A virtual laboratory to support chemical reaction engineering courses using real-life problems and industrial software

A virtual laboratory has been developed to support chemical reaction engineering courses. Real-life engineering challenges that are difficult to address in a university laboratory give the opportunity to illustrate basic concepts of chemical reaction engineering such as the relationship between temperature and reaction rate, space time and conversion, and inert concentration and selectivity. Six virtual experiments covering topics from petroleum refining, diesel combustion, nanoparticle growth, and hydrogen combustion form the basis of the virtual laboratory. The characteristics embedded in the experiments include the use of economic analysis to give closure to open-ended problems, the solution of engineering problems with high environmental relevance and finally, the ability to solve complex engineering problems related to state-of-the-art technologies, for example the synthesis of functionalized nanoparticles. Trial tests with senior students, with continual feedback and freedom in terms of the delivery date were used to evaluate and improve the experiments. Subsequently, a classroom test with 45 undergraduate students with a fixed deadline was performed. The challenges and opportunities to use virtual experiments supported by industrial software to teach real-life problems to undergraduate students have been critically assessed

Evolución al alta de pacientes con Infecciones Nosocomiales de Terapia Intensiva

Introducción: El 5 al 30 % de pacientes infectados en terapia intensiva se complican, fallecen en sala o reingresan. Objetivos: Determinar mortalidad, complicaciones, riesgo de mortalidad en este grupo de pacientes al alta hospitalaria. Materiales y métodos: Estudio descriptivo y de casos y controles, entre Julio 1999 - Diciembre 2004. Incluidos pacientes con infecciones nosocomiales, trasladados a salas de internación. Análisis de casos y controles para factores de riesgo de mortalidad. Resultados en porcentajes y medias con OR y DE, p < 0,05 significativa. Resultados: Evaluados 71 pacientes, presentando 110 infecciones. Complicaciones en sala (41) en 37 pacientes (52,1%), antes del 5º día 43,9%. Complicaciones infecciosas 24 (58,5%): neumonías 29 %, infecciones urinarias 29%. Complicaciones no infecciosas 17 (42%): respiratorias 32,3%, cardiovasculares 23,5%. Reingresaron 10 pacientes (14,1%). De 61 pacientes no reingresados, fallecieron 8 (13,1%), antes del 4º día 37,5%. Las causas más frecuente de muerte (n=8) fueron infecciones (75%). El factor de riesgo para mortalidad: ≥ 65 años, OR 8,12(1,28-65,21); p =0,009. Conclusiones: Complicaciones en pacientes con infecciones nosocomiales de terapia intensiva transferidos a salas de internación son frecuentes, precoces y predominantemente infecciosas. Mortalidad y reingresos bajos. Edad avanzada es factor de riesgo relacionado con la mortalidad

Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.

Glomerular planted antigens (histones,DNA,andC1q) arepotential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patientswith LN. Prevalent antibody isotypes were defined, levelswere determined, and glomerular colocalization was investigated. Renal and circulating antibodieswerematched, and serum levelswere compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (antia-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti a-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and antia-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. We used everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to EGFR inhibitors, both in vitro and in vivo. We demonstrated that everolimus is active against EGFR-resistant cancer cell lines and partially restores the ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the expression of EGFR-related signalling effectors and VEGF production, inhibiting proliferation and capillary tube formation of endothelial cells, both alone and in combination with gefitinib. Finally, combination of everolimus and gefitinib inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts, activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with everolimus overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting

Preventable hospitalization and access to primary health care in an area of Southern Italy

<p>Abstract</p> <p>Background</p> <p>Ambulatory care-sensitive conditions (ACSC), such as hypertension, diabetes, chronic heart failure, chronic obstructive pulmonary disease and asthma, are conditions that can be managed with timely and effective outpatient care reducing the need of hospitalization. Avoidable hospitalizations for ACSC have been used to assess access, quality and performance of the primary care delivery system. The aims of this study were to quantify the proportion of avoidable hospital admissions for ACSCs, to identify the related patient's socio-demographic profile and health conditions, to assess the relationship between the primary care access characteristics and preventable hospitalizations, and the usefulness of avoidable hospitalizations for ACSCs to monitor the effectiveness of primary health care.</p> <p>Methods</p> <p>A random sample of 520 medical records of patients admitted to medical wards (Cardiology, Internal Medicine, Pneumology, Geriatrics) of a non-teaching acute care 717-bed hospital located in Catanzaro (Italy) were reviewed.</p> <p>Results</p> <p>A total of 31.5% of the hospitalizations in the sample were judged to be preventable. Of these, 40% were for congestive heart failure, 23.2% for chronic obstructive pulmonary disease, 13.5% for angina without procedure, 8.4% for hypertension, and 7.1% for bacterial pneumonia. Preventable hospitalizations were significantly associated to age and sex since they were higher in older patients and in males. The proportion of patients who had a preventable hospitalization significantly increased with regard to the number of hospital admissions in the previous year and to the number of patients for each primary care physician (PCP), with lower number of PCP accesses and PCP medical visits in the previous year, with less satisfaction about PCP health services, and, finally, with worse self-reported health status and shorter length of hospital stay.</p> <p>Conclusion</p> <p>The findings from this study add to the evidence and the urgency of developing and implementing effective interventions to improve delivery of health care at the community level and provided support to the usefulness of avoidable hospitalizations for ACSCs to monitor this process.</p

Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

BACKGROUND: High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. METHODS: Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m(2)/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m(2)/d IV 5 days/week × 4 weeks followed by 10 MU/m(2 )subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. RESULTS: The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m(2)/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m(2)/week) (p = 0.003). CONCLUSION: Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited

Carbon Nanotubes Enhance Cytotoxicity Mediated by Human Lymphocytes In Vitro

With the expansion of the potential applications of carbon nanotubes (CNT) in biomedical fields, the toxicity and biocompatibility of CNT have become issues of growing concern. Since the immune system often mediates tissue damage during pathogenesis, it is important to explore whether CNT can trigger cytotoxicity through affecting the immune functions. In the current study, we evaluated the influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The results showed that while CNT at low concentrations (0.001 to 0.1 µg/ml) did not cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated cytotoxicity against multiple human cell lines. In addition, CNT increased the secretion of IFN-γ and TNF-α by the lymphocytes. CNT also upregulated the NF-κB expression in lymphocytes, and the blockage of the NF-κB pathway reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results suggest that CNT at lower concentrations may prospectively initiate an indirect cytotoxicity through affecting the function of lymphocytes