1,873 research outputs found
Theoretical Investigations of the Effects of J-Aggregation on the Linear and Nonlinear Optical Properties of E-4-(4-Dimethylaminostyryl)-1-methylpyridinium [DAMS + ]
J-type aggregation of organic chromophores into inorganic host matrixes provides a useful route toward materials showing strong second-order nonlinear optical (NLO) response. The increased NLO response of J-aggregates is related to the peculiar arrangement of the NLO-phores into the host matrix, which produces the appearance of a narrow and intense band in the material electronic absorption spectrum, red-shifted with respect to the main absorption band of the isolated NLO-phore. A theoretical investigation, based on DFT, TDDFT, and ZINDO calculations on the relationship between the structural features of various or oligomeric aggregates and their linear and nonlinear optical properties shows that the appearance of a new red-shifted absorption band, typical of J-aggregation, is associated with interchromophoric transitions of charge-transfer character, due to the splitting of HOMO and LUMO levels. The intensity of this latter band increases by increasing the number of NLO-phores in a model of oligomeric arrangement of J-aggregates. The calculated quadratic hyperpolarizabilities for the mostly responsive J-type trimeric aggregates of [DAMS + ] are found to largely exceed that of three isolated NLO-phores, confirming a cooperative NLO strong contribution due to J-aggregation. Finally, our DFT and TDDFT calculations on eclipsed or with opposite dipole dimeric H-aggregates of [DAMS + ] show a splitting of HOMO and LUMO levels, which gives place to interchromophoric transitions of chargetransfer character but blue-shifted, as observed experimentally
Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: A meta-analysis
Background: We sought to evaluate the diagnostic accuracy of 64-slice multi-detector row computed tomography (MDCT) compared with invasive coronary angiography for in-stent restenosis (ISR) detection. Methods: MEDLINE, Cochrane library, and BioMed Central database searches were performed until April 2009 for original articles. Inclusion criteria were (1) 64-MDCT was used as a diagnostic test for ISR, with >50% diameter stenosis selected as the cut-off criterion for significant ISR, using invasive coronary angiography and quantitative coronary angiography as the standard of reference; (2) absolute numbers of true positive, false positive, true negative, and false negative results could be derived. Standard meta-analytic methods were applied. Results: Nine studies with a total of 598 patients with 978 stents included were considered eligible. On average, 9% of stents were unassessable (range 0-42%). Accuracy tests with 95% confidence intervals (CIs) comparing 64-MDCT vs invasive coronary angiography showed that pooled sensitivity, specificity, positive and negative likelihood ratio (random effect model) values were: 86% (95% CI 80-91%), 93% (95% CI 91-95%), 12.32 (95% CI 7.26-20.92), 0.18 (95% CI 0.12-0.28) for binary ISR detection. The symmetric area under the curve value was 0.94, indicating good agreement between 64-MDCT and invasive coronary angiography. Conclusions: 64-MDCT has a good diagnostic accuracy for ISR detection with a particularly high negative predictive value. However, still a relatively large proportion of stents remains uninterpretable. Accordingly, only in selected patients, 64-MDCT may serve as a potential alternative noninvasive method to rule out ISR
Whole-body low-dose CT recognizes two distinct patterns of lytic lesions in multiple myeloma patients with different disease metabolism at PET/MRI
We evaluated differences in density and 18F-FDG PET/MRI features of lytic bone lesions (LBLs) identified by whole-body low-dose CT (WB-LDCT) in patients affected by newly diagnosed multiple myeloma (MM). In 18 MM patients, 135 unequivocal LBLs identified by WB-LDCT were characterized for inner density (negative or positive Hounsfield unit (HU)), where negative density (HU\u2009<\u20090) characterizes normal yellow marrow whereas positive HU correlates with tissue-like infiltrative pattern. The same LBLs were analyzed by 18F-FDG PET/DWI-MRI, registering DWI signal with ADC and SUV max values. According to HU, 35 lesions had a negative density (-\u200956.94\u2009\ub1\u200931.87 HU) while 100 lesions presented positive density (44.87\u2009\ub1\u200923.89 HU). In seven patients, only positive HU LBLs were demonstrated whereas in eight patients, both positive and negative HU LBLs were detected. Intriguingly, in three patients (16%), only negative HU LBLs were shown. At 18F-FDG PET/DWI-MRI analysis, negative HU LBLs presented low ADC values (360.69\u2009\ub1\u2009154.38\u2009
7\u200910-6 mm2/s) and low SUV max values (1.69\u2009\ub1\u20090.56), consistent with fatty marrow, whereas positive HU LBLs showed an infiltrative pattern, characterized by higher ADC (mean 868.46\u2009\ub1\u2009207.67\u2009
7\u200910-6 mm2/s) and SUV max (mean 5.04\u2009\ub1\u20091.94) values. Surprisingly, histology of negative HU LBLs documented infiltration by neoplastic plasma cells scattered among adipocytes. In conclusion, two different patterns of LBLs were detected by WB-LDCT in MM patients. Both types of lesions were indicative for active disease, although only positive HU LBL were captured by 18F-FDG PET/DWI-MRI imaging, indicating that WB-LDCT adds specific information
Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients
Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib produced historical rates of about 50% complete cytogenetic response (CCyR) and about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML) patients failing imatinib. Direct comparisons between dasatinib and nilotinib are lacking, and few studies addressed the dynamics of deep molecular response (DMR) in a "real-life" setting. We retrospectively analyzed 163 patients receiving dasatinib (n= 95) or nilotinib (n= 68) as second-line therapy after imatinib. The two cohorts were comparable for disease's characteristics, although there was a higher rate of dasatinib use in imatinib-resistant and of nilotinib in intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median follow-up of 48 months, 60% of patients persisted on their second-line treatment. Rates and kinetics of cytogenetic and molecular responses, progression-free and overall survival were similar for dasatinib and nilotinib. In a "real-life" setting, dasatinib and nilotinib resulted equally effective and safe after imatinib failure, determining high rates of CCyR and MMR, and a significant chance of stable DMR, a prerequisite for treatment discontinuation
Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model
Abstract: Although medicinal mushroomextracts have been proposed as promising anti-cancer agents,
their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present
study exploited the eect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1
triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care,
consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa,
and Lentinula edodes. The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in
both supplemented and non-supplemented mice. After sacrifice 35 days later, specific endpoints and
pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and
ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2,
SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively
evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the
end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a
decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1
results were also discussed. These findings support the valuable potential of Micotherapy U-care as
adjuvant therapy in the critical management of triple-negative breast cancer
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The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients
Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals
Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia
Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1
7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100
7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings
Notulae to the Italian flora of algae, bryophytes, fungi and lichens: 7
In this contribution, new data concerning algae, bryophytes, fungi, and lichens of the Italian flora are presented. It includes new records and confirmations for the algae genus Chara, the bryophyte genera Cephalozia, Conardia, Conocephalum, Didymodon, Sphagnum, Tetraplodon, and Tortula, the fungal genera Endophyllum, Gymnosporangium, Microbotryum, Phragmidium, and Pluteus, and the lichen genera Candelariella, Cladonia, Flavoplaca, Lichenothelia, Peltigera, Placolecis, Rinodina, Scytinium, and Solenopsora
Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.
OBJECTIVE: To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A-ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). METHODS: Cross-modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype-phenotype correlations, 3D-protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. RESULTS: Fifty-nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross-sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild-to-moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: -0.81/year). Explorative sample size calculations indicate that ≥48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. INTERPRETATION: This study provides a deeper understanding of the disease, and paves the way toward large-scale natural history studies and treatment trials in COQ8A-ataxia. ANN NEUROL 2020;88:251-263
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