Bioremediation of soil contaminated with toxic mixed reactive azo dyes by co-cultured cells of Enterobacter cloacae and Bacillus subtilis.

Azo dyes, known for its toxicity and mutagenicity, are used by textile industries. Bioremediation serves the best alternative treatment process due to its eco-friendly nature and cost-effectiveness. Degradation using individual bacteria promotes azo dye removal, while the degradation is enhanced using the immobilization method. Bio-carrier promotes the attachment of the bacterial strains and increases azo dye degradation. The present study focuses on the biodegradation of Reactive Red (RR), Reactive Brown (RB), Reactive Black dye (RBL), and mixed dyes in a soil slurry bioreactor containing free cells, co-culture, and immobilized cells. The physico-chemical analysis and soil characteristics were determined. The free cells of Bacillus cereus showed degradation of azo dyes - 79.42 ± 0.03% RR, 78.78 ± 0.02% RBL; 70.76 ± 0.03% RB, and 84.89 ± 0.05% of mixed dyes respectively. Enterobacter cloacae free cells resulted in degradation of 72.87 ± 0.01% RR, 75.21 ± 0.01% RBL, 74.50 ± 0.02% RB, and 73.39 ± 0.04% mixed dyes respectively. Co-cultured bacterial strains resulted in 77.18 ± 0.03% RR, 80.27 ± 0.02% RBL, 76.97 ± 0.02% RB and 86.29 ± 0.05% mixed dyes respectively. The immobilization of Bacillus cereus and Enterobacter cloacae on 2% corn starch resulted in 98.4 ± 0.01% degradation of RR, 89.8 ± 0.09% degradation of RB, 99.4 ± 0.05% of RBL, and 98.1 ± 0.08% of mixed reactive dyes respectively.

Effect of shape and anthocyanin capping on antibacterial activity of CuI particles.

The recent upsurge of antibiotic-resistant infections has posed to be a serious health concern worldwide. In the present paper, the effect of shape & capping agent on the antibacterial activity (on Skin and Urinary Tract Infection (UTI) causing bacteria) of copper iodide (CuI) particles was probed. CuI synthesized without a capping agent was leaf-like, and that with one was prismatic in shape. XRD of the synthesized CuI confirmed their high crystalline nature and purity. The average crystallite sizes of capped and uncapped CuI were calculated to be 91.10 nm and 89.01 nm respectively from X-Ray powder diffraction data. The average particle size of capped CuI was found to be 492.7 nm and that of uncapped CuI was found to be 2.96 µm using HR-SEM analysis. The crystals obtained were further characterized using EDAX, FTIR spectroscopy and UV-Visible spectroscopy. Antibacterial activity of prismatic CuI capped with the flower extract of Hibiscus rosa-sinensis showed better activity than that of uncapped CuI. AFM analysis was carried out to confirm the proposed mechanism for antibacterial activity through the morphological changes on the bacterial cell wall in the presence of capped CuI. Molecular docking studies were performed to reaffirm the enhanced antibacterial activity of prismatic CuI further. The present study demonstrates the superior antibacterial propensity of prismatic CuI, consequently making it a potent antibacterial agent.

Quality of Service Routing in Manet Using a Hybrid Intelligent Algorithm Inspired by Cuckoo Search.

A hybrid computational intelligent algorithm is proposed by integrating the salient features of two different heuristic techniques to solve a multiconstrained Quality of Service Routing (QoSR) problem in Mobile Ad Hoc Networks (MANETs) is presented. The QoSR is always a tricky problem to determine an optimum route that satisfies variety of necessary constraints in a MANET. The problem is also declared as NP-hard due to the nature of constant topology variation of the MANETs. Thus a solution technique that embarks upon the challenges of the QoSR problem is needed to be underpinned. This paper proposes a hybrid algorithm by modifying the Cuckoo Search Algorithm (CSA) with the new position updating mechanism. This updating mechanism is derived from the differential evolution (DE) algorithm, where the candidates learn from diversified search regions. Thus the CSA will act as the main search procedure guided by the updating mechanism derived from DE, called tuned CSA (TCSA). Numerical simulations on MANETs are performed to demonstrate the effectiveness of the proposed TCSA method by determining an optimum route that satisfies various Quality of Service (QoS) constraints. The results are compared with some of the existing techniques in the literature; therefore the superiority of the proposed method is established.

Comparison of Marginal Gap and Microleakage in Copy-Milled and Cad-Milled Zirconia Copings Bonded Using Light Cure and Chemical Cure Resin Bonding Systems.

This in vitro study assessed the marginal gap and marginal microleakage in zirconia copings fabricated using two computer aided techniques- CAD milling and Copy milling and cemented to respective tooth preparations using two resin bonding systems, light cure and self-cure resin bonding systems. 32 extracted premolars were prepared to receive zirconia copings fabricated using CAD/CAM and Copy milling techniques. Once the copings were fabricated, the samples were evaluated for marginal fit prior to cementation through microscopic observation. Evaluation of marginal gap was done again after cementation, in order to incorporate the influence of the resin bonding system on the marginal microgap. The specimens were evaluated under the stereomicroscope for micro-leakage using commercial software. A comparative statistical analysis was done following data collection using Mann-Whitney U test, Wilcoxon test and chi-square test. The data collected regarding marginal gap was well within 120 µ, which is in accordance with previous studies. However, Copy milled specimens showed statistically lesser marginal gap when compared to CAD milled specimens. While comparing microleakage, it was observed that the microleakage in Copy milled specimens bonded with light cure resin bonded cement was statistically lesser than that of specimens cemented with chemical cure resin cement.(P = 0.003). This in vitro study concluded that Copy milling technique fabricated zirconia restorations with lesser marginal gap and microleakage score in comparison to CAD milled samples. Light cure resin bonding system also proved to be more effective option compared to self cure resin bonding systems. However, the limitations of this study should be taken into concern and further research should be aimed at a larger sample size to validate the results.

Isolation, susceptibility profiles and genomic analysis of a colistin-resistant Salmonella enterica serovar Kentucky strain COL-R.

Salmonella enterica serovar Kentucky is a frequent cause for clinical infections in human patients. They are isolated and reported with multidrug resistance from the foods of animal origin from various countries. However, studies inferring the colistin resistance are limited. Hence, the current study reports the genetic factors and genomic analysis of the colistin-resistant Salmonella enterica serovar Kentucky strain COL-R for better understanding of its pathogenic potential and phylogenetic relatedness. The S. Kentucky strain COL-R was successfully isolated from chicken meat during ongoing surveillance of food of animal origin. Antimicrobial susceptibility testing revealed resistance to cefoxitin, erythromycin, gentamicin, tetracycline, and most disturbingly to ciprofloxacin and colistin (broth microdilution method). Whole-genome sequence of the COL-R strain was subjected to various in silico analysis to identify the virulence factors, antimicrobial resistance genes, pathogenicity islands and sequence type. The S. Kentucky COL-R strain belonged to sequence type (ST) 198 with a high probability (0.943) of being a human pathogen. Besides presence of integrated phage in the S. Kentucky COL-R genome, 38 genes conferring resistance to various antimicrobials and disinfectants were also identified. Nucleotide Polymorphism analysis indicated triple mutations in gyrA and parC genes conferring fluoroquinolone resistance. Phylogenomic analysis with 31 other S. Kentucky genomes revealed discernible clusters with S. Kentucky COL-R strain latching onto a cluster of high diversity (geographic location and isolation sources). Taken together, our results document the first occurrence of colistin resistance in a fluoroquinolone resistant S. Kentucky COL-R strain isolated from retail chicken and provide crucial information on the genomic features of the strain. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03559-2.

Palliative care management committees: a model of collaborative governance for primary health care.

SETTING: The community-based primary palliative care programme in Kerala, India, has received international acclaim. Programme functioning is supported through Palliative Care Management Committees (PMCs) at the local government (LG) level. OBJECTIVE: To study the functioning of the PMCs within the decentralised governance space to identify achievements, gaps and notable innovations. DESIGN: This qualitative study included seven key informant interviews (KIIs), 28 in-depth interviews and a review of relevant publicly available policies and documents. Major themes were recognised from the KII transcripts. Codes emerging from the document review and in-depth interview transcripts were mapped into the identified thematic areas. RESULTS: Successful PMCs raised resources like money, human resource, equipment, had good skilled care options for symptom relief and facilitated reduced out-of-pocket expenditure by providing home care and free medicines, and improved access to interventions that addressed the social determinants of suffering like poverty. PMCs had varying managerial and technical capacities. In some LGs, the programme was weak and mostly limited to the supply of medicines, basic aids and appliances to patients' homes. CONCLUSION: Despite varied implementation patterns, PMCs in Kerala are examples of state-supported, community-owned care initiatives, that can potentially address medical and social determinants of suffering.

CONTEXTE: Le programme communautaire de soins palliatifs primaires du Kérala, Inde, a été applaudi sur la scène internationale. Le fonctionnement du programme est soutenu par des Comités de gestion des soins palliatifs (PMC) au niveau des gouvernements locaux (LG). OBJECTIF: Évaluer le fonctionnement des PMC au sein de l'espace de gouvernance décentralisée, afin d'identifier les réussites, les lacunes et les principales innovations. MÉTHODES: Dans le cadre de cette étude qualitative, sept entretiens avec des informateurs clés (KIIs), 28 entretiens approfondis et une analyse des politiques et documents accessibles au public ont été réalisés. Les transcriptions des KII ont permis de faire émerger les thèmes principaux. Les codes émergeant de l'analyse documentaire et des transcriptions des entretiens approfondis ont été associés aux domaines thématiques identifiés. RÉSULTATS: Les PMC les plus performants ont pu mobiliser des ressources, telles que de l'argent, des ressources humaines ou des équipements. Ils proposaient également des options de soins de qualité pour soulager les symptômes, facilitaient la réduction des frais à la charge du patient en fournissant des soins à domicile et des médicaments gratuits, et ont permis d'améliorer l'accès aux interventions qui s'attaquaient aux déterminants sociaux de la souffrance, tels que la pauvreté. Les capacités techniques et de gestion variaient d'un PMC à l'autre. Le programme de certains LG était faible, principalement limité à la fourniture de médicaments et d'aides et de matériels de base pour le domicile des patients. CONCLUSION: Malgré des schémas de mise en œuvre variés, les PMC du Kérala sont des exemples d'initiatives communautaires de santé soutenues par l'état qui peuvent potentiellement s'attaquer aux déterminants sociaux et médicaux de la souffrance.

A comprehensive review on comparison among effluent treatment methods and modern methods of treatment of industrial wastewater effluent from different sources.

In recent years, rapid development in the industrial sector has offered console to the people but at the same time, generates numerous amounts of effluent composed of toxic elements like nitrogen, phosphorus, hydrocarbons, and heavy metals that influences the environment and mankind hazardously. While the technological advancements are made in industrial effluent treatment, there arising stretch in the techniques directing on hybrid system that are effective in resource recovery from effluent in an economical, less time consuming and viable manner. The key objective of this article is to study, propose and deliberate the process and products obtained from different industries and the quantity of effluents produced, and the most advanced and ultra-modern theoretical and scientific improvements in treatment methods to remove those dissolved matter and toxic substances and also the challenges and perspectives in these developments. The findings of this review appraise new eco-friendly technologies, provide intuition into the efficiency in contaminants removal and aids in interpreting degradation mechanism of toxic elements by various treatment assemblages.

Reverse Axillary Mapping in Breast Cancer Using Blue Dye: A Tertiary Setup Experience.

The concept of reverse axillary mapping originated with the main purpose of reducing lymphedema. In this study, we test the advantage of reverse axillary mapping to delineate the arm-draining lymph nodes and their involvement in various stages of breast carcinoma. In this study, we also attempt to redefine the template for axillary dissection in breast cancer. During the period of September 30, 2020, to August 30, 2021, 46 patients were recruited to undergo a procedure in which isosulfan blue dye was injected into the upper arm and the axilla was explored to isolate the lymph nodes. The lymph nodes were submitted for examination histopathologically. The results conclusively showed that axillary lymph node metastasis was only influenced by the advanced stage of the disease (p=0.014) and the visualization of the lymphatics was independent of the stage, type of surgery, decubitus, or age. The study conclusively shows that attempts to preserve the upper limb-draining nodes in advanced stages would be futile and the preservation of such lymph nodes should be limited to the early stages of breast cancer.

A Community-Based Cross-Sectional Study about the Quality of Life in Postmenopausal Women in Rural Puducherry.

BACKGROUND: The aim of this study was to assess the quality of life (QOL) of postmenopausal women, in the rural areas of Puducherry and to find the associated factors. MATERIALS AND METHODS: A cross-sectional study was done in the rural field practicing area of SLIMS, Puducherry. The sample size was 172 based on the previous study, and simple random sampling technique was used. The women who were receiving hormonal treatment, having chronic illness and those who refused to participate were excluded from the study. The sociodemographic information and menopause-specific QOL questionnaire were used, and data were analyzed using the SPSS 21. RESULTS: In this study, mean age of the postmenopausal women was 61 ± 7.5 years, 42.4% belonged to socioeconomic status (SES) Class IV. The prevalence of one or more symptoms of vasomotor, psychological, and sexual domains were 23.8%, 87%, and 68%, respectively. We found an association between SES and both vasomotor and psychological symptoms. Furthermore, age and psychological symptoms were associated. CONCLUSION: The menopause-related symptoms had a negative effect on the QOL of postmenopausal women. The study can help in creating awareness and also in helping in educating women for early identification of the frequent menopausal symptoms.

Isolation and characterization of low density structures from orotic acid-induced fatty livers.

Centrifugation of a sucrose homogenate of the livers of female albino rats fed a 1.5% orotic acid diet for 3 wk yielded a pellicle containing low density structures. In morphology and biochemical properties these structures resembled those portions of endoplasmic reticulum which accumulated lipid. Electron microscopy indicated large droplets of lipid bounded by a membrane with attached ribosome-like particles. The presence of ribosomes in these structures was established by treatment with deoxycholate and centrifugation. The proportion of 18S and 29S RNA was the same as that found in the ribosomes from normal liver; however, the distribution of radioactivity between the 18S and the 29S RNA after injection of 8-(14)C-adenine was distinctly different. The RNA isolated from these structures contained a higher guanylic acid to cytidylic acid ratio than that found in the microsomes of the normal liver. It is proposed that these low density structures may be those portions of the endoplasmic reticulum in which there exists a defect responsible for the block in the assembly or secretion of plasma lipoprotein.

Chemical induction of the bystander effect in normal human lymphoblastoid cells.

Many studies investigating the bystander effect have used ionizing radiation to evaluate this phenomenon, whereas very few have determined whether genotoxic chemicals are also capable of inducing this effect. Here, we show that two such chemicals, mitomycin C, a bifunctional alkylating agent and phleomycin, a glycopeptide antibiotic of the bleomycin family, cause normal human B lymphoblastoid cells to produce media soluble factors that induce a bystander effect in unexposed cells. Ionizing radiation was used in parallel experiments to verify the existence of the bystander effect in these cells. Micronuclei in Cytochalasin B-blocked binucleated cells were used as the endpoint. Conditioned media obtained from cells exposed to mitomycin C induced a 1.5-3 fold increase, while conditioned media from phleomycin induced a 1.5-4 fold increase, and conditioned media from irradiated cells induced a 2-8 fold increase in micronuclei. We conclude that the bystander effect is not restricted to ionizing radiation, suggesting it may be a part of a general cellular stress response.

First Report of Anthracnose Disease of Black Pepper (Piper nigrum) Caused by an Unknown Species of Colletotrichum.

Black pepper is cultivated in Andaman and Nicobar Islands, India as a spice crop. During a survey performed in June of 2007 in South Andaman, two kinds of leaf anthracnose symptoms were observed. The classic symptom, angular to irregular or circular brownish lesions with a chlorotic halo and pinhead size acervuli on the leaves, was consistent with the disease previously reported on pepper caused by Colletotrichum gloeosporioides (2). This symptom also caused splitting and the production of hollow berries. The new symptom was novel, with leaves initially exhibiting pale green or yellowish green lesions. As the disease progressed, lesion margins became brown to black with slightly raised areas containing numerous acervuli. Unlike the classic symptom, the new symptom was characterized as leaf lesions that rarely caused defoliation; berries showed no lesions. The foliar disease incidence was up to 15%, but direct economic loss of berries was not noticed. This new symptom was similar to symptoms caused by C. dracaenophilum, a species identified as a pathogen on lucky bamboo (Dracaena sanderiana) (1). A fungus was isolated in pure culture from the pale green lesions and cultured on potato dextrose agar (PDA). At room temperature (28 ± 2°C), fungal growth on PDA was slow and mycelium appeared whitish at the margin with pale pink centers. A pinkish color was observed on the reverse side of the plate, reflecting profuse sporulation. The conidia were hyaline, broadly clavate to cylindrical, and measured 12.5 to 15 × 5 to 7.5 µm (average 14 × 7.5 µm). The internal transcribed spacer (ITS) region of the fungal DNA was amplified, sequenced, and submitted to NCBI GenBank (Accession No. EU744584). The specimen was deposited in the MTCC of IMTECH, Chandigarh, India (Accession No. MTCC9344). Pathogenicity was tested in five replications on 15- to 20-day-old pepper plants and repeated twice. A 1-ml conidial suspension (108 spores/ml) of the fungus was brushed on two intact leaves of each pepper plant and incubated for 2 weeks in a glasshouse at 28°C and 70% relative humidity with natural daylight conditions. Plants brushed with sterile water served as control. Similar pale green symptoms were observed only on treated leaves and the same organism was reisolated from lesions. BLAST searches of the GenBank using the ITS sequence revealed that this fungus was a member of the genus Colletotrichum, but a species level identification could not be made with these data. The fungus was most similar in sequence to unnamed endophytic strains of Colletotrichum (96% sequence identity) and phytopathogenic isolates of C. dracaenophilum (93% sequence similarity). Although the symptomatology and sequence data were most closely matched with those documented for C. dracaenophilum (1), the morphological and cultural characteristics of the black pepper anthracnose fungus differed from C. dracaenophilum and other known species of Colletotrichum (3). Together these morphological and molecular data suggest that this form of anthracnose disease on black pepper may be caused by a novel, undescribed species of Colletotrichum. Further investigations will be required to characterize this organism to the species level. References: (1) S. G. Bobev et al. Plant Dis. 92:173, 2008. (2) P. Santha Kumari and A. Sanker. J. Mycol. Plant Pathol. 33:329, 2003. (3) B. C. Sutton. In: Colletotrichum. Biology, Pathology and Control. CAB International, Wallingford, 1992.

Growth inhibitory activity of fatty acid methyl esters in the whole seed oil of madagascar periwinkle (Apocyanaceae) against Helicoverpa armigera (Lepidoptera: Noctuidae).

Crude hexane and water extracts of Catharanthus roseus Linn. (Syn: Vinca rosea) (Apocyanaceae) stem, leaf, and seed exhibited pesticidal activity against Helicoverpa armigera (Hübner) (Lepidoptera Noctuidae). The extracts differed significantly in their efficacy, with the crude hexane extract of whole seed being the most effective in curtailing pupal survivorship to 18% followed by the hexane extracts of leaf (21%) and stem (24%). Average pupal weight (68.2 mg) and length (1.5 cm) in the whole seed treatment were drastically reduced, compared with the controls (415.2 mg and 2.72 cm), subsequently reducing adult emergence to 15.7%. SiO2 column purification yielded eight fractions of which fraction 1 exhibited 90% larval mortality, with severe reduction of the larvae weight (12.7 mg) and length (1.5 cm). Gas chromatographic-mass spectrometric analysis of fraction 1 suggested the presence of 16 compounds, among which oleic, linoleic, palmitic, and margaric acids were detected as major constituents. Presence of the alkane hydrocarbons triacontane, tetracosane, and heptacosane also was noted.

Role of computed tomography of abdomen in difficult to diagnose typhoid fever: a case series.

Background and Aim Diagnosis of typhoid is challenging when blood cultures fail to isolate Salmonella species. We report our experience with interpreting computed tomography (CT) abdomen findings in a case series of typhoid fever. Methods The case series consisted of patients who had a CT abdomen done as part of their investigations and a final diagnosis of typhoid fever. The CT films were reviewed and findings evaluated for distinctive features. Results During 2011-2017, 11 patients met the inclusion criteria. Indication for CT was pyrexia of unknown origin in the majority of patients. Review of CT films revealed mesenteric lymphadenopathy (100%), terminal ileum thickening (85%), hepatosplenomegaly (45%), retroperitoneal lymphadenopathy (18%) and ascites (9%). Conclusions Enhancing discrete mesenteric lymphadenopathy and terminal ileum thickening are non-specific findings noted in typhoid fever. Absence of matted necrotic nodes and peritoneal thickening rule out tuberculosis and raise suspicion of typhoid fever in endemic regions.

Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Development of novel biofunctionalized chitosan decorated nanocochleates as a cancer targeted drug delivery platform.

A new family of biofunctionalized chitosan decorated nanocochleates-mediated drug delivery system was developed that involves uniquely combining nanocochleates with anticancer drug for controlled drug release, targeted delivery, improved bioavailability with reduced toxicity. This system was developed by loading of doxorubicin (DOX) to nanocochleates (DOX-NC) through conversion of negatively charged dimyristoylphosphatidylcholine (DMPC) phospholipid and cholesterol-bearing vesicles on addition of calcium ions, followed by encapsulation DOX-NC with folic acid conjugated chitosan (FA-CHI-DOX-NC). The release of DOX indicated strong pH dependence and implies hydrogen-bonding interaction between nanocochleates and DOX. Formulated FA-CHI-DOX-NC demonstrated higher in-vitro anticancer activity in folate overexpressed human breast cancer MCF-7 cells. The targeting effect for the FA-CHI-DOX-NC was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 9.1 µg/ml for DOX while it was decreased by 31.68% for the DOX-NC (6.2 µg/ml). Furthermore, the GI50 value of FA-CHI-DOX-NC was 4.4 µg/ml, i.e. a 51.64% decrease was observed as compared to DOX solution. Moreover, bioavailability of DOX from FA-CHI-DOX-NC increased by 4-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to DOX solution. The proposed strategy is advantageous in terms of targeted drug delivery and has high potential to address the current challenges in drug delivery. Thus, the prepared new carrier offers a novel formulation that combines the unique properties of a biodegradable material, chitosan and nanocochleates for biomedical applications.

Current development in novel drug delivery systems of bioactive molecule plumbagin.

Plumbagin (PLB), a member of the quinine family, mainly found in the plant Plumbago zeylanica Linn., potentially exhibit anticancer, anti-inflammatory, anti-oxidant, antifungal, neuroprotective, hypolipidemic and antibacterial activities. However, it has been well known that the application of PLB was limited owing to its water insolubility, instability and poor bioavailability. For decades, many attempts have been made to compensate for these disadvantages with the development of improved delivery platforms as the feasible approaches. This review aims to describe the various studies supporting the biopharmaceutical aspects of PLB. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of PLB such as solubility, stability and bioavailability. Also, this paper summarizes the recent works on the design and development of novel delivery systems of PLB such as liposomes, niosomes, microsphares, nanoparticles, micelles, complexization, metal nanoparticles, crystals modification, etc., with the goal of harnessing the true difficulties of this multifunctional agent in the clinical arena.

Clinical Outcomes of Novel Long-Tapered Sirolimus-Eluting Coronary Stent System in Real-World Patients With Long Diffused De Novo Coronary Lesions.

BACKGROUND: When coronary lesions involve segments > 48 mm, the only treatment possibility is stent overlapping which is associated with higher neointimal proliferation that lead to more restenosis. Furthermore, tapering of coronary arteries is a major challenge observed with long diffuse coronary lesions. This study attempted to assess the safety and performance of world's first commercialised long-tapered (60 mm) sirolimus-eluting coronary stent (SES) system for the treatment of long diffused de novo coronary lesions in real world scenario. METHODS: This was a retrospective, non-randomised, multicentre study which included 362 consecutive patients implanted with long-tapered BioMime™ Morph SES system for the treatment of long diffused de novo coronary lesions. Safety endpoint was major adverse cardiac events (MACE), which was defined as composite of cardiac death, myocardial infarction (MI) and ischemic-driven target lesion revascularization (ID-TLR), at 12-month follow-up. RESULTS: Out of 362 patients included, 170 (47.0%) were diabetic and 159 (43.9%) were hypertensive. The mean age of all patients was 61.09 ± 9.04 years. A total of 625 lesions were identified; out of which 402 lesions were intervened successfully using BioMime Morph. The cumulative incidence of MACE was 7 (2.0%) at 12-month follow-up which included four (1.1%) cardiac deaths, one (0.3%) case of MI and two (0.6%) ID-TLR. Acute stent thrombosis was reported in one (0.3%) patient. CONCLUSIONS: The present study confirms the safety and performance of BioMime Morph, and hence, can be considered as a treatment of choice for long diffused tapered de novo coronary lesions in routine clinical practice.

Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype.

BACKGROUND: Fanconi anemia (FA) is a rare disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer. Patients harboring X-linked FANCB pathogenic variants usually present with severe congenital malformations resembling VACTERL syndrome with hydrocephalus. METHODS: We employed the diepoxybutane (DEB) test for FA diagnosis, arrayCGH for detection of duplication, targeted capture and next-gen sequencing for defining the duplication breakpoint, PacBio sequencing of full-length FANCB aberrant transcript, FANCD2 ubiquitination and foci formation assays for the evaluation of FANCB protein function by viral transduction of FANCB-null cells with lentiviral FANCB WT and mutant expression constructs, and droplet digital PCR for quantitation of the duplication in the genomic DNA and cDNA. RESULTS: We describe here an FA-B patient with a mild phenotype. The DEB diagnostic test for FA revealed somatic mosaicism. We identified a 9154 bp intragenic duplication in FANCB, covering the first coding exon 3 and the flanking regions. A four bp homology (GTAG) present at both ends of the breakpoint is consistent with microhomology-mediated duplication mechanism. The duplicated allele gives rise to an aberrant transcript containing exon 3 duplication, predicted to introduce a stop codon in FANCB protein (p.A319*). Duplication levels in the peripheral blood DNA declined from 93% to 7.9% in the span of eleven years. Moreover, the patient fibroblasts have shown 8% of wild-type (WT) allele and his carrier mother showed higher than expected levels of WT allele (79% vs. 50%) in peripheral blood, suggesting that the duplication was highly unstable. CONCLUSION: Unlike sequence point variants, intragenic duplications are difficult to precisely define, accurately quantify, and may be very unstable, challenging the proper diagnosis. The reversion of genomic duplication to the WT allele results in somatic mosaicism and may explain the relatively milder phenotype displayed by the FA-B patient described here.

Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate.

Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1, N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxy-methanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects.