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BACKGROUND: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS: This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years. RESULTS: Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9-85.8), 97.6% (95% CI 93.6-99.1), 90.0% (95% CI 84.3-93.7), 94.7% (95% CI 90.1-97.2), and 94.6% (95% CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9-81.2). CONCLUSIONS: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes.

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BACKGROUND: In patients with locally advanced extraperitoneal rectal cancer, a multidisciplinary approach represents the standard treatment. However, considering the favorable prognosis in patients with major or complete response, radical surgery might represent overtreatment. OBJECTIVE: This study aimed to evaluate postoperative short-term morbidity, functional outcome, and oncologic long-term outcome in patients with rectal cancer treated with local excision by transanal endoscopic microsurgery or radical surgery and to determine who achieved a complete or major pathological response (ypT0-1) after neoadjuvant treatment. DESIGN: This was a retrospective study. SETTING: The study was conducted at a single center. PATIENTS: Patients who had received neoadjuvant treatment by local excision with a major or complete pathological response at histological examination (transanal endoscopic microsurgery group) were compared to patients treated by radical surgery with the same pathological response (total mesorectal excision group). INTERVENTIONS: The interventions included local excision by transanal endoscopic microsurgery and radical surgery with total mesorectal excision. MAIN OUTCOME MEASURES: Postoperative short-term morbidity, functional outcome 1 year after surgery, and oncologic long-term outcome were measured. RESULTS: Ninety-three patients were included in the study (35 in the transanal endoscopic microsurgery group and 58 in the mesorectal excision group). In the total mesorectal excision group, a sphincter-saving approach was possible in 89.7% (vs 100%; p = 0.049); a protective temporary stoma was necessary in 74.1% of radical procedures (vs 0%; p < 0.001), and 13.8% of these became permanent. Short-term postoperative morbidity was lower after local excision (14.3% vs 46.6%; p = 0.002). One year after surgery, the transanal endoscopic microsurgery group recorded better evacuation and continence function than the total mesorectal excision group. Oncologic outcome was similar between the groups. LIMITATIONS: This study had a retrospective design. CONCLUSION: If a major or complete pathological response occurs after neoadjuvant treatment, an organ-sparing approach by local excision seems to offer the same oncologic results as radical surgery, but it has a better postoperative morbidity rate and better functional results. See Video Abstract at http://links.lww.com/DCR/B901 .Microcirugía endoscópica transanal versus escisión total del mesorrecto en cáncer de recto ypT0-1 después de radioquimioterapia preoperatoria: morbilidad posoperatoria, resultados funcionales y resultado oncológico a largo plazo. ANTECEDENTES: En pacientes con cáncer rectal extraperitoneal localmente avanzado, un abordaje multidisciplinario con radioquimioterapia preoperatoria y cirugía con escisión total del mesorrecto representa el tratamiento estándar. En pacientes que obtienen una respuesta mayor o completa, la cirugía radical puede representar un sobretratamiento, considerando el pronóstico favorable de estos casos. OBJETIVO: Evaluar la morbilidad posoperatoria a corto plazo, el resultado funcional y el resultado oncológico a largo plazo en pacientes con cáncer de recto tratados con escisión local mediante microcirugía endoscópica transanal o mediante cirugía radical y que obtuvieron una respuesta patológica completa o mayor (ypT0-1) después del tratamiento neoadyuvante. DISEO: Este fue un estudio retrospectivo. AJUSTE: El estudio se realizó en un solo centro. ESCENARIO: El estudio se realizó en un solo centro. PACIENTES: Se comparó a los pacientes tratados, tras tratamiento neoadyuvante (1996-2016), mediante escisión local con respuesta patológica mayor o completa al examen histológico (grupo de microcirugía endoscópica transanal), con los pacientes tratados mediante cirugía radical con la misma respuesta patológica (grupo de escisión mesorrectal total). INTERVENCIONES: Extirpación local mediante microcirugía endoscópica transanal y cirugía radical con escisión mesorrectal total. PRINCIPALES MEDIDAS DE RESULTADO: Morbilidad posoperatoria a corto plazo, resultado funcional a un año después de la cirugía (evaluado con una puntuación de evacuación y continencia) y resultado oncológico a largo plazo. LIMITACIONES: Las limitaciones de este estudio incluyen su diseño retrospectivo. CONCLUSIN: Si se produce una respuesta patológica mayor o completa después del tratamiento neoadyuvante, un abordaje con preservación de órganos mediante escisión local parece ofrecer los mismos resultados oncológicos que la cirugía radical, pero tiene una menor tasa de morbilidad postoperatoria y mejores resultados funcionales un año después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/B901 . (Traducción-Dr. Felipe Bellolio ).

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In this work the morphologic features of Pele's hair formed during three different eruptions of Kilauea volcano have been investigated: fountaining from Kilauea Iki's 1959 Episode 1, weak explosive activity from Halemaumau lava lake and littoral explosions at Waikupanaha (2009). Morphological studies were performed by optical, stereo- and scanning electron microscopy. For the first time 3D image analysis was carried out by synchrotron radiation X-ray computed microtomography, which allowed a high-resolution 3D reconstruction of the internal structure of each Pele's hair, highlighting several differences in terms of number density, elongation and shape of the vesicles between the samples from the three eruptions. We identified three main parameters determining these differences: initial size of the magma droplet, ejection velocity and magma viscosity. Pele's hair erupted during the Kilauea Iki's fountaining shows the highest thickness and the least elongated shape of the vesicles, though it is related to fast ejection of a low viscosity magma. We therefore suggest that the size of magma droplets is the main parameter influencing the morphology and inner textures of the Pele's hair. The comparison with Pele's hair of similar eruptions elsewhere demonstrates that there is no univocal correspondence between eruptive style and Pele's hair texture.

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PURPOSE: The purpose of this study was to compare metallic coils and glue (n-butyl-2 cyanoacrylate) for varicocele embolization, regarding immediate technical and clinical success, procedure time, complications and recurrence rates. MATERIALS AND METHODS: A retrospective analysis of a consecutive series of varicocele embolization procedures performed between July 2012 and July 2015 was undertaken. A total of 129 procedures were performed, 26 using glue (20.2%; 26 men with a mean age of 32.6 years) and 103 using coils (79.8%; 103 men with a mean age of 32.3 years). Demographic data, indications, technique, procedure time, complications and outcomes were compared. RESULTS: A total of 89 procedures (69%) were motivated by infertility (glue=20, coils=69) and 40 (31%) by testicular pain (glue=6, coils=34). The mean procedure time was 35.58±13.44 (SD) min for glue and 45.97±17.46 (SD) min for coils (P=0.0054). Immediate technical success rate was 100% using glue and 99% using coils (P=1.0000). A single minor complication was observed after coil embolization (0.97%). Both materials showed significant improvement of semen parameters, with similar clinical success rates. For patients referred for testicular pain, clinical success rate was 66.67% using glue and 88.24% using coils (P=0.2147). Recurrence rate was 11.54% with glue and 5.83% with coils (P=0.4000). Procedure time was significantly shorter with glue (P=0.0054). CONCLUSION: Glue and coils are both safe and effective for varicocele embolization. However, the use of glue yields shorter procedure time.

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BACKGROUND: Despite potential renal and cardiovascular advantages of proliferation signal inhibitors, their de novo use in kidney transplantation (KT) from elderly donors (ED) is poorly documented. We retrospectively analyzed two consecutive cohorts of KT from ED: low-dose extended-release tacrolimus (Tac) was used from 2010 to 2012 and cyclosporine (Csa) was used from 2008 to 2010. METHODS: Associated maintenance drugs were everolimus (Eve) and steroids. Outcomes were compared between groups over a 12-month follow-up. Fifty-six patients were analyzed in the Tac-Eve group and 54 in the Csa-Eve group. RESULTS: There were no significant differences at baseline with the exception of older donors age in the Tac-Eve cohort (74 vs 71 years, P = .002). There were no deaths, primary non functions, or graft losses. Eight (14%) Tac-Eve and 15 (28%) Csa-Eve patients had delayed graft function (P = .10). Renal function was fairly stable over time (median cGFR 36-49 mL/min and 51-55 mL/min in single kidney transplantation and dual kidney transplantation patients, respectively) with no significant differences between groups at month 12. Surgical complications were infrequent and observed mostly in dual kidney transplantation recipients. Thirty-nine (70%) and 30 (56%) patients remained under their initial Tac-Eve or Csa-Eve regimen, respectively. CONCLUSIONS: Induction with Thymoglobuline and maintenance with Eve and low-dose extended-release Tac and steroids is safe and effective in renal transplant from ED.

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AIMS: This study aims to identify a high level exopolysaccharide (EPS) producer thermophile that in turn could be used as a model organism to study the biological mechanisms and whole genome organization of EPS-producing thermophilic bacteria. METHODS AND RESULTS: Thermophilic isolates were screened, and then growth and EPS production of the best producer Brevibacillus thermoruber strain 423 were investigated under different carbon and nitrogen sources, temperature, pH and agitation rates. Rheological characterization revealed that the EPS behaved like a typical Newtonian fluid and viscosity of the EPS solution increased with increasing Ca(2+) ion concentration. Chemical characterization by TLC, GC-MS, FT-IR and NMR suggested a heteropolymer structure with glucose as major monomer unit. High biocompatibility of pure EPS fractions suggested their potential use in biomedical applications. CONCLUSIONS: This study reports on the comprehensive description of microbial production conditions as well as chemical, rheological and biological characterization of the EPS produced by B. thermoruber strain 423. The bioreactor cultures were found to reach two times higher yields and three times higher productivities when compared with literature. SIGNIFICANCE AND IMPACT OF THE STUDY: Brevibacillus thermoruber strain 423 combined the advantages of its nonpathogenicity with the advantages of fast productivity and hence proved to be a very promising model organism and cell factory for microbial EPS production.

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In this work we investigated the ability of four extremophilic bacteria from Archaea and Bacteria domains to resist to space environment by exposing them to extreme conditions of temperature, UV radiation, desiccation coupled to low pressure generated in a Mars' conditions simulator. All the investigated extremophilic strains (namely Sulfolobus solfataricus, Haloterrigena hispanica, Thermotoga neapolitana and Geobacillus thermantarcticus) showed a good resistance to the simulation of the temperature variation in the space; on the other hand irradiation with UV at 254 nm affected only slightly the growth of H. hispanica, G. thermantarcticus and S. solfataricus; finally exposition to Mars simulated condition showed that H. hispanica and G. thermantarcticus were resistant to desiccation and low pressure.

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The research of new tyrosinase inhibitors is currently important for the development of skin whitening agents; particularly, birch leaves extracts are included in many skin cosmetic products. In this study, the potential ability of Betula pendula leaves ethanolic extract (BE) was evaluated on mushroom tyrosinase activity. Results showed that BE was capable to inhibit dose-dependently l-DOPA oxidation catalyzed by tyrosinase. The inhibition kinetics, analyzed by Lineweaver-Burk plots, showed a noncompetitive inhibition of BE towards the enzyme, using l-DOPA as substrate. The inhibitory mechanism of BE as studied by spectrophotometric analysis, demonstrated its ability to chelate copper ion in the active site of tyrosinase. In addition, BE exhibited Fe(2+)-chelating ability (IC(50)=614.12±2.14 µg/mL), reducing power and radical-scavenging properties (IC(50)=137.22±1.98 µg/mL). These results suggest the usefulness of birch leaves extracts in cosmetic and pharmaceutical industries for their skin-whitening and antioxidant effects. Determination of the polyphenolic compounds in BE extracts was afterward achieved by means of high-performance liquid chromatography (HPLC) with photodiode array (PDA) and mass spectrometry (MS) detection. A total of 25 compounds were positively identified, through the complementary analytical information, and are reported in such a matrix for the first time. Knowledge on the qualitative composition and contents of these natural sources in fact represents mandatory information, for rational consumption and correlation of the beneficial effects to the specific amounts.

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The present study was designed to define the phenolic profile and the biological potential of berries methanol extract of Juniperus drupacea Labill. from Turkey. The total phenolic content (Folin-Ciocalteau assay) was 48.06±0.99mgGAE/g extract. The HPLC-DAD-ESI-MS analysis allowed the determination of the complete phenolic profile of J. drupacea berries. Phenolic acids represented more than 60% of the total phenolics, and tyrosol was the major one (1324±0.64µg/g extract); within the flavonoids amentoflavone was detected as the main constituent (927±0.35µg/g extract). The extract exhibited good antioxidant properties, as determined by different in vitro models: DPPH test (IC(50) 0.38±0.02mg/mL), reducing power (12.63±0.14ASE/mL), Fe(2+) chelating ability (IC(50) 2.26±0.06mg/mL), and TBA test (IC(50) 2.47±1.13µg/mL). Cytotoxicity against Artemia salina was highlighted (LC(50) 489.47±27.8µg/mL), and a significant decrease (p⩽0.05; p⩽0.01) in HepG2 cells viability was observed at the higher concentrations (5-10µg/mL). The extract displayed good antibacterial activity towards Gram-positive bacteria and in particular Staphylococcus aureus was the most susceptible strain (MIC 78.12µg/mL).

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In such a complicated field as proteomic analysis, scientists are more and more challenged in implementing separation systems capable to provide enhanced separation power, as well as sensitivity of detection for adequate identification and, to a lesser extent, quantification of the separated compounds. To address such issues, several combinations of different separation modes have been investigated in comprehensive liquid chromatographic platforms, in which the entire sample eluted from the first dimension is subjected to a secondary chromatographic separation. The different applications exploited for comprehensive LC analysis of intact or digested proteins are the focus of this review, in which advantages and disadvantages of the different columns combinations, interfaces, and operating modes are pointed out. The combination with mass spectrometry as part of the total system is stressed, and illustrated in more detail. Theoretical concerns and practical requirements will be briefly discussed, as well.

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Advances in surgical techniques are extremely demanding regarding the accuracy and level of detail expected for display of the vascular anatomy of the liver. Precise knowledge of the arterial, portal and hepatic vein territories are mandatory whenever a liver intervention is planned. Sectional anatomy can now be routinely performed on multidetector computed tomography (MDCT) with volumetric data and isotropic voxel display, by means of sub-millimetric slice thickness acquisition. The relevant vascular information can thus be gathered, reviewed and post-processed with unprecedented clarity, obviating the need for digital subtraction angiography. The scope of the present paper is to review the normal vascular liver anatomy, its most relevant variants including additional sources of vascular inflow. Apart from providing the surgeon with a detailed vascular and parenchymal roadmap knowledge of imaging findings may avoid potential confusion with pathologic processes.

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The influence of Erythromycin, Roxithromycin, Amoxicillin, Tetracycline and Sulfamethoxazole on municipal sludge in batch reactors was investigated. The study was focused on extracellular polymeric substances (EPS) as indicator of bacteria sensitivity to toxic agents. The EPS were analysed by UV-Vis and FT-IR spectroscopies and by size exclusion chromatography. It was found that Erythromycin and Roxithromycin induced a significant increase of bound EPS in flocs. This was attributed to a protection mechanism of the bacteria. Erythromycin was the only antibiotic which inhibited COD and nitrogen removal.

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Due to constant innovations in radiological and surgical techniques, more accurate results are expected in the diagnostic and therapeutic procedures related to hepatic pathology. The aim of this work was to demonstrate the normal hepatic vascular and biliary anatomy using cadaveric livers and CT scans of the affected livers. Furthermore, using the CT scans, the authors intended to illustrate the most common morphological variations of the vascular and biliary anatomy. Four human cadaveric livers were injected with colored silicone mixed with radiological contrast solution in the common bile duct, in the proper hepatic artery, in the portal vein and in the inferior vena cava near the ostia of the hepatic veins (only one of these structures was injected in each liver). After obtaining the CT scans, 3D rendered models were created, which demonstrated the normal hepatic anatomy of the vascular and biliary structures. The International Anatomical Nomenclature was used for their classification (based on Couinaud's work). The 3D rendered CT models were also modified to illustrate the most common normal variations of the hepatic anatomy (found in the literature).

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The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist ((p-chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simultaneously optimize the responses resolution and migration times of the two enantiomers. The proposed LC method provided the baseline enantioseparation of the investigated drug. 9.3% (v/v) ethanol added to n-hexane as mobile phase, 1.0 mL min(-1) flow rate, and 18 degrees C column temperature were the optimum experimental conditions allowing to achieve the highest enantioresolution of PS3 in less than 17 min.

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OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

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The effect of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) on the solubility properties and spectroscopic features of hesperetin and its 7-rhamnoglucoside, hesperidin, was qualitatively and quantitatively investigated in water, by means of UV-vis absorption and fluorescence spectroscopy. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in both cases type-A(L) diagrams have been obtained (soluble 1:1 complexes). The higher degree of interaction showed by hesperetin may be attributed to the higher hydrophobicity and smaller size of the aglycone molecule, which therefore exhibits a greater affinity for the CyD and fits better into the cavity. The effect of molecular encapsulation on the two flavanones antioxidant activity was afterwards evaluated by means of different biological assays, concerned to the different mechanisms of in vivo action. The protection efficacy was in all cases higher for the complexed drugs, with respect to the free ones; these results are of great interest for their potential usefulness in pharmaceutics.

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OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

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In the present work the feasibility of beta-cyclodextrin complexation was explored, as a tool for improving the aqueous solubility and antioxidant efficacy of rutin. By means of 1H NMR, UV-vis and circular dichroism spectroscopy the single aromatic ring of rutin was found to be inserted into the beta-cyclodextrin cavity to form a 1:1 inclusion complex. The effect of beta-cyclodextrin on the spectral features of rutin was quantitatively investigated, in fully aqueous medium, by holding the concentration of the guest constant and varying the host concentration. The associated binding constants were estimated to be 142+/-20 and 153+/-20 M(-1), respectively, on the basis of the observed UV-vis absorption and circular dichroism intensities. The antioxidant activity of rutin was also investigated, as affected by molecular encapsulation within beta-cyclodextrin (batophenanthroline test; comet assay; lipid peroxidation); the inclusion complex revealed improved antioxidant efficacy that may be in part explained by an increased solubility in the biological moiety.

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Inclusion complexes of some flavonols (3-hydroxyflavone, morin and quercetin) have been obtained with alpha- and beta-cyclodextrins, by the co-evaporation method. Different analytical techniques (DSC, XRPD, FT-IR, 1H-NMR, UV-Vis) have been employed for a throughout investigation of the structural characteristics of such supramolecular aggregates, which exhibited distinct spectroscopic features and properties from both "guest" and "host" molecules. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility studies; in all cases type-AL diagrams have been obtained (soluble 1:1 complexes). The effect of molecular encapsulation on the flavonols antioxidant activity has been afterwards evaluated, by means of different biological assays (Bathophenanthroline test; Comet assay; Lipid peroxidation). Complexation with cyclodextrins further improved the antioxidant activity, increasing drugs solubility in the biological moiety.

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3-Hydroxyflavone (3-OH-F) photochemistry in solution has been rationalized in terms of an excited state intramolecular proton transfer (ESIPT), which involves the free 3-hydroxy group interacting with the ortho-carbonyl. This photo-rearrangement occurs rapidly and is strongly influenced by the physico-chemical properties of the solvent, which plays an essential role in determining whether a photo-oxidation or a photo-induced molecular rearrangement takes place. 3-OH-F photoreactivity has been deeply investigated and the related mechanisms elucidated, as affected by various solvents, pH values and irradiation wavelengths, leading to different photodegradation rates and pathways. Moreover, the influence of molecular encapsulation upon alpha- and beta-cyclodextrins (alpha- and beta-CyD) on the molecule photoreactivity has been examined, as a potential tool for increasing molecule photostability as well as minimizing photoinduced toxic effects on biosubstrates.

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