Methanol Conversion to Dimethyl Ether in Catalytic Zeolite Membrane Reactors

In this work, two ZSM-5 type zeolite supported membranes were used as catalytic membrane reactors for dimethyl ether (DME) synthesis via MeOH dehydration. The membranes, both commercial and tubular, had the same ZSM-5 zeolite layers, but a different support each (TiO2 and gamma-Al2O3) and were operated as contactors in through flow configuration. The performance of the two membrane reactors was analyzed as a function of the temperature (150-250 degrees C) and feed pressure (120-300 kPa), spanning a wide range of WHSV (1-13.3 g(MeOH) g(Catalyst)(-1) h(-1)) and feed composition (25-100%(mol) MeOH). The ZSM-5-Al2O3 membrane (Si/Al = 200; porosity of the zeolite layer = 0.2; thickness = 50 mu m; area = 50.6 cm(2)) exhibited always a greater conversion than ZSM-5-TiO2 (Si/Al = 200; porosity of the zeolite layer = 0.2; thickness = 63 mu m; area = 18.8 cm(2)), revealing an influence of the membrane support, correspondent to an additional catalytic effect induced by the Al2O3, which further enhanced the DME production. At 200 degrees C and 1 h(-1), this reactor achieved a MeOH conversion of 86.6 +/- 6.7%, very close to thermodynamic equilibrium conversion. In addition, both membrane reactors showed 100% DME selectivity

Evaluation of in vivo labelled dendritic cell migration in cancer patients

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with (99m)Tc-HMPAO or (111)In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20–60 min after inoculation and the maximum concentration was reached after 48–72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC

Extracellular Vesicles Derived from Endothelial Progenitor Cells Protect Human Glomerular Endothelial Cells and Podocytes from Complement- and Cytokine-Mediated Injury

Glomerulonephritis are renal inflammatory processes characterized by increased permeability of the Glomerular Filtration Barrier (GFB) with consequent hematuria and proteinuria. Glomerular endothelial cells (GEC) and podocytes are part of the GFB and contribute to the maintenance of its structural and functional integrity through the release of paracrine mediators. Activation of the complement cascade and pro-inflammatory cytokines (CK) such as Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) can alter GFB function, causing acute glomerular injury and progression toward chronic kidney disease. Endothelial Progenitor Cells (EPC) are bone-marrow-derived hematopoietic stem cells circulating in peripheral blood and able to induce angiogenesis and to repair injured endothelium by releasing paracrine mediators including Extracellular Vesicles (EVs), microparticles involved in intercellular communication by transferring proteins, lipids, and genetic material (mRNA, microRNA, lncRNA) to target cells. We have previously demonstrated that EPC-derived EVs activate an angiogenic program in quiescent endothelial cells and renoprotection in different experimental models. The aim of the present study was to evaluate in vitro the protective effect of EPC-derived EVs on GECs and podocytes cultured in detrimental conditions with CKs (TNF-α/IL-6) and the complement protein C5a. EVs were internalized in both GECs and podocytes mainly through a L-selectin-based mechanism. In GECs, EVs enhanced the formation of capillary-like structures and cell migration by modulating gene expression and inducing the release of growth factors such as VEGF-A and HGF. In the presence of CKs, and C5a, EPC-derived EVs protected GECs from apoptosis by decreasing oxidative stress and prevented leukocyte adhesion by inhibiting the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin). On podocytes, EVs inhibited apoptosis and prevented nephrin shedding induced by CKs and C5a. In a co-culture model of GECs/podocytes that mimicked GFB, EPC-derived EVs protected cell function and permeselectivity from inflammatory-mediated damage. Moreover, RNase pre-treatment of EVs abrogated their protective effects, suggesting the crucial role of RNA transfer from EVs to damaged glomerular cells. In conclusion, EPC-derived EVs preserved GFB integrity from complement- and cytokine-induced damage, suggesting their potential role as therapeutic agents for drug-resistant glomerulonephritis

Detection of patients with COVID-19 by the emergency medical services in Lombardy through an operator-based interview and machine learning models

BackgroundThe regional emergency medical service (EMS) in Lombardy (Italy) developed clinical algorithms based on operator-based interviews to detect patients with COVID-19 and refer them to the most appropriate hospitals. Machine learning (ML)-based models using additional clinical and geospatial epidemiological data may improve the identification of infected patients and guide EMS in detecting COVID-19 cases before confirmation with SARS-CoV-2 reverse transcriptase PCR (rtPCR).MethodsThis was an observational, retrospective cohort study using data from October 2020 to July 2021 (training set) and October 2021 to December 2021 (validation set) from patients who underwent a SARS-CoV-2 rtPCR test within 7 days of an EMS call. The performance of an operator-based interview using close contact history and signs/symptoms of COVID-19 was assessed in the training set for its ability to determine which patients had an rtPCR in the 7 days before or after the call. The interview accuracy was compared with four supervised ML models to predict positivity for SARS-CoV-2 within 7 days using readily available prehospital data retrieved from both training and validation sets.ResultsThe training set includes 264 976 patients, median age 74 (IQR 55-84). Test characteristics for the detection of COVID-19-positive patients of the operator-based interview were: sensitivity 85.5%, specificity 58.7%, positive predictive value (PPV) 37.5% and negative predictive value (NPV) 93.3%. Contact history, fever and cough showed the highest association with SARS-CoV-2 infection. In the validation set (103 336 patients, median age 73 (IQR 50-84)), the best-performing ML model had an AUC of 0.85 (95% CI 0.84 to 0.86), sensitivity 91.4% (95 CI% 0.91 to 0.92), specificity 44.2% (95% CI 0.44 to 0.45) and accuracy 85% (95% CI 0.84 to 0.85). PPV and NPV were 13.3% (95% CI 0.13 to 0.14) and 98.2% (95% CI 0.98 to 0.98), respectively. Contact history, fever, call geographical distribution and cough were the most important variables in determining the outcome.ConclusionML-based models might help EMS identify patients with SARS-CoV-2 infection, and in guiding EMS allocation of hospital resources based on prespecified criteria

Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy

Citrate high volume on-line hemodiafiltration modulates serum Interleukin-6 and Klotho levels: the multicenter randomized controlled study \u201cHephaestus

Background: Studies addressing the anti-inflammatory properties of citrate dialysate enrolled patients in both hemodialysis (HD) and hemodiafiltration (HDF), the latter not adjusted for adequate convective exchange. This is a potential source of confounding in that HDF itself has anti-inflammatory effects regardless of the buffer, and optimal clinical outcomes are related to the amount of convection. Methods: To distinguish the merits of the buffer from those of convection, we performed a 6-month, prospective, randomized, crossover AB-BA study. Comparisons were made during the 3-month study period of on-line HDF with standard dialysate containing three mmol of acetic acid (OL-HDFst) and the 3-month of OL-HDF with dialysate containing one mmol of citric acid (OL-HDFcit). Primary outcome measure of the study was interleukin-6 (IL-6). Klotho, high sensitivity C-reactive protein (hsCRP), fetuin and routine biochemical parameters were also analyzed. Results: We analyzed 47 patients (mean age 64 years, range 27-84 years) enrolled in 10 participating Nephrology Units. Convective volumes were around 25 L/session with 90 percent of sessions > 20 L and f2-microglobulin reduction rate 76% in both HDFs. Baseline median IL-6 values in OL-HDFst were 5.6 pg/ml (25:75 interquartile range IQR 2.9:10.6) and in OL-HDFcit 6.6 pg/ml (IQR 3.4:11.4 pg/ml). The difference was not statistically significant (p 0.88). IL-6 values were lower during OL-HDFcit than during OL-HDFst, both when analyzed as the median difference of overall IL-6 values (p 0.02) and as the median of pairwise differences between the baseline and the 3-month time points (p 0.03). The overall hsCRP values too, were lower during OL-HDFcit than during OL-HDFst (p 0.01). Klotho levels showed a time effect (p 0.02) and the increase was significant only during OL-HDFcit (p 0.01). Conclusions: Citrate buffer modulated IL-6, hsCRP and Klotho levels during high volume OL-HDF. These results are not attributable to differences in the dialysis schedule and may suggest a potential anti-inflammatory and anti-senescent effect of citrate even in dialysis patients with low grade inflammatio

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics

Tuberculosis Diagnostics and Biomarkers: Needs, Challenges, Recent Advances, and Opportunities

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostic

Taking forward the Stop TB Partnership and World Health Organization joint theme for World TB Day March 24th 2018 - "Wanted: Leaders for a TB-Free World. You can make history. End TB"

World TB Day, March 24th commemorates the day in March 1882 when Professor Robert Koch made the groundbreaking announcement in Berlin of his discovery of Mycobacterium tuberculosis as the cause of Tuberculosis (TB) (Koch, 1882). At the time of his announcement, there was a deadly TB epidemic, rampaging throughout Europe and the Americas, causing the death of one out of every seven people. Since Koch’s announcement, Mycobacterium tuberculosis has defied worldwide efforts by public health systems, researchers, governments and the World Health Organization (WHO) to eradicate it. The data presented in the WHO Global TB Report 2017 (World Health Organization, 2017a) makes very gruesome reading. In 2016 there were an estimated 10.4 million people who developed TB disease worldwide, of which 90% were adults, 35% female and 10% were HIV-co-infected people. An estimated 40% of active TB cases go undiagnosed each year. One hundred and thirty-six years since Koch’s announcement, TB remains a major global public health issue and TB has surpassed HIV/AIDS and malaria as the world’s top cause of death from an infectious disease! On World TB Day, March 24th, 2018, we need to reflect on the current status quo of the continuing devastating global TB epidemic

Accuracy of Immunodiagnostic Tests for Active Tuberculosis Using Single and Combined Results: A Multicenter TBNET-Study

The clinical application of IFN-gamma release assays (IGRAs) has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET) we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD) 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia) and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK)