Analysis of small-scale soil CO2 fluxes in an orange orchard under irrigation and soil conservative practices.

The quantification of soil carbon dioxide (CO2) flux represents an indicator of the agro-ecosystems sustainability. However, the monitoring of these fluxes is quite challenging due to their high spatially-temporally variability and dependence on environmental variables and soil management practices.In this study, soil CO2 fluxes were measured using a low-cost accumulation chamber, that was realized ad hoc for the surveys, in an orange orchard managed under different soil management (SM, bare versus mulched soils) and water regime (WR, full irrigation versus regulated deficit irrigation) strategies. In particular, the soil CO2 flux measurements were acquired in discontinuous and continuous modes, together with ancillary agrometeorological and soil-related information, and then compared to the agrosystem scale CO2 fluxes measured by the eddy covariance (EC) technique.Overall significant differences were obtained for the soil CO2 discontinuous fluxes as function of the WR (0.16 ± 0.01 and 0.14 ± 0.01 mg m-2 s-1 under full irrigation and regulated deficit irrigation, respectively). For the continuous soil CO2 measurements, the response observed for the SM factor varied from year to year, indicating for the overall reference period 2022-23 higher soil CO2 flux under the mulched soils (0.24 ± 0.01 mg m-2 s-1) than under bare soil conditions (0.15 ± 0.00 mg m-2 s-1). Inter-annual variations were also observed as function of the day-of-year (DOY), the SM and their interactions, resulting in higher soil CO2 flux under the mulched soils (0.24 ± 0.02 mg m-2 s-1) than under bare soil (0.15 ± 0.01 mg m-2 s-1) in certain periods of the years, according to the environmental conditions. Results: suggest the importance of integrating soil CO2 flux measurements with ancillary variables that explain the variability of the agrosystem and the need to conduct the measurements using different operational modalities, also providing for night-time monitoring of CO2. In addition, the study underlines that the small-scale chamber measurements can be used to estimate soil CO2 fluxes at orchard scale if fluxes are properly scaled.

Burnout symptoms, work motivation and their relationships among Italian ICU's nurses after COVID-19 emergency. A multicenter study.

Background: Despite the end of the health emergency, healthcare professionals are at risk of developing long-term mental health problems. The aim of this study was to observe Burnout symptoms and work motivation among Intensive Care Nurses, one year after admission to the Intensive Care Unit of the last positive SARS-CoV-2 swab patients. Study design: A multicenter cross-sectional study design was carried out and a national web-based survey was conducted between April, 2023 and May, 2023 among 21 Italian Intensive Care Units. Methods: The survey consisted of single- and multiple-choice questions structured into 3 sections: demographic sample data, Maslach Burnout Inventory Scale for the assessment of Burnout-symptoms and Multidimensional Work Motivation Scale for the assessment of work motivation. Results: Four hundred-nine surveyed and questionnaires were included in the study. Of these 272 were male (66.5%). Burnout-related symptoms were identified in at least 79% of ICU nurses. Symptoms of severe Burnout was observed in 169 nurses analysed (41.3%) and they are significantly among nurses who had COVID-19 or positive SARS-COV-2 swab during the pandemic (RR= 1.55; CI= 1.24-1.95, p= .0004) and among nurses with at least one child (RR= 1.37; CI= 1.07-1.76; p= .011). Motivated nurses for the intrinsic motivation's level have been 281 (68.7%). The risk of being intrinsically demotivated is significantly greater among nurses with 5-10 years of work experience (RR= 2.44; CI= 1.48-4.02; p= .0002). Emotional exhaustion was associated in increase in demotivation and introjected estrinsic motivation. Depersonalization was associated with demotivation. Personal accomplishment was associated with increase in external estrinsic motivation and amotivation. Conclusions: High level of Burnout has been observed among Italian ICU nurses associated with low work motivation after COVID-19 emergency. Interventions and strategies should be adopted to prevent burnout and improve work motivation.

Primary cutaneous interdigitating dendritic cell sarcoma (IDCS): Report of a new case and literature review.

Interdigitating dendritic cell sarcoma is a very rare entity in the spectrum of histiocytic and dendritic cell neoplasms that mostly occurs in lymph nodes, generally presenting as solitary lymphadenopathy, but may affect every organ. Among extra nodal sites, cutaneous interdigitating dendritic cell sarcoma is exceedingly rare; to date, only 9 cases have been described in English literature. The mean age at diagnosis was 60 years, with a male-female ratio of 1,5 to 1; clinically, two different modalities of skin presentation have been reported: solitary, represented by a single red-brownish nodular lesion, or diffuse, characterized by multiple nodular lesions in one or more body districts. The extreme rarity of this sarcoma and its morphological similarity to other poorly differentiated tumors may lead to a delay in diagnosis; in particular, cutaneous localization may be difficult to differentiate from follicular dendritic cell sarcoma, Langerhans cell sarcoma, poorly differentiated squamous cell carcinoma and more generally sarcomatoid carcinoma, atypical fibroxanthoma, malignant melanoma and several sarcomas. Immunohistochemistry plays an important role in identifying this rare entity and formulating a correct histological diagnosis, fundamental requirement for choosing the best therapeutic approach. We report herein a further case of an 81-year-old Caucasian woman who presented to the Dermatology Department to remove an asymptomatic skin papule in the left temporal region, clinically diagnosed as dermatofibroma. The overall pathological and immunohistochemical features supported the diagnosis of a malignant dendritic cell tumor, consistent of interdigitating dendritic cell sarcoma.

Qualitative and quantitative analysis of the CTX in relation to the period of intake of bisphosphonates: A systematic review.

The aim of this systematic review was to determinate the true value of C-terminal crosslinking telopeptide test (CTX) in patient who takes Bisphosphonate. A comprehensive search of studies published up to March 2020 and listed in the PubMed/MEDLINE and Cochrane Library databases, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. The search identified 99 publications; 6 studies were finally deemed eligible for inclusion according to the study criteria. These studies included a total 104 patients and was selected 101. The CTX value in the various study groups is less than 150 pg/ml. There is a difference between the age of the patient and the period of taking the drug. This systematic review indicates that the CTX test has diffent predictive value in determining the risk of osteonecrosis in patients taking bisphosphonate compared to previus standard.

The vortex-driven dynamics of droplets within droplets.

Understanding the fluid-structure interaction is crucial for an optimal design and manufacturing of soft mesoscale materials. Multi-core emulsions are a class of soft fluids assembled from cluster configurations of deformable oil-water double droplets (cores), often employed as building-blocks for the realisation of devices of interest in bio-technology, such as drug-delivery, tissue engineering and regenerative medicine. Here, we study the physics of multi-core emulsions flowing in microfluidic channels and report numerical evidence of a surprisingly rich variety of driven non-equilibrium states (NES), whose formation is caused by a dipolar fluid vortex triggered by the sheared structure of the flow carrier within the microchannel. The observed dynamic regimes range from long-lived NES at low core-area fraction, characterised by a planetary-like motion of the internal drops, to short-lived ones at high core-area fraction, in which a pre-chaotic motion results from multi-body collisions of inner drops, as combined with self-consistent hydrodynamic interactions. The onset of pre-chaotic behavior is marked by transitions of the cores from one vortex to another, a process that we interpret as manifestations of the system to maximize its entropy by filling voids, as they arise dynamically within the capsule.

Metal removal processes in a pilot hybrid constructed wetland for the treatment of semi-synthetic stormwater.

This study investigates the reliability of a pilot hybrid constructed wetland (H-CW), located in Eastern Sicily (Italy). To address the uncertainty associated with implementing representative monitoring during highly variable storm events, unique to Mediterranean conditions, a recipe for semi-synthetic stormwater was used to evaluate the removal efficiency of the system. This was characterised by metals (Cd, Cr, Fe, Pb, Cu, Zn) and relative concentrations typically found in urban stormwater runoff (SR). Approximately one month of intensive monitoring activities were carried out and quality analyses were conducted on three matrices comprising the pilot H-CW: water, biomass (Canna indica, Typha latifolia), and volcanic gravel substrate. Metal retention in early clogging matter (SS) was also examined. The results showed a significantly high H-CW efficiency for the removal of all metals (70-98%) already at the horizontal flow unit outflow, confirming its strategic role. A metal mass balance analysis was also conducted to describe the retention capacity and influence of each system component on the overall efficiency (ranging from 87.8% for Cr to 99.2% for Pb). Metal removal was mostly related to sediment and substrate processes, while plants exhibited root bioaccumulation and phytostabilisation capacity even with a limited impact on overall system retention. The pilot H-CW exhibits characteristics suitable for the treatment of metal-enriched stormwater runoff and validates the useful application of decentralised natural systems for water resource management.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies.

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment.

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival (p = 0.009) and overall survival (p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Antimicrobial properties of the medicinal plant Cardiospermum halicacabum L: new evidence and future perspectives.

The emergence and rapid spread of multidrug-resistance in human pathogenic microorganisms urgently require the development of novel therapeutic strategies for the treatment of infectious diseases. From this perspective, the antimicrobial properties of the natural plant-derived products may represent an important alternative therapeutic option to synthetic drugs. Among medicinal plants, the Cardiospermum halicacabum L. (C. halicacabum), belonging to Sapindaceae family, could be a very promising candidate for its antimicrobial activity against a wide range of microorganisms, including both Gram-positive and Gram-negative bacteria, as well as fungal pathogens. Although the antimicrobial properties of C. halicacabum have been intensively studied, the mechanism/s by which it exerts the inhibitory activity towards the pathogenic microbes have not yet been completely understood. This review focuses on the main antimicrobial activities displayed in vitro by the plant extract, with particular attention on our recent advances. We demonstrated that C. halicacabum is able to exert in vitro a dose-dependent fungistatic effect against Trychophyton rubrum (T. rubrum) through molecular interaction with the fungal heat shock protein (Hsp)-90 chaperone. These findings are supported by a growing body of research indicating the crucial role played by the Hsp90 in the virulence of the pathogenic microorganisms, including fungal pathogens. The possible future use of C. halicacabum for treating a wide range of infectious diseases is also discussed.

Efficacy of extended aromatase inhibitors for hormone-receptor-positive breast cancer: A literature-based meta-analysis of randomized trials.

BACKGROUND: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. RESULTS: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84). CONCLUSION: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.

On the performance of a pilot hybrid constructed wetland for stormwater recovery in Mediterranean climate.

The overall efficiency of a pilot-scale hybrid constructed wetland (H-CW), located on a retail store's parking area in Eastern Sicily, for alternative treatment of stormwater runoff and of sequential batch reactor (SBR) effluent was evaluated. Experimental activities were focused on system performances, including wastewater (WW) quality and hydraulic monitoring. System design, macrophyte growth and seasonal factors influenced the pilot plant performance. Very high removal efficiency for microbial indicators were reported within the subsurface horizontal flow unit (HF), playing a strategic role for Clostridium perfringens. The algal growth occurred in the free water surface (FWS) unit and inhibited removal efficiencies of total suspended solids (TSS), biochemical oxygen demand (BOD5) and chemical oxygen demand (COD), impairing water quality. The whole H-CW showed good efficiency in trace metals removal, especially for Pb, Zn, and Cu. Preliminary results suggested the reliability of the H-CW technology in decentralised water treatment facilities for enhancing water recovery and reuse.

Evaluation of frxA and rdxA gene mutations in clinical metronidazole resistance Helicobacter pylori isolates.

Metronidazole resistance is an important factor related to failure in the treatment of Helicobacter pylori. The mutation in the rdxA and frxA genes is the most important cause of resistance to metronidazole. Since the resistance rate of metronidazole is high in our region, we decided to assess the frequency of these mutations among H. pylori clinical isolates. Antral gastric biopsy specimens were cultured and minimal inhibitory concentrations (MICs) of metronidazole were determined by the E-test method. The rdxA and frxA genes were amplified in all isolates through the use of PCR with the specific primers. PCR products were purified for sequencing. The resultant sequences were compared with the wild type reference sequences to find any possible mutations. According to our findings, the rate of metronidazole resistance was 77%, with the MICs ranging from 0.25-1 µg/ml for metronidazolesensitive group and from 16-256 µg/ml for resistance group. H. pylori isolates containing a single mutation in rdxA or frxA genes demonstrated a low MIC (8-16 µg/ml), while those containing mutations in both genes showed a higher MIC (32-256 µg/ml). In this study, all resistant H. pylori isolates contained single or multiple nucleotide substitutions in the mentioned genes. Nevertheless, no nucleotide substitutions were found in the sensitive clinical isolates. The results of our study showed that the mutations in rdxA are mostly related to metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance.

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer.

BACKGROUND: Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. METHODS: In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. RESULTS: The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). CONCLUSION: Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered.

High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a predictive biomarker of disease progression in many malignancies, including imatinib-treated chronic myeloid leukemia (CML). Although high CIP2A levels correlate with disease progression in CML, the underlying molecular mechanisms remain elusive. In a screen of diagnostic chronic phase samples from patients with high and low CIP2A protein levels, high CIP2A levels correlate with an antiapoptotic phenotype, characterized by downregulation of proapoptotic BCL-2 family members, including BIM, PUMA and HRK, and upregulation of the antiapoptotic protein BCL-XL. These results suggest that the poor prognosis of patients with high CIP2A levels is due to an antiapoptotic phenotype. Disrupting this antiapoptotic phenotype by inhibition of BCL-XL via RNA interference or A-1331852, a novel, potent and BCL-XL-selective inhibitor, resulted in extensive apoptosis either alone or in combination with imatinib, dasatinib or nilotinib, both in cell lines and in primary CD34(+) cells from patients with high levels of CIP2A. These results demonstrate that BCL-XL is the major antiapoptotic survival protein and may be a novel therapeutic target in CML.

Study of Antimicrobial Effects of Clarithromycin Loaded PLGA Nanoparticles against Clinical Strains of Helicobacter pylori.

