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Background Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. Materials and methods Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. Results In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. Conclusions Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Objective This phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy. Methods Adults (aged 18 years or older) with American Society of Anesthesiologists physical status of I, II, or III who underwent segmental colectomy, including partial colectomy, sigmoidectomy, cecectomy, or anterior proctosigmoidectomy, via laparotomy with general anesthesia, received intravenous methylnaltrexone 0.30 mg/kg or placebo every 6 h beginning within 90 min after end of surgery. Treatment continued until 24 h after the patient tolerated solid foods, was discharged, or for 7 d maximum. Efficacy endpoints included measures of gastrointestinal recovery and time to discharge eligibility. Results A total of 65 patients (methylnaltrexone, n = 33; placebo, n = 32) were randomized. Mean time to first bowel movement was accelerated by 20 h (p = 0.038) and time to discharge eligibility was accelerated by 33 h (p = 0.049) with methylnaltrexone vs placebo. Opioid use was similar between groups until postoperative day 4, then fluctuated in the placebo group. Methylnaltrexone was generally well tolerated. Conclusions In this study, intravenous methylnaltrexone significantly decreased time to postoperative bowel recovery and eligibility for hospital discharge by ∼1 d, with an adverse event profile similar to placebo. These were two of several exploratory endpoints; not all efficacy endpoints showed a significant difference between methylnaltrexone and placebo. The efficacy results in this trial were not seen in two subsequent large-scale studies.

Methylnaltrexone, a peripherally-acting quaternary opioid antagonist, is an investigational treatment for opioid-induced constipation in patients with advanced illness. This randomized, parallel-group, repeated dose, dose-ranging trial included a double-blind phase for one week followed by an open-label phase for a maximum of three weeks. Opioid-treated patients with advanced illness who met criteria for opioid-induced constipation despite laxative therapy were potentially eligible. Double-blind treatment occurred on Days 1, 3, and 5; open-label therapy could be administered as often as every other day. The initial dose range of 1mg, 5mg, or 12.5mg was extended by adding a 20mg group during the study while still maintaining the double blind; the initial open-label dose of 5mg could be titrated. The primary outcome was a laxation response within four hours after the first dose. Thirty-three patients received at least one dose of methylnaltrexone. Only one of 10 patients (10%) who received the 1mg dose experienced laxation within four hours of dosing. The median time to laxation was >48 hours for the 1mg dose group, compared to 1.26 hours for all patients receiving >or=5mg (P=0.0003). There was no apparent dose-response above 5mg. Most adverse events were related to the gastrointestinal system, were mild, and did not lead to discontinuation. In conclusion, methylnaltrexone relieved opioid-induced constipation at doses >or=5mg in patients with advanced illness, and did not reduce analgesia or cause opioid withdrawal symptoms.

Zinc is released from a subset of cerebral cortical neurons whereupon it exerts a powerful modulatory influence on excitatory and inhibitory neurotransmission. A number of studies have suggested that alterations in the regulation of zinc may contribute to the genesis of epilepsy. Here, we tested this hypothesis by examining the distribution of zinc-containing axon terminals in rats selectively bred for an innate susceptibility (FAST) or resistance (SLOW) to the development of kindling-induced seizures. Zinc was stained histochemically and levels of staining were quantitatively assessed. We found that the levels of synaptic zinc were significantly lower in the SLOW rats throughout the telencephalon. This relative reduction was most pronounced in limbic cortices where levels were less than 30% of FAST rats. These results suggest that innate differences in the homeostatic regulation of synaptic zinc, particularly in limbic cortices, may underlie differences in epileptogenicity.

The homeobox transcription factors Engrailed-1 and Engrailed-2 are required for the survival of mesencephalic dopaminergic neurons in a cell-autonomous and gene-dose-dependent manner. Because of this requirement, the cells die by apoptosis when all four alleles of the Engrailed genes are genetically ablated ( En1 −/−; En2 −/−). In the present study, we show that viable and fertile mice, heterozygous null for Engrailed-1 and homozygous null for Engrailed-2 ( En1 +/−; En2 −/−), have an adult phenotype that resembles key pathological features of Parkinson's disease. Specifically, postnatal mutant mice exhibit a progressive degeneration of dopaminergic neurons in the substantia nigra during the first 3 mo of their lives, leading to diminished storage and release of dopamine in the caudate putamen, motor deficits similar to akinesia and bradykinesia, and a lower body weight. This genetic model may provide access to the molecular etiology for Parkinson's disease and could assist in the development of novel treatments for this neurodegenerative disorder.

We describe a 20-year-old man presenting intraperitoneal metastases from medulloblastoma following surgical insertion of a spinoperitoneal shunt. Medulloblastomas are highly malignant primary tumou...

Dynamic Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA) represent two non-invasive techniques which can perform a pre-therapeutic evaluation of carotid artery disease. Ultrasound (US) is the screening technique for this type of pathology and after US results, surgeons or endovascular therapists need more information for a correct therapeutic approach. We performed a combined diagnostic approach with CTA and dynamic MRA to reduce the need for DSA in which permanent and transitory neurological side effects are still possible and to evaluate the efficacy of these two diagnostic modalities. We performed dynamic MRA and CTA in 80 patients with carotid disease in which a US examination showed the presence of more than 60% stenosis. Dynamic MRA was performed with a 3D coronal volumetric acquistion with a dedicated head-neck coil, 2.5 mm thickness and 18 s acquisition time after contrast media injection to obtain only the visualization of the arterial phase from the origin of the epiaortic vessels through the bifurcation of the siphon without overlap with the venous phase. CTA was done with a spiral technique with contrast media injection (120 ml- 3ml/s) from C6 through the skull base. In 60 patients, we found the same degree of stenosis between carotid CTA and US examination. In eight cases, US showed an occlusion of the internal carotid artery (ICA) while CTA reported severe stenosis between 85–90%. Two cases showed a 85% stenosis of the ICA, while CTA and dynamic MRA disclosed ICA occlusion. CTA showed parietal thrombus and arterial wall calcifications very well. Dynamic MRA overestimated the stenosis in 85% of the patients, almost always in patients with a stenosis greater than 65–70% and in seven cases also showed an abnormal signal intensity of the origin of the epiaortic vessels or of the intracavernous segment of the ICA that was confirmed by DSA only in four patients. With three patients, it was not possible to perform CTA or MRA because of incorrect transit time evaluation or poor patient cooperation. The combined diagnostic approach by CTA and Dynamic MRA can be adequate to give a correct pre-therapeutic evaluation in patients with carotid disease; in doubtful or uncooperative cases, DSA is still required.

It is well known that one of the most critical phases of the Life Cycle Assessment (LCA) is the compilation of the inventory. Indeed we need data that are often not readily available because they relate to processes and emerging technologies where disclosure is limited, for instance when the LCA is involved in a product whose production is not extended on an industrial scale, or is still on an experimental basis. In these cases we can rarely use primary data collected directly on site and representative of the system under review, but we must be satisfied with secondary data, obtained from databases. The case study submitted in this work represents a LCA ‘cradle to the gate’ of a compound of fine chemicals, the [Bmim] [BF4] (1-butyl-3-methyl-imidazolium tetrafluoroborate), whose industrial application is limited and for which the compilation of the inventory is particularly complex and affected by uncertainty. The [Bmim] [BF4] belongs to the class of ionic liquids (ILs) and several research activities have focussed on it. ILs are organic salts that are liquid at room temperature, consisting of asymmetric and bulky ions that prevent the molecular framework necessary to crystallization. Developed over the last decade to be used as “eco-compatible” substitutes of traditional organic solvents, they have found many different and unexpected applications. This study was carried out with the support of the calculation software GaBi IV. Data necessary for the stage inventory, not present in the GaBi IV database, have been implemented using the Aspen Plus engineering software that can run the simulation and dimensioning of industrial chemical plants. The synergy of the two software applications made it possible to reconstruct the entire production process of [Bmim] [BF4] and to identify the steps that more deeply affect the environmental point of view.

