Microbial Biosurfactants: Antimicrobial Activity and Potential Biomedical and Therapeutic Exploits.

The rapid emergence of multidrug-resistant pathogens worldwide has raised concerns regarding the effectiveness of conventional antibiotics. This can be observed in ESKAPE pathogens, among others, whose multiple resistance mechanisms have led to a reduction in effective treatment options. Innovative strategies aimed at mitigating the incidence of antibiotic-resistant pathogens encompass the potential use of biosurfactants. These surface-active agents comprise a group of unique amphiphilic molecules of microbial origin that are capable of interacting with the lipidic components of microorganisms. Biosurfactant interactions with different surfaces can affect their hydrophobic properties and as a result, their ability to alter microorganisms' adhesion abilities and consequent biofilm formation. Unlike synthetic surfactants, biosurfactants present low toxicity and high biodegradability and remain stable under temperature and pH extremes, making them potentially suitable for targeted use in medical and pharmaceutical applications. This review discusses the development of biosurfactants in biomedical and therapeutic uses as antimicrobial and antibiofilm agents, in addition to considering the potential synergistic effect of biosurfactants in combination with antibiotics. Furthermore, the anti-cancer and anti-viral potential of biosurfactants in relation to COVID-19 is also discussed.

Integration of the National Comprehensive Cancer Network (NCCN) Distress Screening Tool as a Guidepost for Telephonic Oncology Case Management.

PURPOSE OF STUDY: Cigna's oncology case management programs identified the opportunity for case managers to integrate distress screening as recommended by the National Comprehensive Cancer Network (NCCN) in oncology populations. Our purpose in conducting this study was to quantify oncology case management program improvements as a result of using the NCCN Distress Screening Tool to guide telephonic case management. The program improvements we measured comprised more efficient identification of biopsychosocial problems and appropriate resource referrals. PRIMARY PRACTICE SETTING: Case managers in a large commercial health plan piloted integration of distress screening into telephonic case management among U.S. oncology customers experiencing a new diagnosis or care transition from September 2016 to April 2017. METHODOLOGY AND SAMPLE: A retrospective, matched case-control study was conducted among Cigna customers eligible for oncology case management. The pilot group of 317 received distress screening early in the oncology case management assessment. Outcomes included distress severity ranging from 0 to 10 (where 0 = no distress, 1-3 = mild, 4-7 = moderate, and 8-10 = severe), identification and number of biopsychosocial health problems, and percentage of direct resource referrals by case managers to supportive services. RESULTS: More than half (54%) of the screened customers reported mild or greater distress, and there was a strong correlation between degree of distress and average numbers of biopsychosocial health problems or direct resource referrals. Screened customers were 16% more likely to be referred to internal and external resources than customers not screened with the tool (66% vs. 50%, χp < .001). IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This study advances evidence-based oncology case management practice during care transitions by providing quantitative evidence for the utility of integrating the NCCN Distress Screening Tool into telephonic oncology case management. Using the tool (thermometer and problem list) to guide telephonic oncology case management and care coordination facilitated more tailored referrals to individuals with cancer enrolled in a large commercial health plan. On the basis of our findings, we integrated distress screening to address unmet biopsychosocial needs in patients with cancer.

Foreign bodies in sigmoid colon diverticulosis.

This review addresses the management of sigmoid colon diverticular disease associated with foreign bodies. In addition, two novel cases are presented. One case describes the management of diverticular bleeding secondary to a chicken bone and the other case reports retrieval of a retained EndoRings™ Device. The review identified 40 relevant publications including 50 subjects. Foreign bodies within sigmoid diverticular disease may be associated with inflammation, perforation, abscess and fistula. In current practice, diagnosis is often achieved with CT scan. Patients with colonic perforation or fistula generally require colonic resection. Patients with inflammation may merit conservative management, including colonoscopic foreign body retrieval. Chicken bones, tooth picks, and biliary stents have been reported in patients with inflammation, perforation and fistula, whereas all published patients with fish bone related diverticulosis complications experienced inflammation. Treatment might be best guided by the consequences of the foreign body rather than the nature of the underlying retained object. Diverticular bleeding secondary to a chicken bone was diagnosed at CT angiography and treated with colonoscopic snare retrieval of the bone and clipping of the bleeding diverticulum. The EndoRings™ Device was retrieved with a colonoscopic balloon.

Methylphenidate transdermal system: clinical applications for attention-deficit/hyperactivity disorder.

The methylphenidate transdermal system (MTS) provides a novel method of delivery for methylphenidate, a well-studied and effective medication for attention-deficit/hyperactivity disorder. The MTS achieves two major goals. First, the delivery system allows for administration throughout the day with a single patch, thus improving adherence. Second, it is the first approved attention-deficit/hyperactivity disorder medication that is not administered orally, thus bypassing gastrointestinal absorption and first-pass metabolism through the enteric circulation. In this article, we review the current data on MTS, including preclinical, clinical and post-marketing studies, and compare efficacy and tolerability to currently available treatments.

Effects of pesticide compounds (chlorothalonil and mancozeb) and benzo[a]pyrene mixture on aryl hydrocarbon receptor, p53 and ubiquitin gene expression levels in haemocytes of soft-shell clams (Mya arenaria).

The aim of this study is to investigate the effects of the pesticides/polycyclic aromatic hydrocarbon mixture on aryl hydrocarbon receptor (AhR), p53 and ubiquitin mRNA level in haemocytes of Mya arenaria exposed to a mixture of chlorothalonil, mancozeb and benzo[a]pyrene (BaP) for 48 and 72 h. AhR, p53 and ubiquitin gene expression levels were quantified using quantitative Real-time PCR. For robust and accurate quantification of transcripts, suitable housekeeping genes were selected from four sets of ribosomal and elongation factors transcripts previously sequenced from Mya arenaria using geNorm open source software. Quantitative Real-time PCR data exhibited a significantly high expression of AhR after 72 h of exposure (P ≤ 0.05). p53 gene expression seems to be up-regulated by the mixture after 48 h, however not significantly; but the level of p53 mRNA is down-regulated by the xenobiotics between 48 and 72 h after exposure. This study postulates that AhR mRNA levels could be used as an indicator of the exposure of clams' haemocytes to a mixture of xenobiotics such as chlorothalonil, mancozeb and BaP. However, further studies have to be pursued in order to unravel the molecular mechanisms involved in the p53 signaling pathway.

Induction of transposase and polyprotein RNA levels in disseminated neoplastic hemocytes of soft-shell clams: Mya arenaria.

In Prince Edward Island, a high mortality of soft-shell clams Mya arenaria was found to be related to the disease known as disseminated neoplasia (DN). However, the molecular mechanisms by which hemocytes of clams are transformed in the course of DN remain by far unknown. This study aims at identifying the transcripts involved in the development of the disease. Four subtractive cDNA sequence libraries were generated and more than 200,000 reads were obtained. Following similarity searches in genome databases, the transcripts were assigned to cellular functions including mitochondrial respiration, structural proteins, cytoskeleton, nucleic acid regulation, general metabolism, signal transduction, apoptosis, cell cycle regulation, as well as virus transcripts. The expression levels of transposase and polyprotein genes were evaluated in clams with various percentages of tetraploid hemocytes. Data have shown that expression levels were significantly higher in clams with a high percentage of tetraploid hemocytes. These results reinforce the hypothesis of endogenous retrotransposon involvement in the etiology of the disease. Further investigations are needed, however, to elucidate the role of transposase and polyprotein in the disease development.

Potential link between exposure to fungicides chlorothalonil and mancozeb and haemic neoplasia development in the soft-shell clam Mya arenaria: a laboratory experiment.

The aetiology of haemic neoplasia (HN) is unknown, so far but many causative factors are suggested such as viral, pollution and genetics. The aim of this study was to determine if, under chronic exposure, two major pesticides (chlorothalonil and mancozeb) which are used in potato production could induce HN in soft-shell clams (Mya arenaria). Short-term experiments with acute exposure were also performed. Clams were collected from an epizootic site (North River, PEI) and from a site free of the disease (Magdalen Islands, Quebec). The tetraploid level of haemocytes was assessed by flow cytometry for each clam to determine the HN status. The bioaccumulation of pesticides in tissues was quantified by gas chromatography/mass spectrometry (GC/MS) for chlorothalonil while mancozeb and manganese were quantified by inductively coupled plasma-mass spectrometer (ICP/MS). Long term exposure to fungicide Bravo 500((R)) did not induce high tetraploid levels on negative calm from North River and the analysis of the digestive gland and the mantle did not reveal any detectable level of chlorothalonil. In the Manzate 200 DF((R)), some clams revealed high level of tetraploid cells but no difference were observed between the treatments and the control. The analysis of the digestive gland and the mantle for manganese did not highlight any significant difference in tissue concentration (p=0.05). For the acute exposure, chlorothalonil analysis showed that the active ingredient is distributed between four chlorinated compounds: 99.5% for chlorothalonil isomers, 0.4% for pentachlorothalonil and 0.1% for trichlorothalonil isomers. For a 72 h experiment, the accumulation was within 4h; the higher tissue concentration of chlorothalonil was 59.2 microg g(-1) in the mantle after 48 h, following by a decrease to an undetectable level at the end. For the manganese, the accumulation was detected after 4h; the higher tissue concentration was 48.8 microg g(-1) in the mantle after 24h and, over the following 48 h, the accumulation decreased until the end of the trial. Based on the data, the accumulation of these fungicides seems to be transitory. Chlorothalonil and mancozeb are both oxidative-stress promoters and could have induced cell dysfunction while in the tissue. Study on the effect of these fungicides on the p53 protein system is an example of strategy that would provide information on cellular events promoting neoplasia.

Immunophenotyping of Mya arenaria neoplastic hemocytes using propidium iodide and a specific monoclonal antibody by flow cytometry.

Disseminated neoplasia (DN) is a disorder referred to as hemic neoplasia (HN) in the soft-shell clam Mya arenaria. Traditionally, diagnosis is performed by hematocytology or histology. The intensity of the disease is generally given as the percentage of transformed neoplastic cells out of total number of hemocytes. Flow cytometry techniques have found a field of application in diagnosis of HN with analysis of ploidy. Hemocytes of the soft-shell clams with HN display tetraploid DNA content, as shown by propidium iodide staining. This feature makes difficult HN diagnosis in the soft-shell clam, especially for early stages of the condition, since the percentage of normal circulating cells undergoing mitosis, which also are tetraploid, remains unknown in molluscs. Use of specific monoclonal antibodies in a flow cytometry assay was foreseen as a way to overcome the difficulty. The purpose of this study was to develop a double staining protocol using propidium iodide for hemocyte cycle analysis and the MAb 1E10 for staining of HN cells. Our results showed a correlation between tetraploid and MAb 1E10-stained hemocytes in a single clam with moderate HN. This protocol offers some potential for further investigation of this cell disorder. However, a validation step will be necessary to confirm our preliminary results.

Assessment of haemic neoplasia in different soft shell clam Mya arenaria populations from eastern Canada by flow cytometry.

Diagnosis of haemic neoplasia (HN) in the soft shell clam, Mya arenaria, is often achieved by hematocytology and histology. Since neoplastic cells display tetraploid DNA contents, haemocyte cell cycle analysis was developed for use as a diagnosis tool. The aim of this study was to assess the application of a flow cytometry procedure of cell cycle analysis established for the common cockle, to clams and to evaluate different thresholds of value for the percentage of tetraploid cells for establishing HN disease status of individual clams and clam populations. HN status of six clam populations from eastern Canada was determined. Results of the present study demonstrate a flow cytometry procedure to be useful for HN diagnosis in clams. Individual clams were considered to be affected by HN when presenting at least 20% of haemocytes in S-4N phase; and negative when presenting less that 5% of haemocytes in S-4N phase. As discussed in this paper, intermediate cases represent uncertain diagnoses including either false-negative or false-positive clams, which are difficult to discriminate. At a population level, an additional threshold of 15% for the mean intensity of the disease is proposed, which means having in the population several individual clams presenting more than 20% of their haemocytes in S-4N phase. Based on these thresholds of value, only one population was considered as free of HN disease, and one population was unequivocally affected by HN. For the four other clam populations, further investigations are needed toward development and use of specific and objective biomarkers of HN.

Antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene.

Infectious salmon anaemia virus (ISAV), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. Virus neutralization of 24 ISAV isolates in the TO cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (HA) genes have allowed elaboration on the variation of ISAV isolates. The 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one American and one European. Sequence analysis of the HA gene also revealed two groups of viruses (genotypes) that correlated with the antigenic groupings. The two HA subtypes had nucleotide sequence identity of only < or =79.4% and amino acid sequence identity of < or =84.5% whereas, within each subtype, the sequence identities were 90.7% or higher. This grouping was also evident upon phylogenetic analysis, which revealed two distinct phylogenetic families. Between the two groups, the amino acid sequence was most variable in the C-terminal region and included deletions of 4-16 amino acids in all isolates relative to ISAV isolate RPC/NB-980 280-2. In order to view the relationships among these sequences and the HA sequences of the established orthomyxoviruses, a second phylogenetic tree was constructed which showed the ISAV sequences to be more closely related to sequences from Influenzavirus A and Influenzavirus B than to sequences from Influenzavirus C and Thogotovirus. The extensive deletions in the gene of European ISAV isolates lead us to speculate that the archetypal ISAV was probably of Canadian origin.