Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.

Table of contents O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa O3 Integration of metagenomics and metabolomics in gut microbiome research Maryam Goudarzi, Albert J. Fornace Jr. O4 A unique integrated system to discern pathogenesis of central nervous system tumors Saleh Baeesa, Deema Hussain, Mohammed Bangash, Fahad Alghamdi, Hans-Juergen Schulten, Angel Carracedo, Ishaq Khan, Hanadi Qashqari, Nawal Madkhali, Mohamad Saka, Kulvinder S. Saini, Awatif Jamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Adeel Chaudhary, Mohammed Al Qahtani, Ghazi Damanhouri O5 RPL27A is a target of miR-595 and deficiency contributes to ribosomal dysgenesis Heba Alkhatabi O6 Next generation DNA sequencing panels for haemostatic and platelet disorders and for Fanconi anaemia in routine diagnostic service Anne Goodeve, Laura Crookes, Nikolas Niksic, Nicholas Beauchamp O7 Targeted sequencing panels and their utilization in personalized medicine Adel M. Abuzenadah O8 International biobanking in the era of precision medicine Jim Vaught O9 Biobank and biodata for clinical and forensic applications Bruce Budowle, Mourad Assidi, Abdelbaset Buhmeida O10 Tissue microarray technique: a powerful adjunct tool for molecular profiling of solid tumors Jaudah Al-Maghrabi O11 The CEGMR biobanking unit: achievements, challenges and future plans Abdelbaset Buhmeida, Mourad Assidi, Leena Merdad O12 Phylomedicine of tumors Sudhir Kumar, Sayaka Miura, Karen Gomez O13 Clinical implementation of pharmacogenomics for colorectal cancer treatment Angel Carracedo, Mahmood Rasool O14 From association to causality: translation of GWAS findings for genomic medicine Ahmed Rebai O15 E-GRASP: an interactive database and web application for efficient analysis of disease-associated genetic information Sajjad Karim, Hend F Nour Eldin, Heba Abusamra, Elham M Alhathli, Nada Salem, Mohammed H Al-Qahtani, Sudhir Kumar O16 The supercomputer facility “AZIZ” at KAU: utility and future prospects Hossam Faheem O17 New research into the causes of male infertility Ashok Agarwa O18 The Klinefelter syndrome: recent progress in pathophysiology and management Eberhard Nieschlag, Joachim Wistuba, Oliver S. Damm, Mohd A. Beg, Taha A. Abdel-Meguid, Hisham A. Mosli, Osama S. Bajouh, Adel M. Abuzenadah, Mohammed H. Al-Q...

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Combined in vivo and in silico studies were undertaken to gain insights into the change in mammalian brain acetylcholinesterase (AChE) activity under acute toxicity conditions in response to two representatives of organophosphates (OPs)--dichlorvos (DCV) and dimethoate (DM). In vivo experiments elucidated that DCV, at multiple sublethal doses for acute time periods, markedly reduced (10-25%) AChE activity, whereas with DM intoxication, a decrease in enzyme activity appeared to be lower, that is, (2-15%), in contrast to respective normal control (100%). Furthermore, a significant inhibition (P < 0.01) in the brain esterase activity was recorded for positive control animals treated with an alkylating agent-cyclophosphamide, with spontaneous reactivation at later time periods. In vivo results were further substantiated with in silico molecular docking analysis using "Autodock 4.2." The lowest binding energy obtained through the computational study strongly augment that DCV binds to brain AChE with greater affinity compared with DM with reference to ∆G and Ki values. Thus, the animal biochemical assay and computational assessment suggest that DM is better to be used over DCV. The precautionary antidote for exposed humans can be developed prior to dealing with OPs. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.

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Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.

The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; χ2 test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non–genotoxic mechanisms.