Effects of paternal and maternal depressive symptoms on child internalizing symptoms and asthma disease activity: Mediation by interparental negativity and parenting.

This study tested a hypothesized model of the relationships among parental depressive symptoms, family process (interparental negativity and negative parenting behavior), child internalizing symptoms, and asthma disease activity. A total of 106 children with asthma, aged 7 to 17, participated with their fathers and mothers. Parental depressive symptoms were assessed by self-report. Interparental and parenting behaviors were observed and rated during family discussion tasks. Child internalizing symptoms were assessed by self-report and by clinician interview and rating. Asthma disease activity was assessed according to National Heart, Lung and Blood Institute guidelines. Results of structural equation modeling generally supported interparental negativity and negative parenting behavior as mediators linking parental depressive symptoms and child emotional and physical dysfunction. However, paternal and maternal depressive symptoms play their role through different pathways of negative family process. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.     

Application of ESI and MALDI‐TOF MS for triacylglycerols analysis in edible oils

Triacylglycerols (TAG) are the most important group of compounds present in vegetable oils. These biomolecules, determining the physical, chemical and nutritional properties of the oils, are considered to be good fingerprints for quality and authenticity control. Therefore, TAGs characterization is a very important task in edible oil field, which has been undertaken by different analytical methods. The analysis of vegetable oils is still dominated by classic determinations, which are however laborious and time‐consuming and cannot be used routinely. More recently, advances in MS instrumentations coupled with online separation techniques and data processing have contributed to great expansion of MS in oil study, allowing the development of innovative analytical approaches that exhibit higher sensitivity, accuracy and rapidity in vegetable oils investigations. In the present contribution, a review of the most relevant applications of novel mass spectrometric techniques, such as ESI and MALDI, both alone and hyphenated with HPLC, used for analysis of the complex TAGs mixture of edible oils is illustrated.     

Design,Synthesis, and Evaluation of WC5 Analogues as Inhibitors of Human Cytomegalovirus Immediate‐Early 2 Protein,a Promising Target for Anti‐HCMV Treatment

Although human cytomegalovirus (HCMV) infection is mostly asymptomatic for immunocompetent individuals, it remains a serious threat for those who are immunocompromised, in whom it is associated with various clinical manifestations. The therapeutic utility of the few available anti‐HCMV drugs is limited by several drawbacks, including cross‐resistance due to their common mechanism of action, i.e., inhibition of viral DNA polymerase. Therefore, compounds that target other essential viral events could overcome this problem. One example of this is the 6‐aminoquinolone WC5 , which acts by directly blocking the transactivation of essential viral Early genes by the Immediate‐Early 2 (IE2) protein. In this study, the quinolone scaffold of the lead compound WC5 was investigated in depth, defining more suitable substituents for each of the scaffold positions explored and identifying novel, potent and nontoxic compounds. Some compounds showed potent anti‐HCMV activity by interfering with IE2‐dependent viral E gene expression. Among them, naphthyridone 1 was also endowed with potent anti‐HIV activity in latently infected cells. Their antiviral profile along with their innovative mechanism of action make these anti‐HCMV quinolones a very promising class of compounds to be exploited for more effective antiviral therapeutic treatment.     

Monitoring Pt and Rh in urban aerosols from Buenos Aires, Argentina

Vehicular traffic is the main source of platinum group elements (PGEs) in highly populated urban areas like Buenos Aires where a traffic density of 1,500,000 vehicles day(-1) (corresponding to 7,500 vehicles km(-2)) is estimated. Since there is no information on the levels of PGEs in Buenos Aires, a pilot study was undertaken to ascertain the amount of two major PGEs, namely Pt and Rh, in the atmosphere of this city. To this end, 49 samples of PM-10 particulate matter were collected during 7 days in seven representative sampling sites located downtown Buenos Aires and spread over an area of about 30 km(2). The collection of particulate matter was performed on ash-free glass-fiber filters using high volume samplers with PM-10 sampling heads. Filters loaded with the particulate matter were subjected to microwave (MW)-assisted acid digestion using a combination of HNO(3), HF and HClO(4). The resulting solutions were evaporated and then diluted with 0.1 mol l(-1) HCl. Analyses were performed by sector field inductively coupled plasma-mass spectrometry (SF-ICP-MS) and special attention was paid to the control of mass interferences. Statistical analysis was performed on the experimental data obtained for the element concentrations taking also into account local meteorological data for the monitored period. The highest concentrations of Pt and Rh were detected at two sites (Hospital Alemán and Casa Rapallini) located in streets with traffic consisting mostly of passenger cars. The Pt content (in pg m(-3)) in airborne particulate matter was found to vary from 2.3 to 47.7, with a mean value of 12.9+/-7, and that of Rh from 0.3 to 16.8, with a mean value of 3.9+/-2.8. These concentrations are by far below the levels for which adverse health effects might be expected to occur, i.e., around 100 ng m(-3). On the other hand, monitoring of PGEs should be carried out in a systematic fashion to detect possible dramatic increases from today's levels.     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Prevention of Bone Destruction by Mechanical Loading Is Not Enhanced by the Bruton’s Tyrosine Kinase Inhibitor CC-292 in Myeloma Bone Disease

Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton’s tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.