Clarithromycin (CLR) formulation was prepared as PLGA nanoparticles in order to enhance the therapeutic effects using the distinctive features of a nanoparticulate delivery system. CLR loaded PLGA nanoparticles were prepared by Quasi Emulsion Solvent Diffusion (QESD) method using Poly lactic-co-Glycolic Acid (PLGA) as a biodegradable polymer. Antibacterial activity of the prepared formulations was evaluated against clinical strains of Helicobacter pylori, isolated from gastric biopsies of patients with gastritis, duodenal ulcer, peptic ulcer, and gastroesophageal reflux disease undergoing endoscopy, by using agar dilution method.Spherical nanoparticles with relatively narrow size distribution (between 200 and 800 nm) in the size range of 305 ± 138, 344 ± 148 and 362 ± 110 nm were achieved for F22, F23 and F23 respectively. CLR encapsulation percentages were measured to be 57.4 ± 4.3 to 80.2 ± 4.0%. CLR loaded PLGA nanoparticles showed equal or enhanced eradication effect against H. pylori strains according to the declined MIC values in comparison with the untreated CLR.In conclusion, the prepared CLR nanoformulation showed appropriate physicochemical properties and improved activity against H. pylori that could be a suitable candidate for oral preparations.

Efficacy and tolerability of nitric-zinc complex in the treatment of external genital warts and "difficult-to-treat" warts: a "proof of concept", prospective, multicentre, open study.

AIM: Treatment of plantar and periungueal warts (so called "difficult-to-treat" warts, DTW) and external genital warts (EGW) remains unsatisfactory. Medical or invasive procedures are partially effective and/or painful. Furthermore recurrences rates after treatments are still a relevant problem for all the available therapies. Nitric-zinc complex is a solution for topical application containing nitric acid, zinc, copper and organic acids able to induce a caustic effect of the wart trough mummification and proteins denaturation/coagulation action. Nitric-zinc complex has been shown to be an effective and well tolerated treatment of common warts. METHODS: We evaluated in a prospective open label 4-centre trial, the efficacy and local tolerability of nitric-zinc complex in the treatment of EGW and DTW. A total of 37 immunocompetent subjects (20 men and 17 women; mean age: 45 years) with single or multiple lesions, were enrolled, after their informed consent. A total of 30 subjects had EGW, 2 subjects had plantar warts, 2 warts of the hand and 3 periungueal lesions. Nitric-zinc aqueous solution was applied topically using a 30 mL capillary tube over the lesions until a whitening/yellowish reaction appeared. A second (or more, if needed) application was performed at two-week interval until a complete clinical cure rate was observed. Primary outcome of the study was the clinical evaluation with picture documentation of the evolution of lesions classified as total cure, partial disappearance or no effect. Topical tolerability was evaluated through patient's reported adverse events. RESULTS: All subjects completed the study. A complete cure of lesions was observed in 31 subjects (90%) after one and up to four applications. Three patients with EGW (8%) showed a partial disappearance of lesions and one (2%) subject was no responder to four nitric-zinc complex applications. The product was well tolerated. No serious adverse events were observed or recorded. CONCLUSION: Nitric-zinc complex topical solution has shown to be an effective and well tolerated treatment of EGW and "difficult-to-treat" warts with a 90% of subjects with a total cure after one or up to four applications. A total or partial response was observed in 99% of the subjects. Nitric-zinc complex could be considered an easy-to-use effective treatment strategy of "difficult-to-treat" warts and external genital warts. Additional studies comparing nitric-zinc complex to other strategies are warranted.

Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer.

PURPOSE: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). METHODS: Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. RESULTS: Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by (18)FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively). CONCLUSIONS: The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active.

Reuse of constructed wetland effluents for irrigation of energy crops.

The aim of this study was to evaluate biomass production of promising 'no-food' energy crops, Vetiveria zizanoides (L.) Nash, Miscanthus × giganteus Greef et Deu. and Arundo donax (L.), irrigated with low quality water at different evapotranspiration restitutions. Two horizontal subsurface flow (H-SSF) constructed wetland (CW) beds, with different operation life (12 and 6 years), were used to treat secondary municipal wastewaters for crop irrigation. Water chemical, physical and microbiological parameters as well as plant bio-agronomic characters were evaluated. The results confirm the high reliability of CWs for tertiary wastewater treatment given that the H-SSF1 treatment capacity remained largely unchanged after 12 years of operation. Average total suspended solids, chemical oxygen demand and total nitrogen removal for CWs were about 68, 58 and 71%, respectively. The Escherichia coli removal was satisfactory, about 3.3 log unit for both CW beds on average, but caution should be taken as this parameter did not achieve the restrictive Italian law limits for wastewater reuse. The average above-ground dry matter productions were 7 t ha⁻¹ for Vetiveria zizanoides, 24 t ha⁻¹ for Miscanthus × giganteus and 50 t ha⁻¹ for Arundo donax. These results highlight attractive biomass yield by using treated wastewater for irrigation with a complete restitution of evapotranspiration losses.