Artificial recharge by means of careo channels versus natural aquifer recharge in a semi-arid, high-mountain watershed (Sierra Nevada, Spain)

This research was undertaken as part of the project "Impact, monitoring and assessment of global and climate change on water resources in high-mountain National Parks (CCPM) ", with reference number CANOA-51.3.00.43.00 and funded by Organismo Autonomo Parques Nacionales from the Ministerio para la Transicion Ecologica y el Reto Demografico. The authors thank the Ibero-American Science and Technology for Devel-opment Programme (CYTED) for its financial support to the network "Wa-ter Sowing and Harvesting in Protected Natural Areas" (419RT0577) . This work is a contribution to the Research Group RNM-126 of the Junta de Andalucia. Special thanks goes to the irrigation community in Berchules and the Sierra Nevada National Park for their collaboration. We also appre-ciate the support of AEMET and REDIAM, who provided meteorological and hydrological data. The authors would also like to thank the anonymous reviewers for their constructive comments and suggestions which led to a substantial improvement of the paper.The acequias de careo are ancestral water channels excavated during the early Al-Andalus period (8th–10th centuries), which are used to recharge aquifers in the watersheds of the Sierra Nevada mountain range (Southeastern Spain). The water channels are maintained by local communities, and their main function is collecting snowmelt, but also runoff from rainfall fromthe headwaters of river basins and distributing it throughout the upper parts of the slopes. Thismethod of aquifer artificial recharge extends the availability of water resources in the lowlands of the river basins during the dry season when there is almost no precipitation and water demand is higher. This study investigates the contribution of the careo channels in the watershed of Bérchules concerning the total aquifer recharge during the 2014–2015 hydrological year. Several channels were gauged, and the runoff data were compared with those obtained from a semi-distributed hydrological model applied to the same hydrological basin. The natural infiltration of meteoric waters accounted for 52%of the total recharge, while the remaining 48% corresponded to water transported and infiltrated by the careo channels. In other words, the careo recharge system enhances by 92% the natural recharge to the aquifer. Our results demonstrate the importance of this ancestral and efficient channel system for recharging slope aquifers developed in hard rocks. The acequias de careo are nature-based solutions for increasing water resources availability that have contributed to a prosperous life in the Sierra Nevada. Its long history (>1200 years) suggests that the system has remarkable resilience properties, which have allowed adaptation and permance for centuries in drastically changing climatic and socioeconomic conditions. This recharge system could also be applied to—or inspire similar adaptation measures in— semi-arid mountain areas around the world where it may help in mitigating climate change effects.Organismo Autonomo Parques Nacionales CANOA-51.3.00.43.00Ibero-American Science and Technology for Devel-opment Programme (CYTED) 419RT0577 RNM-126Junta de Andaluci

Balancing porosity and mechanical properties of titanium samples to favor cellular growth against bacteria

Two main problems limit the success of titanium implants: bacterial infection, which restricts their osseointegration capacity; and the stiffness mismatch between the implant and the host cortical bone, which promotes bone resorption and risk of fracture. Porosity incorporation may reduce this difference in stiffness but compromise biomechanical behavior. In this work, the relationship between the microstructure (content, size, and shape of pores) and the antibacterial and cellular behavior of samples fabricated by the space-holder technique (50 vol % NH4HCO3 and three ranges of particle sizes) is established. Results are discussed in terms of the best biomechanical properties and biofunctional activity balance (cell biocompatibility and antibacterial behavior). All substrates achieved suitable cell biocompatibility of premioblast and osteoblast in adhesion and proliferation processes. It is worth to highlighting that samples fabricated with the 100–200 μm space-holder present better mechanical behavior—in terms of stiffness, microhardness, and yield strength—which make them a very suitable material to replace cortical bone tissues. Those results exposed the relationship between the surface properties and the race of bacteria and mammalian cells for the surface with the aim to promote cellular growth over bacteria.University of Seville (Spain) VI Plan Propio de Investigación y Transferencia—US 2018, I.3A

Porous Titanium surfaces to control bacteria growth: mechanical properties and sulfonated polyetheretherketone coating as antibiofounling approaches

Here, titanium porous substrates were fabricated by a space holder technique. The relationship between microstructural characteristics (pore equivalent diameter, mean free-path between pores, roughness and contact surface), mechanical properties (Young’s modulus, yield strength and dynamic micro-hardness) and bacterial behavior are discussed. The bacterial strains evaluated are often found on dental implants: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The colony-forming units increased with the size of the spacer for both types of studied strains. An antibiofouling synthetic coating based on a sulfonated polyetheretherketone polymer revealed an effective chemical surface modification for inhibiting MRSA adhesion and growth. These findings collectively suggest that porous titanium implants designed with a pore size of 100–200 µm can be considered most suitable, assuring the best biomechanical and bifunctional anti-bacterial properties.University of Seville VI Plan Propio de Investigación y Transferencia—US 2018, I.3A

Metastatic Squamous Cell Carcinoma to the Cervical Lymph Nodes From an Unknown Primary Cancer : Management in the HPV Era

Background Patients with metastases in the lymph nodes of the neck and no obvious primary tumor, neck cancer with unknown primary (NCUP), represent a management challenge. A majority of patients have metastatic squamous cell carcinoma (SCC), although other histologies do occur. Methods We comprehensively reviewed the literature, compared available guidelines, and conferred with an international team of experts. Results Positron emission tomography-computed tomography (PET-CT) and fine needle aspiration (FNA) under ultrasound guidance increase accuracy of diagnosis. Immunohistochemistry (IHC), determination of human papilloma virus (HPV) status, by p16 staining or by in situ hybridization (ISH), and next-generation gene sequencing can guide us regarding probable primary sites and tumor biology. Narrow Band Imaging (NBI) has been introduced for the early detection of subtle mucosal lesions. Direct laryngoscopy (DL) and tonsillectomy have long been procedures used in the search for a primary site. More recently, TransOral Robotic Surgery (TORS) or Transoral LASER Microsurgery (TLM) have been introduced for lingual tonsillectomy. Conclusions New technologies have been developed which can better detect, diagnose, and treat occult primary tumors. Decisions regarding therapy are based on the primary tumor site (if discovered) and N stage. Options include neck dissection with or without postoperative adjuvant therapy, primary irradiation, or combined chemotherapy with irradiation. The preferred treatment of patients whose primary remains unidentified is controversial.Peer reviewe

Plant communities and landscape diversity in NW Sicily: The MEMOLA EU FP7 Project case study

The MEMOLA EU FP7 Project case study\u201d was presented at IV International Plant Science Conference (IPSC) held in Parma (Italy) on September 20-22, 2017. The poster focuses on the contribution of botany in the interdisciplinary debate of Memola Project and underline the role plant communities play in understanding the formative processes of the Mediterranean Landscapes

What is the role of sentinel lymph node biopsy in the management of oral cancer in 2010?

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Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering Green chemoprevention. © 2013 AACR

Serum amyloid a1/toll-like receptor-4 Axis, an important link between inflammation and outcome of TBI patients

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability world-wide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patientsThis work was supported by grants from Fundación Mutua Madrileña and Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet CP14/00008; CPII19/00005; PI16/00735; PI19/00082) to JE, RYC2019-026870-I to JMR and PI18/01387 to A

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibition. Here we report for the first time interim results of our ongoing phase I clinical trial (NCT02544880) in patients with recurrent HNSCC to evaluate the safety of and immunological effects of combining Tadalafil with the antitumor vaccine composed of Mucin1 (MUC1) and polyICLC. The combined treatment of Tadalafil and MUC1/polyICLC vaccine was well-tolerated with no serious adverse events or treatment limiting toxicities. Immunologically, this trial also confirms the positive immunomodulation of Tadalafil in patients with recurrent HNSCC and suggests an adjuvant effect of the anti-tumor vaccine MUC1/polyICLC. Additionally, image cytometry analysis of scanned tumors indicates that the PDE5 inhibitor Tadalafil in conjunction with the MUC1/polyICLC vaccine effectively reduces the number of PDL1+macrophages present at the tumor edge, and increases the number of activated tumor infiltrating T cells, suggesting reversion of immune exclusion. However, this analysis shows also that CD163 negative cells within the tumor upregulate PDL1 after treatment, suggesting the instauration of additional mechanisms of immune evasion. In summary, our data confirm the safety and immunologic potential of PDE5 inhibition in HNSCC but also point to PDL1 as additional mechanism of tumor evasion. This supports the rationale for combining checkpoint and PDE5 inhibitors for the treatment of human malignancies