Biocatalytic Regioselective O-acylation of Sesquiterpene Lactones from Chicory: A Pathway to Novel Ester Derivatives.

We report the first biocatalytic modification of sesquiterpene lactones (STLs) found in the chicory plants, specifically lactucin (Lc), 11ß,13-dihydrolactucin (DHLc), lactucopicrin (Lp), and 11ß,13-dihydrolactucopicrin (DHLp). The selective O-acylation of their primary alcohol group was carried out by the lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set up the desired O-acetylation reaction by comparing the use of acetic acid and vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, where five novel ester chains were selectively introduced onto the primary alcohol group, with conversions going from >99 % (acetate and propionate) to 69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, and DHLp was also successfully achieved with near-quantitative conversion. Molecular docking simulations were then performed to elucidate the preferred enzyme-substrate binding modes in the acylation reactions with STLs, as well as to understand their interactions with crucial amino acid residues at the active site. Our methodology enables the selective O-acylation of the primary alcohol group in four different STLs, offering possibilities for synthesizing novel derivatives with significant potential applications in pharmaceuticals or as biocontrol agents.

Toxicological aspects of cannabinoid, pesticide and metal levels detected in light Cannabis inflorescences grown in Italy.

Recently, the cultivation of light Cannabis, with a total THC content less than 0.6%, has been encouraged due to its industrial and therapeutic potential. This has increased the consumption of hemp for both smoking purposes and food preparation. Even so, Cannabis inflorescences are not subject to EU regulations and standards provided for food and tobacco products. A study was carried out on thirty-one inflorescences samples, collected in different Italian regions, in order to determine cannabinoids, pesticides and metals and to evaluate the exposure of consumers to contaminants and ensure a safe consumption. Contents of THC were always below 0.5%, while CBD ranged between 0.3 and 8.64%. The determination of 154 pesticides showed that 87% of the samples contained fungicides and insecticides in the range 0.01-185 µg/g. The most found are spinosad and cyprodinil. The concentration of metals ranged from 1 to more than 100 µg/g and As, Cd, Co, Cr, Hg, Cu, Mo, Ni and V exceeded the regulatory US limits for inhaled Cannabis products, while Pb exceeded them for both oral and inhaled products. These contaminants are intrinsically toxic and may affect public health. Actions are needed to establish regulatory measures and reduce the adverse effects caused by contaminants in Cannabis.

Crop diversity management: Sereer smallholders' response to climatic variability in Senegal.

Beyond the observation of climatic variations and their impact on livelihoods, farmers' knowledge about climate change? can help understand how rural populations respond to environmental changes and what factors should policies consider when planning rural adaptation. This study documents Sereer farmers' observations of local environmental changes in the Fatick region of Senegal and explores how the farmers use crop diversity to adapt to those changes. Their observations of environmental changes were documented through focus group discussions and semi-structured interviews. Variations in crop diversity as well as farmers' explanations for these variations were assessed through surveys in two villages (n=126 households). Sereer farmers identify four distinct periods of similar climate trends and reported how they managed crop diversity in response to the climate variations between periods. Three management responses stand out: abandonment of long-cycle varieties during drought periods, adoption of short-cycle varieties during periods with shorter rainy seasons, and reinstating of long-cycle varieties with the return of rains. Sereer farmers consider that climate variations are important reasons to modify their crop varieties, although variety selection is also affected by other socio-economic and cultural reasons. This study illustrates the contributions that local knowledge can bring to understanding the local impact of climate change on smallholder farmers. Understanding how they use crop diversity to adapt to climate variations can be the bases of climate change adaptation policies that address local needs and constraints.

Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer

Background. To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer. Methods. A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week. Results. Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05). Conclusion. Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary (AU)

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Development of molecularly imprinted polymeric nanofibers by electrospinning and applications to pesticide adsorption.

Novel polystyrene-based molecularly imprinted polymer nanofibers were synthesized through the electrospinning technique. The molecularly imprinted polymers were prepared using a non-covalent approach and atrazine as template. For comparison, nonimprinted polymer nanofibers were also synthesized. The morphology of the synthesized nanofibers was characterized using scanning electron microscopy. The adsorption of pesticides, atrazine, atrazine desisopropyl, atraton, carboxin, linuron, and chlorpyrifos was studied under equilibrium (batch) conditions. To describe the adsorption capability of the synthesized polymers, Langmuir and Freundlich models were used. The Freundlich model provided a better mathematical approximation of the sorption characteristic for polymers nanofibers. To evaluate the adsorption capacity in the presence of interferents experiments on river water samples spiked with a mixture of six pesticides were also performed. The results obtained for the highest concentration levels investigated, show a greater amount of pesticide adsorbed on molecularly imprinted polymers and non-imprinted polymers compared to those obtained using commercial stationary phases used as reference.

Depression, pathological dependence, and risky behaviour in adolescence.

During adolescence, there is an increased chance of increased incidence of depression and the development of addictive/dependent behaviours such as pathological gambling, excessive Internet use and compulsive shopping, Here we present a psychoeducational approach in the schools of Pescara and Penne to identify and treat these problems.

Contribution of volcanic ashes to the regional geochemical balance: the 2008 eruption of Chaitén volcano, Southern Chile.

The environmental geochemical behaviour of the rhyolitic ashes from the 2008 eruption of Chaitén volcano, Southern Chile, has been studied. After the bulk characterisation, the potential contribution to the regional geochemical fluxes was examined using: i) single batch leaching tests to provide a rapid screening of the implied major and trace elements; and ii) column experiments to evaluate the temporal mobility of leached elements. The environmental concerns of these ashes are related to the fine grained component present in each sample (independent of distance from the source), in particular the presence of cristobalite, and the geochemical hazards posed by ash-water interaction. Leaching experiments show the fast dissolution of surface salts and aerosols, which dominate over glass dissolution during the first steps of the ash-water interaction. Chaitén ashes could transfer to the environment more than 1×10(10)g or 10,000 metric tonnes (mt) of Cl, S, Ca, Na, Si, and K; between 1000 and 10,000 mt of F, Mg, and Al; between 100 and 1000 mt of As, Pb, P, Fe, Sr, Zn, Mn, and Br; between 10 and 100 mt of Ba, Li, Ti, Ni, Nb, Cu, Rb, Zr, V, Mo, Co, and Sc; and less than 10 mt of Cr, Sb, Ce, Ga, Cs, and Y. These results show the fertilising potential of the ashes (e.g., providing Ca and Fe) but also the input of potentially toxic trace elements (e.g., F and As) in the regional geochemical mass balance. The Chaitén results evidence lower potentials for poisoning and fertilising than low silica ashes due to the lower contents released of practically all elements.

Induction chemotherapy in head and neck cancer patients followed by concomitant docetaxel-based radiochemotherapy.

Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty-nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m(2) . Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate >90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.

Environmental geochemistry of ancient volcanic ashes.

Volcanic ashes from the Puna and surrounding Andean areas in northern Argentina show that sometimes volcanic ash deposits are very well preserved (up to several million years) and can remain a potential hazard for the environment in a similar way as current deposits. Eight ashes have been characterized by SEM-EDX and DRX, and their potential released geochemical fluxes were examined by using water and nitric acid batches, which are analyzed by ICP-OES, ICP-MS and ISE (F). Results demonstrate that water batch system is better medium than nitric acid for this study. The high and fast reactivity of these ancient ashes is mainly associated with their high content in glass. The order of magnitude of released contents of implied elements is consistent among the samples, i.e., Al>B>Fe>Zn>F>P>Mn>Ba>Sr>Li>Ti>Rb>Cu>Ni>Sb>Pb>As>Cr>V. Ash-water interaction, although infrequent in arid regions such as the Puna Region in northern Argentina, introduces rapid changes in the geochemical fluxes of elements and pH and may constitute a potential hazard for the environment. In fact, many of these elements are included in the drinking water guidelines due to their potential toxicity and may constitute potential hazards for the environment and human health.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

Mapping the intake of different elements in vegetal tissues by dual-energy X-ray imaging at DaPhine synchrotron light source.

This article reports on the first utilization of the soft X-ray beamline at the DaPhine synchrotron light source for mapping the intake of different elements in plant tissues. As a test, the method of dual-energy X-ray microradiography was applied to the investigation of the natural sulfur content in dried leaf and root samples. Our ultimate goal was to monitor the pollutant lead and its intake, which was added in controlled doses to the hydroponic medium of laboratory-controlled samples of vegetal species. The results obtained by the nondestructive X-ray radiographic analysis are compared to the values of concentrations determined by a standard chemical analysis utilizing atomic absorption spectroscopy. From this comparison the validity of the X-ray detection of heavy metals in biological samples has been confirmed. The superposition of the dual energy results on the simple planar radiography shows the representation of the pollutant intake directly on the sample structures. It should be pointed out that this method, developed here for plant root and leaves could be applied to any biological sample of interest, but the preparation and observation conditions necessitate different strategies according to the type of sample under analysis.

Effect of morbid obesity on kinetic of desflurane: wash-in wash-out curves and recovery times.

AIM: The aim of this paper was to compare wash-in and wash-out curves of desflurane in morbidly obese and nonobese patients. METHODS: Fourteen patients (7 obese and 7 nonobese) were studied. In the nonobese patients, anaesthesia was started by administering 2 mg/kg propofol bolus and a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. Obese patients were intubated using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, general anaesthesia was started by administering a 1.5 mg/kg propofol bolus dose. Ten minutes after induction of anaesthesia, 4% desflurane was administered for 30 min. Desflurane kinetics was determined by collecting end-tidal samples from first breaths at 1, 5, 10, 15, 20, 25 and 30 min. At last skin suture, the end-tidal concentration of desflurane was recorded from 5 consecutive breaths before their discontinuation, then the end-tidal samples of the inhalational agent were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 and 5 min after terminating its administration. The period of time from discontinuation of desflurane to opening eyes, squeezing the observer's hand, extubation, stating the patients' name and providing date of birth was also recorded. RESULTS: The FA/FI ratio was higher in the nonobese group from the 10th to the 15th min. Wash-out curves of desflurane and recovery times were similar. CONCLUSION: Our results show that desflurane provides similar kinetic and recovery profiles in obese and nonobese patients.

[Neck pain and fever after peginterferon alpha-2a]. / Halsschmerzen und Fieber nach Peginterferon alpha-2a.

A 39-year-old woman presented to the emergency room with fever and tender swollen neck two days after the first injection of Peginterferon alpha-2a (Pegasys). She had been under Interferon therapy for melanoma over the last five months. Because of side effects Interferon alpha-2a (Roferon-A) was discontinued and she was given Peginterferon alpha-2a. On examination, she was unwell, febrile (38.8 degrees C) and her pulse was 110/min. Laboratory findings were as follow: erythrocyte sedimentation rate 85 mm/h, C-reactive protein 143 mg/L, white cell count of 11 x 10(9)/L (3.0-9.6), TSH 0.10 mU/L (0.27-4.20), fT4 24.2 pmol/L (12-22), fT3 5.5 pmol/L (2.8-7.1) antinuclear antibodies 1:80, antithyreoglobulin antibodies 212 IE/ml (< 100), thyreoglobulin 442 microg/L, anti-TPO normal and TSH receptor antibodies were negative. Ultrasonography revealed an enlarged, focally hypoechoic thyroid. We suspected she had a Peginterferon alpha-2a induced thyroiditis de Quervain and started a therapy with NSAR and thereafter with Prednison 20 mg. Her symptoms resolved within few days. Thyroiditis in association with Interferon alpha-2a have already been reported. Not known is, to our knowledge, an acute thyroiditis as a side effect of treatment with Peginterferon alpha-2a. Our case shows that also Peginterferon alpha-2a can induce an inflammation of the thyroid similar to de Quervain's thyroiditis.

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.

[Exercise-induced left arm pain and thrombocytosis]. / Belastungsinduzierte Schmerzen im linken Arm und erhöhte Thrombozytenzahl.

We describe the case of a 45-year-old male smoker who presented with an acute anterior wall myocardial infarction and a platelet count on admission of 1030000/mm3. Emergent coronary angiography revealead left anterior wall akinesia caused by a spontaneously resolved thrombosis of the left anterior descending artery with residual stenosis. Primary percutaneous coronary angioplasty and stenting were performed. Postangioplasty course was uneventful. He was diagnosed with essential thrombocythemia based on the findings of marked thrombocytosis of 1,030,000/mm3, splenomegaly and numerous clumping giant megakaryocytes on bone marrow biopsy. In addition to standard therapy with aspirin, heparin, betablocking agent, ACE-inhibitor and statine he received additional anti-platelet therapy with Clopidogrel. Cytoreductive therapy was not necessary.

Feasibility of preoperative chemoradiation in rectal cancer patients aged 70 and older.

In the present study, we report results of 28 rectal cancer patients, aged 70 years and older, treated with preoperative radiotherapy and 5FU concomitant chemotherapy. Twenty-eight out of 136 patients treated in our Department between 1997 and 2004 aged > or = 70 years, mean 73 (range 70-81); 3 T2, 18 T3, 7 T4; 15 N0, 5N1, 8 N2; Radiotherapy (5040 cGy, 28 fractions) was delivered combined with 5FU - based concomitant chemotherapy. Compliance to chemoradiotherapy was excellent. Major acute toxicity (> or = G3) evaluation showed haematological Grade 3 only in 2 patients. No severe acute Gastrointestinal toxicity was observed. All patients underwent surgery without severe perioperative complications. Complete pathological response pT0 was found in 3 patients (11%). Overall T downstaging occurred in 61% of the cases. Mean follow up was 34 months (range 4- 84). Kaplan Meier Overall Survival and Disease Free Survival at 5 years were 74% (95% CI 54 -95) and 65% (95% CI 38-93), respectively. Only 1 patient showed G3 diarrhea according to CTCAE that interfered with his Quality of Life and required hospitalization. In conclusion, concomitant radiochemotherapy 5FU based is safe in rectal cancer patients aged > or = 70 with a good tumour downstaging (61% of patients) and excellent feasibility. No treatment related death was observed.

[Spontaneous dissection of visceral blood vesssels--a rare cause of epigastric pain]. / Spontane Dissektion von Viszeralgefässen--eine seltene Ursache für Oberbauchschmerzen.

A 51 year-old man presented with acute abdominal pain in our emergency room. The first examination revealed no pathological findings except coprostasis and after an enteroclysis the patient was sent home without any complaints. During a recent episode of abdominal pain a computer tomography was performed, showing dissection of the superior mesenteric and the celiac artery. Without any signs of mesenteric ischemia additional examinations like laboratory studies, x-rays, and abdominal ultrasound might be normal and therefore not helpful for diagnosis. In patients presenting with persistent abdominal pain and unspecific clinical and laboratory findings rare causes of abdominal symptoms should be considered. Despite the rarity of visceral artery dissection, awareness of this pathology is crucial because of its possible lifethreatening complications. Appropriate diagnostic imaging tests may avoid postmortem diagnosis by the pathologist.

High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis.

BACKGROUND: Emerging evidence suggests a potential role for ubiquitous environmental contaminants in the physiopathology of endometriosis. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride (PVC) formulations, is a widespread environmental contaminant with potentially adverse effects on fertility in animal models. In the present study, we tested the hypothesis that DEHP and/or and its main metabolite, mono-ethylhexyl phthalate (MEHP), play a role in the pathogenesis of endometriosis. METHODS: Specimens of blood and peritoneal fluid were collected in a group of women with endometriosis (n = 55), and in age-matched control women (n = 24). Concentrations of DEHP and MEHP were measured in plasma and peritoneal fluid by using high performance liquid chromatography (HPLC). Differences between groups were tested using the Fisher's exact test, Wilcoxon-test, and Kruskal-Wallis analysis of variance. RESULTS: Endometriotic women showed significantly higher plasma DEHP concentrations than controls (median 0.57 micro g/ml, interquartile range: 0.06-1.23; values range: 0-3.24 versus median 0.18 micro g/ml, interquartile range: 0-0.44; values range: 0-1.03; P = 0.0047) and 92.6% of them had detectable DEHP and /or MEHP in the peritoneal fluid. No significant differences in either the DEHP/MEHP plasma concentrations (P >/= 0.31) or DEHP/MEHP peritoneal fluid concentrations (P >/= 0.66) were observed in the endometriotic patients as a function of the disease stage at the time of diagnosis. CONCLUSIONS: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.