Geothermal characterization of the coastal aquifer near Ravenna (Italy)

The coastal aquifer near Ravenna (Italy) contains a large volume of groundwater (2,5x109 m3) whose quality has been compromised by sea-water intrusion. Today, the phreatic groundwater is mostly brackish with some lenses of freshwater floating on top of more saline water. This water, although impossible to use as drink-water or for irrigation, is still important to guarantee the health of wetland habitats and especially of the roman historical and coastal pine forests of Ravenna. With the objective of defining the flow pattern within the aquifer and the exchange between surface and ground water, we characterized the temperature distribution in the shallow subsurface by means of a dense network of piezometers. At the same time we had the opportunity to characterize the phreatic aquifer from the geothermal point of view, so that it could eventually be considered for use as a "low enthalpy" heat source. Heat pumps are able to extract heat during the winter and dissipate it during the summer. The temperature of the groundwater in the top layer of the aquifer (surficial zone) is sensitive to the changes in atmospheric temperature throughout the year whereas the temperature of the deeper groundwater follows the geothermal gradient (geothermal zone). One of the scopes of the project is to discover at what depth is located the geothermal zone, so that the aquifer has a constant temperature throughout the year. A constant temperature is needed for storage of heat at low enthalpy. The thickness of the surficial zone and the temperature at the top of the geothermal zone are essentially related to land use, distance from the sea, sediment type, and amount of interaction between surface and groundwater. A knowledge of these factors allows to better exploit the geothermal potential of the aquifer when choosing the optimal placement of the heat pumps

Does MtN5 play a double role in root responses to symbiontic and pathogenic microorganisms?

MtN5, a new Lipid Transfer Protein, has been identified in nodulated roots of Medicago truncatula andpreliminarily classified as early nodulin, which is expressed in response to rhizobial symbiosis. Wehave shown that the recombinant MtN5 exerts antifungal and antimicrobial activity in vitro againstFusarium semitectum and Rhizobium leguminosarum, respectively. In vivo, the fungal infection leadsto the expression of MtN5 in the whole root apparatus of M. truncatula plants, whereas the inoculationwith rhizobia induces an early and nodule-specific expression of the protein, that is also maintained inmature nodules. These two different expression patterns suggest a putative double role for MtN5, whichcould be involved both in a general response mechanism against fungi and in sensing or controlling theinfection of the symbiont. This last hypothesis is supported by the observation that M.truncatula rootstransformed with an hairpin construct aiming to silence endogenous MtN5, are impaired in noduleformation respect to control roots. Therefore, MtN5 is hereby proposed as a novel, multifunctionalprotein taking part in the symbiotic process

The boy who refused an IV: a case report of subcutaneous clodronate for bone pain in a child with Ewing Sarcoma

BACKGROUND: Bone pain in malignancy can be challenging to treat. Bisphosphonates have been found to be useful in adults with bone pain, but there are no reports of their use in children for this indication. In pediatric palliative medicine there are hurdles in translating knowledge gained primarily in adult studies into application in children. Obstacles exist in initially determining whether the evidence supports using a drug in children, and once a drug is chosen, then determining the optimal route of delivery. There is very little data to guide pediatric practitioners in this situation. CASE PRESENTATION: A 9 year old boy with disseminated Ewing Sarcoma presented with extremity pain not responsive to a combination of opiates, gabapentin and non-steroidal anti-inflammatory drugs. Clodronate, a bisphosphonate, was added to the regimen to treat bone pain. It was given subcutaneously every 4 weeks with a good response and no side effects. CONCLUSION: This case report describes the use of a bisphosphonate, clodronate, given subcutaneously to a child with Ewing sarcoma with effective relief of bone pain. It describes how the care team encountered the challenges inherent in translating adult therapy into a pediatric regimen. Furthermore the report details how a regimen was developed to address this child's concerns regarding medication administration. Further effort needs to be made at finding solutions to address the lack of good evidence for pediatric palliative therapies

A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism

The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698)

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children

Assessment of antibody library diversity through next generation sequencing and technical error compensation

Antibody libraries are important resources to derive antibodies to be used for a wide range of applications, from structural and functional studies to intracellular protein interference studies to developing new diagnostics and therapeutics. Whatever the goal, the key parameter for an antibody library is its complexity (also known as diversity), i.e. the number of distinct elements in the collection, which directly reflects the probability of finding in the library an antibody against a given antigen, of sufficiently high affinity. Quantitative evaluation of antibody library complexity and quality has been for a long time inadequately addressed, due to the high similarity and length of the sequences of the library. Complexity was usually inferred by the transformation efficiency and tested either by fingerprinting and/or sequencing of a few hundred random library elements. Inferring complexity from such a small sampling is, however, very rudimental and gives limited information about the real diversity, because complexity does not scale linearly with sample size. Next-generation sequencing (NGS) has opened new ways to tackle the antibody library complexity quality assessment. However, much remains to be done to fully exploit the potential of NGS for the quantitative analysis of antibody repertoires and to overcome current limitations. To obtain a more reliable antibody library complexity estimate here we show a new, PCR-free, NGS approach to sequence antibody libraries on Illumina platform, coupled to a new bioinformatic analysis and software (Diversity Estimator of Antibody Library, DEAL) that allows to reliably estimate the complexity, taking in consideration the sequencing error.Funded by European Union Seventh Framework Program [grant No. 604102 A.C.] (Human Brain Project). https://www.humanbrainproject.eu/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

BACKGROUND: Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. RESULTS: We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. CONCLUSIONS: We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.This work was funded by: FIRB RBAP10L8TY (MIUR), Fondazione Roma and PAINCAGE FP7 Collaborative Project number 603191 (RB,MD); Flagship Project InterOmics PB.05 and MIUR-PRIN-2012 (FC); Wellcome Trust Core Grant reference 092096 and Cancer Research UK Grant Reference C6946/A14492 (LP); CRUK-Cambridge Institute Core Grant reference C14303/A17197 (DB)

Off-label Utilization of Antihypertensive Medications in Children

Objective— To examine off-label utilization and costs of antihypertensive drugs in children using a national sample of prescription claims. Design— Cross-sectional study. Setting— 2002 Medstat MarketScan Database, a national sample of outpatient prescription claims of children ≥18 years old enrolled in private, employer-sponsored health plans. Main Outcome Measures— Off-label use of antihypertensive drugs by patient age and costs of antihypertensives calculated as mean cost per child per 30-day fill. Results— One-half of the index antihypertensive prescription claims were off-label, based on minimum age criteria. Boys were more likely (56%) than girls (46%) to be prescribed off-label antihypertensives (p<0.001). Children aged ≥12 years were more likely to be prescribed off-label antihypertensives (53%) compared with children aged ≥5 (46%) and 6–11 years (42%, p<0.001). Off-label use varied significantly by class of antihypertensive drugs (p<0.001). Overall, off-label antihypertensives were significantly more expensive than on-label antihypertensives. Conclusions— Despite availability of often less expensive on-label alternatives for the same class of antihypertensive drugs, off-label antihypertensive drugs were prescribed frequently in children. These findings underscore the potential clinical and economic implications of common off-label prescribing, for children, their parents, physicians and payers. Originally published Ambulatory Pediatrics, Vol. 7, No. 4, July 200

Genetically modified parthenocarpic eggplants: improved fruit productivity under both greenhouse and open field cultivation

BACKGROUND: Parthenocarpy, or fruit development in the absence of fertilization, has been genetically engineered in eggplant and in other horticultural species by using the DefH9-iaaM gene. The iaaM gene codes for tryptophan monoxygenase and confers auxin synthesis, while the DefH9 controlling regions drive expression of the gene specifically in the ovules and placenta. A previous greenhouse trial for winter production of genetically engineered (GM) parthenocarpic eggplants demonstrated a significant increase (an average of 33% increase) in fruit production concomitant with a reduction in cultivation costs. RESULTS: GM parthenocarpic eggplants have been evaluated in three field trials. Two greenhouse spring trials have shown that these plants outyielded the corresponding untransformed genotypes, while a summer trial has shown that improved fruit productivity in GM eggplants can also be achieved in open field cultivation. Since the fruits were always seedless, the quality of GM eggplant fruits was improved as well. RT-PCR analysis demonstrated that the DefH9-iaaM gene is expressed during late stages of fruit development. CONCLUSIONS: The DefH9-iaaM parthenocarpic gene is a biotechnological tool that enhances the agronomic value of all eggplant genotypes tested. The main advantages of DefH9-iaaM eggplants are: i) improved fruit productivity (at least 30-35%) under both greenhouse and open field cultivation; ii) production of good quality (marketable) fruits during different types of cultivation; iii) seedless fruit with improved quality. Such advantages have been achieved without the use of either male or female sterility genes