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A 29-year-old girl presented complaining of acute bilateral visual loss associated with mild headache and retrobulbar pain. She was diagnosed with chiasmal optic neuritis caused by multiple sclerosis. Her visual acuity and visual field defect promptly improved after steroid therapy. However optical coherence tomography angiography showed a progressive reduction of superficial capillary plexus density of the retina and optic nerve consistent with the progressive impairment of the retinal ganglionar cell layer. Contrary to chiasmal compression, in chiasmal optic neuritis, the superficial capillary plexus density reduction is diffuse and does not reflect the peculiar anatomy of the chiasm.

Este artículo se centra en la Exposición Internacional de Carteles de 1934, presentada en la Ciudad de México y en otras urbes del país. Desde la perspectiva de la historia conectada, se argumenta que dicha exposición dio cuenta de la inserción de México en el campo de las artes gráficas con fines didácticos y de propaganda, al tiempo que desembocó en la incorporación de nuevos estilos, técnicas y contenidos en la cartelería mexicana que eventualmente tendrían repercusión en la Liga de Escritores y Artistas Revolucionarios y luego en el Taller de Gráfica Popular. Al prestar atención a las transmisiones iconográficas, estilísticas y de contenido de los carteles soviéticos e italianos a la iconografía mexicana, se muestra cómo se incorporaron las vanguardias extranjeras en el proceso de definición de un estilo “nacional”.

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas. An eight-gene signature with copy number variations (CNVs) in neuroendocrine neoplasms (NENs), namely MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53, was used to classify an independent cohort of 54 surgically resectable tumors [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 small cell lung carcinomas (SCLC)], for which transcriptome and mutation data were available. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.5%) carcinoids and all the SCLC samples fell into the latter. CL2 carcinoids affected survival adversely, were enriched in T to G transversions and T>C/C>T transitions in the context of specific mutational signatures, presented with at least 1.5-fold change (FC) increase of gene mutations including TSC2, SMARCA2, SMARCA4, ERBB4 and PTPRZ1, differed for gene expression and showed epigenetic changes in charge of MYC and MTORC1 pathways, cellular senescence, inflammation, high- plasticity cell state and immune system exhaustion. Similar results were also confirmed in an independent validation set of 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC). We herein propose an unexpected shifting to the current pathogenesis paradigm, suggesting that some NECs could secondarily originate from a subset of genomically transformed carcinoids prone to epigenetic mechanism-driven progression.

There is evidence in the literature for high-fidelity in situ simulation training programs being an effective modality for physicians training. This quality initiative focused on implementation of the procedural sedation and analgesia (PSA) in our pediatric emergency department (PED). The primary outcomes of this study were to evaluate the impact of blended in situ simulation training (BST) program on PSA for closed forearm fracture reduction in the PED and to assess its cost-effectiveness. The secondary outcomes were to estimate this change on PSA's clinical efficacy and safety.Between 2014 and 2018, a single-center, quasi-experimental, uncontrolled before and after study on forearm fracture reduction management was conducted. To assess the impact of our BST-PSA course, both historical control and prospective analyses were performed. Statistical significance was based on Fisher exact test or Pearson χ 2 test.Eight hundred eighty-five children met inclusion criteria. A significant difference in the number of PSAs performed in the PED, before and after BST, was found (37% vs. 85.3%, P0.001). Furthermore, a reduction in the number of hospitalizations for closed fracture reduction was measured (68.2% vs. 31.8%, P0.001). The overall cost savings from the BST-enabled increase in PSAs carried out in the PED was €370,714 ($440,838) with a return on investment of 64:1. No significant increase of PSA-related adverse events was found, and no serious adverse events occurred.Findings provide evidence of the benefits of implementing BST to enable PSA use in the PED, with an improved patient flow and significant cost savings from avoiding unnecessary hospitalizations.

Objective: to describe risk factors associated with SARS-CoV-2 infection. Methods: this is a retrospective descriptive cross-sectional study aimed at describing the epidemiological profile of laboratory and clinical diagnosis of unvaccinated patients seen at a basic health unit in Araçatuba – SP, infected with SARS-CoV-2 between June 2020 and January 2021.The results were analyzed through inferential and descriptive statistics. Additionally, Chi-square and Fisher exact tests were used (p

The success in acquiring a precision impression in the dental field is a compromise between the processing time and the setting time of the impression material. A device called "Impression Heater" (EU application n ° EP20186042.6) has recently been patented, which consists of a self-heating disposable adhesive patch with an exothermic chemical reaction to be placed on the dental impression tray. The aim of the study was to evaluate the effectiveness of a thermal impression accelerator in reducing the setting time of different elastomers.3 samples of 5 different elastomeric materials (width 6 mm x length 50 mm x depth 3-5-7 mm) the hardening of the material was evaluated at intervals of 15 seconds using an ASTM 2240 Shore-A durometer at 20°C. The same procedure was replicated 3 times after positioning on a Impression Heater at temperatures of 35 °C, 50 °C and 65 °C, for each material.An increase in the impression material temperature from 35 °C to 50 °C reduces the setting time of an amount between 38.1% and 45.8%. Increasing the temperature from 35 °C to 65 °C results in a reduction of the setting time between 52.4% and 66.9%. At higher temperatures, the greater thickness of the impression material requires longer hardening times.The tests carried out confirm the validity of the patented idea which reduces the time of impression taking while keeping the working time sufficiently long for the operator to manoeuvre.

An otherwise healthy 72-year-old Chinese patient diagnosed with exudative age-related macular degeneration and decreased vision in left eye was fully investigated. The retrospective analysis of past multimodal imaging revealed bilateral severe choroidal neovascularization and choroiditis associated with a positive tuberculin skin testing and interferon-gamma release assay (QuantiFERON-TB Gold – Cellestis®, Chadstone, VIC, Australia) suggestive of latent ocular tuberculosis. The variable presentation and tests’ results interpretation represent the greatest limitations in understanding and treating intraocular TB (IOTB). This may present without any other systemic symptoms, the intraocular tissues are of limited access to biopsies and other tests, including imaging and immunological tests, are of relative value. This case highlights how variable may be the presentation of IOTB, which can be easily misdiagnosed leading to a delayed treatment and worse prognosis.

Pediatric cardiac arrest is a rare emergency with associated high mortality. Its management is challenging and deviations from guidelines can affect clinical outcomes.To evaluate the adherence to guideline recommendations in the management of a pediatric cardiac arrest scenario by teams of pediatric residents. Secondarily, the association between the use of the Pediatric Advanced Life Support-2015 (PALS-2015) pocket card, and the teams' adherence to international guidelines, were explored.Multicentre observational simulation-based study at three Italian University Hospitals in 2018, including PALS-2015 certified pediatric residents in their 3rd-5th year of residency program, divided in teams of three.Each team conducted a standard nonshockable pediatric cardiac arrest scenario and independently decided whether to use the PALS-2015 pocket card.The primary outcome was the overall number and frequency of individual deviations from the PALS-2015 guidelines, measured by the novel c-DEV15plus score (range 0-15). Secondarily, the performance on the validated Clinical Performance Tool for asystole scenarios, the time to perform resuscitation tasks and cardiopulmonary resuscitation (CPR) quality metrics were compared between the teams that used and did not use the PALS-2015 pocket card.Twenty-seven teams (81 residents) were included. Overall, the median number of deviations per scenario was 7 out of 15 [interquartile range (IQR), 6-8]. The most frequent deviations were delays in positioning of a CPR board (92.6%), calling for adrenaline (92.6%), calling for help (88.9%) and incorrect/delayed administration of adrenaline (88.9%). The median Clinical Performance Tool score was 9 out of 13 (IQR, 7-10). The comparison between teams that used ( n = 13) and did not use ( n = 14) the PALS-2015 pocket card showed only significantly higher Clinical Performance Tool scores in the former group [9 (IQR 9-10) vs. 7 (IQR 6-8); P = 0.002].Deviations from guidelines, although measured by means of a nonvalidated tool, were frequent in the management of a pediatric cardiac arrest scenario by pediatric residents. The use of the PALS-2015 pocket card was associated with better Clinical Performance Tool scores but was not associated with less deviations or shorter times to resuscitation tasks.

Purpose: To describe a case of fulminant idiopathic intracranial hypertension (IIH) in a child with “malignant” presentation. Case report: A 16-year-old, previously healthy, girl presented with bilateral visual loss and bilateral global limitation of eye movements in the absence of headache. Extensive laboratory evaluation for infectious, inflammatory, autoimmune, and neoplastic conditions was negative. Magnetic resonance imaging (MRI) of the brain and lumbar puncture findings were consistent with a diagnosis of IIH. Extraocular motility improved in the next few days as well as optic disc edema but visual acuity remained poor. Conclusion: The authors believe that the acute, severe, and fulminant (“malignant”) presentation with markedly elevated intracranial pressure may produce the unique presentation of severe vision loss and bilateral complete ophthalmoplegia. Interestingly, there was no headache. To our knowledge this is the first such case to be reported in the English language ophthalmic literature.

A 46-year-old female with a history of 5 months of progressive painless visual loss in the left eye was found to have an optic nerve sheath meningioma. Optical coherence tomography angiography showed a reduction in the superficial capillary plexus density consistent with her visual field defect and peripapillary retinal nerve fiber layer thinning. Moreover, abnormalities in the choriocapillaris were found in the affected eye compared to the fellow eye. Possible explanations for these findings are discussed. Further studies and a consistent number of cases are needed to correctly assess the impairment of ocular blood flow in optic nerve sheath meningioma.

Neuroendocrine tumours (NETs) are rare tumors. 55% of NETs originate in the gastrointestinal tract and the liver is the most common site of distant metastases. Serum chromogranin A is the most common biomarker for assessing the extent of disease and monitoring treatment; carcinoid syndrome occurs in 19% of NETs and is characterized by chronic diarrhea or flushing. Primary mesenteric NETs are rare and have been described only in case reports in literature; our case is an apparent primary mesenteric NETs with a surgical program to remove the mesenteric mass and subrenal interaortocaval and retrocaval lymphadenectomies.A 73-year old man came to us because he had been experiencing abdominal pain for a year and he had recently developed diabetes mellitus. He was an active smoker with arterial hypertension.After a computed tomography scan and 68 Gallium-positron emission tomography, a diagnosis of what appeared to be a primary mesenteric NET with retrocaval and interaortocaval lymph nodes was made. Laparoscopic biopsy showed NET G2 positive for serotonin, chromogranin A, synaptophysin.The intraoperative finding of a primitive ileum-NET changed the surgical program. We removed the mesenteric mass with the lymph nodes of the superior mesenteric vessel and the middle distal ileum along with the cecum.The postoperative course was normal, and the patient was discharged on the seventh postoperative day without signs of short bowel syndrome. Follow-up at 6 months revealed no evidence of short bowel syndrome or disease progression.68 Gallium-positron emission tomography does not show NETs smaller than 0.5 mm. Accurate palpation of the intestine is essential during surgery for NETs for two reasons: to find the primitive, and because of the risk of multiple intestinal primitives.

Objective: to describe risk factors associated with SARS-CoV-2 infection. Methods: this is a retrospective descriptive cross-sectional study aimed at describing the epidemiological profile of laboratory and clinical diagnosis of unvaccinated patients seen at a basic health unit in Araçatuba – SP, infected with SARS-CoV-2 between June 2020 and January 2021.The results were analyzed through inferential and descriptive statistics. Additionally, Chi-square and Fisher exact tests were used (p

Acute management of a severely burned patient is an infrequent and stressful situation that requires medical knowledge as well as immediate coordinated action. Many adverse events in health care result from issues related to the application of 'non-technical' skills such as communication, teamwork, leadership and decision making rather than lack of medical knowledge. Training in these skills is known as Crisis Resource Management (CRM) training. In order to create well-prepared burn teams, it is critical to teach CRM principles through high-fidelity simulation (HFS). While CRM teaches foundational non-technical skills, HFS incorporates lifelike, whole-body, fully-responsive mannequins in order to provide a realistic emergency situation. The aim of the study is to describe the development of a novel high-fidelity simulation course called "SIMBurns: High Fidelity Simulation Program for Emergency Burn Management" that uses CRM as its foundation and is focused on management of burn injuries. The course was designed by a panel of simulation and burns experts from Meyer Children's Hospital in Italy and Birmingham Children's Hospital in the U.K. Simulation Program experts were certified by Boston Children's Hospital's Simulation Program. In this paper, we describe the course's design, development, structure, and participant's assessment of the course. Since the creation of the SIMBurns course in 2013, 9 courses have been conducted and 101 participants have attended the course. The course was well-received and its "Overall Satisfaction" was rated at 4.8/5. The primary objective in the SIMBurns course - to teach teamwork and CRM skills to medical staff involved in emergency burn care - was also met at 4.8/5. Participants felt that the course developed their ability to interact with other team members, further improved their understanding of how to appropriately use resources, emphasized the importance of role clarity and developed their communication skills. Additional quantitative and qualitative analyses obtained from participants were also reviewed after each course. The SIMBurns course aims to contribute to the education of those in healthcare in order to improve patient safety and to continue advancing the education of our emergency burn care teams.

En las décadas de 1920 y 1930 Italia y México vivieron procesos de centralización educativa comparables. En Italia el Parlamento decretó la obligatoriedad del libro de texto único de Estado para la escuela primaria con la ley del 1 de noviembre de 1928. Fue una medida de la cual se valió el gobierno para forzar a los maestros a emplear una herramienta pensada directamente por el régimen y garantizar su fidelidad ideológica al fascismo. En México, la reforma cardenista al artículo tercero constitucional en 1934 decretó que la educación impartida por el Estado sería socialista, combatiría el fanatismo religioso y los prejuicios. Ello concedió un mayor control al Estado sobre la educación primaria, tanto la que se impartía en las escuelas públicas como en las particulares, y sobre la publicación de libros de texto. En México e Italia las ilustraciones presentes en los libros de texto de los años treinta irradiaban una carga ideológica explícita. A través de ella los gobiernos imponían (en Italia) o sugerían (en México) los contenidos políticos bajo los cuales adoctrinar a los alumnos. Las imágenes están cargadas de civismo, valores políticos y militarismo, y sus temas, muy análogos, se repiten en ambos países. Las metáforas y los símbolos son parte del lenguaje artístico, y también del lenguaje político. Históricamente los artistas, filósofos políticos patrocinados por los gobiernos, han dado forma sensible al simbolismo y los mitos patrios (Skinner, 2009). Las obras de arte han sido utilizadas para inspirar en la población los sentimientos que ellos querían infundir. El objetivo de esta ponencia es explorar de qué manera las ilustraciones de los libros de texto producidos en ambos países contribuyeron a fomentar esos procesos modernos de formación del Estado y construcción de la nación, mostrando luego su isomorfismo en el ámbito educativo.

Since the publication of the 1999 IOM report “To Err Is Human: Building a Safer Health System,” much has been learned about pediatric patient safety. However, adverse events still affect one-third of all hospitalized children [1]. The main areas of adverse events are hospital-acquired infections, intravenous line complications, surgical complications, and medication errors [2].

Groin hernioplasty is the most performed intervention in the adults worldwide. Small bowel occlusion after hernioplasty with anterior approach is an unusual complication because the peritoneum is not opened during this procedure. However during TAPP the closure of the peritoneal flap is mandatory. In literature some cases of small bowel occlusion related to the barbed suture for the closure the peritoneum are reported.Here we describe a case of a 64-year old male with small bowel obstruction after TAPP caused by the barbed suture used for peritoneal closure.Intrabdominal use of self-anchoring suture is controversial. Some studies reported good results by using this device, while others from gynecologists describe bowel occlusion and volvulus caused by barbed suture.Self-anchoring device is innovative and reduces operation time. It is most important to know the correct use of this device to reduce some possible troubles.

The aim of this study is to describe the clinicopathological characteristics of intranasal pleomorphic adenomas (PAs), as well as the role and outcomes of endoscopic endonasal resection. A retrospective review of the clinical data from patients with PA of the nasal cavity who were treated by the authors at three tertiary medical centers between June 1998 and December 2019. A total of five patients with PA were found. Three patients were male, two were female and their mean age was 62.2 years. All cases were resected "en bloc" with endoscopic endonasal approach. No evidence of disease was observed during a mean follow-up of 10.6 years. No case presented with malignant transformation into carcinoma ex-PA. PA of the sinonasal tract and the nasopharynx is difficult to diagnose due to nonspecific clinical and radiological findings. Endoscopic endonasal approaches can be considered the gold standard in the treatment of these tumors and provide excellent visual control of the surgical field and clear margins.

Introduction Paediatric cardiac arrest (PCA), despite its low incidence, has a high mortality. Its management is complex and deviations from guideline recommendations occur frequently. We developed a new interactive tablet app, named PediAppRREST, to support the management of PCA. The app received a good usability evaluation in a previous pilot trial. The aim of the study is to evaluate the effectiveness of the PediAppRREST app in reducing deviations from guideline recommendations in PCA management. Methods and analysis This is a multicentre, simulation-based, randomised controlled, three-parallel-arm study. Participants are residents in Paediatric, Emergency Medicine, and Anaesthesiology programmes in Italy. All 105 teams (315 participants) manage the same scenario of in-hospital PCA. Teams are randomised by the study statistician into one of three study arms for the management of the PCA scenario: (1) an intervention group using the PediAppRREST app or (2) a control group Paediatric Advanced Life Support (CtrlPALS+) using the PALS pocket reference card; or (3) a control group (CtrlPALS-) not allowed to use any PALS-related cognitive aid. The primary outcome of the study is the number of deviations (delays and errors) in PCA management from PALS guideline recommendations, according to a novel checklist, named c-DEV15plus. The c-DEV15plus scores will be compared between groups with a one-way analysis of variance model, followed by the Tukey-Kramer multiple comparisons adjustment procedure in case of statistical significance. Ethics and dissemination The Ethics Committee of the University Hospital of Padova, coordinating centre of the trial, deemed the project to be a negligible risk study and approved it through an expedited review process. The results of the study will be disseminated in peer-reviewed journals, and at national and international scientific conferences. Based on the study results, the PediAppRREST app will be further refined and will be available for download by institutions/healthcare professionals. Trial registration number NCT04619498; Pre-results.

Groin hernioplasty is most intervention performed in the worldwide. The present study aimed to evaluate a combination between ultralight mesh and fibrin human sealant in the laparoscopic treatment of inguinal hernia.This retrospective study included consecutive patients who underwent laparoscopic transabdominal preperitoneal hernioplasty (TAPP) from 1st of January 2015 to 31st of December 2016. Demographics, surgical data and postoperative outcomes were entered in an anonymized prospective database. Prospective longterm follow-up carried out in all patients.One hundred eighty-four patients with a median age 57.5 (range 19-84) and median BMI (Body Mass Index) of 28.5 (range 18.5-31.5) were included. A median follow-up of 25 months (median 13-35) was carried out. Five recurrences (1.5%) and two cases of missed lipoma were observed and operated. Chronic pain (CP) was observed in eleven (9%) patients but in 9 patients it decreased spontaneously.Combination of ultralight mesh and Evicel® in TAPP operation is a safe solution for the treatment of groin hernia. Recurrences and chronic pain are similar to other combination of fibrin sealant and meshes. Moreover action of Evicel® may provide to improve the hemostasis and consequently hematoma of the cord.

Background A prompt start to an appropriate neonatal and paediatric resuscitation is critical to reduce mortality and morbidity. However, residents are rarely exposed to real emergency situations. Simulation-based medical training (SBMT) offers the opportunity to improve medical and non-technical skills in a controlled setting. This survey describes the availability and current use of SBMT by paediatric residents in Italy with the purpose of understanding residents’ expectations regarding neonatal and paediatric emergency training, and identifying gaps and potential areas for future implementation. Methods A survey was developed and distributed to Italian residents. SBMT was defined as any kind of training with a mannequin in a contextualised clinically realistic scenario. Results The response rate was 14.4%, covering the 71% of Italian paediatric residency programmes. Among them, 88% stated that Out of the 274 residents, 88% stated that they received less than 5 h of SBMT during the past training year, with 66% not participating in any kind of simulation activity. In 62% of the programmes no simulation training facility was available to residents. Among those who received SBMT, 46% used it for procedures and skills, 30% for clinical scenarios, but only 24% of them reported a regular use for debriefing. Of the overall respondents, 93% were interested in receiving SBMT to improve decision-making abilities in complex medical situations, to improve technical/procedural skills, and to improve overall competency in neonatal and paediatric emergencies, including non-technical skills. The main barriers to the implementation of SBMT programmes in Italian paediatric residencies were: the lack of experts (57%), the lack of support from the school director (56%), the lack of organisation in planning simulation centre courses (42%) and the lack of teaching materials (42%). Conclusions This survey shows the scarce use of SBMT during paediatric training programmes in Italy and points out the main limitations to its diffusion. This is a call to action to develop organised SBMT during paediatric residency programs, to train qualified personnel, and to improve the quality of education and care in this field. Electronic supplementary material The online version of this article (10.1186/s12909-019-1581-3) contains supplementary material, which is available to authorized users.

AIM: To evaluate the functional outcome after removal of silicone oil (ROSO) in patients undergoing retinectomy for complex retinal detachment. METHODS: We performed a retrospective case note review of patients who underwent ROSO after retinectomy for complex retinal detachment. Patients with less than 6mo follow up and recurrent retinal detachment following ROSO were excluded. RESULTS: Thirty-six patients were included. The mean best corrected visual acuity (BCVA) pre-ROSO was 1.13 logMAR (SD 0.5). The mean BCVA 3mo following ROSO was 1.16 logMAR (SD 0.53), 6mo following ROSO 1.13 (SD 0.63), and 12mo following ROSO 1.18 (SD 0.69). At 12mo after ROSO, the BCVA improved in 38.9% of patients, remained unchanged in 25%, and deteriorated in 36.1%, although there was no statistical significant difference in BCVA after ROSO at 3, 6 and 12mo (P=0.93). The size of retinectomy ranged from 15° to 270° (SD 53) and did not influence the visual outcome (P=0.11). CONCLUSION: There was no statistically significanT difference in BCVA between pre- and post- ROSO following retinectomy for complex retinal detachment. There was no statistical difference in visual outcome related to the size of the retinectomy.

On last December 2014, Security brokers (SB)—“Targeted Threats Team”—successfully completed a full analysis, which started back on January 2013, operating over 24 months of deep research and data correlation. Analyzing those main and biggest security incidents and data breaches occurred over the last ten years, starting from the faraway year 2004. The lesson learned was quite impressive and may somehow shake the modus operandi and the mental approach we are used to. This paper aims to recap those key points emerged from that research project, and those new logics we should internally apply within our organizations over the next months and upcoming years. This paper aims to provide, on its first section, the so-called big picture toward those main threats linked with information theft and leaks, and Web defacements, along with those consequent impacts on organizations, through keywords such as Cyber Intelligence, both from open and from closed sources. The second section of the paper provides a general overview of the importance of the so-called secure programming and on those typical mistakes that pop-up when running security testing projects, and advanced penetration testing activities, toward Web applications.

In the past decade there has been a rapid growth of the use of adaptive automated trading systems, commonly referred to in the finance industry as ``robot traders'': AI applications replacing highly-paid human traders in the global financial markets. The academic roots of this industry-changing deployment of AI technologies can be traced back to research published by a team of researchers at IBM at IJCAI 2001, which was subsequently replicated and extended by De Luca and Cliff at IJCAI 2011 and ICAART 2011. Here, we focus on the order management policy enforced by Open Exchange (OpEx), the open source algorithmic trading system designed by De Luca, for both human and robot traders: while humans are allowed to manage multiple orders simultaneously, robots only deal with one order at the time. We hypothesise that such unbalance may have strongly influenced the victory of human traders over robot traders, reported in past studies by De Luca et al., and by Cartlidge and Cliff. We employed OpEx to implement a multiple-order policy for robots as well as humans, and ran several human vs. robot trading experiments. Using aggregated market metrics and time analysis, we reached two important conclusions. First, we demonstrated that, in mixed human-robot markets, robots dealing multiple simultaneous orders consistently outperform robots dealing one order at a time. And second, we showed that while human traders outperform single-order robot traders under specific circumstances, multiple-order robot traders are never outperformed by human traders. We thus conclude that the performance of robot traders in a human-robot mixed market is strongly influenced by the order management policy they employ.

An angiogenic response originating from peritumoral sinusoids and portal tracts that leads to the formation of metastases with sinusoidal- and portal-type angiogenic patterns, respectively, occurs during the course of liver colonization by murine 51b colon carcinoma (51b-CC) cells. We found a 5-fold increase in endogenous endostatin levels from hepatic blood over baseline (25 +/- 6 ng/mL) when micrometastatic foci had a detectable size and a 14-fold increase when macrometastases were developed. Despite this endogenous endostatin production, subcutaneous administration of recombinant human endostatin (rh-E; 50 mg/kg) decreased metastasis number by 60% when dosed from days 1 to 20 after 51b-CC cell injection, by 40% when given from days 10 to 20, and by 30% when administered as a single dose 30 minutes before 51b-CC cell injection compared with controls. In addition, administration of rh-E from days 10 to 20 decreased overall metastasis volume by 90% compared with controls. rh-E increased the number of necrotic sinusoidal-type metastases by 7-fold and decreased their intrametastatic CD31(+)-microvessel density by 80% without affecting portal-type metastases. Flow cytometry showed rh-E binding to mouse liver sinusoidal cells but not to CD45(+) cells (leukocytes and Kupffer cells) or 51b-CC cells. Furthermore, rh-E induced sinusoidal endothelium cell apoptosis. In conclusion, despite the direct correlation between metastasis development and endogenous endostatin generation in the liver, administration of rh-E inhibited micrometastasis generation and macrometastasis growth very efficiently. The antiangiogenic mechanism was selective for sinusoidal-type metastases, in which the neovasculature originating from sinusoidal endothelium cells was targeted by rh-E.

The increasing speed of medicine updating required a change in the training system: the classic teaching mode "see one-do one" is increasingly called into question for ethical reasons in order to protect patients from possible damages deriving from health personnel education [1]. This concept finds its implication in pediatric patients, where any unnecessary suffering must be avoided: for this reason new methodologies based on simulation have been introduced to prevent this type of problem. Simulation is a technique that allows replacing or amplifying real experiences with guided experiences, artificially designed, which evoke or replicate substantial aspects of the real world in an entirely interactive situation. The growing interest in this approach is due to three main factors: the development of simulator technologies, the evolution of medical education understood as a set of competences in the field of knowledge, skills and behavior and finally the increasing attention to limit errors in team work. Simulation in medicine is not only a training tool, but also a way of reducing clinical risk and of improving patient safety. Pediatric emergencies are an example of how simulation can actually be a tool for health workers to achieve a performance improvement in medical assistance [2]. Pediatric emergency events are clinically rare, high-risk, and frequently involve the simultaneous presence of several subjects: pediatricians, nurses, specialists and the patient’s family. In situ simulation is a particular form of simulation, distinct from simulation conducted in a simulation center: it may be defined as, “Simulations that occur in the actual clinical environment and whose participants are on-duty clinical providers during their actual workday.” The required materials can either be used specifically for simulation and taken each time to the site of the scenario, or they can be routinely available. In situ simulation training offers many advantages: it gives the opportunity to test systems, to reinforce training in authentic ways, and also to identify hazards and deficiencies in the clinical systems, in the environment and in the provider team [3].

The mechanism of intrasinusoidal arrest of circulating cancer cells, which is a critical step in liver metastasis, appears to be facilitated by tumor-derived proinflammatory factors that increase sinusoidal cell adhesion receptors for cancer cells. However, how this prometastatic microenvironment is up-regulated remains unknown. Using intrasplenically injected B16 melanoma (B16M) cells, we show that the expression of vascular cell adhesion molecule-1 (VCAM-1) significantly increased in hepatic sinusoidal endothelium (HSE) cells over physiologic baseline within the first 24 hours of metastatic cancer cell infiltration in the liver. This correlated with increased in vitro adhesion of B16M cells to HSE cells isolated from B16M cell-injected mice. In vivo VCAM-1 blockade with specific antibodies before B16M cell injection decreased sinusoidal retention of luciferase-transfected B16M cells by 85%, and metastasis development by 75%, indicating that VCAM-1 expression on tumor-activated HSE cells had a prometastatic contribution. Because VCAM-1 expression is oxidative stress-inducible, recombinant catalase was in vivo administered, resulting in a complete abrogation of both VCAM-1 expression and B16M cell adhesion increases in HSE cells isolated from B16M cell-injected mice. Catalase also abrogated the proadhesive response of HSE cells to B16M-conditioned medium (B16M-CM) in vitro, although this did not affect the concomitant release of major proinflammatory cytokines by HSE cells. HSE cells treated with B16M-CM released interleukin (IL)-18 via tumor necrosis factor-alpha (TNF-alpha)-dependent IL-1beta in vitro. In turn, H(2)O(2) production from B16M-CM-treated HSE cells was regulated by IL-18. Thus, liver-infiltrating B16M cells activated their adhesion to HSE through a sequential process involving TNF-alpha-dependent IL-1beta, which induced IL-18 to up-regulate VCAM-1 via H(2)O(2). The pivotal position of H(2)O(2) was further supported by the fact that incubation of HSE cells with nontoxic concentrations of H(2)O(2) directly enhanced VCAM-1-dependent B16M cell adhesion in vitro without proinflammatory cytokine mediation, which emphasizes the key role of oxidative stress in the pathogenesis of liver inflammation and metastasis.

The engulfment of cells undergoing apoptosis can be considered a specialized form of phagocytosis, playing a major role in general tissue homeostasis in physiological and pathological conditions. Although several systems of recognition on the surface of the phagocyte have been proposed to trigger or execute the apoptotic engulfment, the nature of the molecules involved and their molecular roles are still ill defined. In the present work, the molecular mechanisms of recognition of apoptotic cells by the hepatic sinusoidal wall were further investigated. The adhesion of apoptotic cells, i.e., lymphocytes isolated from human peripheral blood and a monocytic cell line U937, was studied in in vivo and in vitro experiments. Liver endothelial cells were able to recognize apoptotic lymphocytes in vivo as well as in vitro but failed, in the same conditions, to recognize apoptotic U937. A possible explanation could derive from the differences in the cell surface glycoconjugates of apoptotic lymphocytes and...

By using a detailed radiative transfer model, we show that the observed far-infrared spectrum of the Bok globule Barnard 335 can be explained by dust emission whose only energy source is the interstellar radiation field. The anomalous excess radiation observed around 60 μm in B335 and other globules can be accounted for by a «non-conventional» dust component, the very small grains already proposed for other celestial objects

The Authors report a case of hemoperitoneum after breaking of luteal cyst of corpus luteum and stress the main characteristics of this pathology. Ovarian cysts are frequently observed in the annexa; they are distinguished in folliculis cysts, luteal cysts, luteal cysts of corpus luteum. Their evolution, influenzed so both by endocrine factors so many from plogistic stimulation, pass through three essential moments: - obliteration for quick cicatrization of the stigma Graafian follicle; - hematic pouring and central softening; - increase of intracavitary fluid that stops with constitution of the fibrous tissue. In the second phase of the menstrual cycle, functional-anatomic changes occur that cause the formation of gravidic corpus luteum or menstrual corpus luteum. The luteal cysts of corpus luteum represent the result of the cystic evolution of the corpus luteum. These cysts are characterized by an intense endocrine activity and can frequently produce a surplus of steroids, particulary of progesterone. They can cause bleeding, often of slight entity but also severe that; these represent a frequent and dangerous complication, especially in women subjected to anticoagulant treatment with warfarin. This drug can determine a raise of intracystic pressure with consequent breaking of the capsule and hemoperitoneum for which is necessary emergency operation like in the case here described.

The box model is a component model for the object-oriented paradigm, that defines components (the boxes) with clear encapsulation boundaries. Having well-defined boundaries is crucial in component-based software development, because it enables to argue about the interference and interaction between a component and its context. In general, boxes contain several objects and inner boxes, of which some are local to the box and cannot be accessed from other boxes and some can be accessible by other boxes. A trait is a set of methods divorced from any class hierarchy. Traits can be composed together to form classes or other traits. We present a calculus for boxes and traits. Traits are units of fine-grained reuse, whereas boxes can be seen as units of coarse-grained reuse. The calculus is equipped with an ownership type system and allows us to combine coarse- and fine-grained reuse of code by maintaining encapsulation of components.

A multiparty session forms a unit of structured interactions among many participants which follow a prescribed scenario specified as a global type signature. This paper develops, besides a more traditional communicationtype system, a novel static interactiontype system for global progress in dynamically interleaved multiparty sessions.