Assessment of EtQxBox complexation in solution by steady-state and time-resolved fluorescence spectroscopy

Reliable chemical sensors with high selectivity and sensitivity toward specific target molecules require rational synthesis of receptors, in-depth characterization of their complexation abilities and highly efficient transduction of the molecular recognition event. Here we report a steady-state and time-resolved fluorescence investigation of EtQxBox, a fluorescent conformationally blocked quinoxaline-based cavitand, aimed at assessing its selectivity toward aromatic versus non-aromatic analytes in solution. Fluorescence quenching of the EtQxBox in acetone is observed at increasing concentration of both aromatic (i.e. benzonitrile) and aliphatic (i.e. acetonitrile) compounds. The combination with fluorescence lifetime measurements permits to discriminate the predominantly static quenching of the aromatic analyte, due to non-fluorescent host–guest complex formation, from the mostly dynamic quenching of the non-aromatic compound, resulting from aspecific diffusive collisions between the fluorophore and the quencher. The equilibrium association constants for both the complexes have been estimated using Stern–Volmer model.

We investigate the role of combined static and dynamic quenching in fluorescence transduction of benzonitrile and acetonitrile complexation by a rigid quinoxaline-based cavitand.     

Implementing Adolescent Screening,Brief Intervention,and Referral to Treatment (SBIRT) Education in a Pediatric Residency Curriculum

Background: Screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care for adolescents as well as adults. In an effort to promote universal SBIRT, the Substance Abuse and Mental Health Services Administration awarded funding to residency programs to develop and implement SBIRT education and training. Our project focused on creating scientifically based, developmentally appropriate strategies and teaching materials for the adolescent age range. This paper describes curriculum development and implementation and presents evaluation data. Methods: Pediatric and child psychiatry residents were trained. The training consisted of 4 activities: (1) case-based teaching modules, (2) role-play of motivational interviewing and brief interventions, (3) mock interviews with trained adolescents, and (4) supervised “hands-on” screening and brief interventions. Main outcome measures included trainee satisfaction, and SBIRT knowledge, perceived self-efficacy, and self- and observer report of use of the SBIRT algorithm. Results: Among 150 total participants completing the SBIRT training modules, nearly all (92.3%) were satisfied/very satisfied with the training modules. Knowledge accuracy immediately post training was high, but declined significantly by the end of the first residency year, with little change across subsequent years of residency. Confidence ratings also declined over time. Use of the SBIRT algorithm during the Adolescent Medicine rotation was high according to trainee self- and faculty observer report. Conclusions: We found evidence of training satisfaction, increased confidence in talking to adolescents about substance use, and widespread use of recommended practices immediately following training. Use of a highly structured algorithm to guide practice, and simple, highly structured brief interventions was a successful training approach, as residents self-reported accurate use of the SBIRT algorithm immediately after training. Knowledge and self-confidence declined over time. It is possible that “booster” sessions and ongoing opportunities to review materials could help residents retain knowledge and skills.     

Non-coronary cardiac events,younger age,and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease

Clinical Rheumatology - Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for...     

Contrast-Enhanced Spectral Mammography and tumor size assessment: a valuable tool for appropriate surgical management of breast lesions

Purpose

To compare the accuracy of Contrast-Enhanced Spectral Mammography (CESM), MG, US, and breast MRI in estimating the size of breast lesions requiring surgery. The postoperative histology size of the lesion was used as the gold standard.

Material and methods

Two hundred thirty-three non-benign lesions in 189 patients were included in the analyses. All the selected patients underwent CESM and at least one other conventional diagnostic exam (US, MG, or MRI). Subsequently, all the patients underwent surgery preceded by cytological/histological examination. The largest diameter of the lesion at imaging was measured by a radiologist with more than 10 years’ experience and then compared with the size of the lesion in the histological sample at the surgery (gold standard).

Results

Among the 233 breast lesions, 196 were evaluated with US, 206 with MG and 160 with MRI. We found no statistically significant differences between size measurements using CESM and MRI compared with the measurements at the surgery (p value 0.63 and 0.51), whereas a significant difference was found for MG and US (p?<?0.001).

Conclusion

CESM is a reliable method for estimating the size of breast lesions: its performance seems superior to US and MG and comparable to MRI.

     

Two peculiar cases of cranial fractures running through craniotomy burr holes: may this be a kind of “exception” to the Puppe rule

International Journal of Legal Medicine - A correct assessment on the position, path, and direction of fracture lines is crucial when the sequence of different injuries on the skull has to be...     

Inhibition of influenza A virus replication by resveratrol

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.     

Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies

Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects.