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The late nineteenth and early twentieth centuries in Egypt saw new concepts of community emerge to replace the extant, traditional forms of identity based on local loyalties. This paper will explore the role played by language and journalism in this re-imagining of identity, and its use by the elite in shaping perceptions of the Egyptian people, nation and language. A fundamental element of this process was the development in the use of the term ummah in the discourse of many thinkers of the Nahḍah, from its meaning signifying the global community of Muslim believers, into a symbol of the modern nation-state, a re-interpretation which I discuss drawing, notably, on the unpublished writings of the journalist Aḥmad Luṭfī al-Sayyid. This perspective enables an exploration both of the competition between traditionalist values and the secular, multicultural model of early Egyptian nationalism, and of the multifarious colonial influences on the pro-Europe anelite in this struggle for a vision of Egypt’s future.

In the era of asymmetrical conflicts, information and communication technologies (ICT) play an essential role due to their importance in the manipulation and conditioning of public opinion.[1] Several threats are linked to the use of ICT but, in terms of interstate, strategic competition, one of the main dangers is represented by socalled “cyber election interference” (i.e., cyber election-meddling activities carried out by foreign states to influence the electorate of a target state through the diffusion of “fake news” or “alternative truths,” principally via the media and social networks (Facebook, Twitter, YouTube, etc.)). The aim of this paper is to clarify whether and when this kind of interference constitutes a breach of international obligations—in particular, of the principle of nonintervention in the internal affairs of a state—and to envisage possible lawful responses under international law by states targeted by said interference.

Il presente documento illustra le attività realizzate nell'ambito del WP5 dell'Accordo di Collaborazione tra la Regione Puglia e l'Istituto di Ricerca per la Protezione Idrogeologica (IRPI) del Consiglio Nazionale delle Ricerche (CNR) per la "Valutazione Integrata di Dissesti Geo - Idrologici nel Territorio della Regione Puglia, Modelli Interpretativi dei Fenomeni e Definizione di Soglie di Pioggia per il possibile innesco di frane superficiali". Il documento è stato realizzato nell'ambito del WP5: Redazione di cartografia tematica su frane nel Sub-Appennino Dauno, e descrive i "Criteri per la interpretazione delle frane da immagini aeree e satellitari". Gli argomenti trattati riguardano: (i) le principali tecniche per l'identificazione delle frane, (ii) le caratteristiche delle tecniche di interpretazione di fotografie aeree stereoscopiche (foto-interpretazione), (iii) i principali criteri per il riconoscimento, l'interpretazione e la mappatura delle frane tramite l'uso di tecniche foto-interpretative (elementi della foto-interpretazione).

Floods are frequent and widespread in Italy and pose a severe risk for the population. Local administrations commonly use flow propagation models to delineate the flood prone areas. These modeling approaches require a detail geoenvironmental data knowledge, intensive calculation and long computational times. Conversely, statistical methods can be used to asses flood hazard over large areas, or to extend the flood hazard zonation to the portion of the river networks where hydraulic models have still not been applied or can be applied with difficulties. In this paper, we describe a statistical approach to prepare flood hazard maps for the whole of Italy. The proposed method is based on a multivariate machine learning algorithm calibrated using in input flood hazard maps delineated by the local authorities and terrain elevation data. The preliminary results obtained in several major Italian catchments indicate good performances of the statistical algorithm in matching the training data. Results are promising giving the possibility to obtain reliable delineations of flood prone areas obtained in the rest of the Italian territory.

Inundations and landslides are common phenomena that cause serious damage and pose a severe threat to the population of Italy. The societal and economic impact of landslides and floods in Italy is particularly severe, and strategies that target the mitigation of the effects of these events are essential. Although, in the last few years, the scientific community has wanted to communicate information on research activities regarding geo-hydrological hazards and the associated risks to society through thematic websites, very often, communication achieves specific technical purposes for experts. To address the problem posed by the lack of communication on geo-hydrological hazards with potential human consequences in Italy to the broader society, we designed the POLARIS website. The POLARIS website publishes accurate and detailed information on geo-hydrological risks, including periodical reports on landslide and flood risk to the population of Italy, data and analysis on specific damaging events and blog posts on landslide and flood events that able to encourage mass media and citizens' engagement. By monitoring the access of users to POLARIS since January 2014, when the website was published, we registered maximum access during the occurrence of the worst geo-hydrological events and for the promotion of relevant new content through press releases. In particular, in the latter case, we noted the highest access value when journalists promoted the website through television channels. The POLARIS initiative demonstrates how the scientific community can implement suitable communication strategies that address different societal audiences by exploiting the role of mass media and social media. These strategies can help these audiences to understand how risks can be reduced through appropriate measures and behaviors; thus, they can contribute to increasing the resilience of the population to geo-hydrological events.

A new method to increase circuit functionality and power density per unit area in power electronic modules has been developed. This new method uses the present power hybrids production technology platform on ceramic substrates and implements direct bonded copper (DBC) "partial" multilayer structures on application specific substrates. With this novel approach a more than 50% increased power density and a 40% increased circuit complexity has been achieved. Reliability tests (thermal cycling (TC), power cycling (PC), high temperature reverse bias...) have been performed for several new layout solutions, the most relevant results are shown in this paper.

PURPOSE: The purpose of this study was to review our results in patients undergoing treatment with 4 percent formalin for radiation-induced injury to the rectum. METHODS: A retrospective review of office charts was performed, identifying all patients undergoing formalin treatment. Patient gender, initial malignancy, prior treatments, response to treatment with formalin, complications, and length of follow-up were reviewed. All patients had flexible endoscopy to assess for proximal sources of bleeding. The indication for treatment was a symptomatic patient with endoscopic evidence of radiation injury. A cotton pledget was used for direct application of 4 percent formalin to the affected area via a rigid proctoscope or anoscope. The treatment was repeated if blanching did not occur or if bleeding continued. Patients were followed up at three-week to four-week intervals and treatment was repeated based on the above indications. Treatments were continued until cessation of bleeding occurred or, when treatment failed, operative treatment was required. RESULTS: Thirty-six patients were identified. Three were lost to follow-up. Symptoms included bleeding in all but one patient, who presented with an ulcer. There were 33 (26 male) patients. Seventeen (51.5 percent) patients had prior treatment. The number of formalin treatments ranged from 1 to 13, with a mean of 3.4. The follow-up ranged from 1 to 60 months, with a mean of 18 months. Twenty-nine (88 percent) patients had improvement or cessation of symptoms. Four (12 percent) patients failed treatment. Two patients were noted to have full-thickness ulcers and both failed formalin treatment. No complications were noted related to formalin treatment. CONCLUSION: We conclude that formalin therapy is a safe and effective form of treatment that can be performed in the office with minimal discomfort and no complications. It can be performed multiple times until results are achieved. Formalin therapy may be useful as a first-line treatment for chronic radiation proctitis, however, a prospective controlled trial comparing modalities is required to prove this to be true.

Inverted duplications associated with terminal deletions are complex anomalies described in an increasing of chromosome ends. We report on the cytogenetic characterization of the first de novo inv dup del(4) with partial 4p duplication and 4q deletion in a girl with clinical signs consistent with “recombinant 4 syndrome”. This abnormality was suspected by banding, but high-resolution molecular cytogenetic investigations allowed us to define the breakpoints of the rearrangement. The terminal duplicated region extending from 4p15.1 to the telomere was estimated to be 29.27 Mb, while the size of the terminal deletion was 3.114 Mb in the 4q35.1 region. Until now, 10 patients with duplicated 4p14-p15 and deleted 4q35 chromosome 4 have been described. In all cases the abnormal chromosome 4 was derived from a pericentric inversion inherited from one of the parents. In conclusion, we have identified the first case of inv dup del(4) with normal parents suggesting that, often, terminal duplications or terminal deletions mask complex rearrangements.

Cerebral ischaemia results in significant brain damage, but the molecular mechanisms associated with ischaemia-induced brain injury are not well defined. We have adopted an improved differential-display method to search for new ischaemia-related genes. Among the different cDNAs isolated following transient forebrain ischaemia in rat, PH3.3 was selected for further studies. The search for homologies revealed that it is the rat homologue to human zinc finger motif 1 (ZFM1), also called mammalian splicing factor 1 (SF1). With Northern blot, PH3.3 hybridized with three mRNA species of 2.3, 2.9 and 3.6 kb, significantly increased at 6 h and 5 days after the ischaemic insult. These findings were extended also to another animal model. In situ hybridization in ischaemic gerbils showed that PH3.3 mRNA was induced in the dentate gyrus as early as 4 h post-ischaemia. Expression peaked at 2 days in the whole hippocampus and cortex, and then progressively decreased towards sham levels. By day 4, expression had disappeared almost entirely from the cells in the CA1 region of the hippocampus, concomitant with the degeneration of pyramidal neurons. Interestingly, ZFM1/SF1 has been recently identified as activated following p53-induced apoptosis. Several lines of evidence suggest that p53 may play two roles in the post-ischaemic brain. The primary role of p53 is to activate DNA repair processes, but if repair fails, apoptosis will be initiated. Thus, ZFM1/SF1 may represent a relevant link between p53 and the neuroprotective/neurodegenerative processes which follow cerebral ischaemia.

Fourteen patients presenting with presacral cystic lesions were managed over a 20-year period. Retrospective review identified 12 females and 2 males. Fifty-seven per cent were symptomatic at diagnosis. Forty-three per cent presented with pain; half of these patients had infected cysts. All lesions were palpable on digital rectal exam. Computed tomography identified the cyst in all seven patients in which it was performed. The transrectal approach was used for cyst excision in ten patients. One patient had transrectal drainage and wall biopsy only. Three patients underwent posterior parasacral excision. Pathologic review demonstrated four dermoid cysts, four epidermoid cysts, four cyst hamartomas, and two benign teratomas. One cyst hamartoma had a focus of invasive adenocarcinoma. Two complications occurred. There were no deaths. Follow-up averaged 39 months, at which time there were no recurrences. Developmental cysts are the most common presacral tumors. Excision is recommended, and the transrectal approach may be used in select patients with low morbidity and minimal recurrence.

International audience; Flood estimation and flood management have traditionally been the domain of hydrologists, water resources engineers and statisticians, and disciplinary approaches abound. Dominant views have been shaped; one example is the catchment perspective: floods are formed and influenced by the interaction of local, catchment-specific characteristics, such as meteorology, topography and geology. These traditional views have been beneficial, but they have a narrow framing. In this paper we contrast traditional views with broader perspectives that are emerging from an improved understanding of the climatic context of floods. We come to the following conclusions: (1) extending the traditional system boundaries (local catchment, recent decades, hydrological/hydraulic processes) opens up exciting possibilities for better understanding and improved tools for flood risk assessment and management. (2) Statistical approaches in flood estimation need to be complemented by the search for the causal mechanisms and dominant processes in the atmosphere, catchment and river system that leave their fingerprints on flood characteristics. (3) Natural climate variability leads to time-varying flood characteristics, and this variation may be partially quantifiable and predictable, with the perspective of dynamic, climate-informed flood risk management. (4) Efforts are needed to fully account for factors that contribute to changes in all three risk components (hazard, exposure, vulnerability) and to better understand the interactions between society and floods. (5) Given the global scale and societal importance, we call for the organization of an international multidisciplinary collaboration and data-sharing initiative to further understand the links between climate and flooding and to advance flood research.

In Italy, rainfall-induced slope failures occur every year, claiming lives and causing severe economic damage. We have designed and implemented a landslide warning system, named SANF (an acronym for national early warning system for rainfall-induced landslides), to forecast the possible occurrence of rainfall-induced landslides in Italy. The system is based on: (i) rainfall thresholds for pos- sible landslide occurrence, (ii) sub-hourly rainfall measurements obtained by a national network of 1950 rain gauges, and (iii) quantitative rainfall forecasts. Twice a day, the system compares the measured and the forecasted rainfall amounts against pre-defined ID thresholds, and assigns to each rain gauge a prob- ability of landslide occurrence. This information is used to prepare synoptic-scale maps showing where rainfall-induced landslides are expected in the next 24 hours.

In Regenerative Medicine one or more regenerative factors can be applied inside a cartilagine or bone defect to obtain a more rapid and complete healing. Bone Marrow Cells (BMC) added to Platelet-Rich Plasma (PRP) contain stromal cells which can differentiate in osteoclasts and osteoblasts and can be able to form osteogenic tissue and to repair bone defects secondary to degenerative processes.

Computed tomography (CT) was used in place of contrast enemas as the initial imaging study to evaluate patients with the clinical diagnosis of acute sigmoid diverticulitis. This report attempts to clarify the role of CT in the management of acute sigmoid diverticulitis by reviewing its usefulness in the diagnosis and treatment of 59 patients. CT established that three patients (5 percent) were hospitalized with an incorrect clinical diagnosis. Thirty-seven patients (62.7 percent) were identified as having uncomplicated acute diverticulitis. These patients were all treated successfully with nonsurgical therapies and were discharged in an average of 6.8 days. In the remaining 19 patients (32.2 percent), CT revealed complicated acute diverticulitis by identifying abscess, fistula, peritonitis, or obstruction. Eleven of these 19 patients required urgent surgery or CT-guided percutaneous drainage of an abscess. The four patients whose abscesses were drained percutaneously responded favorably and underwent an elective single-stage resection. The average hospital stay for patients with complicated diverticulitis was 13.6 days. Computed tomography is a useful aid in the initial management of patients with acute diverticulitis. It is a noninvasive test that recognizes and stratifies patients according to the severity of their disease. It has the further advantage of providing information about extracolonic pathology and anatomic variation useful for surgical planning. Additionally, early CT-guided needle drainage allowed downstaging of complicated diverticulitis, avoided emergent surgery, and permitted single-stage elective surgical resection.

Results Our patient, boy, 19 years old, 63.5 kg (50°centile), 161 cm, (3°centile), is affected by JIA, diagnosed at the age of 7 years. Since he presented many acute phases of illness, though on therapy with immunosuppressant (methotrexate 10 mg/m2/week), steroid and NSAID, in 2001 we introduced an anti-TNF drug (etanercept 0.5 mg/kg/twice a week) while reducing progressively steroid dose. However the patient showed still numerous articular acute phases. We decided to associate thalidomide (100 mg/ die). After two months, the boy showed an improvement of the articular symptoms. After six months JIA was in remission. After 16 months of thalidomide therapy, he presented electrophysiological PN, without clinical signs;we decided to stop the thalidomide therapy. Now, after 3 years of thalidomide suspension, no acute phases of JIA were observed and an electrophysiological improvement of PN was confirmed.

JIA is a chronic disease that can involve many different joints including TMJ. TMJ involvement leads to: chewing function alteration due to synovial membrane thickening, masticator muscle weakness and facial pain; craniofacial growth disturbance (micrognathia or facial asymmetry). The aim of our study is to evaluate the TMJ in people affected by JIA for early diagnosis of TMJ arthritis. Our series included 51 consecutive patients with JIA, 16 males and 35 females (age range 4 – 19 years), that were evaluated through a rheumatologic and dentist examination. Clinically suspected cases were studied with Magnetic Resonance Imaging (MRI). Our results showed that 19/51 patients (37%) (age range 9 – 19 years) had TMJ alterations, 10/19 (19,6%) concerning the left one while 7/19 (13,7%) the right one. Only 2/19 (4%) had a bilateral involvement. TMJ arthritis can severely affect the growth of mandibular, it can be asymptomatic in the majority of cases but it is present in about 50% of children with JIA. MRI is useful to evidence the assessment of disease activity with precious informations about its evolution. Besides, this imaging technique allows to eliminate X-rays exposure and, in according to its high definition, can show early joints alterations also in apparently asymptomatic children. In our patients, MRI was the gold standard for an early diagnosis showing that 37% of cases had TMJ involvement.

Results When Enbrel plus Methotrexate was started she got into remission. After one year of this therapy, she presented uveitis in both eyes, so oral steroids were started again. She obtained only partial ocular improvement, even when she received Infliximab associated with Methotrexate. Meantime she underwent cataract surgery with visus reduction. After one year, Infliximab was suspended because of an adverse reaction (dyspnea and rash) and Adalimumab (0.7 mg/kg subcutaneous/14 days) associated with Methotrexate was started, with no side effects. Fourteen months later there are no flare for uveitis and/or arthritis. Following SUN criteria [1] we demonstrated ocular clinical improvement, not withstanding the presence of signs of cataract and glaucoma.

PURPOSE: Technetium-99m-labeled red blood cell scintigraphy, commonly used in the evaluation of acute lower gastrointestinal hemorrhage, often fails to demonstrate a source of bleeding. It would be helpful to characterize a subset of patients more likely to have a positive scan. This study was undertaken to determine whether hemodynamic instability can predict tagged red blood cell scan positivity. METHODS: The records of 50 consecutive patients who underwent tagged red blood cell scanning for the evaluation of acute lower gastrointestinal bleeding were reviewed retrospectively. RESULTS: Patients presenting with a heart rate >100 beats per minute or a systolic blood pressure

Lysyl oxidase (LOX), a copper-dependent amine oxidase, has been implicated in tumor suppression and cell growth regulation. The chromosomal locus of LOX, 5q23, is affected by loss of heterozygosity (LOH) in colon cancer, suggesting that the LOX gene could be affected by LOH and consequently, loss or reduction of LOX function contribute to the tumorigenic process. Identification of microsatellite markers within the LOX locus has allowed us to map the LOX gene within the 5q23.1 region. Analysis of this locus and flanking loci in matched tumor and blood DNA samples from a panel of colorectal cancer patients, demonstrated that 38% (16/42) of informative samples were affected by LOH or allelic imbalance. Furthermore, 75% (6/8) of these tumor samples were shown to have significantly reduced LOX mRNA levels. Similar reduction in LOX levels were detected in a panel of matched normal colon and colon tumor samples. Tumor samples demonstrating LOH by RFLP, were subject to mutational analysis, including RT-PCR, exonic deletion detection by PCR, cDNA and genomic DNA sequencing, and were found to have a spectrum of alterations and mutations affecting the LOX gene. These results confirm that loss or reduction of LOX function during tumor development is a direct consequence of somatic mutations and is associated with colon tumor pathogenesis. © 2001 Wiley-Liss, Inc.

Background Interleukin (IL)-1 and metalloproteinases (MMP) are thought to play a crucial role in the cartilage degradation of osteoarthritis (OA). Recently it has been proposed that CRP may be useful index of OA activity and severity. Objectives We studied the relationships between synovial fluid (SF) IL-1b, MMP1 and MMP3, and serum levels of CRP in patients with OA of the knee (KOA) to investigate the role of CRP in KOA. Methods In the SF from 25 patients with KOA (Altman criteria, Kellgren and Lawrence score of 2 or greater on X-ray plan films) we determined the levels of IL-1b, MMP-1 and MMP-3 (ELISA), along with WBC number. In the same patients serum concentration of CRP was analysed by ultrasensitive rate nephelometry. No patients were taking NSAIDs or other antirheumatic drugs. Results In SF, MMP1 was correlated with MMP3 (r = 0.61, p = 0.0009), and MMP3 with IL-1b (r = 0.67, p = 0.0002). In turn, serum CRP was correlated with MMP3 (r = 0.76, p Conclusion The correlations found between serum CRP and SF levels of substances believed to be crucial in OA cartilage degradation, such as MMPs and IL-1, confirm the role of marker of disease severity recently proposed for this acute phase protein.

NW-1015 is a novel Na+ and Ca2+ channel blocker with broad spectrum anticonvulsant activity and an excellent safety margin. As the compound also shows sigma-1 receptor ligand properties it was deemed important to determine whether it possesses anticonvulsant properties in primates without causing behavioral and EEG abnormalities. Thus, the effects of NW-1015 on limbic electrically-induced afterdischarge (AD) were evaluated in four cynomolgus monkeys, and its activity compared to a single effective dose of phenytoin (PHT). The four male cynomolgus monkeys were chronically implanted for EEG recordings, from cortex and limbic structures. AD was induced in limbic areas by electrical stimulation. The effects of NW-1015 on the duration and the behavioral component of the AD were randomly tested at doses from 25 to 75 mg/kg and compared with the effects of PHT 50 mg/kg. Similarly to PHT, 50 mg/kg of NW-1015 significantly shortened the EEG AD and almost abolished AD elicited behavioral seizure. Only the behavioral effects of AD were reduced after administration of 25 mg/kg p.o. NW-1015 did not cause EEG or interictal behavioral alterations at doses up to 75 mg/kg p.o. These data further confirm the broad-spectrum anticonvulsant activity and a good safety profile of NW-1015 even in a primate model of complex partial seizures and suggest that its affinity for sigma-1 receptors is behaviorally irrelevant.

PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drug (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU-151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state.Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation 1 day before drug treatment.PNU-151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose-dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose-related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU-151774E were comparable to those of LTG and GBP.The activity shown by PNU-151774E at doses similar to those that are active in models of generalized seizures indicates that PNU-151774E would also have potential efficacy in the treatment of complex partial seizures.

Fourteen patients presenting with presacral cystic lesions were managed over a 20-year period. Retrospective review identified 12 females and 2 males. Fifty-seven per cent were symptomatic at diagnosis. Forty-three per cent presented with pain; half of these patients had infected cysts. All lesions were palpable on digital rectal exam. Computed tomography identified the cyst in all seven patients in which it was performed. The transrectal approach was used for cyst excision in ten patients. One patient had transrectal drainage and wall biopsy only. Three patients underwent posterior parasacral excision. Pathologic review demonstrated four dermoid cysts, four epidermoid cysts, four cyst hamartomas, and two benign teratomas. One cyst hamartoma had a focus of invasive adenocarcinoma. Two complications occurred. There were no deaths. Follow-up averaged 39 months, at which time there were no recurrences. Developmental cysts are the most common presacral tumors. Excision is recommended, and the transrectal approach may be used in select patients with low morbidity and minimal recurrence.

Cerebral ischaemia results in significant brain damage, but the molecular mechanisms associated with ischaemia-induced brain injury are not well defined. We have adopted an improved differential-display method to search for new ischaemia-related genes. Among the different cDNAs isolated following transient forebrain ischaemia in rat, PH3.3 was selected for further studies. The search for homologies revealed that it is the rat homologue to human zinc finger motif 1 (ZFM1), also called mammalian splicing factor 1 (SF1). With Northern blot, PH3.3 hybridized with three mRNA species of 2.3, 2.9 and 3.6 kb, significantly increased at 6 h and 5 days after the ischaemic insult. These findings were extended also to another animal model. In situ hybridization in ischaemic gerbils showed that PH3.3 mRNA was induced in the dentate gyrus as early as 4 h post-ischaemia. Expression peaked at 2 days in the whole hippocampus and cortex, and then progressively decreased towards sham levels. By day 4, expression had disappeared almost entirely from the cells in the CA1 region of the hippocampus, concomitant with the degeneration of pyramidal neurons. Interestingly, ZFM1/SF1 has been recently identified as activated following p53-induced apoptosis. Several lines of evidence suggest that p53 may play two roles in the post-ischaemic brain. The primary role of p53 is to activate DNA repair processes, but if repair fails, apoptosis will be initiated. Thus, ZFM1/SF1 may represent a relevant link between p53 and the neuroprotective/neurodegenerative processes which follow cerebral ischaemia.

Quinolinic acid (QUIN) is an endogenous neurotoxin which originates from the kynurenine pathway of tryptophan metabolism. An increase of brain QUIN level occurs in several degenerative and inflammatory disorders, but the cellular source of QUIN is still a matter of controversy. In the present study, the gerbil model of transient global ischemia was used to investigate the time course and the cellular localization of QUIN immunoreactivity. Neurodegeneration was evident in the subiculum and in the CA1 area of the hippocampus 4, 7 and 14 days after ischemia. QUIN positive cells, with microglia-like morphology, appeared in the subiculum and in the CA1, 4 days after ischemia. At 7 days post-ischemia they extended to the whole CA1, disappearing at 14 days. Neither neurodegeneration nor QUIN positive cells could be detected in ischemic gerbils sacrificed at 1 and 2 days after ischemia and in sham-operated animals. These findings suggest that microglia-like cells infiltrating the degenerating areas of the hippocampus represent the major source of QUIN following transient ischemia in the gerbil. Thus, in situ production of QUIN in vulnerable brain regions may contribute to the pathophysiological mechanisms of delayed brain injury.

In Regenerative Medicine one or more regenerative factors can be applied inside a cartilagine or bone defect to obtain a more rapid and complete healing. Bone Marrow Cells (BMC) added to Platelet-Rich Plasma (PRP) contain stromal cells which can differentiate in osteoclasts and osteoblasts and can be able to form osteogenic tissue and to repair bone defects secondary to degenerative processes.

Background In Regenerative Medicine one or more regenerative factors can be applied inside a cartilagine or bone defect to obtain a more rapid and complete healing. Bone Marrow Cells (BMC) added to Platelet-Rich Plasma (PRP) contain stromal cells which can differentiate in osteoclasts and osteoblasts and can be able to form osteogenic tissue and to repair bone defects secondary to degenerative processes. Methods We report on a 15-year and 8 month-old boy, followed at our Department, affected by JIA since he was 2 years old. He presented a systemic form, evolved into a polyarticular form, treated with steroids and immunosuppressor drugs. The patient had a good response to treatment with Enbrel, which he is still taking. In January 2009, he presented right hip pain and functional limitation. In July 2009 he underwent MRI of the hip joints which showed osteonecrosis in chondral/subchondral regions at the superior-external convexity of the right femoral head. We recommended deambulation with crutches and no weight bearing. Because of the persistence of joint symptoms, in July 2010 we implanted BMC plus PRP in the osteonecrotic region with improvement of pain and mobilization. In October 2010, he presented left hip pain. MRI showed focal osteonecrosis in subchodral region of left femoral head convexity. For this reason, we made a second BMC plus PRP implantation in the left hip. The last MRI, made on January 2012, showed any changes concerning the morphology of femoral heads and subchondral erosions but our patient autonomous walks, without joint pain and with improved ankle movements, since January 2011; he keeps on Enbrel and NSAIDs. Conclusions To the best of our knowledge, there are no literature data on the use of BMC plus PRP in pediatric patients affected by JIA. Considering the obvious limitations of our single case report, we observed a good short-term outcome. Therefore, follow-up is essential to check if BMC plus PRP implantation represents only a palliative care to delay surgical treatment or if it is a valid alternative to traditional orthopedic surgery. References Gothard D et al. In search of the skeletal stem cell: isolation and separation strategies at the macro/micro scale for skeletal regeneration. Lab Chip. 2011 Apr 7; 11(7): 1206-20. Epub 2011 Feb 25. Nauth A et al. Growth factors: beyond bone morphogenetic proteins. J Orthop Trauma. 2010 Sep; 24 (9): 543-6. Calori GM et al. Bone morphogenetic proteins and tissue engineering: future directions. Injury. 2009 Dec; 40 Suppl 3: S67-76. Disclosure of Interest None Declared

Quinolinic acid (QUIN) and kynurenic acid (KYNA) are two metabolites of the L-tryptophan degradation belonging to the kynurenine pathway and showing opposite effects on the brain. KYNA is a neuroprotectant and acts as an antagonist on the ionotropic excitatory amino acid receptors. In particular KYNA has an high affinity to the glycine site associated to the N-Methyl-D-Aspartate (NMDA) receptor complex (Foster et al., 1984; Kessler et al., 1989). On the contrary, QUIN is a neurotoxin and the observation that QUIN is a potent NMDA receptor agonist as well as a potent lipid peroxidant in brain homogenates has suggested the involvement of this metabolite in many neurodegenerative disorders (Schwarcz et al., 1983; Rios and Santamaria, 1991).

When injected into the brain of experimental animals, quinolinic acid (QUIN) and kynurenic acid (KYNA) act as a neurotoxin and neuroprotectant, respectively, and these effects are mediated by excitatory amino acid (EAA) receptors (Stone, 1993). Since their identification in the mammalian brain, QUIN and KYNA have therefore been proposed to play roles as endogenous modulators of EAA receptors. Both compounds are metabolites of the kynurenine pathway in the periphery and in the brain, and a large number of studies have been performed to examine their source, metabolism and disposition in the central nervous system in physiological and pathological conditions (see Stone, 1993, for review). In particular, an increased formation of QUIN was observed in several models of nerve cell damage, such as excitotoxin lesions (Speciale et al., 1987), spinal cord trauma (Popovich et al., 1994) and global ischemia (Heyes and Nowak, 1990; Saito et al., 1993), and in humans infected with the HIV virus (Heyes et al., 1991). This enhancement of QUIN production was suggested to contribute to the loss of neurological function. On the other hand, KYNA was found to be likely involved in cerebral self-defence (Schwarcz et al., 1992). This is supported both by occurrence of cell death following the pharmacologically induced decrease in brain KYNA (McMaster et al., 1991) and by the increase in cerebral KYNA production following acute excitotoxic (Schwarcz et al., this volume) or convulsive (Wu and Schwarcz, 1994; Baran et al., 1995) insults.

