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Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity than most other beta-lactams antibiotics and are the most effective against Gram-positive and Gram-negative bacteria. All β-lactams antibiotics have a similar molecular structure: the carbapenems together with the β-lactams. This combination gives an extraordinary stability to the molecule against the enzymes inactivating the β-lactams. They are safe to use and therefore widespread use in many countries has given rise to carbapenem resistance which is a major global public health problem. The carbapenem resistance in some species is intrinsic and consists of the capacity to resist the action of antibiotics with several mechanisms: for the absence of a specific target, or an intrinsic difference in the composition of cytoplasmatic membrane or the inability to cross the outer membrane. In addition to intrinsic resistance, bacteria can develop resistance to antibiotics with several mechanisms that can be gathered in three main groups. The first group includes antibiotics with poor penetration into the outer membrane of bacterium or antibiotic efflux. The second includes bacteria that modify the target of the antibiotics through genetic mutations or post-translational modification of the target. The third includes bacteria that act with enzyme-catalyzed modification and this is due to the production of beta-lactamases, that are able to inactivate carbapenems and so called carbapenemases. In this review, we focus on the mode of action of carbapenem and the mechanisms of carbapenem resistance.

All critically ill adult patients in intensive care units (ICU) typically experience pain. Critically ill adults suffer pain of different intensities. It depends on individual characteristics, specific procedural interventions, and underlying diseases. Inadequate management of acute pain is a risk factor for the emergence of chronic pain, where the incidence is up to 33% into the ICU survivor population. For the management of pain, agitation, and delirium, several coexisting clinical practice guidelines have been published. The first problem is that the patient recovered in intensive care unit should not be able to communicate its pain state. Opioids are the analgesic drugs of choice in critically ill patients with non-neuropathic pain. All intravenous opioids have the same effects, respecting the equianalgesic table. Observational research has shown that opioids are the main analgesic treatment in over 80% of mechanically ventilated patients. It is interesting that opioid consumption in an ICU and the memory of painful experience are linked to the development of post-traumatic stress disorder after ICU discharge. In order to reduce the side effects and maintain analgesia, it is useful to associate adjuvant medications with opioids. An opportunity to improve patients' experience in an ICU is to manage pain through multimodal approaches.

Pain following brain surgery can compromise the result of surgery. Several pharmacological interventions have been used to prevent postoperative pain in adults undergoing brain surgery. Pain following craniotomy is considered to be moderate to severe during the first two post-operative days. Opioids have been historically the mainstay and are the current prominent strategy for pain treatment. They produce analgesia but may alter respiratory, cardiovascular, gastrointestinal, and neuroendocrine functions. All these side effects may affect the normal postoperative course of craniotomy by affecting neurological function and increasing intracranial pressure. Therefore, their use in neurosurgery is limited, and opioids are used in case of strict necessity or as rescue medication. In addition to opioids, drugs with differing mechanisms of actions target pain pathways, resulting in additive and/or synergistic effects. Some of these agents include acetaminophen/non-steroidal anti-inflammatory drugs (NSAIDs), alpha-2 agonists, NMDA receptor antagonists, gabapentinoids, and local anesthesia techniques. Multimodal analgesia should be a balance between adequate analgesia and less drug-induced sedation, respiratory depression, hypercapnia, nausea, and vomiting, which may increase intracranial pressure. Non-opioid analgesics can be an useful pharmacological alternative in multimodal regimes to manage post-craniotomy pain. This narrative review aims to outline the current clinical evidence of multimodal analgesia for post craniotomy pain control.

Purpose: Advances in surgical phase recognition are generally led by training deeper networks. Rather than going further with a more complex solution, we believe that current models can be exploited better. We propose a self-knowledge distillation framework that can be integrated into current state-of-the-art (SOTA) models without requiring any extra complexity to the models or annotations. Methods: Knowledge distillation is a framework for network regularization where knowledge is distilled from a teacher network to a student network. In self-knowledge distillation, the student model becomes the teacher such that the network learns from itself. Most phase recognition models follow an encoder-decoder framework. Our framework utilizes self-knowledge distillation in both stages. The teacher model guides the training process of the student model to extract enhanced feature representations from the encoder and build a more robust temporal decoder to tackle the over-segmentation problem. Results: We validate our proposed framework on the public dataset Cholec80. Our framework is embedded on top of four popular SOTA approaches and consistently improves their performance. Specifically, our best GRU model boosts performance by +3.33% accuracy and +3.95% F1-score over the same baseline model. Conclusion: We embed a self-knowledge distillation framework for the first time in the surgical phase recognition training pipeline. Experimental results demonstrate that our simple yet powerful framework can improve performance of existing phase recognition models. Moreover, our extensive experiments show that even with 75% of the training set we still achieve performance on par with the same baseline model trained on the full set.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-κB and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies. Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-B and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.

We report the case of an endovascular repair of an aortic arch aneurysm by a surgeon-modified fenestrated endograft with a single fenestration in a high-risk patient unfit for open surgery. A patient of 84 years, chronic ischemic cardiopathic, suffering from prostate adenocarcinoma in chemotherapy treatment, came to our hospital for post-traumatic fracture of the right femur. During the hospitalization, the patient exhibited dysphonia and respiratory disorders for several days, therefore, the patient performed Computed Tomography Angiography (CTA) that found the presence of voluminous aneurysm of the aortic arch with a maximum diameter of about 74 mm. The patient was treated with a hybrid-staged procedure; in the first instance, with a carotid-carotid-succlavium bypass to preserve the cerebral and upper limb vascularization and then, the procedure was completed by implanting the surgeon-modified fenestrated endograft with stent delivery to the patient with a fenestration on the anonymous trunk. This surgeon-modified fenestrated endograft was created by modifying a standard endograft by a single fenestration following the three-dimensional reconstructions of the CTA images. The procedure was successfully completed and postoperative course was uneventful. Computed Tomography Angiography demonstrated the exclusion of the aneurysm, patency of the implanted endograft modules, and absence of signs of endoleaks and / or cerebral or medullary ischemic complications.

(1) Background: healthcare-associated infections are one of the most frequent adverse events in healthcare delivery worldwide. Several antibiotic resistance mechanisms have been developed, including those to carbapenemase. Cefiderocol (CFD) is a novel siderophore cephalosporin designed to treat carbapenem-resistant bacteria. (2) Methods: we performed a systematic review of all cases reported in the literature to outline the existing evidence. We evaluated real-world evidence studies of CFD in the treatment of carbapenem-resistant (CR) bacteria. (3) Results: a total of 19 publications treating cases of infection by CR bacteria were included. The three most frequent CR pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. A regimen of 2 g every 8 h was most frequently adopted for CFD with a mean treatment duration of 25.6 days. CFD was generally well tolerated, with fewer side effects. The success rate of CFD therapy was satisfactory and almost 70% of patients showed clinical recovery; of these, nearly half showed negative blood cultures and infection-free status. (4) Conclusions: This review indicates that CFD is active against important GN organisms including Enterobacteriaceae, P. aeruginosa, and A. baumannii. CFD seems to have a safe profile.

Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment. Glioblastoma multiforme is the most common and aggressive primary brain cancer with only approximate to 3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment.

Hyaluronic acid (HA)-based prodrugs bearing double-responsive (acid pH or oxidation) boronates of catechol-containing drugs were used to treat xenografted human prostate tumours (LNCaP) in SCID mice. The HA prodrugs accumulated significantly only in tumours (impressively, up to 40% of the injected dose after 24 h) and in liver, with negligible – actually anti-inflammatory - consequences in the latter. A quercetin-HA prodrug significantly slowed down tumour growth, in a dose-dependent fashion and with a much higher efficacy (up to 4 times) than equivalent doses of free quercetin. In short, boronated HA appears to be a very promising platform for targeted chemotherapy.

The goals of the current research were to assess the immediate impact of invasive wild boar (Sus scrofa L.) in olive orchards of southern Italy. Over a one-year study, in grubbed and ungrubbed areas, we measured the seasonal changes on the fast soil biological and chemical responses at depths of 0–15 cm and 15–40 cm, and several leaf and fruit characteristics. The impact factor, IFG, was used to quantify the effects of wild boar on individual soil parameters. Grubbing induced an increase in the soil moisture at both depths. Soil pH, organic matter, and C/N ratio were higher in grubbed soils at 0–15 cm and lower at 15–40 cm compared to ungrubbed soils. These trends were reflected in the higher microbial community biomass and the inhibition of fungal fraction in grubbed topsoil, while an opposite tendency at 15–40 cm was found. Microbial biomass had the highest IFG in topsoil (94%) and metabolic quotient (85%) at a 15–40 cm depth. Microbial stress condition and C loss were found in grubbed soil at both depths. Furthermore, these soils were also shown to be of lower quality than ungrubbed soils, especially at 0–15 cm (SQI = 0.40 vs. 0.50, respectively). A stronger negative impact of wild boar grubbing was observed in the Autumn/Winter and for fruit polyphenol content.

We report the case of an endovascular repair of an aortic arch aneurysm by a self-made endograft with a single fenestration in a high-risk patient unfit for open surgery. A patient of 81 years, chronic ischemic cardiopathic, suffering from prostate K in chemotherapy treatment, came to our hospital for post-traumatic fracture of the right femur, associated with dysphonia and respiratory disorders for several days. During the hospitalization, the patient performed angio-CT that found the presence of voluminous aneurysm of the aortic arch with a maximum diameter of about 70mm. The patient was treated in the first instance with a carotid-carotid-succlavium bypass to preserve the cerebral and upper limb vascularization. The self-made endograft was created by modifying a standard endograft by a single fenestration following the three-dimensional reconstructions of the CT images. The procedure was completed by implanting this endograft with stent delivery to the patient with a fenestration on the anonymous trunk. The procedure was successfully completed and postoperative course was uneventful. Computed tomography angiography demonstrated the exclusion of the aneurysm, patency of the implanted endograft modules, and absence of signs of endoleaks and / or cerebral or medullary ischemic complications.

Community pharmacies represent unusual enterprises as their main function is intrinsically related to the provision of healthcare services. Hence, market competition in this sector needs to be regulated, in order to ensure equitable accessibility, efficiency and quality of services. However, recently a general deregulation trend may be observed in Europe. In this paper, we focus on location restrictions, i.e. on demographic and geographic constraints to open new pharmacies, and we evaluate the impact of their relaxation. In particular, we analyze the case of the city of Pamplona (ES), where a striking increase in the number of pharmacies occurred, after the introduction of a new regulatory system in 2000. We evaluate, thanks to an in-depth spatial analysis, the evolution of the system to date and the effects produced on the consumers, in terms of accessibility, and on the competitors, in terms of market shares distribution. By comparing the obtained results with the ones related to the case of a second Spanish city, characterized by more strict restrictions, it emerges that the deregulation risks to produce a limited improvement in terms of accessibility and to exacerbate differences among consumers. Moreover, an increasing number of competitors does not necessarily imply a more equitable distribution of market shares, thus putting at risk the desired effects in terms of cost reduction and service quality improvement.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown ( n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32–0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

We report a case of hookworm infection presenting as recurrent severe anaemia in an adult Pakistani migrant to Italy. Clinicians working in non-endemic countries should be aware of this possible cause of anaemia, approachable by a microscopic stool examination that could avoid invasive and time-consuming diagnostic work-up.

Butyric acid (BA) has been reported to induce anticancer effects on hepatocellular carcinoma (HCC) cells both in vitro and in vivo. However, its delivery and release in cancer tissues must be optimized. On the basis of these requirements, we prepared liposomes coated with chitosan and uncoated liposomes and both types were loaded with BA through a thin-film hydration method. The liposomes coated or uncoated with chitosan had a mean hydrodynamic size of 83.5 and 110.3 nm, respectively, with a homogeneous size distribution of the particles. For evaluation of the biological effects of the nanoformulations, the hepatoblastoma (HB) HepG2 cell line was utilized. BA-loaded liposomes coated with chitosan showed a considerable higher cytotoxicity than both uncoated liposomes and free BA, with IC 50 values, after 72 h of incubation, of 7.5, 2.5 and 1.6 mM, respectively. Treatment of HepG2 cells for 5 h with the BA-loaded liposomes coated with chitosan at 5 mM lowered the extent of the increase in IL-8, IL-6, TNF-α and TGF-β expression of approximately 64, 58, 85 and 73.8%, respectively, when compared to the untreated cells. The BA-loaded liposomes coated with chitosan had marked capacity to be internalized in human HB cells showing an increased cytotoxic activity when compared with free BA and important anti-inflammatory effects by inhibiting production of cytokines with a central role in liver cell survival. Butyric acid (BA) has been reported to induce anticancer effects on hepatocellular carcinoma (HCC) cells both in vitro and in vivo. However, its delivery and release in cancer tissues must be optimized. On the basis of these requirements, we prepared liposomes coated with chitosan and uncoated liposomes and both types were loaded with BA through a thin-film hydration method. The liposomes coated or uncoated with chitosan had a mean hydrodynamic size of 83.5 and 110.3 nm, respectively, with a homogeneous size distribution of the particles. For evaluation of the biological effects of the nanoformulations, the hepatoblastoma (HB) HepG2 cell line was utilized. BA-loaded liposomes coated with chitosan showed a considerable higher cytotoxicity than both uncoated liposomes and free BA, with IC 50 values, after 72 h of incubation, of 7.5, 2.5 and 1.6 mM, respectively. Treatment of HepG2 cells for 5 h with the BA-loaded liposomes coated with chitosan at 5 mM lowered the extent of the increase in IL-8, IL-6, TNF-α and TGF-β expression of approximately 64, 58, 85 and 73.8%, respectively, when compared to the untreated cells. The BA-loaded liposomes coated with chitosan had marked capacity to be internalized in human HB cells showing an increased cytotoxic activity when compared with free BA and important anti-inflammatory effects by inhibiting production of cytokines with a central role in liver cell survival.

A 90-year-old male developed acute onset of abdominal and lumbar pain due to the rupture of an 11-cm abdominal aortic aneurysm. A congenital fused pelvic kidney perfused by three renal arteries arising from iliac axes was detected. In an emergent setting, an aorto-uni-iliac endograft was deployed through right femoral surgical access with occlusion of the upper right renal artery. An occluder device was placed in the common iliac artery above the renal artery through left femoral access. A femorofemoral crossover bypass completed the procedure. The patient developed acute renal failure, with no dialysis necessity. One-month computed tomography angiography showed procedure success.

The combined used of thrombectomy with direct intravenous thrombolytic infusion provided effective treatment of DVT and uncovered an underlying left common iliac vein stenosis, which was successfully managed by angioplasty and stenting.

Purpose: To evaluate the potential confounding effect of concomitant pneumonia (PNM) on lung ultrasound (LUS) B-lines in acute heart failure (AHF).Methods: We enrolled 86 AHF patients with (31 pts, AHF/PNM) and without (55 pts, AHF) concomitant PNM. LUS B-lines were evaluated using a combined antero-lateral (AL) and posterior (POST) approach at admission (T0), after 24 h from T0 (T1), after 48 h from T0 (T2) and before discharge (T3). B-lines score was calculated at each time point on AL and POST chest, dividing the number of B-lines by the number of explorable scanning sites. The decongestion rate (DR) was calculated as the difference between the absolute B-lines number at discharge and admission, divided by the number of days of hospitalization. Patients were followed-up and hospital readmission for AHF was considered as adverse outcome.Results: At admission, AHF/PNM patients showed no difference in AL B-lines score compared with AHF patients [AHF/PNM: 2.00 (IQR: 1.44–2.94) vs. AHF: 1.65 (IQR: 0.50–2.66), p = 0.072], whereas POST B-lines score was higher [AHF/PNM: 3.76 (IQR: 2.70–4.77) vs. AHF = 2.44 (IQR: 1.20–3.60), p < 0.0001]. At discharge, AL B-lines score [HR: 1.907 (1.097–3.313), p = 0.022] and not POST B-lines score was found to predict adverse events (AHF rehospitalization) after a median follow-up of 96 days (IQR: 30–265) in the overall population.Conclusions: Assessing AL B-lines alone is adequate for diagnosis, pulmonary congestion (PC) monitoring and prognostic stratification in AHF patients, despite concomitant PNM.

In this study, Sea Water Bread (SWB), made with food grade sea water was compared with control bread made with Tap Water (TWB). Sea water's influence on chemical-nutritional properties of bread was investigated. Contents of salt, macro/micro-elements, basic nutrients, polyphenols, antioxidant activity, olfactory characteristics, and volatile components were analyzed. Chlorides' analysis showed SWB had a lower salt content than TWB and it was confirmed by ICP-OES investigation. An electronic nose confirmed differences between the groups of aromatic molecules of the bread typologies, as well as the profiles of the volatile molecules by GC-MS.

The primary goal of this treatment is the restoration of venous outflow and can be achieved by combined endovascular techniques. We report a case of 38 years-old female, with leg pain and edema, skin changes, venous claudication and dyspnea for polmunary embolism.

The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017. © 2016 Wiley Periodicals, Inc. The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017. © 2016 Wiley Periodicals, Inc.

Adipose tissue is an easily accessible source of stem cells for use in tissue regenerative medicine. In the literature, different methods have been used to stimulate acquisition of neuronal characteristics by adipose-derived stem cells (ADSC). Herein we study the growth and neuronal differentiation potential of ADSC seeded onto a porous polycaprolactone (PCL) scaffold. The objective of this study is to demonstrate that PCL can be used as a scaffold to support reconstruction of new nervous tissue using adipose stem cells. We have previously shown that undifferentiated ADSC adhere and grow on PCL. Herein we show that, after culture on PCL in neuronal differentiation medium, ADSC expressed molecular markers characteristic of neuronal cells (β-tubulin-III, Neuron-Specific Enolase (NSE), Nestin) and secrete brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). This study suggests that PCL can be used as a scaffold to generate nervous tissue in vitro. PLC has excellent mechanical properties and a slow degradation rate. Moreover, on the basis of our results, we propose that PCL could be used for to make in vitro, scaffold coated with neuronal cells derived from Adipose stem cells (ADSC). Neuronal cells-coated PCL could find several applications to replace damaged area of ​​the body; for example, a possible use could be the generation of nerves. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014. Adipose tissue is an easily accessible source of stem cells for use in tissue regenerative medicine. In the literature, different methods have been used to stimulate acquisition of neuronal characteristics by adipose-derived stem cells (ADSC). Herein we study the growth and neuronal differentiation potential of ADSC seeded onto a porous polycaprolactone (PCL) scaffold. The objective of this study is to demonstrate that PCL can be used as a scaffold to support reconstruction of new nervous tissue using adipose stem cells. We have previously shown that undifferentiated ADSC adhere and grow on PCL. Herein we show that, after culture on PCL in neuronal differentiation medium, ADSC expressed molecular markers characteristic of neuronal cells (β-tubulin-III, Neuron-Specific Enolase (NSE), Nestin) and secrete brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). This study suggests that PCL can be used as a scaffold to generate nervous tissue in vitro. PLC has excellent mechanical properties and a slow degradation rate. Moreover, on the basis of our results, we propose that PCL could be used for to make in vitro, scaffold coated with neuronal cells derived from Adipose stem cells (ADSC). Neuronal cells-coated PCL could find several applications to replace damaged area of the body; for example, a possible use could be the generation of nerves.

Background: Surgical site infection (SSI) is a common complication of surgical procedures.Aim: Our study aimed at investigating a new method based on assessment of suture thread colonization to identify patients developing an SSI.Materials and Methods: We prospectively enrolled 119 patients undergoing elective surgery. For each patient, a synthetic absorbable thread in Lactomer 9-1 (Polisorb Gauge 2) inserted in the surgical site at the end of surgery was sent to the microbiology laboratory after 48 h to assess colonization of its inner tract.Results: Forty (33.6% of cases) patients had a colonized thread. Antibiotic prophylaxis was administered to 66 of 79 patients who did not display a colonized thread and to 20 of the 40 patients with a colonized thread (83.5% versus 50%, respectively, P = 0.0002). An SSI was observed only in patients with a colonized thread (10% versus 0, P = 0.02). The microorganisms identified in colonized threads were the same identified in SSIs.Conclusions: Since an SSI was found only in patients with colonized threads, the method described here may be valuable for identifying patients developing an SSI. Moreover, the method can also be useful for targeting efficient antibiotic therapy to the culprit microorganisms. (C) 2017 Elsevier Inc. All rights reserved.

Background: This pilot study was designed to compare the efficacy of ultramicronized palmitoylethanolamide (um-PEA) as add-on therapy to tapentadol (TP) with TP therapy only in patients suffering from chronic low back pain (LBP). Methods: This pilot observational study consists in two arms: the prospective arm and the retrospective one. In the prospective arm patients consecutively selected received um-PEA as add-on therapy to TP for 6 months; in the retrospective arm patients were treated with TP only for 6 months. Pain intensity and neuropathic component were evaluated at baseline, during and after 6 months. The degree of disability and TP dosage assumption were evaluated at baseline and after 6 months. Results: Statistical analysis performed with generalized linear mixed model on 55 patients (30 in the prospective group and 25 in the retrospective group) demonstrated that um-PEA as add-on treatment to TP in patients with chronic LBP, in comparison to TP alone, led to a significantly higher reduction in pain intensity, in the neuropathic component, the degree of disability and TP dosage assumption. No serious side effects were observed. Conclusion: Overall, the present findings suggest that um-PEA may be an innovative therapeutic intervention as add-on therapy to TP for the management of chronic LBP with a neuropathic component, as well as to improve patient quality of life. Additionally, this combination treatment allowed a reduction in TP dose over time and did not show any serious side effects. Background: This pilot study was designed to compare the efficacy of ultramicronized palmitoylethanolamide (um-PEA) as add-on therapy to tapentadol (TP) with TP therapy only in patients suffering from chronic low back pain (LBP). Methods: This pilot observational study consists in two arms: the prospective arm and the retrospective one. In the prospective arm patients consecutively selected received um-PEA as add-on therapy to TP for 6 months; in the retrospective arm patients were treated with TP only for 6 months. Pain intensity and neuropathic component were evaluated at baseline, during and after 6 months. The degree of disability and TP dosage assumption were evaluated at baseline and after 6 months. Results: Statistical analysis performed with generalized linear mixed model on 55 patients (30 in the prospective group and 25 in the retrospective group) demonstrated that um-PEA as add-on treatment to TP in patients with chronic LBP, in comparison to TP alone, led to a significantly higher reduction in pain intensity, in the neuropathic component, the degree of disability and TP dosage assumption. No serious side effects were observed. Conclusion: Overall, the present findings suggest that um-PEA may be an innovative therapeutic intervention as add-on therapy to TP for the management of chronic LBP with a neuropathic component, as well as to improve patient quality of life. Additionally, this combination treatment allowed a reduction in TP dose over time and did not show any serious side effects.

Objectives: Vascular occlusion of hemodialysis arteriovenous access (AVA) using an Amplatzer vascular plug (AVP; St. Jude Medical, St. Paul, MN, USA) is an arising and alternative practice in selected patients; however, few reported cases can be found in the literature. Herein, we report on our experience with endovascular treatment of complicated AVA. Materials and Methods: From September 2015 to December 2016, 3 patients at our clinic underwent an occlusion of hemodialysis AVA with 2 different Amplatzer vascular plugs: 2 patients with type II and 1 patient with type IV. Of these, 1 patient was treated for an autologous radiocephalic fistula, the second patient was treated for an autologous brachiocephalic fistula located at the elbow, and the third was, instead, treated for a radiocephalic forearm fistula. The reason for closing the AVA in all patients was due to the presence of dialysis-associated steal syndrome with critical hand ischemia and intractable ipsilateral edema. Results: All AVAs were treated using an AVP. No plug migration, access revascularization, persistent ischemia, nor other complications were observed. Conclusion: This report suggests that the use of AVP for embolization of complicated AVA is a safe and reasonable alternative to open surgery in selected patients.

