Acidification and solar drying of manure-based digestate to produce improved fertilizing products.

The increase in energy and fertilizer consumption makes it necessary to develop sustainable alternatives for agriculture. Anaerobic digestion and digestates appeared to be suitable options. However, untreated digestates still have high water content and can increase greenhouse gas emissions during storage and land application. In this study, manure-derived digestate and solid fraction of digestate after separation were treated with a novel solar drying technology to reduce their water content, combined with acidification to reduce the gaseous emissions. The acidified digestate and acidified solid fraction of digestate recovered more nitrogen and ammonia nitrogen than their respective non-acidified products (1.5-1.3 times for TN; 14 times for TAN). Ammonia and methane emissions were reduced up to 94% and 72% respectively, compared to the non-acidified ones, while N2O increased more than 3 times. Dried digestate and dried acidified digestate can be labeled as NPK organic fertilizer regarding the European regulation, and the dried solid fraction and the improved dried acidified solid fraction can be labeled as N or P organic fertilizer. Moreover, plant tests showed that N concentrations in fresh lettuce leaves were within the EU limit with all products in all the cases. However, zinc concentration appeared to be a limitation in some of the products as their concentration exceeded the European legal limits.

COVID-19 vaccines and decreased transmission of SARS-CoV-2.

A massive COVID-19 vaccination campaign is underway worldwide. Epidemiological data from studies indicate excellent efficacy and safety profile for COVID-19 vaccines. However, there are few data from studies on the effect of decreasing the probability of infection of vaccinated subjects compared to unvaccinated subjects. In this short communication, we describe some evidence on this important and current topic providing useful personal reflections.

Neonatal alloimmune thrombocytopenia due to anti-HPA 5a in a HPA-5a homozygous neonate.

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Cases of FNAIT caused by HPA-5a antigen are extremely rare, and usually not severe. We report a case of FNAIT caused by anti-HPA antibodies directed to the HPA-5a antigen. The thrombocytopenia was moderate with a minimal platelet count of 36 × 109/L by day 3, and spontaneously resolved by day 10. The pregnancy had been obtained by in vitro fertilization using embryo donation, creating a complete genetic disparity between the HPA 5b5b mother and the HPA 5a5a homozygous neonate. The use of ART with gamete donation can increase the risk and the severity of alloimmune thrombocytopenia and must be considered in new and subsequent pregnancies.

Transglutaminase-mediated macromolecular assembly: production of conjugates for food and pharmaceutical applications.

Various strategies have been explored in the last 20 years to modify the functional properties of proteins and, among these, protein/polymer conjugation resulted one of the most successful approaches. Thus, the surface modification of polypeptides of potential industrial interest by covalent attachment of different macromolecules is nowadays regarded as an extremely valuable technique to manipulate protein activities. Protein derivatives with a number of either natural or synthetic polymers, like different polysaccharides or polyethylene glycol, have been obtained by both chemical and enzymatic treatments, and in this context, the crosslinking enzyme transglutaminase is attracting an increasing attention as a simple and safe means for protein processing in vitro. In this short review, we summarized the most significant experimental findings demonstrating that a microbial form of the enzyme is an effective tool to obtain several biopolymer-based conjugates potentially useful for both food and pharmaceutical applications.

Lung ultrasound protocol decreases radiation in newborn population without side effects: A quality improvement project.

OBJECTIVE: To reduce radiation exposure in newborns admitted due respiratory distress based on the implementation of lung ultrasound (LUS). DESIGN: Quality improvement (QI), prospective, before-after, pilot study. SETTING: Third level neonatal intensive care unit (NICU) level with 25-bed and 1800 deliveries/year. PATIENTS: Inclusion criteria were neonates admitted with respiratory distress. INTERVENTIONS: After a theoretical and practical LUS training a new protocol was approved and introduced to the unit were LUS was the first-line image. To study the effect of the intervention we compare two 6-month periods: group 1, with the previous chest X-ray (CXR)-protocol (CXR as the first diagnostic technique) vs. group 2, once LUS-protocol had been implemented. MAIN VARIABLES OF INTEREST: The main QI measures were the total exposure to radiation. Secondary QI were to evaluate if the LUS protocol modified the clinical evolution as well as the frequency of complications. RESULTS: 122 patients were included. The number of CXR was inferior in group 2 (group 1: 2 CXR (IQR 1-3) vs. Group 2: 0 (IQR 0-1), p<0.001), as well as had lower median radiation per baby which received at least one CXR: 56 iGy (IQR 32-90) vs. 30 iGy (IQR 30-32), p<0.001. Respiratory support was similar in both groups, with lower duration of non-invasive mechanical ventilation and oxygen duration the second group (p<0.05). No differences regarding respiratory development complications, length of stay and mortality were found. CONCLUSIONS: The introduction of LUS protocol in unit decreases the exposure radiation in infants without side effects.

Evaluating the efficacy of an avian-specific probiotic to reduce the colonization of Campylobacter jejuni in broiler chickens.

Campylobacteriosis is the most frequent zoonotic disease in humans worldwide, and the contaminated poultry meat by Campylobacter jejuni can be considered one of the important sources of enteric infections in humans. The use of probiotics, which can help to improve the natural defense of animals against pathogenic bacteria, is an alternative and effective approach to antibiotic administration for livestock to reduce bacterial contamination. In vitro experiments showed that Enterococcus faecium, Pediococcus acidilactici, Lactobacillus salivarius, and Lactobacillus reuteri isolated from healthy chicken gut inhibited the growth of C. jejuni. To demonstrate this effect in vivo, 1-d-old broiler chicks received 2 mg/bird per day of a multispecies probiotic product via the drinking water. Controls received no probiotic treatment, and all chicks were infected with C. jejuni orally. Results showed that the cecal colonization by C. jejuni was significantly reduced by probiotic treatment at both 8 and 15 d postchallenge. To confirm this effect, in a second in vivo experiment, 1-d-old broiler chicks received the same dose of the same probiotic via the drinking water and controls received no probiotic, and all chicks were infected with C. jejuni orally. Similarly, probiotic treatment reduced (P=0.001) cecal colonization by C. jejuni at both 8 and 15 d postchallenge. The results of our in vivo experiments conclude that probiotic administration reduced the colonization of C. jejuni in broiler chickens.

Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation.

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.

Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

The objective of the present study was to elaborate a survival model that integrates anatomic factors, according to the 2010 seventh edition of the tumour, node and metastasis (TNM) staging system, with clinical and molecular factors. Pathologic TNM descriptors (group A), clinical variables (group B), laboratory parameters (group C) and molecular markers (tissue microarrays; group D) were collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with complete resection. A multivariate analysis stepped supervised learning classification algorithm was used. The prognostic performance by groups was: areas under the receiver operating characteristic curve (C-index): 0.67 (group A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables together selected for each of the four groups (integrated group) the C-index was 0.74 (95% CI 0.70-0.79), with statistically significant differences compared with each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest prognostic discrimination were the presence of another ipsilobar nodule and tumour size > 3 cm, followed by other anatomical and clinical factors, and molecular expressions of phosphorylated mammalian target of rapamycin (phospho-mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A carboxylase. This study on early-stage NSCLC shows the benefit from integrating pathological TNM, clinical and molecular factors into a composite prognostic model. The model of the integrated group classified patients with significantly higher accuracy compared to the TNM 2010 staging.

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade.

The novel Coronavirus SARS-CoV-2 is the viral pathogen responsible for the ongoing global pandemic, COVID-19 (Coronavirus disease 2019). To date, the data recorded indicate 1.62 Mln deaths and 72.8 Mln people infected (WHO situation report Dec 2020). On December 27, the first anti-COVID-19 vaccinations started in Europe. There are no direct antivirals against SARS-CoV-2. Understanding the pathophysiological and inflammatory/immunological processes of SARS-CoV-2 infection is essential to identify new drug therapies. In the most severe COVID-19 cases, an unregulated immunological/inflammatory system results in organ injury that can be fatal to the host in some cases. Pharmacologic approaches to normalize the unregulated inflammatory/immunologic response is an important therapeutic solution. Evidence associates a non-regulation of the "complement system" as one of the causes of generalized inflammation causing multi-organ dysfunction. Serum levels of a complement cascade mediator, factor "C5a", have been found in high concentrations in the blood of COVID-19 patients with severe disease. In this article we discuss the correlation between complement system and COVID-19 infection and pharmacological solutions directed to regulate.

Swelling, mechanical, and barrier properties of albedo-based films prepared in the presence of phaseolin cross-linked or not by transglutaminase.

Edible films were obtained from Citrus paradisi grapefruit albedo homogenates and bean protein phaseolin modified or not by the enzyme transglutaminase. Swelling capability, barrier performance to water vapor, oxygen and carbon dioxide, and mechanical properties of such films were investigated. The addition of the protein, mostly in the presence of transglutaminase, provide films less swellable at pH values above 5 compared to films made by albedo homogenates only, whereas the action of the enzyme clearly improves mechanical properties producing more stretchable and elastic films. Moreover, transglutaminase-mediated cross-linking of phaseolin gives rise to films less permeable to carbon dioxide and able to offer a high barrier to water vapor. These findings suggest that albedo-phaseolin film prepared in the presence of transglutaminase can be a promising candidate to be used as food edible wrap.

Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.

BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

Sublobar resection for lung cancer.

Sublobar resection for small lung cancers has been debated frequently and is still a controversial issue. The only randomised trial comparing lobectomy with sublobar resections found a significantly higher recurrence rate for the latter, but failed to show significant differences in survival, although survival was better for the lobectomy group. One meta-analysis and several nonrandomised comparisons have confirmed these results. In general, lobectomy and sublobar resections have similar 5-yr survival rates. Local recurrence after wedge resection is higher than after segmentectomy. However, for patients aged >71 yrs, lobectomy and wedge resection are associated with similar survival. For tumours of /=1 cm wide to avoid recurrence. For pure bronchioloalveolar carcinoma of

Transglutaminase-mediated modifications of the rat sperm surface in vitro.

Two transglutaminase-mediated modifications of the rat epididymal spermatozoon surface were demonstrated in vitro. Transglutaminase was effective in promoting the binding of spermidine to the sperm. Moreover, the enzyme, by reacting with one of the major proteins secreted by the rat seminal vesicle epithelium, produced a modified form of the protein with a higher molecular weight and the capability of binding to the sperm cells. A specific physiological role for the enzyme, bringing about modifications of the rat sperm surface in the seminal fluid environment, is suggested.

tTGase/G alpha h protein expression inhibits adenylate cyclase activity in Balb-C 3T3 fibroblasts membranes.

Stably transfected Balb-C 3T3 fibroblasts (clone 5), overexpressing a catalytically active tissue transglutaminase, showed a basal adenylate cyclase activity lower than control cells (clone 1). Several modulators of the adenylate cyclase activity (forskolin, Mn2+ and pertussis toxin) showed the existence of a marked negative control on the adenylate cyclase activity present in clone 5 cells. Very interestingly, this same marked negative control was also found in a Balb-C 3T3 fibroblast clone stably transfected with a mutagenized human tissue transglutaminase (mut277 cys > ser) virtually devoid of transglutaminase catalytic activity (clone Ser). Conversely, a significant increase of the adenylate cyclase activity was observed in bovine aortic endothelial cells after the lowering of tissue transglutaminase expression levels by the transfection of an eukaryotic expression vector containing the gene for tissue transglutaminase in antisense orientation. All these findings suggest a possible role for type II tissue transglutaminase as a negative modulator of the adenylate cyclase activity in different cell types, beside its transglutaminase enzyme activity.

Recombinant human tissue transglutaminase produced into tobacco suspension cell cultures is active and recognizes autoantibodies in the serum of coeliac patients.

Human tissue transglutaminase (htTG) is one of the most important member within the transglutaminase family, enzymes that for their capacity of catalyzing post-translational modifications of proteins and peptides, rise an high interest for industrial applications. More recently, for its implication as the major autoantigen in the coeliac disease, availability of human tissue transglutaminase as recombinant form is required for accurate diagnostic tests. The aim of this study was to find an alternative and inexpensive source to produce human tissue transglutaminase. To date, plant systems are proposed as heterologous hosts to produce recombinant proteins for use in disease diagnosis and therapy. Here, we describe the stable expression of human tissue transglutaminase into Nicotiana tabacum cultured cells (cultivar Bright Yellow 2 (BY-2)). The recombinant enzyme was successfully expressed in different plant cell compartments and both apoplast (apo) and chloroplast (chl) purified proteins were shown to be catalytically active and able to bind GTP, a property possessed by the natural counterpart. Importantly, plant produced human tissue transglutaminase recognized autoantibodies in the serum of coeliac patients, suggesting possible applications in the diagnosis of coeliac disease.

Inhibitory effect of SV-IV, a major protein secreted from the rat seminal vesicle epithelium, on phagocytosis and chemotaxis of human polymorphonuclear leukocytes.

The effect of SV-IV, one of the major proteins secreted from the rat seminal vesicle epithelium, on phagocytosis and chemotaxis of human polymorphonuclear leukocytes (PMNs) has been studied. Various cytological, biochemical, metabolic, and physical correlates of both biological activities have been found to be markedly reduced by the presence in the medium of micromolar concentrations of protein SV-IV. Moreover, the Scatchard analysis of the labeled SV-IV binding to PMN cell surface has demonstrated that such binding is specific. The binding sites contain only saturable components, completely displaceable by unlabeled SV-IV. The number of the specific sites has been calculated to be 87,000/cell, with a Kd of 1.72 X 10(-7) M. The molecular mechanism of the inhibitory effect is discussed along with the possible biological and clinical implications of the experimental findings.

Surgical sealant for preventing air leaks after pulmonary resections in patients with lung cancer.

BACKGROUND: Postoperative air leak is a frequent complication after pulmonary resection for lung cancer. It may cause serious complications, such as empyema, or prolong the need for chest tube and hospitalisation. Surgical sealants of different types have been developed to prevent or to reduce postoperative air leaks. A systematic review was therefore undertaken to evaluate the evidence on their effectiveness. OBJECTIVES: To evaluate the effectiveness of surgical sealants in preventing or in reducing postoperative air leaks after pulmonary resection for lung cancer. SEARCH STRATEGY: The electronic databases MEDLINE (1966 to 2004), EMBASE (1974 to 2004), Cancerlit (1993 to 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3/2004) and listed references were searched, and handsearching of conference proceedings was conducted to identify published and unpublished trials. SELECTION CRITERIA: Randomised controlled clinical trials were included in which standard closure techniques plus a sealant were compared with the same intervention with no use of any sealant in patients undergoing elective pulmonary resection provided that a large proportion of the patients included in the studies had undergone pulmonary resection for lung cancer. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials to be included in the review, assessed methodological quality of each trial and extracted data using a standardised form. Because of several limitations, narrative synthesis was used at this stage. MAIN RESULTS: Twelve trials, with 1097 patients in total, were included. In eight trials there was a statistically significant difference between treatment and control patients in reducing postoperative air leaks. However this reduction only proved a significant reduction of hospital stay in one trial. Only in one trial reduction of time of chest drain removal and reduction of percentage of patient with persistent air leak were significantly smaller in the treatment group. AUTHORS' CONCLUSIONS: Although surgical sealants seem to reduce postoperative air leaks, length of hospitalisation is not affected and infectious complications may be increased. Therefore, systematic use of surgical sealants in clinical practice cannot be recommended at the moment. More randomised controlled clinical trials are needed.

Viral genotyping of infectious bursal disease viruses isolated from the 2002 acute outbreak in Spain and comparison with previous isolates.

An infectious bursal disease (IBD) outbreak occurred in the east region of Spain in the spring of 2002 and rapidly spread thorough the whole country, although proper vaccination programs were applied. In this report, 33 infectious bursal disease viruses (IBDVs) isolated from this outbreak were characterized by nucleotide sequencing of the VP2 gene hypervariable region and were compared with reference IBD strains and the 1990s Spanish IBDVs in order to determine possible emergence of IBDV isolates with modified antigenic or virulent properties. Moreover, histopathologic and immunohistochemical studies of those cases where bursal tissues were available were carried out. Of the 33 isolates, 23 were identified as very virulent IBDVs (vvIBDVs), whereas the other 10 isolates were classified as attenuated or intermediate virulence classical strains and could possibly be IBDV live vaccine strains used in the immunization of these chickens. Results of this study indicate that wIBDV isolates from the 2002 Spanish outbreak are closely related with those from the 1990s outbreak. However, acute IBD cases have not been reported in Spain during these 10 yr. Genetic, management, and environmental factors likely related with IBD reemergence in Spain are discussed. Moreover, our results indicate that good correlation exists between the IBDV subtype present in the field and the degree of lesions in bursa tissue, as well as the immunohistochemistry staining.