Comparative profiling of biomarker psoralen in antioxidant active extracts of different species of genus Ficus by validated HPTLC method

Background: A simple but sensitive HPTLC method was developed for the comparative evaluation of psoralen in antioxidant active extracts of leaves of five different species of genus Ficus (Ficus carica, Ficus nitida, Ficus ingens, Ficus palmata and Ficus vasta).Materials and Methods: HPTLC studies were carried out using CAMAG HPTLC system on Glass-backed silica gel 60F254 HPTLC pre-coated plates using selected mobile phase toluene: methanol (9:1). The antioxidant activity was carried out, using DPPH free radical method.Results: Among all the five species of genus Ficus, F. palmata and F. carica exhibited comparatively good antioxidant activity in DPPH assay. The developed HPTLC method was found to give a compact spot for psoralen (Rf = 0.55±0.001) at 305 nm. The regression equation and r2 for psoralen was found to be Y= 4.516X+35.894 and 0.998. The quantification result revealed the presence of psoralen in only two species, F. carica (0.24%, w/w) and F. palmata (1.88%, w/w) which supported their supremacy for anti-oxidant potential over other species. The statistical analysis proved that the developed method was reproducible and selective.Conclusion: The developed method can be used as an important tool to assure the therapeutic dose of active ingredients in herbal formulations as well as for standardization and quality control of bulk drugs and in-process formulations. This method can also be employed for the further study of degradation kinetics and determination of psoralen in plasma and other biological fluids.Key words: Ficus species, psoralen, antioxidant, HPTLC, Validation

Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?

BACKGROUND: Leiomyomatosis peritonealis disseminata (LPD) is defined as the occurrence of multiple tumorous intraabdominal lesions, which are myomatous nodules. LPD is a rare disease with only about 100 cases reported. The usual course of LPD is benign with the majority of the patients being premenopausal females. Only two cases involving men have been reported, no syndrome or familial occurrence of LPD has been described. CASE PRESENTATION: We describe a Caucasian-American family in which six members (three men) are diagnosed with Leiomyomatosis peritonealis disseminata (LPD) and three deceased family members most likely had LPD (based on the autopsy reports). Furthermore we describe the association of LPD with Raynaud's syndrome and Prurigo nodularis. CONCLUSION: Familial clustering of Leiomyomatosis peritonealis disseminata (LPD) has not been reported so far. The etiology of LPD is unknown and no mode of inheritance is known. We discuss possible modes of inheritance in the presented case, taking into account the possibility of a genetic syndrome. Given the similarity to other genetic syndromes with leiomyomatosis and skin alterations, we describe possible similar genetic pathomechanisms

The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency

<p>Abstract</p> <p>Background</p> <p>Fumarate hydratase (HGNC approved gene symbol – <it>FH</it>), also known as fumarase, is an enzyme of the tricarboxylic acid (TCA) cycle, involved in fundamental cellular energy production. First described by Zinn <it>et al </it>in 1986, deficiency of FH results in early onset, severe encephalopathy. In 2002, the Multiple Leiomyoma Consortium identified heterozygous germline mutations of <it>FH </it>in patients with multiple cutaneous and uterine leiomyomas, (MCUL: OMIM 150800). In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839). The identification of FH as a tumor suppressor was an unexpected finding and following the identification of subunits of succinate dehydrogenase in 2000 and 2001, was only the second description of the involvement of an enzyme of intermediary metabolism in tumorigenesis.</p> <p>Description</p> <p>The <it>FH </it>mutation database is a part of the TCA cycle gene mutation database (formerly the succinate dehydrogenase gene mutation database) and is based on the Leiden Open (source) Variation Database (LOVD) system. The variants included in the database were derived from the published literature and annotated to conform to current mutation nomenclature. The <it>FH </it>database applies HGVS nomenclature guidelines, and will assist researchers in applying these guidelines when directly submitting new sequence variants online. Since the first molecular characterization of an <it>FH </it>mutation by Bourgeron <it>et al </it>in 1994, a series of reports of both FH deficiency patients and patients with MCUL/HLRRC have described 107 variants, of which 93 are thought to be pathogenic. The most common type of mutation is missense (57%), followed by frameshifts & nonsense (27%), and diverse deletions, insertions and duplications. Here we introduce an online database detailing all reported <it>FH </it>sequence variants.</p> <p>Conclusion</p> <p>The <it>FH </it>mutation database strives to systematically unify all current genetic knowledge of <it>FH </it>variants. We believe that this knowledge will assist clinical geneticists and treating physicians when advising patients and their families, will provide a rapid and convenient resource for research scientists, and may eventually assist in gaining novel insights into FH and its related clinical syndromes.</p

Highly sensitive active pixel image sensor array driven by large-area bilayer MoS2 transistor circuitry

Various large-area growth methods for two-dimensional transition metal dichalcogenides have been developed recently for future electronic and photonic applications. However, they have not yet been employed for synthesizing active pixel image sensors. Here, we report on an active pixel image sensor array with a bilayer MoS2 film prepared via a two-step large-area growth method. The active pixel of image sensor is composed of 2D MoS2 switching transistors and 2D MoS2 phototransistors. The maximum photoresponsivity (Rph) of the bilayer MoS2 phototransistors in an 8 7 8 active pixel image sensor array is statistically measured as high as 119.16 AW 121. With the aid of computational modeling, we find that the main mechanism for the high Rph of the bilayer MoS2 phototransistor is a photo-gating effect by the holes trapped at subgap states. The image-sensing characteristics of the bilayer MoS2 active pixel image sensor array are successfully investigated using light stencil projection

Salbutamol in acute organophosphorus insecticide poisoning - a pilotdose-response phase II study

Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation.We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60 min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to 'atropinization', atropine dose required, and mortality.Seventy-five patients were randomized to receive 5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10-16] min and 12.6 [8.0-13.4] mg, Salb2.5 15.0 [10-16] min and 12.6 [9.3-16.8] mg, and Salb5 15.0 [10-20] min and 12.6 [10.7-20.6] mg; p = .4805 and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group.This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning

Effective Treatment Strategies for the Removal of Antibiotic-Resistant Bacteria, Antibiotic-Resistance Genes, and Antibiotic Residues in the Effluent From Wastewater Treatment Plants Receiving Municipal, Hospital, and Domestic Wastewater: Protocol for a Systematic Review.

BACKGROUND: The widespread and unrestricted use of antibiotics has led to the emergence and spread of antibiotic-resistant bacteria (ARB), antibiotic-resistance genes (ARGs), and antibiotic residues in the environment. Conventional wastewater treatment plants (WWTPs) are not designed for effective and adequate removal of ARB, ARGs, and antibiotic residues, and therefore, they play an important role in the dissemination of antimicrobial resistance (AMR) in the natural environment. OBJECTIVE: We will conduct a systematic review to determine the most effective treatment strategies for the removal of ARB, ARGs, and antibiotic residues from the treated effluent disposed into the environment from WWTPs that receive municipal, hospital, and domestic discharge. METHODS: We will search the MEDLINE, EMBASE, Web of Science, World Health Organization Global Index Medicus, and ProQuest Environmental Science Collection databases for full-text peer-reviewed journal articles published between January 2001 and December 2020. We will select only articles published in the English language. We will include studies that measured (1) the presence, concentration, and removal rate of ARB/ARGs going from WWTP influent to effluent, (2) the presence, concentration, and types of antibiotics in the effluent, and (3) the possible selection of ARB in the effluent after undergoing treatment processes in WWTPs. At least two independent reviewers will extract data and perform risk of bias assessment. An acceptable or narrative synthesis method will be followed to synthesize the data and present descriptive characteristics of the included studies in a tabular form. The study has been approved by the Ethics Review Board at the International Centre for Diarrhoeal Disease Research, Bangladesh (protocol number: PR-20113). RESULTS: This protocol outlines our proposed methodology for conducting a systematic review. Our results will provide an update to the existing literature by searching additional databases. CONCLUSIONS: Findings from our systematic review will inform the planning of proper treatment methods that can effectively reduce the levels of ARB, ARGs, and residual antibiotics in effluent, thus lowering the risk of the environmental spread of AMR and its further transmission to humans and animals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33365

Metagenomic assessment of the diversity and ubiquity of antimicrobial resistance genes in Bangladeshi aquaculture ponds

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability: Raw sequencing reads were deposited in the ENA under BioProject PRJEB53918. Scripts for all bioinformatic processes are available on GitHub (https://github.com/ash-bell/Bangladesh_ARG_analysis/).In Bangladesh, fish provide over 60% of animal-source food with 56.2% of this coming from aquaculture produced predominantly in rural freshwater ponds. Increasing demand for fish products is driving intensification and resulting in higher disease prevalence, posing a risk to food security. Biosecurity is often absent in rural aquaculture practices in Bangladesh and antibiotics are commonly used to treat and prevent disease outbreaks. Antibiotics are often administered incorrectly - a key factor associated with the development of antimicrobial resistance (AMR). AMR can be disseminated rapidly within microbial ecosystems via mobile genetic elements, posing a risk for humans and animals infected with AMR pathogens as treatments with antibiotics become ineffective. Early AMR detection and understanding of the spread of antimicrobial resistance genes (ARGs) in rural aquaculture practices is critical for both food security, human health protection and food safety. Here, we apply a metagenomic approach to assess the ARG composition in pond water from six finfish (tilapia and pangasius) farms in the Mymensingh division of North-central Bangladesh. We found microbial communities within the ponds had similar alpha and beta diversities, with multiple ARGs predicted to confer resistance to eighteen different classes of antimicrobials. The most common ARGs conferred resistance to aminoglycosides and sulphonamides and were present in taxa associated with both fish and human pathogens. This ARG diversity potentially confers resistance to a wide variety of antibiotic classes and questions the effectiveness of current and future treatment of diseases with antibiotics in earthen aquaculture ponds. The microbial and ARG compositions between fish ponds within each farm were similar, which may relate to parallels in farming practices creating similar microbial selection pressures and thus comparable microbial populations. Without a more controlled approach towards antibiotic usage, we will inevitably further exacerbate the challenges in treating and preventing disease outbreaks as aquaculture production intensifies in Bangladesh.Biotechnology & Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC

The Segment Matters: Probable Reassortment of Tilapia Lake Virus (TiLV) Complicates Phylogenetic Analysis and Inference of Geographical Origin of New Isolate from Bangladesh

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability: The raw RNA-seq data are available in the NCBI Sequence Read Archive under BioProject number PRJNA604966. The assembled genome sequence of Bangladesh TiLV isolate BD-2017 is available in NCBI GenBank, accession numbers MN939372-MN939381 (segments 1–10). QualiMap output from genome assembly is Supplementary data 1 and on Figshare, Viruses 2020, 12, 258 5 of 17 10.6084/m9.figshare.11812143. Multiple sequence alignments of partial segments 1, 2, 3, 4 and 9 are available as Supplementary data 2 and on Figshare, doi:10.6084/m9.figshare.11617563. Multiple sequence alignments of full coding regions of all ten segments are available as Supplementary data 3 and on Figshare, doi:10.6084/m9.figshare.11617545. Results from each quartet analysis are available as Supplementary data 4 and on Figshare, doi:10.6084/m9.figshare.11625774.Tilapia lake virus (TiLV), a negative sense RNA virus with a 10 segment genome, is an emerging threat to tilapia aquaculture worldwide, with outbreaks causing over 90% mortality reported on several continents since 2014. Following a severe tilapia mortality event in July 2017, we confirmed the presence of TiLV in Bangladesh and obtained the near-complete genome of this isolate, BD-2017. Phylogenetic analysis of the concatenated 10 segment coding regions placed BD-2017 in a clade with the two isolates from Thailand, separate from the Israeli and South American isolates. However, phylogenetic analysis of individual segments gave conflicting results, sometimes clustering BD-2017 with one of the Israeli isolates, and splitting pairs of isolates from the same region. By comparing patterns of topological difference among segments of quartets of isolates, we showed that TiLV likely has a history of reassortment. Segments 5 and 6, in particular, appear to have undergone a relatively recent reassortment event involving Ecuador isolate EC-2012 and Israel isolate Til-4-2011. The phylogeny of TiLV isolates therefore depends on the segment sequenced. Our findings illustrate the need to exercise caution when using phylogenetic analysis to infer geographic origin and track the movement of TiLV, and we recommend using whole genomes wherever possible.Newton FundDepartment for International DevelopmentIndian Department of BiotechnologyBiotechnology and Biological Sciences Research Council (BBSRC)Economic and Social Research Council (ESRC