The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063-2074, 2017. © 2016 Wiley Periodicals, Inc.

Background The aim of this study is to retrospectively analyze the early and long-term outcomes of endovascular treatment of Trans-Atlantic Inter-Society Consensus II class C and D (TASC II) aortoiliac occlusive disease with an expanded polytetrafluoroethylene–covered stent graft. Methods Between January 2006 and November 2017, 61 patients (53 males, 8 females), with symptomatic aortoiliac stenotic and/or occlusive disease, were treated with VIABAHN (W.L. Gore and Associates, Flagstaff, Ariz) at 2 University medical centers. The morphology of the lesions was evaluated and classified by contrast-enhanced computed tomography angiography. Demographic data, operation details, and postoperative outcomes were collected. Follow-up data were analyzed by a life-table analysis (Kaplan-Meier test). Results Mean age of the patients was 64.89 ± 10.77 years (range 44–89). Thirty-seven patients (60.7%) presented with severe claudication (Rutherford 3), whereas 21 (34.4%) were in Rutherford class 4 and the remaining 3 patients (4.9%) suffered from necrotic lesions (Rutherford 5/6). Fifty-six patients were smokers (91.8%), 38 (62.3%) had hypertension, 23 (37.7%) had coronary artery disease, 30 (40.2%) had dyslipidemia, 18 (29.5%) had chronic obstructive pulmonary disease, 6 (9.5%) had renal insufficiency (serum creatinine>2.0 mg/dL) and 24 (39.3%) had diabetes. Technical success was achieved in 59/61 patients (96.7%) with 16 patients (26.2%) requiring combined percutaneous brachial access to obtain iliac recanalization. Perioperative mortality was 1.6%, whereas postoperative major complications occurred in 2 patients (3.6%). The mean number of VIABAHN placed was 1.77/patient. Mean follow-up was 31.5 months (range 1–108) and primary patency at 36 months was 94.9%. Two major amputations of the lower limbs occurred during the follow-up. Conclusions Open surgery with the aortobifemoral bypass has been the gold standard treatment for complex aortoiliac occlusive disease although complications and mortality still remain significant issues. Our results suggest that endovascular therapy of TASC C and D iliac lesions using the VIABAHN stent graft is feasible, effective, and has good, long-term patency.

Background: Palmitoylethanolamide (PEA) belong to endocannabinoid family, a group of fatty acid amides. PEA has been proven to have analgesic and anti-inflammatory activity and has been used in several controlled studies focused on the management of chronic pain among adult patients with different underlying clinical conditions. Methods/design: A literature search will be performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The population will be patients who have chronic pain, the intervention will be the administration of PEA alone or in combination with other drugs for the pain management; the comparison will be the standard therapy in accordance with the current guidelines for the treatment of pain. The Outcomes will be the reduction of pain not restricted to specific scales laying out the pain outcome data described in the included studies. Discussion: This scoping review aims to describe the clinical applications of the PEA in chronic pain management and its outcome. Scoping review registration: Open Science Framework https://osf.io/74tmx/. Background: Palmitoylethanolamide (PEA) belong to endocannabinoid family, a group of fatty acid amides. PEA has been proven to have analgesic and anti-inflammatory activity and has been used in several controlled studies focused on the management of chronic pain among adult patients with different underlying clinical conditions. Methods/design: A literature search will be performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The population will be patients who have chronic pain, the intervention will be the administration of PEA alone or in combination with other drugs for the pain management; the comparison will be the standard therapy in accordance with the current guidelines for the treatment of pain. The Outcomes will be the reduction of pain not restricted to specific scales laying out the pain outcome data described in the included studies. Discussion: This scoping review aims to describe the clinical applications of the PEA in chronic pain management and its outcome. Scoping review registration: Open Science Framework https://osf.io/74tmx/.

Background: Head and neck cancer affects approximately 382,000 new patients per year worldwide with a significant portion undergoing surgical treatment. During postoperative period key elements in the Intensive Care Unit (ICU) are airway management and pain control. Objective: We evaluated the average change of inpatient pain control using a Numerical Rating Score (NRS). We also evaluated the time of extubation after ICU admission recording the incidence of desaturation and the necessity of re-intubation. Secondary outcomes were the incidence of postoperative complications, included those narcotics-related, and the use of rescue analgesics. Methods: In this retrospective observational study, we analyzed data of registry before and after we have changed our postoperative analgesic protocol from remifentanil infusion to ketamine infusion. Results: Medical records of 20 patients were examined. 10 patients received 0.5 mg/kg ketamine bolus at the end of surgery, followed by a continuous infusion of 0.25 mg/kg/h. All patients presented a significant decrease in pain intensity from the 4th to 48th postoperative hour (p < 0.05), but statically not a significant difference in NRS score was recorded between the two groups. Time to extubation was shorter in ketamine group compared to the remifentanil group (112.30 min ± 16.78 vs. 78 min ± 14.17; p < 0.05). Desaturation rate was 10% in the remifentanil group, while no case was recorded in the ketamine group. Conclusion: The level of analgesia provided by ketamine and remifentanil was comparable. Ketamine was superior in ventilatory management of the patient with more rapid extubation and with no case of desaturation.