Riportiamo due casi di “duplicazione” del peduncolo ipofisario scoperti in modo fortuito nel corso di esami RM eseguiti senza che fossero presenti dati clinici o bio-umorali che inducessero al sospetto di una anomalia congenita di questo tipo. L'esame RM, nel primo dei nostri pazienti, un bambino di 5 anni, veniva richiesto per ritardo psico-motorio, e veniva, pertanto, condotto con tecnica di “routine”, mentre nel secondo, una donna di 42 anni, l'indagine aveva una indicazione più elettiva sulla regione sellare, per la presenza di irregolarità del ciclo mestruale ed iperprolattinemia. Entrambi i pazienti non mostravano alcuna anomalia fisica né segni clinici tali da poter indurre al sospetto di una patologia malformativa. Dopo una breve descrizione sulle tappe dello sviluppo embriologico della ghiandola ipofisaria e dopo un cenno sulla sua anatomia macroscopica normale, vengono analizzati i pochi articoli apparsi in letteratura sull'argomento. Nella maggior parte di questi, tuttavia, la “duplicazione” riguarda oltre che il peduncolo anche la ghiandola ipofisaria ed è quasi sempre collegata ad anomalie di sviluppo più o meno pronunciate dello scheletro facciale, mentre una “duplicazione” isolata del peduncolo non è stata, a nostra conoscenza, mai descritta. Il motivo principale, probabilmente, risiede nel fatto che l'anomalia del peduncolo da noi riscontrata è di tipo essenzialmente morfologico, da considerarsi di lieve entità e verosimilmente non correlata a specifici disturbi della funzionalità dell'asse ipotalamo-ipofisario. Pur non essendo noti i precisi meccanismi patogenetici che inducono alla realizzazione di questa particolare anomalia malformativa viene ipotizzata la possibilità di uno “spettro” entro il quale i nostri due casi si pongono all'estremo finale, cioè per un arresto o deviazione dei normali processi di sviluppo embriologico avvenuti in una tappa terminale.

Presentiamo due casi di malattia da deposito di pirofosfato di-idrato di calcio (CPPD) a localizzazione nella cerniera occipito-vertebrale, giunti alla nostra osservazione negli ultimi due anni studiati con TC ed RM, entrambi con riscontro operatorio ed anatomo-patologico uno dei quali associate ad anomalia di fusione del nucleo di ossificazione apicale del dente dell'epistrofeo, il cosiddetto “os odontoideum”. Da una revisione della letteratura sull'argomento si è potuto constatare la relativa rarità della localizzazione cervicale ed in particolare di quella che riguarda i legamenti anteriori dell'articolazione atlo-assiale, ed, ancora di più, l'associazione con la già accennata anomalia rappresentata dall' “os odontoideum”, per cui si è ritenuto utile l'apporto di questo ulteriore contributo casistico. Dopo una breve introduzione sulle caratteristiche generali clinico-radiologiche di questa particolare forma di artropatia cronica vengono descritti i quadri neuroradiologici nei nostri due pazienti confrontando i reperti riscontrati con quanto già viene riportato in letteratura. Vengono, quindi, discussi gli elementi di diagnosi neuroradiologia e le possibili diagnosi differenziali soprattutto nei confronti della patologia neoplastica con la quale la CPPD potrebbe essere confusa. Il riscontro radiologico di un tessuto che mima una lesione “espansiva” interessante la regione della cerniera occipito-vertebrale, in un soggetto anziano, specie se associato a depositi calcifici ed a segni di artropatia degenerativa cronica, deve far pensare, fra le altre possibili ipotesi diagnostiche, anche alla meno frequente CPPD, la cui esatta diagnosi pre-operatoria, come facilmente intuibile, modifica radicalmente la prognosi e l'attegiamento terapeutico.

I liquidi ionici sono considerati i possibili sostituti eco-compatibili dei solventi organici industriali tradizionali, tuttavia i loro potenziali impatti ambientali sono ancora da accertare. Questo lavoro presenta uno studio di LCA della produzione dell’1-butil-3-metilimidazolo tetrafluoroborato [Bmim][BF4], il liquido ionico più conosciuto. I risultati ottenuti hanno mostrato per la produzione del [Bmim][BF4] impatti ambientali non trascurabili per tutte le categorie di impatto prescelte. Tale risultato è stato confermato dal confronto, eseguito sulla stessa unità di massa, tra i cicli produttivi del [Bmim][BF4] e di alcuni solventi organici tradizionali considerati: acetone, benzene e acqua deionizzata.

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.

Ischemic stroke is one of the most pervasive life-threatening neurological conditions for which there currently exists limited therapeutic intervention beyond prevention. As calcium-focused neuroprotective strategies have met with limited clinical success, it is imperative that alternative therapeutic targets be considered in the attempt to antagonize ischemic-mediated injury. As such, zinc, which is able to function both as a signaling mediator and neurotoxin, has been implicated in cerebral ischemia. While zinc was first purported to have a role in cerebral ischemia nearly twenty years ago, our understanding of how zinc mediates ischemic injury is still in its relative infancy. Within this review, we examine some of the studies by which zinc has exerted either neuroprotective or neurotoxic effects during global and focal cerebral ischemia.

Recently, demand for mobile computing environments has been increasing greatly, and easy access from remote sites has become desirable. To meet this requirement, NTT has proposed a "Logical Office" service, which enables terminal plug & play, multiprotocol, and ubiquitous communication. NTT has already done some Logical Office service experiments, in LAN and Internet environments, which focused on the service offered in the early stages. The paper investigates our proposed Logical Office service over international ATM networks, which focuses on the future stage international ATM test beds between Japan and the US, provided by AT&T, KDD, and NTT, are used for this experiment. It was verified that the Logical Office service worked correctly in the international ATM environments, and that it provided sufficiently practical performance even there.

Poisoning of noble metal catalysts by sulfur-containing organic compounds is a well-known phenomenon. These compounds are frequently present in hydrotreating feedstocks and cause a selective decrease in the metal hydrogenation function of noblemetal-based hydrotreating catalysts. The effects of H 2 S, considered as a model sulfiding compound, were studied on a supported platinum catalyst. Low coverages of H 2 S are found to cause a selective poisoning of noble metal particles, which with increasing coverage becomes unable to chemisorb H 2 at room temperature. At higher coverages H 2 S spills over to the support, modifying its acidic properties. Eventually new weak acid sites are formed.

The nature and the origin of organic residues, present in spent catalysts afterisobutane/1-butene alkylation, have been studied by combined TG-DSC, UV-VIS, FT-IR techniques. Two kinds of organic compounds are present: high molecular weight unsaturated byproducts, responsible of pore blockage, and light hydrocarbons, such as alkylates and small oligomers, entrapped in the catalysts. The latter desorb in inert gas flow at medium-low temperature, whereas the former must burned off in order to regenerate the catalyst.

A comprehensive literature review on the destructive and/or protective role played by the immune system in the etiopathogenesis of Periodontal Disease and on the potential clinical applications of the immunological parameters has been carried out.

The importance of perfect knowledge of the anatomy and physiology of the stomatognathic complex for any understanding of the aetiopathogenic mechanisms behind temporomandibular joint pain dysfunction syndrome is emphasised and the fundamental concepts underlying the use of the bite plane as a valuable aid in the diagnosis and initial treatment of articular dysfunction are described.

Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The "TT" polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors. The aim of our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, according to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1 patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45 patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (2) had a DD genotype. The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.

Implantation of drug eluting stents following percutaneous transluminal angioplasty has revealed a well established technique for treating occlusions caused by the atherosclerotic plaque. However, due to the risk of vascular re-occlusion, other alternative therapeutic strategies of drug delivery are currently being investigated. Polymeric endoluminal pave stenting is an emerging technology for preventing blood erosion and for optimizing drug release. The classical and novel methodologies are compared through a mathematical model able to predict the evolution of the drug concentration in a cross-section of the wall. Though limited to an idealized configuration, the present model is shown to catch most of the relevant aspects of the drug dynamics in a delivery system. Results of numerical simulations shows that a bi-layer gel paved stenting guarantees a uniform drug elution and a prolonged perfusion of the tissues, and remains a promising and effective technique in drug delivery.