Search

People's subjective response to any thermal environment is commonly investigated by using rating scales describing the degree of thermal sensation, comfort, and acceptability. Subsequent analyses of results collected in this way rely on the assumption that specific distances between verbal anchors placed on the scale exist and that relationships between verbal anchors from different dimensions that are assessed (e.g. thermal sensation and comfort) do not change. Another inherent assumption is that such scales are independent of the context in which they are used (climate zone, season, etc.). Despite their use worldwide, there is indication that contextual differences influence the way the scales are perceived and therefore question the reliability of the scales’ interpretation. To address this issue, a large international collaborative questionnaire study was conducted in 26 countries, using 21 different languages, which led to a dataset of 8225 questionnaires. Results, analysed by means of robust statistical techniques, revealed that only a subset of the responses are in accordance with the mentioned assumptions. Significant differences appeared between groups of participants in their perception of the scales, both in relation to distances of the anchors and relationships between scales. It was also found that respondents’ interpretations of scales changed with contextual factors, such as climate, season, and language. These findings highlight the need to carefully consider context-dependent factors in interpreting and reporting results from thermal comfort studies or post-occupancy evaluations, as well as to revisit the use of rating scales and the analysis methods used in thermal comfort studies to improve their reliability.

The use of personal fans allows improving thermal comfort and energy savings in warm office spaces. This is due to individual adjustment and extended indoor temperature acceptability. However, to achieve that, the usability of fans must be assured. Therefore, an experiment with 40 people of various age groups was carried out to assess four types of fans, one of which is an evaporative cooling device. The goal was to find out which criteria should be used for selecting a fan to implement in an office space. Results show that airflow sensation and speed adjustment are considered the most important, although, noise is also very important, and cost can be an eliminatory criterion. The evaporative device was the best rated even in a space with 70 to 80% relative humidity, as users considered it to have a smooth controllable airflow. The results highlight these aspects should be considered in the selection of a personal fan and could also drive the industry to improve fans design for increasing usability and expanding the use of these systems. [ABSTRACT FROM AUTHOR]

The continuous outbreak of drug-resistant bacterial and viral infections imposes the need to search for new drug candidates. Natural products from marine bacteria still inspire the design of pharmaceuticals. Indeed, marine bacteria have unique metabolic flexibility to inhabit each ecological niche, thus expanding their biosynthetic ability to assemble unprecedented molecules. The One-Strain-Many-Compounds approach and tandem mass spectrometry allowed the discovery of a Shewanella aquimarina strain as a source of novel imidazolium alkaloids via molecular networking. The alkaloid mixture was shown to exert bioactivities such as: (a) antibacterial activity against antibiotic-resistant Staphylococcus aureus clinical isolates at 100 µg/mL, (b) synergistic effects with tigecycline and linezolid, (c) restoration of MRSA sensitivity to fosfomycin, and (d) interference with the biofilm formation of S. aureus 6538 and MRSA. Moreover, the mixture showed antiviral activity against viruses with and without envelopes. Indeed, it inhibited the entry of coronavirus HcoV-229E and herpes simplex viruses into human cells and inactivated poliovirus PV-1 in post-infection assay at 200 µg/mL. Finally, at the same concentration, the fraction showed anthelminthic activity against Caenorhabditis elegans , causing 99% mortality after 48 h. The broad-spectrum activities of these compounds are partially due to their biosurfactant behavior and make them promising candidates for breaking down drug-resistant infectious diseases.

Staphylococcus aureus is a Gram-positive opportunistic human pathogen responsible for severe infections and thousands of deaths annually, mostly due to its multidrug-resistant (MDR) variants. The cell membrane has emerged as a promising new therapeutic target, and lipophilic molecules, such as biosurfactants, are currently being utilized. Herein, we evaluated the antimicrobial activity of a rhamnolipids mixture produced by the Antarctic marine bacterium Pseudomonas gessardii M15. We demonstrated that our mixture has bactericidal activity in the range of 12.5-50 µg/mL against a panel of clinical MDR isolates of S. aureus , and that the mixture eradicated the bacterial population in 30 min at MIC value, and in 5 min after doubling the concentration. We also tested abilities of RLs to interfere with biofilm at different stages and determined that RLs can penetrate biofilm and kill the bacteria at sub-MICs values. The mixture was then used to functionalize a cotton swab to evaluate the prevention of S. aureus proliferation. We showed that by using 8 µg of rhamnolipids per swab, the entire bacterial load is eradicated, and just 0.5 µg is sufficient to reduce the growth by 99.99%. Our results strongly indicate the possibility of using this mixture as an additive for wound dressings for chronic wounds.

The production and disposal of plastics from limited fossil reserves, has prompted research for greener and sustainable alternatives. Polyhydroxyalkanoates (PHAs) are biocompatible, biodegradable, and thermoprocessable polyester produced by microbes. PHAs found several applications but their use is limited due to high production cost and low yields. Herein, for the first time, the isolation and characterization of Pseudohalocynthiibacter aestuariivivens P96, a marine bacterium able to produce surprising amount of PHAs is reported. In the best growth condition P96 was able to reach a maximum production of 4.73 g/L, corresponding to the 87 % of total cell dry-weight. Using scanning and transmission microscopy, lab-scale fermentation, spectroscopic techniques, and genome analysis, the production of thermoprocessable polymer Polyhydroxybutyrate P(3HB), a PHAs class, endowed with mechanical and thermal properties comparable to that of petroleum-based plastics was confirmed. This study represents a milestone toward the use of this unexplored marine bacterium for P(3HB) production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Although several antibiotics are already widely used against a large number of pathogens, the discovery of new antimicrobial compounds with new mechanisms of action is critical today in order to overcome the spreading of antimicrobial resistance among pathogen bacteria. In this regard, marine organisms represent a potential source of a wide diversity of unique secondary metabolites produced as an adaptation strategy to survive in competitive and hostile environments. Among the multidrug-resistant Gram-negative bacteria, Pseudomonas aeruginosa is undoubtedly one of the most important species due to its high intrinsic resistance to different classes of antibiotics on the market and its ability to cause serious therapeutic problems. In the present review, we first discuss the general mechanisms involved in the antibiotic resistance of P. aeruginosa . Subsequently, we list the marine molecules identified up until now showing activity against P. aeruginosa , dividing them according to whether they act as antimicrobial or anti-virulence compounds.

Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas . Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes' survival by mediating biofilm formation and virulence. In this review, we reorganize the information produced in recent years regarding PVDs biosynthesis and pathogenic mechanisms, since PVDs are extremely valuable compounds. Additionally, we summarize the therapeutic applications deriving from the PVDs' use and focus on their role as therapeutic target themselves. We assess the current biotechnological applications of different sectors and evaluate the state-of-the-art technology relating to the use of synthetic biology tools for pathway engineering. Finally, we review the most recent methods and techniques capable of identifying such molecules in complex matrices for drug-discovery purposes.

Emerging and re-emerging viruses represent a serious threat to human health at a global level. In particular, enveloped viruses are one of the main causes of viral outbreaks, as recently demonstrated by SARS-CoV-2. An effective strategy to counteract these viruses could be to target the envelope by using surface-active compounds. Rhamnolipids (RLs) are microbial biosurfactants displaying a wide range of bioactivities, such as antibacterial, antifungal and antibiofilm, among others. Being of microbial origin, they are environmentally-friendly, biodegradable, and less toxic than synthetic surfactants. In this work, we explored the antiviral activity of the rhamnolipids mixture (M15RL) produced by the Antarctic bacteria Pseudomonas gessardii M15 against viruses belonging to Coronaviridae and Herpesviridae families. In addition, we investigated the rhamnolipids' mode of action and the possibility of inactivating viruses on treated surfaces. Our results show complete inactivation of HSV-1 and HSV-2 by M15RLs at 6 µg/mL, and of HCoV-229E and SARS-CoV-2 at 25 and 50 µg/mL, respectively. Concerning activity against HCoV-OC43, 80% inhibition of cytopathic effect was recorded, while no activity against naked Poliovirus Type 1 (PV-1) was detectable, suggesting that the antiviral action is mainly directed towards the envelope. In conclusion, we report a significant activity of M15RL against enveloped viruses and demonstrated for the first time the antiviral effect of rhamnolipids against SARS-CoV-2.

A catchment model for river basins and a hydrodynamic model were combined in order to simulate the spreading of the turbidity plume produced by sediment discharges from the Guadalquivir River basin within the Gulf of Cádiz under different meteorological conditions. The current fields provided by the hydrodynamic model and a transport-diffusion scheme based on tracking virtual particles tracking released at the river mouth have enabled us to simulate turbidity plumes that show great similarity with the plumes observed in satellite images. The most relevant results of the study show that in the absence of winds, the plume tends to spread very slowly, gradually progressing northwards; this is because of the symmetry between the filling and draining flows at the mouth of the Guadalquivir and low intensity of the tidal currents beyond the mouth. In addition, the transport of the plume towards the Strait of Gibraltar requires wind conditions with a northerly, north-westerly or westerly component. Westwards transport, however, requires winds with an easterly, southerly, or south-easterly component. The periods of heaviest rainfall in the Guadalquivir River basin coincide with winds mainly from the west; therefore, the times of maximum discharge at the mouth of the river occur when there are wind conditions that favour the transport of the matter suspended in the plume, southwards along the coast, towards the Strait of Gibraltar and the Alboran Sea. Linking the watershed catchment and hydrodynamic models has proved its suitability to predict the evolution and reaching of the sediment plumes from the Guadalquivir River discharges and the experience encourages the use of that methodology to be applied in a future prediction system for the creation and evolution of those sediment plumes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.

Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 μg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines.

Extreme marine environments are potential sources of novel microbial isolations with dynamic metabolic activity. Dietzia psychralcaliphila J1ID was isolated from sediments originated from Deception Island, Antarctica, grown over phenanthrene. This strain was also assessed for its emulsifying activity. In liquid media, Dietzia psychralcaliphila J1ID showed 84.66% degradation of phenanthrene examined with HPLC-PDA. The identification of metabolites by GC-MS combined with its whole genome analysis provided the pathway involved in the degradation process. Whole genome sequencing indicated a genome size of 4,216,480 bp with 3961 annotated genes. The presence of a wide range of monooxygenase and dioxygenase, as well as dehydrogenase catabolic genes provided the genomic basis for the biodegradation. The strain possesses the genetic compartments for a wide range of toxic aromatic compounds, which includes the ben ABCD and cat ABC clusters. COG2146, COG4638, and COG0654 through COG analysis confirmed the genes involved in the oxygenation reaction of the hydrocarbons by the strain. Insights into assessing the depletion of phenanthrene throughout the incubation process and the genetic components involved were obtained. This study indicates the degradation potential of the strain, which can also be further expanded to other model polyaromatic hydrocarbons.

Summary: Introduction. The formulation of the suitability for risk assessment from exposure to ionizing radiation in workers diagnosed with malignant tumor disease entails important implications of a professional, human, social, but also medical-legal, nature. By now, the management of such situations is an event anything but infrequent in the activity of the Authorized Physician: the increase in the number of people staying in wore and the rise in the incidence and prevalence of malignant neoplastic diseases in the working-age population make the problem more relevant than ever. This is not only because of the improvement of the diagnostic and treatment capacity but also for the increased survival that follows from them. The result is therefore an increase in the cases that can potentially reach the antention of the Authorized Physician/Competent Physician who - in compliance with the provisions of current legislation - will be thus called to express the suitability assessment for the specific task by applying criteria that respect the highest and current scientific evidence in this field. Materials and Methods. Through the guided illustration of two clinical cases, it is intended to propose here a - practical and reasoned - path towards the formulation of the assessment on the occupational reintegration of the worker with diagnosis of neoplastic disease. This methodology is applied and developed through the systematic recourse to objective and specific orientation criteria, able to guide the decision-making process of the Authorized Doctor/Competent Doctor. Results. The proposed criteria were applied to workers operating in the healthcare sector and assigned to different types of activities who were at risk from exposure to ionizing sources. Conclusions. The proposed evaluation path is intended to represent a clinical and rational methodology of approach and management to the problem of assessing the suitability of workers with previous neoplastic diseases, all that by fully safeguarding the decision-making autonomy - variable from case to case - which is characteristic of the activity of the Authorized Physician/Competent Physician., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by GIMLE.)

Summary: The term monoclonal gammopathy refers to a clinical condition characterized by the presence in serum and/or urine of clonal immunoglobulins, i.e. homogeneous immunoglobulins, structurally identical both as a heavy chain and as a light chain, produced by a B cell clone (1). The prevalence of MGUS is low in young subjects (less than 2% of patients with MGUS are less than 40 years of age, while in the population aged over 50 years it is relatively high (3.2%) and increases considerably with age. Although historically considered to be a benign condition, patients with MGUS are at risk to develop multiple myeloma over time. Therefore, MGUS may be framed as a preneoplastic stage of the plasma cell that precedes the possible development of a multiple myeloma. In a limited percentage of cases, it can be considered the asymptomatic pre-malignant stage preceding multiple myeloma (MM) on a probabilistic basis. Few studies have assessed the prevalence of MGUS in people occupationally exposed to pesticides. Several other studies on atomic bomb survivors in Hiroshima and Nagasaki have revealed a possible association with exposure to ionizing radiation (IR). Routine laboratory tests performed on the subjects exposed to the risk factors studied appear to be indicated for workers from the age of 50 years. The finding of a GMUS in the absence of further laboratory alterations is the most frequent finding and does not require further action, if it is not to plan include blood chemistry tests at least every two years. In this situation, no restrictions appear to be justified on the work activity involving the risk of exposure to IR or pesticides. In case of concurrent presence of alterations that may be indicative or suggestive of an increased risk of evolution in a neoplastic way a close periodicity - every 3-6 months - of haematological checks is recommended. In such cases, it appears justified to move away from activities involving exposure to ionizing radiation for a period of time which should be evaluated on the basis of the evolution of the picture and the progress of laboratory tests during the monitoring period., Competing Interests: The authors of this article have no conflict of interests to disclose., (Copyright© by GIMLE.)

The search for new approaches for developing antimicrobial surfaces is a challenge of great urgency to prevent and control microbial growth on surfaces. The strategy herein proposed relies on the design of a new, simple and general tool for creating antimicrobial surfaces, based on a hydrophobin chimeric protein which fuses the adhesive self-assembling class I hydrophobin Vmh2 from Pleurotus ostreatus to the human antimicrobial peptide LL-37. The recombinant LL37-Vmh2 protein displayed both the adhesive and the antimicrobic properties of its members, and when deposited on polystyrene surface, a positive effect due to the fusion was observed in terms of both efficacy and versatility of the coating. Indeed, the chimeric protein significantly enlarges the range of pathogens affected by Vmh2 layer rendering it able to inhibit three Gram-positive and two Gram-negative pathogens, selected among the renowned biofilm producer bacteria. Confocal Laser Scanning Microscopy analysis performed on Staphylococcus epidermidis biofilms formed on coated surfaces proved that, besides inhibiting biofilm formation, the LL37-Vmh2 coating also displayed biocidal activity, since dead cells were present in the biofilm layer. The reported results open new perspectives in various fields of application of LL37, and of antimicrobial peptides in general. LL37-Vmh2 increases the inventory of chimeric hydrophobins, further proving their effectiveness and versatility in surface functionalization., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The marine environment represents a prosperous existing resource for bioprospecting, covering 70% of the planet earth, and hosting a huge biodiversity. Advances in the research are progressively uncovering the presence of unknown microorganisms, which have evolved unique metabolic and genetic pathways for the production of uncommon secondary metabolites. Fungi have a leading role in marine bioprospecting since they represent a prolific source of structurally diverse bioactive metabolites. Several bioactive compounds from marine fungi have already been characterized including antibiotics, anticancer, antioxidants and antivirals. Nowadays, the search for natural antioxidant molecules capable of replacing those synthetic currently used, is an aspect that is receiving significant attention. Antioxidants can inactivate reactive oxygen and nitrogen species, preventing the insurgence of several degenerative diseases including cancer, autoimmune disorders, cardiovascular and neurodegenerative diseases. Moreover, they also find applications in different fields, including food preservation, healthcare and cosmetics. This review focuses on the production of antioxidants from marine fungi. We begin by proposing a survey of the available tools suitable for the evaluation of antioxidants, followed by the description of various classes of marine fungi antioxidants together with their extraction strategies. In addition, a view of the future perspectives and trends of these natural products within the "blue economy" is also presented.

The Gram-negative Pantoea eucrina D2 was isolated from the marine sponge Chondrosia reniformis . Sponges were collected in a shallow volcanic vents system in Ischia island (South Italy), influenced by CO 2 emissions and lowered pH. The chemical diversity of the secondary metabolites produced by this strain, under different culture conditions, was explored by a combined approach including molecular networking, pure compound isolation and NMR spectroscopy. The metabolome of Pantoea cf. eucrina D2 yielded a very complex molecular network, allowing the annotation of several metabolites, among them two biosurfactant clusters: lipoamino acids and surfactins. The production of each class of metabolites was highly dependent on the culture conditions, in particular, the production of unusual surfactins derivatives was reported for the first time from this genus; interestingly the production of these metabolites only arises by utilizing inorganic nitrogen as a sole nitrogen source. Major components of the extract obtained under standard medium culture conditions were isolated and identified as N-lipoamino acids by a combination of 1D and 2D NMR spectroscopy and HRESI-MS analysis. Assessment of the antimicrobial activity of the pure compounds towards some human pathogens, indicated a moderate activity of leucine containing N-lipoamino acids towards Staphylococcus aureus , Staphylococcus epidermidis and a clinical isolate of the emerging food pathogen Listeria monocytogenes .

Rhamnolipids (RLs) are surface-active molecules mainly produced by Pseudomonas spp. Antarctica is one of the less explored places on Earth and bioprospecting for novel RL producer strains represents a promising strategy for the discovery of novel structures. In the present study, 34 cultivable bacteria isolated from Edmonson Point Lake, Ross Sea, Antarctica were subjected to preliminary screening for the biosurfactant activity. The positive strains were identified by 16S rRNA gene sequencing and the produced RLs were characterized by liquid chromatography coupled to high resolution mass spectrometry (LC-HRESIMS) and liquid chromatography coupled with tandem spectrometry (LC-MS/MS), resulting in a new mixture of 17 different RL congeners, with six previously undescribed RLs. We explored the influence of the carbon source on the RL composition using 12 different raw materials, such as monosaccharides, polysaccharides and petroleum industry derivatives, reporting for the first time the production of RLs using, as sole carbon source, anthracene and benzene. Moreover, we investigated the antimicrobial potential of the RL mixture, towards a panel of both Gram-positive and Gram-negative pathogens, reporting very interesting results towards Listeria monocytogenes with a minimum inhibitory concentration (MIC) value of 3.13 µg/mL. Finally, we report for the first time the antimicrobial activity of RLs towards three strains of the emerging multidrug resistant Stenotrophomonas maltophilia with MIC values of 12.5 µg/ml., Competing Interests: The authors declare no conflict of interest.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.

Introduction: Primary malignant mixed mesodermal tumor (MMMt, also called malignant mixed Mullerian tumor and designated in the WHO classification of female genital tract neoplasms as carcinosarcoma) is an infrequent tumor that develops usually in the uterus and more rarely in the ovary. Extragenital tumor, including primary peritoneal MMMt, is an extremely rare and aggressive neoplasm with only few case reported in the literature., Presentation of Case: We report a case of a 70-year's old female who presented with nausea and abdominal discomfort for 6 months. Workup revealed an abdominal mass. Patient was treated with surgical removal in a general hospital., Discussion: Most peritoneal carcinosarcomas originate in the pelvic peritoneum, followed by decreasing frequency in the serosal surface of the colon, retroperitoneum, anterolateral abdominal peritoneum, and omentum. Surgical excision is the most effective treatment in carcinosarcomas. A complete cytoreduction, with resection of cancer to a status of no evidence of disease by the surgeon's unaided eye should be attempted., Conclusion: Owing to the rarity of the disease, limited data regarding the management of peritoneal MMMT exists. Recommendations for the treatment of MMMT are based on individual cases only. In our case, the patient is alive with a follow-up of 15 months and she did not receive any cycle of chemotherapy., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Acetaminophen (APAP) is an antipyretic analgesic drug that when taken in overdose causes depletion of glutathione (GSH) and hepatotoxicity. N-acetylcysteine (NAC) is the antidote of choice for the treatment of APAP toxicity; however, due to its short-half-life repeated dosing of NAC is required., Purpose: To determine whether a NAC-loaded liposomal formulation (Lipo-NAC) is more effective than the conventional NAC in protecting against acute APAP-induced hepatotoxicity., Methods: Male Sprague-Dawley rats were challenged with an intragastric dose of APAP (850 mg/kg b.wt.); 4 h later, animals were administered saline, NAC, Lipo-NAC or empty liposomes and sacrificed 24 h post-APAP treatment., Results: APAP administration resulted in hepatic injury as evidenced by increases in plasma bilirubin, alanine (AST) and aspartate (ALT) aminotransferase levels and tissue levels of lipid peroxidation and myeloperoxidase as well as decreases in hepatic levels of reduced GSH, GSH peroxidase and GSH reductase. Treatment of animals with Lipo-NAC was significantly more effective than free NAC in reducing APAP-induced hepatotoxicity. Histological evaluation showed that APAP caused periacinar hepatocellular apoptosis and/or necrosis of hepatocytes around the terminal hepatic venules which was reduced by NAC treatment, the degree of reduction being greater for Lipo-NAC., Conclusion: These data suggest that administration of Lipo-NAC ameliorated the APAP-induced hepatotoxicity.

Background: The toxicity of ricin resides in the ricin A-chain (RTA) and is attributed to the inhibition of protein synthesis but inflammation and oxidative stress have also been implicated. RTA can independently enter cells producing comparable tissue injury and inflammation, although at much higher concentrations than intact ricin. Treatment for exposure to ricin or RTA is supportive., Purpose: To examine the effectiveness of conventional or liposome-encapsulated N-acetylcysteine (Lipo-NAC) in ameliorating RTA-induced hepatotoxicity., Methods: Four hours after RTA administration (90 µg/kg b.wt, iv), rats were treated with conventional NAC or Lipo-NAC (25 mg/kg NAC). The hepatoprotective effects of the antioxidant formulations were assessed by measuring indexes for liver injury (alanine [ALT] and aspartate [AST] aminotransferase activities), inflammation (myeloperoxidase, tumor necrosis factor-α, chloramine levels), and oxidant response (lipid peroxidation, nitrotyrosine, glutathione levels) 24-h post-RTA exposure., Results: Administration of RTA to animals resulted in hepatotoxicity as demonstrated by elevated plasma ALT and AST levels, increases in an inflammatory response, and increases in oxidant response. Treatment of animals with the antioxidant formulations reversed the RTA-induced hepatotoxicity, being most evident following the administration of Lipo-NAC., Conclusion: NAC, administered in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of RTA-induced liver injuries.

Introduction: The aim of the present work is to evaluate the efficacy and safety data used by the European Medicines Agency (EMEA) between 1995 and June 2006 to approve new immunosuppressive drugs with indications in solid organ transplantation., Materials and Methods: The information about the approval of new agents was retrieved mainly from the European Public Assessment Report (EPAR) and Summary of Product Characteristics (SPC) on the EMEA web site. The design, type of control, primary endpoints, duration of follow-up, and safety profile of pivotal trials were examined., Results: Four immunosuppressive drugs belonging to three different therapeutic classes, with different clinical uses, were identified. Not all pivotal clinical trials compared the investigational agent with cyclosporin/corticosteroid/azathioprine triple therapy, which was the best therapeutic option available at the time of approval. Acute rejection, graft survival and efficacy failure at 6 months or 1 year post-transplant were the most frequent endpoints. Although some of the new agents reduce calcineurin inhibitor-associated nephrotoxicity, their adverse cardiovascular profile is of particular concern., Discussion: Recent improvements in the short-term efficacy of immunosuppressive therapy make short-term outcome measures inadequate for predicting long-term clinical benefit. Clinical outcomes such as 3- or 5-year graft and patient survival should be used in clinical trials in order to take into account non-immunosuppressive-related morbidity and to assess better whether the therapeutic advantage of the new agents over standard therapy is maintained in the long term.

Epidemiological and experimental studies have indicated that consumption of more n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of diseases, including cardiovascular, neurological and immunological disorders, diabetes and cancer. This article focuses on the role of marine n-3 long-chain polyunsaturated fatty acids in brain functions, including the development of the central nervous system and neurological disorders. An overview of the major animal studies and clinical trials is provided here, focusing on fatty acid supplementation during pregnancy and infancy, and prevention and management of Alzheimer's disease, schizophrenia, depression and attention deficit hyperactive disorder. Although an optimal balance in n-3/n-6 long-chain polyunsaturated fatty acid ratio is important for proper neurodevelopment and cognitive functions, results from randomized controlled trials are controversial and do not confirm any useful effect of supplementation on development of preterm and term infants. The relationship between fatty acid status and mental disorders is confirmed by reduced levels of n-3 long-chain polyunsaturated fatty acids in erythrocyte membranes of patients with central nervous system disorders. Nevertheless, there are very little data supporting the use of fish oil in those patients. The only way to verify whether n-3 long-chain polyunsaturated fatty acids are a potential therapeutic option in the management and prevention of mental disorders is to conduct a large definitive randomized controlled trials similar to those required for the licensing of any new pharmacological treatment.

Background: The prevalence of diagnosed asthma and wheezing in young subjects is increasing; among environmental risk factors, occupational exposure can play a relevant role., Study Objectives: The purpose of the study was to evaluate the effects of occupational exposure to a large variety of irritants and/or sensitizers on the incidence of respiratory symptoms and pulmonary function impairment in a group of young apprentices during the first year of work exposure, and to determine the prevalence of asthma-like symptoms and the role of different risk factors (gender, smoking habit, atopy and occupational exposure) in this young population., Design and Methods: We studied 448 young apprentices at the first pre-employment evaluation with a standardized questionnaire, spirometry and skin prick tests; in 244 of them clinical and functional evaluation was repeated after 1 year exposure to respiratory irritants or sensitizers., Results: At the first examination, males had higher prevalence of attacks of shortness of breath with wheeze, diagnosis of asthma, smoking habit and atopy than females. At the second examination there was no significant increase in the prevalence of respiratory symptoms. However, incident cases for cough, phlegm, wheezing, shortness of breath with wheeze (SOBWHZ) and asthma were all higher than remittent cases. Incidence of respiratory symptoms was associated with atopy and smoking habit., Conclusions: Respiratory symptoms slightly increase over 1 year occupational exposure to sensitizers or irritants. The loss at the follow-up of subjects with higher smoking habit suggests a small "health worker effect" and could underestimate the effect of occupational exposure in apprentices.

Background: For a few years now in Italy there has been wide discussion on the advisability of developing health surveillance programmes for workers who were exposed to occupational carcinogens in the past (incompliance with Italian D.Lgs. 626/94, art. No. 69). The purpose of the present paper was to contribute to the discussion on operative guidelines for public or private Occupational Health Services intending to address this issue., Methods: A cross-sectional survey was undertaken on former workers of a glass factory located in Leghorn, Italy. Six hundred and seventy-seven workers discharged in the period 1/1/1942 - 30/6/1992, with at least 1 year of service, resident in the area of Leghorn, were identified from the personnel records of the company and invited to medical examination at the local public Occupational Health Service. A structured questionnaire was developed in order to standardize the collection of occupational and health histories., Results: 370 subjects were examined and for each of them occupational and health histories were collected. Occupational exposure to carcinogens in the factory in the last decades was reconstructed using the workers' occupational histories and the available plant records: 3 periods with different production activities (1942/49, 1950/69, 1970/92), and 4 main carcinogens (asbestos, PAH, silica and glass fibres) were identified. Thirty cancers were recorded and 10 of these were occupationally related., Conclusions: The health survey allowed occupational exposures to carcinogens to be defined in a factory where historical environmental data were not available. It was also possible to assess individual past occupational risk and provide information to each former worker on his risk, on available preventive measures, and on possible diagnostic, therapeutic and insurance procedures available in relation to diseases related to the different hazards. Via this survey it was also possible to identify and notify the Italian Institute of Insurance against Occupational Diseases and Accidents of 6 cases of bladder cancer, i.e., cancers with long survival that would be impossible to identify via current health data bases.

The authors report a case of a male 86 years old patient with peritoneal pseudomyxoma associated to cystoadenoma of the appendix. Preoperative CT scan showed the presence of a mass in the appendiceal site containing a gelatinous fluid collection and calcifications. Notwithstanding, diagnosis of pseudomyxoma was preoperatively considered less probable due to the rarity of the affection and the advanced age. At laparatomy was revealed the presence of the large mass observed at CT scan, involving the caecum and occupying the retroperitoneal space along the ascending colon. Mucinous ascites was present without invasive mucinous implants in the peritoneum. Operation consisted in a right hemicolectomy with total removal of the retroperitoneal mass and evacuation of the mucinous ascites. Histology confirmed the clinical diagnosis of pseudomyxoma peritonei associated to cystoadenoma of the appendix. The case is of paradigmatic interest as being quite correspondent to the classical Ronnett's definition of pseudomyxoma: a clinicopathological entity characterized by mucinous ascites and non-invasive mucinous implants with a characteristic distribution and containing histologically benign mucinous epithelium derived from an appendiceal mucinous adenoma and having a benign course. According to such definition, the authors stress the importance of an appropriate classification of the observed cases of pseudomyxoma, under whose term is often collected a heterogeneous group of pathological lesions, in order to better evaluate the prognosis and treatment.