We have previously shown that the administration of a thromboxane A2 (TXA2) synthase inhibitor (FCE 22178) reduced the progression of glomerular lesions and protein-uria in MNS rats, an inbred strain which develops an age-related nephrotic syndrome. In the present study we investigated the effect of FCE 22178 on the plasma lipoproteins of MNS rats at 28 weeks of age (with mild proteinuria andmoderate dyslipoproteinemia) and at 48 weeks of age (with heavy proteinuria and severe dyslipoproteinemia). Drug treatment reduced proteinuria (by 70% and 36% at 28 and 48 weeks of age, respectively) plasma cholesterol (by 36% and 27% at 28 and 48 weeks of age, respectively) and prevented the decrease of plasma albumin observed in untreated rats (C-MNS) 48 weeks old. In treated rats (T-MNS), the decrease of proteinuria was positively correlated with that of plasma cholesterol. FCE 22178 reduced the elevation in plasma HDL1 (by 17.4%) and HDL2 levels (by 30%), a key feature of nephrotic dyslipoproteinemia in the rat. From 28 to 48 weeks of age plasma apo A-I and apo E increased 217% and 128%, respectively, in C-MNS rats and 191% and 121%, respectively, in T-MNS rats. A significant increase of apo A-I/apo E ratio was found in C-MNS rats from 28 (2.28±0.36) to 48 weeks of age (3.84±0.9) but not in T-MNS rats. FCE 22178 altered the lipid composition of VLDL and HDL2 by reducing the content of cholesteryl esters and increasing that of free cholesterol and phospholipids. These findings suggest that the beneficial effect of FCE 22178 on the dyslipoproteinemia of nephrotic MNS rats is secondary to the amelioration in kidney function and to the reduction of proteinuria produced by this drug. (Aging Clin. Exp. Res. 6; 381–390, 1994)

PURPOSE: This study was designed to assess the results of a minimally invasive surgical procedure for the correction of complete rectal prolapse in a poor surgical risk group. METHODS: Over a ten-year period, 40 patients underwent 41 Delorme operations when advanced age and/or poor overall health mitigated against an abdominal approach. Mean age was 82 (range, 30–100) years. Eighty-eight percent were females. Surgery was performed in the prone jackknife position utilizing intravenous sedation and local anesthesia. RESULTS: Follow-up ranges from 1 year to 2 years (mean, 47 months). There have been 9 recurrences in 8 patients (22 percent). Mean time to recurrence was 13 months (range, 1 month to 6 years). One death occurred in an 81-year-old patient within 24 hours of surgery from cardiopulmonary arrest. Minor complications occurred in 25 percent of patients. CONCLUSION: Satisfactory prolapse repair was safely performed in 78 percent of this high-risk group. Pitfalls in performing this procedure relate primarily to associated perineal and colonic conditions. Most prominent among these conditions are weak or absent anal sphincter tone, perineal descent, and previous sphincter injury. Extensive diverticular disease may prohibit effective and complete proximal mucosectomy. An inadequate mucosectomy sets the stage for early recurrence of prolapse.

The combination of thromboxane (TX) synthase inhibition and prostaglandin (PG) H2/TXA2 receptor antagonism yields enhanced antithrombotic effects as compared with either intervention alone. However, it is not known whether the enhancing effect of TX synthase inhibition is expressed also in the presence of complete blockade of PGH2/TXA2 receptors. Thus we evaluated the antithrombotic effects of increasing doses of the PGH2/TXA2 receptor antagonist L 670596 alone and in combination with a dose of the TX synthase inhibitor FCE 22178 causing95% inhibition of platelet TXB2 production. In the dog model of electrically induced coronary thrombosis, occlusion time in control animals (n = 14) averaged 72 +/- 29 min. L 670596 alone dose-dependently antagonized platelet PGH2/TXA2 receptors and prolonged occlusion time. The addition of FCE 22178 displaced the dose-occlusion time relation of L 670596 in a parallel fashion without modifying receptor occupancy. In the rabbit model of copper coil-induced carotid artery thrombosis, occlusion was very rapid (14 +/- 4 min) in control animals (n = 17) and was not modified by either aspirin or FCE 22178. L 670596 caused a dose-related receptor blockade and prolongation of occlusion time. The association with FCE 22178 enhanced significantly the antithrombotic effect of L 670596 at all doses. We conclude that the full therapeutic potential of PGH2/TXA2 receptor antagonism is expressed at90% platelet receptor occupancy. The additive effect of TX synthase inhibition suggests that conversion of PGH2 to platelet-inhibitor and vasodilator prostaglandins might be of therapeutic importance, irrespective of the extent of PGH2/TXA2 receptor blockade.

Uveitis in JIA can be severe and immunosoppressive therapies may not be sufficient. Anti-TNF-alfa agents (Infliximab, Adalimumab) have been proposed. The percentage of success is different among series and no controlled trials have been published yet. Abatacept, a selective T-cell co-stimulation modulator, has been shown to be a valid alternative to anti-TNF-alfa agents in patients with refractory uveitis (Angels-Han S.2008; Zulian 2010).

PURPOSE: Controversy exists over the appropriate preoperative evaluation of colorectal cancer patients. Most surgeons agree that basic laboratory studies are indicated. Computerized tomography of the abdomen and pelvis has been used in our practice to augment the preoperative evaluation of these patients. METHODS: One hundred fifty-eight consecutive patients with primary colorectal carcinoma underwent computerized tomography (CT) of the abdomen as part of their preoperative evaluation. Their medical records were retrospectively reviewed. RESULTS: In 88 patients, 120 findings present on CT were otherwise unknown. Of these, 35 percent were clinically significant in that they allowed the surgeon to alter the proposed operative procedure or added additional technical information for consideration preoperatively. Findings include liver metastasis (26), atrophic kidney (3), and abdominal wall or contiguous organ invasion (11). In addition, two other solid organ carcinomas were detected. In the remaining 70 patients, CT contributed no additional pertinent information about the patient prior to this initial operative procedure. CONCLUSIONS: CT aids in the preoperative evaluation of individuals with colorectal carcinoma. It provides important clinical information that is useful to the surgeon planning the procedure. Additionally, CT permits the patient and his family to be aware of their overall status and to subsequent treatment options. Computerized tomography eliminates the need for preoperative intravenous pyelogram, improves the preoperative staging for metastatic disease, and provides a baseline for comparison during the postoperative follow-up period should recurrence be suspected or adjuvant therapy be planned.

The literature supports the hypothesis that the association of a thromboxane (TX)A2 synthase inhibitor and a PGH2/TXA2 receptor antagonist has a superior antithrombotic effect when compared to both aspirin and single agent alone; a compound endowed with the dual mechanism of action might therefore be of therapeutic value for the management of thrombotic disorders. FCE 27262, an imidazol-1-yl-ethylideneaminooxypentanoic acid, displaces in vitro the binding of [3H]SQ 29,548 to washed human platelets (IC50 = 6.0 +/- 0.6 x 10(-8) M) and antagonizes human platelet aggregation induced by U 46619 in PRP with an IC50 (95% confidence limits) of 4.5(3.3-5.1) x 10(-7) M. It also selectively antagonizes the isolated vessel contraction induced by U 46619. In the rat aorta the Kb (95% confidence limits) was 1.6(0.6-4.3) x 10(-7) M. Additionally it inhibits in vitro TXB2 production in rat and human whole blood, the IC50 being, respectively, 5.9(3.3-9.6) x 10(-8) M and 3.8(2.9-5.0) x 10(-8) M. When administered orally to fed rats it also inhibits ex vivo TXB2 production in whole blood during clotting, the ID50 being 0.62(0.4-0.8) mg/kg. Both in vitro and ex vivo the effect of FCE 27262 on TXA2 synthase was selective, the production of PGE2, the product of a different isomerase from the common precursors, PG-endoperoxides, being concomitantly enhanced. In a canine model of electrically-induced coronary thrombosis, FCE 27262 (1 mg/kg i.v.) inhibits ex vivo TXB2 synthesis (95%), antagonizes U 46619-induced platelet aggregation and prolongs occlusion time (controls: 72 +/- 8 min, FCE 27262: 215 +/- 38 min; p0.01). In the same model both aspirin (5 mg/kg i.v.) and a pure PGH2/TXA2 receptor antagonist (L 670596), at a dose giving a similar degree of TXA2 synthase inhibition and receptor blockade, respectively, are significantly less effective. Thus, FCE 27262 combines thromboxane synthase inhibition and PGH2/TXA2 receptor antagonism in one molecule, resulting in enhanced antithrombotic activity. FCE 27262 thus may be an appropriate pharmacological tool to test the therapeutic potential of the dual mechanism of action.

Psoriatic arthritis (PsA) is an inflammatory joint disease in which environmental factors, particularly trauma and infections, are thought to play an important role. The authors describe the case of a patient with a mild and long-untreated form of PsA which was severely exacerbated by Salmonella typhimurium infection. This case confirms the importance of infectious agents in the occurrence and course of PsA.