13 research outputs found

    A preliminary study on a novel bioaugmentation technique enhancing lactic acid production by mixed cultures fermentation

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    The paper is a preliminary study on the selection of lactic acid producing microorganisms from a mixed microbial population via bioaugmentation. The bioaugmentation technique is based on pH sudden variations occurring in sequential batch steps of a dark fermentation process applied to simple substrates. Different conditions are tested and compared. The structure of microbial communities and concentrations of metabolic intermediates are analyzed to study the possible substrate conversion routes. Obtained results indicate that the initial mixed culture produced a lactic acid percentage of 5% in terms of CODLA/CODPRODUCTS. In the most favourable conditions, the selected culture produced a lactic acid percentage of 59%. The analysis of the composition of microbial communities before and after the bioaugmentation processes, indicates that lactic acid production mainly results from the population change to bacteria belonging to the genus Bacillus. Indeed, the relative abundance of Bacilli increased from 0.67%, to 8.40% during the bioaugmentation cycle

    Use of wound infusion catheters for postoperative local anaesthetic administration in cats

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    Objectives The present study aimed to document the use of the wound infusion catheter (WIC) following a variety of surgical procedures in cats, investigating complications and risk factors associated with catheter placement or local anaesthetic (LA) administration. Methods A retrospective, multicentric study was performed. Medical databases of eight veterinary referral hospitals from 2010 to 2021 were searched to identify records of cats where WICs were used. Information regarding signalment, type of surgery, size and type of WIC placed, and LA protocol used, as well as postoperative complications, were retrieved. Results One hundred and sixty-six cases fulfilled the inclusion criteria. Feline injection site sarcoma resection was the most common surgery. Overall complications were identified in 22/166 cats (13.2%). Thirteen cats (7.8%) experienced wound-related complications, whereas nine cats (5.4%) experienced drug-delivery complications. The only factor associated with an increased risk of complications was the amount of a single dose of LA delivered through the catheter ( P <0.001). An amount higher than 2.5 ml of LA delivered at each administration was associated with an increased risk of complications. All complications were minor and self-limiting. Conclusions and relevance WICs were used for a large variety of surgical procedures with different protocols of LA administration as part of a multimodal analgesic plan in cats. The risk of complications was relatively low and self-limiting, suggesting its safe use in cats. Further prospective studies are required to evaluate efficacy of postoperative analgesia and to determine the suitable protocol for WIC handling and maintenance

    High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

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    Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

    Evaluation of reconfiguration cost and energy aware virtual network embedding policies

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    Network virtualization techniques allow for the coexistence of many virtual networks hosted in a same substrate network. Virtual router migrations allow for resource consolidation with the consequence to reduce the power consumption in low traffic periods. Unfortunately virtual router migrations have the effect of degrading the Quality of Service during the downtime in which the router is not able to carry on its forwarding function. For this reason, despite the advantages in power consumption saving, the migration technique should be applied with parsimony to avoid an excessive QoS degradation. The objective of this paper is to study Virtual Network Embedding problems aware of both operation and reconfiguration costs that are characterized by the energy consumption and the revenue loss due to QoS degradation. An Embedding Optimization Problem formulation will be given in which the objective is to minimize an objective function taking into account both the operation and reconfiguration costs. Because the problem is NP-hard, we propose a feasible solution to the problem in cycle-stationary traffic scenario and when the possible embeddings are a-priory determined. The solution consists in determining the optimal policy of a Markov Decision Process. The results obtained show how the application of the introduced solution allows for cost reduction in the order of 30% as well as to limit the reconfiguration costs with respect to traditional migration policies

    Determination of marbofloxacin in plasma and synovial fluid by ultrafiltration followed by HPLC-MS/MS

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    A rapid LC-MS/MS method for the determination of marbofloxacin in plasma and synovial fluid is presented in this study. The method uses a rapid sample preparation which only requires an ultrafiltration step with centrifugal filter devices. The optimized procedure allows a minimal need of sample (175ÎĽL), particularly useful for synovial fluid samples which amount is rather limited; it is simple, rapid and easily applicable providing anyhow a satisfactory clean up, demonstrated by post-infusion experiments. On the other hand to maximize the speed of the analysis an ultrafast chromatographic separation has been obtained by selecting a column of 20mm; the reduced run-time is suitable for processing numerous samples on a daily basis. Linearity was assessed in the range 5-2500ngmL(-1); ofloxacin was used as internal standard. LOD and LOQ were respectively 1 and 5ng/mL. The method was successfully applied to a set of samples generated during an experimental veterinary study

    Preoperative Chemoradiation With VMAT-SIB in Rectal Cancer: A Phase II Study

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    Purpose: The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)-simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer. Methods: Radiation therapy was performed using the VMAT-SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2-cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m2 twice daily, 5 days per week) and oxaliplatin (130 mg/m2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria. Results: A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0-Tmic: 11/18 = 61.1%; 95% CI, 36.2-86.1). Acute grade 65 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One-, 3-, and 5-year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One-, 3-, and 5-year cumulative disease-free survival was 88.9%, 66.7%, and 66.7%, respectively. One-, 3-, and 5-year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively. Conclusion: The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one-third of patients had severe acute toxicity

    Nutlin-3a Enhances Natural Killer Cell-Mediated Killing of Neuroblastoma by Restoring p53-Dependent Expression of Ligands for NKG2D and DNAM-1 Receptors

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    In this study, we explored whether Nutlin-3a, a well-known, nontoxic small-molecule compound antagonizing the inhibitory interaction of MDM2 with the tumor suppressor p53, may restore ligands for natural killer (NK) cell-activating receptors (NK-AR) on neuroblastoma cells to enhance the NK cell-mediated killing. Neuroblastoma cell lines were treated with Nutlin-3a, and the expression of ligands for NKG2D and DNAM-1 NK-ARs and the neuroblastoma susceptibility to NK cells were evaluated. Adoptive transfer of human NK cells in a xenograft neuroblastoma-bearing NSG murine model was assessed. Two data sets of neuroblastoma patients were explored to correlate p53 expression with ligand expression. Luciferase assays and chromatin immunoprecipitation analysis of p53 functional binding on PVR promoter were performed. Primary neuroblastoma cells were also treated with Nutlin-3a, and neuroblastoma spheroids obtained from one high-risk patient were assayed for NK-cell cytotoxicity. We provide evidence showing that the Nutlin-3a-dependent rescue of p53 function in neuroblastoma cells resulted in (i) increased surface expression of ligands for NK-ARs, thus rendering neuroblastoma cell lines significantly more susceptible to NK cell-mediated killing; (ii) shrinkage of human neuroblastoma tumor masses that correlated with overall survival upon adoptive transfer of NK cells in neuroblastoma-bearing mice; (iii) and increased expression of ligands in primary neuroblastoma cells and boosting of NK cell-mediated disaggregation of neuroblastoma spheroids. We also found that p53 was a direct transcription factor regulating the expression of PVR ligand recognized by DNAM-1. Our findings demonstrated an immunomodulatory role of Nutlin-3a, which might be prospectively used for a novel NK cell-based immunotherapy for neuroblastoma

    Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases: A Phase 1 Study (ISIDE-BM-1)

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    Purpose To investigate the maximum tolerated dose of intensity modulated radiation&nbsp;therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with &lt;5 brain metastases using a standard linear accelerator. Materials and Methods The whole brain plus 3-mm margin was defined as the planning target volume (PTVwb), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTVm). Radiation therapy was delivered in 10 daily fractions (2&nbsp;weeks). Only the dose to PTVm was progressively increased in the patient cohorts (35&nbsp;Gy, 40&nbsp;Gy, 45&nbsp;Gy, 50&nbsp;Gy), whereas the PTVwb was always treated with 30&nbsp;Gy (3&nbsp;Gy per fraction) in all patients. The dose-limiting toxicity was evaluated providing that 3&nbsp;months of follow-up had occurred after the treatment of a 6-patient cohort. Results Thirty patients were enrolled in the study (dose PTVm: 35&nbsp;Gy, 8 patients; 40&nbsp;Gy, 6 patients; 45&nbsp;Gy, 6 patients; 50&nbsp;Gy, 10 patients). The number of treated brain metastases was 1 in 18 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. Three patients experienced dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12&nbsp;months and 53%, respectively. No patient showed late toxicity. Conclusions In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50&nbsp;Gy in 10 fractions was tolerable according to the study design
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