An urban biorefinery for food waste and biological sludge conversion into polyhydroxyalkanoates and biogas

This study focuses on the application of the concept of circular economy, with the creation of added-value marketable products and energy from organic waste while minimizing environmental impacts. Within this purpose, an urban biorefinery technology chain has been developed at pilot scale in the territorial context of the Treviso municipality (northeast Italy) for the production of biopolymers (polyhydroxyalkanoates, PHAs) and biogas from waste of urban origin. The piloting system (100\u2013380 L) comprised the following units: a) acidogenic fermentation of the organic fraction of municipal solid waste (OFMSW) and biological sludge; b) two solid/liquid separation steps consisting of a coaxial centrifuge and a tubular membrane (0.2 \u3bcm porosity); c) a Sequencing Batch Reactor (SBR) for aerobic PHA-storing biomass production; d) aerobic fed-batch PHA accumulation reactor and e) Anaerobic co-digestion (ACoD). The thermal pre-treatment (72 \ub0C, 48 h) of the feedstock enhanced the solubilization of the organic matter, which was converted into volatile fatty acids (VFAs) in batch mode under mesophilic fermentation conditions (37 \ub0C). The VFA content increased up to 30 \ub1 3 g COD/L (overall yield 0.65 \ub1 0.04 g CODVFA/g VS(0)), with high CODVFA/CODSOL (0.86 \ub1 0.05). The high CODVFA/CODSOL ratio enhanced the PHA-storing biomass selection in the SBR by limiting the growth of the non-storing microbial population. Under fully aerobic feast-famine regime, the selection reactor was continuously operated for 6 months at an average organic loading rate (OLR) of 4.4 \ub1 0.6 g COD/L d and hydraulic retention time (HRT) of 1 day (equal to SRT). The ACoD process (HRT 15 days, OLR 3.0\u20133.5 kg VS/m3 d) allowed to recover the residual solid-rich overflows generated by the two solid/liquid separation units with the production of biogas (SGP 0.44\u20130.51 m3/kg VS) and digestate. An overall yield of 7.6% wt PHA/VS(0) has been estimated from the mass balance. In addition, a preliminary insight into potential social acceptance and barriers regarding organic waste-derived products was obtained

Nanocoated fiber label-free biosensing for perfluorooctanoic acid detection by lossy mode resonance

The determination of per- and polyfluoroalkyl substances (PFAS) in environmental samples, such as drinking waters, requires the design of high performing and versatile sensing strategies. Label-free biosensing platforms based on specialty fiber optics are a valid option to face this challenge. Among them, lossy mode resonance (LMR) fiber optic biosensors are showing remarkable performance in terms of detection limit, selectivity, and reproducibility. The detection of small molecules, such as perfluorooctanoic acid (PFOA), can be achieved with the help of well-designed biological recognition layers. In this study, the biosensing potentialities of a label-free LMR-assisted optical platform based on nanocoated fibers are investigated. Delipidated human serum albumin (hSA) was used as biological recognition layer for PFOA in aqueous solution. Different fiber functionalization protocols based on the covalent immobilization of hSA were tested. The conformational changes related to the formation of hSA/PFOA complex were followed via optical monitoring of LMR spectral shift, showing a trend that can be modeled with Langmuir adsorption isotherm. These results confirmed the potentiality of LMR-based fiber biosensors for the detection of small molecules, such as PFOA, in synthetic samples

Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K(+) current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP(2)). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP(2) levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP(2) is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies

Insights into the secondary glass production in Roman Aquileia: A preliminary study

A set of 29 glass shards, selected from numerous ones recovered in 2017 in Aquileia (NE Italy), was studied to provide evidence of local glass production for that specific area in antiquity. These shards can be dated between the 1st and the 4th century AD. The chemical composition of glass samples was obtained using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) that enables to quantify the concentration of major, minor, and trace elements needed to investigate provenance and compositional groups and sometimes to suggest a chronological frame of the samples. To ensure that the samples are homogeneous enough to perform accurate quantification, some of them were also analysed by instrumental neutron activation analysis (INAA). Most of the chunks, working wastes, and artefact shards considered in this work exhibited similarities among them in terms of composition, which likely indicates that glass working activities were practised at the site of recovery. The analyses demonstrated the presence of both recycled glass and primary glass. Interestingly, the compositional data of raw primary glass point to both Syro-Palestinian and Egyptian regions as sourcing areas, confirming the role of the Roman city of Aquileia as a network node for the trade of goods. In addition, some particularly coloured glass fragments showed a composition typical of glass produced starting from the 1st or 2nd century AD, requiring specific types of furnaces and procedures for its manufacture, and suggesting the possibility of local highly-specialised production. The preliminary results of this work strengthen the hypothesis that Aquileia was a thriving centre, either for working primary glass or for glass recycling and production of objects with particular colours

Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e

Objective: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. Materials and methods: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). Results: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58–0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67–0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85–4.78) than without (4.14; SD: ±2.97; range: 2.18–5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08–32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14–48.72). Conclusions: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols. Keywords: Rectal cancer, Neoadjuvant radiotherapy, Interobserver variability, Contouring, Target volume delineatio

TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m 2, oxaliplatin 85 mg/m 2, L-leucovorin 200 mg/m 2, 5-fluoruracil 2400 mg/m 2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD

National variations in perioperative assessment and surgical management of Crohn's disease: a multicentre study

Aim: Crohn's disease (CD) requires a multidisciplinary approach and surgery should be undertaken by dedicated colorectal surgeons with audited outcomes. We present a national, multicentre study, with the aim to collect benchmark data on key performance indicators in CD surgery, to highlight areas where standards of CD surgery excel and to facilitate targeted quality improvement where indicated. Methods: All patients undergoing ileocaecal or redo ileocolic resection in the participating centres for primary and recurrent CD from June 2018 to May 2019 were included. The main objective was to collect national data on hospital volume and practice variations. Postoperative morbidity was the primary outcome. Laparoscopic surgery and stoma rate were the secondary outcomes. Results: In all, 715 patients were included: 457 primary CD and 258 recurrent CD with a postoperative morbidity of 21.6% and 34.7%, respectively. Laparoscopy was used in 83.8% of primary CD compared to 31% of recurrent CD. Twenty-five hospitals participated and the total number of patients per hospital ranged from 2 to 169. Hospitals performing more than 10 primary CD procedures per year showed a higher adoption of laparoscopy and bowel sparing surgery. Conclusions: There is significant heterogeneity in the number of CD surgeries performed per year nationally in Italy. Our data suggest that high-volume hospitals perform more complex procedures, with a higher adoption of bowel sparing surgery. The rate of laparoscopy in high-volume hospitals is higher for primary CD but not for recurrent CD compared with low-volume hospitals