With new missions being selected, missions moving to post-operations, and missions starting their journey to various targets in the Solar System, the European Space Agency’s Planetary Science Archive [1] (http://psa.esa.int) (PSA) is in constant evolution to support the needs of the projects and of the scientific community. What happened since last year? The past year has been good for the European Space Agency (ESA) Solar System missions and the PSA, with the successful flyby of Earth by the BepiColombo mission to Mercury. The ExoMars 2016 mission is performing nominally and is quickly delivering numerous scientific observations. As is common for ESA missions, access to the data is protected and reserved to members of the science team for the first months of the mission. Once the products are ready to go public, the PSA performs a scientific peer-review to ensure that the products to be made public are of excellent quality for all future users. During the first half of 2020, the PSA has successfully peer-reviewed the CaSSIS and NOMAD observations. Those products are now being made public on a systematic basis once the proprietary period elapses (generally between 6 and 12 months). Early in 2020, filters to search data with geometrical values (i.e., longitude, phase angle, slant distance, etc.) were enabled. For now this service works for Mars Express and Rosetta, but will be soon extended to other missions. One of the main new services provided to the scientific community in 2020 is the Guest Storage Facility (GSF), which allows users to archive derived products. Products such as geological maps, Digital Terrains Models, new calibrated files, and others can be stored in the GSF in the format most used by the users. Contact us to preserve your science! Finally, by the end of 2020 users of the PSA will have access to new services based on Geographical Information Systems. You can contribute to the PSA! At the PSA we constantly interact with our users to ensure that our services are in line with the expectations and needs of the community. We encourage feedback from community scientists through: PSA Users Group: A group of scientific experts advising the PSA on strategic development; Direct interactions: Scientists from the PSA are available and eager to receive your comments and suggestions; ESA missions: If you are part of a mission archiving its data at the PSA, tell us how your data should best be searched and used. Acknowledgement The authors are very grateful to all the people who have contributed over the last 17 years to ESA's Planetary Science Archive. We are also thankful to ESA’s teams who are operating the missions and to the instrument science teams who are generating and delivering scientific calibrated products to the archive. References [1] Besse, S. et al. (2017) Planetary and Space Science, 10.1016/j.pss.2017.07.013, ESA's Planetary Science Archive: Preserve and present reliable scientific data sets.

Geographical information systems (GIS) are becoming increasingly used for planetary science. GIS are computerised systems for the storage, retrieval, manipulation, analysis, and display of geographically referenced data. Some data stored in the Planetary Science Archive (PSA)[1] have spatial metadata associated to them. To facilitate users in handling and visualising spatial data in GIS applications, the PSA should support interoperability with interfaces implementing the standards approved by the Open Geospatial Consortium (OGC). These standards are followed in order to develop open interfaces and encoding that allow data to be exchanged with GIS Client Applications (e.g. OpenLayers, Cesium...). Access to this data for use in applications can be provided through OGC Web Service (OWS) implementations. An existing open source server is GeoServer, an instance of which has been deployed for the PSA, that uses the OGC standards to allow the sharing, processing and editing of data and spatial data through the Web Map Service (WMS) and Web Feature Service (WFS) standards. On the back-end side, a PostgreSQL/PostGIS instance allows the spatial queries. The final goal is to enhance the PSA (accessible through http://psa.esa.int) further as a portal which enables science exploitation of ESA's planetary missions datasets. This can be facilitated through the GIS framework, offering interfaces (both web GUI and scriptable APIs) that can be used more easily and scientifically by the community, and that will also enable the community to build added value services on top of the PSA. Introduction Some of the current operational ESA planetary missions, such as Mars Express, ExoMars 2016, and BepiColombo, as well as other future missions such as ExoMars 2020, Juice, etc. will benefit of a GIS tool to visualize their targets (Mars, Mercury, Jupiter…) allowing spatial queries to retrieve geometrical information like features, footprints, rover path tracking, rover drill sites, etc. GIS Architecture The PSA relies on 3-tiered system for the GIS architecture (see Figure 1). The database layer is composed of a PostgreSQL database with the PostGIS extension to store the spatial information. The server layer uses GeoServer as a map server to provide WMS/WFS responses (e.g. GeoJson, kml…) to the web application’s requests (implemented on the Vaadin framework). Finally, the client layer (browser) runs the OpenLayer Javascript library to render the map. Other external GIS tools like QGIS might be used to get the PSA spatial data from either the GeoServer or the database. Figure 1: GIS architecture diagram for the PSA Views Consistency The PSA provides different views to show the same planetary data. These views are integrated and synchronized to each other to visualize the information as the data type requires. All of them use the filter menu to search by a given criteria and offer similar features such as sorting, pagination, downloading and product detailed info. Once a query is executed on a view, the information is automatically loaded when changing views. The map view is integrated in the current PSA (see Figure 2) as the other views (Table, Image) giving other perspective of displaying results when it comes to search for spatial data. Figure 2: Views Consistency in the PSA GIS Applicability GIS technology on the PSA will offer a common way to filter (by mission, instrument, target, dates, geometry…) and search for spatial data, even for legacy missions, thanks to the homogenization of the geometrical information with per-product spatial metadata computed in a consistent way via SPICE. PSA will provide spatial data retrieval of both versions of the NASA Planetary Data Systems archival formats, PDS3 and PDS4, based on a criteria search, and, the possibility of selecting PDS3/PDS4 products from a particular region of interest (ROI) (see Figure 3). Figure 3: Query by ROI and footprint selection PSA also provides other useful GIS tools such as switching projections for better visualization and analysis of footprints over the poles (see Figure 4) as well as switching between different base maps of Mars for better visualization, enabling/disabling layer feature, overlapping footprint selection by popup and a grid/graticule layer. Figure 4: Footprints over the Mars North Polar projection PSA also allows the user to add customized and external data through a GeoJSON file uploader tool (see Figure 5). Figure 5: GeoJSON data uploader feature Acknowledgement Although the whole PSA team has somehow been involved in this GIS implementation, I would specially like to thank Francisco Raga for his huge contribution in many of the presented GIS features. References [1] Besse, S. et al. (2017) Planetary and Space Science, 10.1016/j.pss.2017.07.013, ESA's Planetary Science Archive: Preserve and present reliable scientific data sets.

A pectin coated dehydrated apple snack containing ≥9 log colony forming units/20 g portion of the probiotic Lactobacillus paracasei IMPC2.1, was developed. The strain was incorporated into the apple slices using vacuum impregnation (IP1) or soaking/stirring (IP2); apple slices were then coated with citrus pectin and dehydrated at 4 °C for 14 days. Microbial application led to colonization of the apple surface, as seen using scanning electron microscope images, and all probiotic products showed comparable radical scavenging activity and total phenol content. IP2 led to better bacterial survival during 30 days storage at 4 °C and color parameters comparable to the fresh apple. The simulated gastro-intestinal (GI) digestion suggested the ability of the strain to survive the digestive process. This inclusion/coating/dehydration process led to a probiotic snack, which could successfully deliver bacterial cells in a viable form to the GI tract.

The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific data sets through various interfaces at http://psa.esa.int . All data sets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. Mostly driven by the evolution of the PDS standards which all new ESA planetary missions shall follow and the need to update the interfaces to the archive, the PSA has undergone an important re-engineering. In order to maximise the scientific exploitation of ESA's planetary data holdings, significant improvements have been made by utilising the latest technologies and implementing widely recognised open standards. To facilitate users in handling and visualising the many products stored in the archive which have spatial data associated, the new PSA supports Geographical Information Systems (GIS) by implementing the standards approved by the Open Geospatial Consortium (OGC). The modernised PSA also attempts to increase interoperability with the international community by implementing recognised planetary science specific protocols such as the PDAP (Planetary Data Access Protocol) and EPN-TAP (EuroPlanet-Table Access Protocol). In this paper we describe some of the methods by which the archive may be accessed and present the challenges that are being faced in consolidating data sets of the older PDS3 version of the standards with the new PDS4 deliveries into a single data model mapping to ensure transparent access to the data for users and services whilst maintaining a high performance.

The European Space Agency (ESA) Planetary Science Archive (PSA) is undergoing a significant refactoring of all its components to improve the services provided to the scientific community and the public. The PSA supports ESA's missions exploring the Solar System by archiving scientific peer-reviewed observations as well as engineering data sets. This includes the Giotto, SMART-1, Huygens, Venus Express, Mars Express, Rosetta, Exomars 2016, Exomars RSP, BepiColombo, and JUICE missions. The PSA is offering a newly designed graphical user interface which is simultaneously meant to maximize the interaction with scientific observations and also minimise the efforts needed to download these scientific observations. The PSA still offers the same services as before (i.e., FTP, documentation, helpdesk, etc.). In addition, it will support the two formats of the Planetary Data System (i.e., PDS3 and PDS4), as well as providing new ways for searching the data products with specific metadata and geometrical parameters. As well as enhanced services, the PSA will also provide new services to improve the visualisation of data products and scientific content (e.g., spectra, etc.). Together with improved access to the spacecraft engineering data sets, the PSA will provide easier access to scientific data products that will help to maximize the science return of ESA's space missions.

The present invention relates to a polymer-drug conjugate wherein the polymer is hyaluronic acid and the drug is an anticancer compound. The anticancer compound is covalently linked to the hyaluronic acid by a pH-labile boronic acid-containing linkage. These conjugates can be used for the treatment of cancer

The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc.

Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ADSC). Herein, we study the growth and endothelial differentiation potential of ADSC seeded onto a porous polycaprolactone (PCL) scaffold. The objective of this study is to demonstrate that PCL is a good material to be used as a scaffold to support reconstruction of new endothelial tissue using adipose stem cells. We found that undifferentiated ADSC adhere and grow on PCL. We show that, after culture in endothelial differentiation medium, ADSC were positive to LDL uptake and expressed molecular markers characteristic of endothelial cells (CD31; eNOS and vWF). In addition, our study defines the time required for the differentiation of ADSC directly onto PCL. This study suggests that PCL can be used as a scaffold to generate endothelial tissue in vitro. PLC has excellent mechanical properties and a slow degradation rate. Moreover, based on our results, we propose that PCL could be used to graft scaffolds coated with endothelial cells derived from ADSC stem cells. Endothelial cells-coated PCL could find several applications to replace damaged area of the body; for example, a possible use could be the generation of vascular grafts.

Before bariatric surgery (BS), moderate weight loss, left hepatic lobe volume reduction, and micronutrient deficiency (MD) identification and correction are desirable.The objective of this study was to assess the safety and the effectiveness of a 4-week preoperative ketogenic micronutrient-enriched diet (KMED) in reducing body weight (BW), left hepatic lobe volume, and correcting MD in patients scheduled for BS.In this prospective pilot study, a cohort of morbidly obese patients (n = 27, 17 females, 10 males) with a mean body mass index (BMI) of 45.2 kg/m(2) scheduled for BS underwent a 4-week preoperative KMED. Their BW, BMI, fat mass (FM), fat-free mass (FFM), resting metabolic rate (RMR), left hepatic lobe volume, micronutrient status, and biochemical and metabolic patterns were measured before and after the 4-week KMED. Patient compliance was assessed by validated questionnaires (3-day estimated food records and 72-h recall). Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects.All patients completed the study. We observed highly significant decreases in BW (- 10.3%, p < 0.001, in males; - 8.2%, p < 0.001, in females), left hepatic lobe volume (- 19.8%, p < 0.001), and an amelioration of patient micronutrient status. All patients showed a high frequency of acceptability and compliance in following the diet. No adverse side effect was reported.This study demonstrates that a 4-week preoperative KMED is safe and effective in reducing BW, left hepatic lobe volume, and correcting MD in obese patients scheduled for BS.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling adverse event of most of commonly used antineoplastic agents. Previous studies have focused on several chemotherapeutic agents and reported that CIPN incidence varies from 19% to >85%. The mechanisms underlying CIPN are currently unknown. However, different theories have been proposed including microtubules dysfunction, mitochondrial dysfunction and mitochondrial toxicity, Glial pathway, substance P pathway, adenosine receptor pathway. CIPN is not simply to treat, and most randomized controlled trials failed to identify an effective therapy. Recent evidence supports the efficacy of serotonin (5-HT) and norepinephrine (NE) dual reuptake inhibitors (SNRI) in the treatment of neuropathy-related pain. Based on current evidence, we can speculate that duloxetine and topical menthol would improve CIPN pain as symptomatic treatment while, based on preclinical data, pifithrin-μ could be considered in future for the prevention of CIPN.

Several positron emission tomography (PET) radiopharmaceuticals have been emerged in the last decade as feasible in the management of brain lesions, due to the low performance in this field of the 18F-fluoro-deoxyglucose (18F-FDG), for its high physiological gradient of distribution in the brain. Beyond its usefulness in prostate cancer imaging, the radiolabeled choline is becoming a promising tool in diagnosing benign and malignant lesions of the brain, due to a very low rate of distribution in normal white and grey matters. The aim of our review was to assess the real impact of the radiolabeled choline PET/CT in the management of brain benign lesions, brain tumors, and metastases. Furthermore, emphasis was given to the comparison between the radiolabeled choline and the other radiopharmaceuticals in this field. A literature review was performed. The radiolabeled choline is useful in the management of patients with suspected brain tumor relapse, especially in association with magnetic resonance imaging (MRI), with caution regarding its intrinsic characteristic of non-tumor-specific tracer. For the same reason, it is not useful in the early evaluation of brain lesions. Similar results are reported for other radiopharmaceuticals. The inclusion of the head in the whole-body scans for somatic tumors is necessary to ensure metastases in the brain or choline-avid benign lesions.

In this work we used a combination of immunogold labelling (IGL) and environmental scanning electron microscopy (ESEM) to detect the presence of a protein on the cell surface. To achieve this purpose we chose as experimental system 3T3 Swiss Albino Mouse Fibroblasts and galectin-3. This protein, whose sub-cellular distribution is still under discussion, is involved in a large number of cell physiological and pathological processes. IGL technique has been utilised by many authors in combination with SEM and TEM to obtain the identification/localisation of receptors and antigens, both in cells and tissues. ESEM represents an important tool in biomedical research, since it does not require any severe processing of the sample, lowering the risk of generating artefacts and interfere with IGL procedure. The absence of metal coating could yield further advantages for our purpose as the labelling detection is based on the atomic number difference between Nanogold spheres and the biological material. Using the gaseous secondary electron detector (GSED) compositional contrast is easily revealed by the backscattered electrons component of the signal. In spite of this fact, only few published papers present a combination of ESEM and IGL. Hereby we present our method, optimised to improve the intensity and the specificity of the labelling signal, in order to obtain a semi-quantitative evaluation of the labelling signal. J. Cell. Physiol. 214: 769–776, 2008. © 2007 Wiley-Liss, Inc.

The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules.

Background Lung ultrasound assessment of B-lines is a sonographic method for a semi-quantitative evaluation of extravascular lung water, that can be employed to asssess and monitor pulmonary congestion in acute heart failure. Purpose To assess the degree and changes in B-lines during hospitalization for acute heart failure, independently of the etiology, and their correlation with patients' comorbidities. Methods Two-hundred and forty-one complete antero-lateral B-lines assessments were recorded in an old population of 73 patients (mean age 83.0±7.6 years, 54.8% males) admitted with a diagnosis of acute heart failure (AHF). Chronic obstructive pulmonary disease (COPD) was present in 30% patients, chronic kidney disease (CKD) was present in 31% patients, a previously known cardiac condition was present in 73% of patients. B-lines were evaluated according to standard protocol at admission (T1), at 24 hours (T2), 48 hours (T3) and at discharge (T4). NT-proBNP was assessed at admission and at discharge. Results Mean antero-lateral B-lines at T1 were 42±39 with a statistically significant reduction at T3 (25±23, p Dynamic changes of B-lines over time Conclusions In older patients hospitalized with AHF with multiple comorbidities, B-lines are present at admission and significantly reduce at 48 hours, although with high variability among different patients at all time points, and persistent significant congestion at discharge in about one third of patients. Lung ultrasound B-lines provide a specific and dynamic information about the degree and changes of pulmonary congestion, which is additive to other patient's characteristics.

We present a different approach for annotating laparoscopic images for segmentation in a weak fashion and experimentally prove that its accuracy when trained with partial cross-entropy is close to that obtained with fully supervised approaches. We propose an approach that relies on weak annotations provided as stripes over the different objects in the image and partial cross-entropy as the loss function of a fully convolutional neural network to obtain a dense pixel-level prediction map. We validate our method on three different datasets, providing qualitative results for all of them and quantitative results for two of them. The experiments show that our approach is able to obtain at least $$90\%$$ of the accuracy obtained with fully supervised methods for all the tested datasets, while requiring $$\sim 13$$ $$\times $$ less time to create the annotations compared to full supervision. With this work, we demonstrate that laparoscopic data can be segmented using very few annotated data while maintaining levels of accuracy comparable to those obtained with full supervision.

Background Palmitoylethanolamide (PEA) belong to endocannabinoid family, a group of fatty acid amides. PEA has been proven to have analgesic and anti-inflammatory activity and has been used in several controlled studies focused on the management of chronic pain among adult patients with different underlying clinical conditions. Methods/design A literature search will be performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The population will be patients who have chronic pain, the intervention will be the administration of PEA alone or in combination with other drugs for the pain management; the comparison will be the standard therapy in accordance with the current guidelines for the treatment of pain. The Outcomes will be the reduction of pain not restricted to specific scales laying out the pain outcome data described in the included studies. Discussion This scoping review aims to describe the clinical applications of the PEA in chronic pain management and its outcome. Scoping review registration Open Science Framework https://osf.io/74tmx/.

Laparoscopic scene segmentation is one of the key building blocks required for developing advanced computer assisted interventions and robotic automation. Scene segmentation approaches often rely on encoder-decoder architectures that encode a representation of the input to be decoded to semantic pixel labels. In this paper, we propose to use the deep Xception model for the encoder and a simple yet effective decoder that relies on a feature aggregation module. Our feature aggregation module constructs a mapping function that reuses and transfers encoder features and combines information across all feature scales to build a richer representation that keeps both high-level context and low-level boundary information. We argue that this aggregation module enables us to simplify the decoder and reduce the number of parameters in the decoder. We have evaluated our approach on two datasets and our experimental results show that our model outperforms state-of-the-art models on the same experimental setup and significantly improves the previous results, \(98.44\%\) vs \(89.00\%\), on the EndoVis’15 dataset.