). Patients with eRVEF ≤34% and RV-EDV ≥100 ml/m2 or eRVEF ≤34% and TRF ≥40% had the worst prognosis (p < 0.01 for both).
RVS and eRVEF identify higher rates of RV dysfunction beyond RVEF. Among all measures, eRVEF held the strongest association with outcomes, incremental to RVEF.
•Accurate assessment of RV size and systolic function is determinant in patients with severe tricuspid regurgitation (TR).•For the moment RV thresholds of poor outcomes to support intervention are lacking. · While RVEF by CMR remain the gold standard, it can overestimate RV function in severe TR.•RV shortening and effective RVEF can be easily calculated in conventional studies without additional sequences or dedicated software’s.•Both parameters detect higher rates of RV dysfunction. Among all, eRVEF has the strongest association with outcomes, incremental to RVEF.
Interstitial fibrosis, myocardial fiber disarray and non-uniform shortening are common histological features of hypertrophic cardiomyopathy (HCM). The degree of LV hypertrophy and fibrosis are ...postulated to contribute to the impairment of myocardial shortening. Cardiovascular magnetic resonance myocardial (CMR) feature tracking (CMR-FT) has emerged as a robust method that provides quantitative measurements of myocardial deformation. Our aim was first to evaluate LV strain parameters in HCM by CMR-FT and their dependence on both functional parameters and late gadolinium enhancement (LGE); and secondly we sought to determine their association with major cardiovascular outcomes.
74 patients with HCM and 75 controls subjects underwent a CMR study including LGE imaging. Global peak longitudinal, circumferential and radial systolic strain values (GLS, GCS, GRS) were measured by CMR-FT. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Patients with HCM showed attenuation of all LV strain values (p<0.001). Multivariate analysis showed that both LV hypertrophy and %of LGE were independent predictors of attenuated LV strains. All systolic LV strain parameters were impaired in patients with primary and secondary endpoints (follow up time: 25.6±9.9months, p<0.05 and p<0.01 respectively). Abnormal GLS, GCS and GRS were significantly associated with primary and secondary endpoints.
Both LV hypertrophy and fibrosis contribute to the impairment of LV myocardial mechanics in HCM. In this population, reduced LV strain is associated with poor cardiac outcomes, particularly cardiovascular mortality and HF.
Sistema CRISPR/Cas: Edición genómica de precisión Riveros-Maidana, Rocío; Méndez-Ferreira, Alejandro; Benítez-Candia, Nidia ...
Memorias del Instituto de Investigaciones en Ciencias de la Salud,
04/2020, Letnik:
18, Številka:
1
Journal Article
Cow's milk protein can cause food allergy. The different mechanisms of action involved, the clinical variability depending on the stage of pediatric life in which it manifests, leads to difficulties ...in its approach, with the risk of under- or over-diagnosis. Professionals from various areas intervene in this process and their interaction is recommended. That is why the objective of this consensus has been to reflect the updated knowledge in an interdisciplinary mode, generating recommendations for its correct diagnosis. We have worked with the Delphi method to add to the scientific evidence, the experience from neonatologists, pediatricians, experts in allergy, nutrition and gastroenterology. We think that this interdisciplinary approach will be of practical use and will promote more comprehensive care for these patients.
To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with ...anti-VEGF drugs nationwide.
Multicenter national nAMD database observational study.
One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide.
Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification.
Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation.
A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions.
This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several ...problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L. braziliensis 9and L. donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had IC50 values in the micromolar range against the amastigote of L. mexicana and L. braziliensis. However, both compounds did not show better activity against L. donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L. mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives.
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•A series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives were synthesized.•Compounds 7 and 8 were very active against L. mexicana promastigotes and amastigotes.•Compound 8 had high selectivity index against L. mexicana and L. braziliensis.•Compound 8 inhibited 68.27% the activity of recombinant Leishmania mexicana Arginase.•Compound 8 is a good scaffold for the development of new antileishmanial agents.
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