A partnership between academic and public librarians: “What the Health” workshop series

Background: Public librarians are in a unique position to assist the general public with health information inquiries. However, public librarians might not have the training, detailed knowledge, and confidence to provide high-quality health information. Case Presentation: The authors created and delivered three workshops to public librarians in Suffolk County, New York, highlighting several National Library of Medicine resources. Each workshop focused on a different topic: general consumer health resources, genetics health resources, and environmental/toxicology resources. At the end of each workshop, participants were asked to complete the Training Session Evaluation form provided by the National Network of Libraries of Medicine (NNLM). All participants reported that they learned a new skill or about a new tool, that their ability to locate online health information improved, and that they planned to use the knowledge they gained in the future. Online tutorials covering the major resources from each workshop were created and made accessible to the public on several organizations’ websites. Virtual reference services were initiated for public librarians who need further assistance with these resources and will continue to be provided on an ongoing basis. Financial support for the equipment and software utilized in each of these tasks was awarded by NNLM. Conclusions: Based on attendance and participant feedback, this model of health information outreach appears to have been successful in furthering the educational needs of public librarians and may be useful to others in creating a similar program in their communities

Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression *

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway that is responsible for the generation of NADPH, which is required in many detoxifying reactions. We have recently demonstrated that G6PD expression is induced by a variety of chemical agents acting at different steps in the biochemical pathway controlling the intracellular redox status. Although we obtained evidence that the oxidative stress-mediated enhancement of G6PD expression is a general phenomenon, the functional significance of such G6PD induction after oxidant insult is still poorly understood. In this report, we used a GSH-depleting drug that determines a marked decrease in the intracellular pool of reduced glutathione and a gradual but notable increase in G6PD expression. Both effects are seen soon after drug addition. Once G6PD activity has reached the maximum, the GSH pool is restored. We suggest and also provide the first direct evidence that G6PD induction serves to maintain and regenerate the intracellular GSH pool. We used HeLa cell clones stably transfected with the human G6PD gene that display higher G6PD activity than the parent HeLa cells. Although the activities of glutathione peroxidase, glutathione reductase, and catalase were comparable in all strains, the concentrations of GSH were significantly higher in G6PD-overexpressing clones. A direct consequence of GSH increase in these cells is a decreased reactive oxygen species production, which makes these cells less sensitive to the oxidative burst produced by external stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong protection against oxidants-mediated cell killing. We also observe that NF-kappa B activation, in response to tumor necrosis factor-alpha treatment, is strongly reduced in human HeLa cells overexpressing G6PD

Design, synthesis, biophysical and biological studies of trisubstitutednaphthalimides as G-quadruplex ligands

A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)3 binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UVmelting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment

La comunicazione con il mercato

Una gestione unitaria e coerernte della comunicazione è indispensabile per un'azienda di servizi pubblici che voglia orientarsi al cliente e rispondere con prontezza ai mutamenti del mercato. Una ricerca condotta per l'Atan di Napoli ha fornito preziose informazioni sul profilo degli utenti e sui loro livelli di soddisfazione, permettendo così azioni di miglioramento del servizio di trasporto pubblico urbano

Anti-cancer activity of grape seed semi-polar extracts in human mesothelioma cell lines

Malignant mesothelioma is a tumor that affects pleural surface and has very poor prognosis. The standard therapeutic modalities for this cancer have yielded unsatisfactory outcomes, therefore the development of alternative and effective therapies is currently an urgent requirement. Grapevine is a plant rich of bioactive compounds, known for its therapeutic effects. Here, we describe the anti-cancer activity of grape seeds semi-polar extracts of two Italian grape varieties (Aglianico and Falanghina) in mesothelioma in vitro. Seed extracts from both varieties induced intrinsic apoptosis in a dose and time-dependent manner in three different human mesothelioma cell lines. Global metabolic analysis of this fraction revealed a higher accumulation of phenylpropanoid precursors and proanthocyanidins and expression of genes involved in the aforementioned pathways. These findings suggest that new phenolic molecules from grape seeds could be viewed as new drugs to be used alone or in combinations with standard chemotherapeutics in mesothelioma treatment

Granulocyte–colony stimulating factor plus plerixafor in patients with β-thalassemia major results in the effective mobilization of primitive CD34+ cells with specific gene expression profile

Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic stem and progenitor cells (HSPCs) with high repopulating capacity. Previous studies suggested superior mobilization in these patients by the combination of granulocyte–colony stimulating factor (G-CSF) plus plerixafor over single agents. We mobilized four adult patients using G-CSF+plerixafor to assess the intra-individual variation of the circulating CD34+ cells number and subtypes preand post-plerixafor administration. The procedure was well-tolerated and the target cell dose of ≥8×106 CD34+ cells/kg was achieved in three of them with one apheresis procedure. The addition of plerixafor unanimously increased the number of circulating CD34+ cells, and the frequency of the most primitive CD34+ subtypes: CD34+/38- and CD34+/133+/38- as well as the in vitro clonogenic potency. Microarray analyses of CD34+ cells purified from the leukapheresis of one patient mobilized twice, with G-CSF and with G-CSF+plerixafor, highlighted in G-CSF+plerixafor-mobilized CD34+ cells, higher levels of expression genes involved in HSPC motility, homing, and cell cycles. In conclusion, G-CSF+plerixafor in β-thalassemia patients mobilizes optimal numbers of HSPCs with characteristics that suggest high capacity of engraftment after transplantation.   β地中海贫血的成功基因治疗需要最佳数量具有较高再生能力的自体基因转导的造血干细胞和祖细胞（HSPC）。之前的研究表明，与单药相比，通过组合粒细胞集落刺激因子（G-CSF）加普乐沙福在这些患者中有出色的动员作用。我们使用G-CSF+普乐沙福对四例成年患者进行了动员，以评估服用普乐沙福之前和之后的循环CD34+细胞数量和亚型的个体内差异。这种方式的耐受性好，其中的三例患者仅通过一次分离技术即获得≥8×106 CD34+细胞/kg的细胞采集目标。加用普乐沙福毫无例外地增加了循环CD34+细胞的数量和最原始CD34+亚型（CD34+/38-和CD34+/133+/38+）的频率以及体外克隆效力。一例血细胞分离术中纯化的CD34+细胞微阵列分析（患者使用G-CSF和G-CSF+普乐沙福动员两次）强调，在G-CSF+普乐沙福动员的CD34+细胞中，有更高水平的表达基因牵涉到HSPC运动性、归巢和细胞周期。总之，G-CSF+普乐沙福在β地中海贫血病患者中可以动员最优数量的HSPC，具有移植后的移植成活率高的特征

Nociceptin/Orphanin Fq in inflammation and remodeling of the small airways in experimental model of airway hyperresponsiveness

It is widely recognized that airway inflammation and remodeling play a key role not only in the central airway but also small airway pathology during asthma. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide, and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). We studied a murine model of AHR in order to understand the role of N/OFQ in the inflammation and remodeling of the small airways. Balb/c mice were sensitized to ovalbumin (OVA). At days 0 and 7 (pre-OVA sensitization) or from day 21 to 23 (post-OVA sensitization), the mice were treated intraperitoneally with N/OFQ or saline solution. After the last OVA challenge, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS for 48 h, and then euthanized. Small airway compliance (sCaw ) was measured and lung samples were collected for histological and molecular evaluations such as perimeter and diameter of small airway, total wall area, airway smooth muscle (ASM) thickness and number of alveolar attachments. Both pre- and post-OVA sensitization N/OFQ treatments induced: (1) increases in sCaw ; (2) reduction of the bronchial wall thickness; (3) attenuation of the hyperplastic phase of airway smooth muscle mass; and (4) protection against loss of alveolar attachments compared with saline solution treatments. These results suggest that N/OFQ protects against inflammation, and mechanical damage and remodeling of small airways caused by OVA sensitization, suggesting a new potential therapeutic target for asthma

Genetic Inactivation of Kcnj16 Identifies Kir5.1 as an Important Determinant of Neuronal PCO2/pH Sensitivity*

The molecular identity of ion channels which confer PCO2/pH sensitivity in the brain is unclear. Heteromeric Kir4.1/Kir5.1 channels are highly sensitive to inhibition by intracellular pH and are widely expressed in several brainstem nuclei involved in cardiorespiratory control, including the locus coeruleus. This has therefore led to a proposed role for these channels in neuronal CO2 chemosensitivity. To examine this, we generated mutant mice lacking the Kir5.1 (Kcnj16) gene. We show that although locus coeruleus neurons from Kcnj16(+/+) mice rapidly respond to cytoplasmic alkalinization and acidification, those from Kcnj16(−/−) mice display a dramatically reduced and delayed response. These results identify Kir5.1 as an important determinant of PCO2/pH sensitivity in locus coeruleus neurons and suggest that Kir5.1 may be involved in the response to hypercapnic acidosis