Data on schizophrenia (SZ), epilepsy (EPD) and bipolar disorders (BPD) suggested an association of DNMT1 overexpression whereas certain variants of the gene were predicted to result in its increased ...expression in autism spectrum disorder (ASD). In addition, loss of DNMT1 in frontal cortex resulted in behavioral abnormalities in mice. Here we investigated the effects of increased as well as lack of DNMT1 expression using
neurons as a model for abnormal neurogenesis and 10,861 genes showing transcript level dysregulation in datasets from the four disorders. In case of overexpression, 3,211 (∼ 30%) genes were dysregulated, affecting pathways involved in neurogenesis, semaphorin signaling, ephrin receptor activity, etc. A disproportionately higher proportion of dysregulated genes were associated with epilepsy. When transcriptome data of
neurons treated with doxycycline that downregulated DNMT1 was used, 3,356 genes (∼31%) were dysregulated with a significant proportion involved in pathways similar to those in untreated cells. Both conditions resulted in ∼68% of dysregulated genes wherein a majority showed similar patterns of transcript level changes. Among the genes with transcripts returning to normal levels, ribosome assembly/biogenesis was most significant whereas in absence of DNMT1, a new set of 903 genes became dysregulated and are involved in similar pathways as mentioned above. These findings provide support for overexpression of DNMT1 as well as its downregulation as risk factor for the four disorders and that its levels within a tight range are essential for normal neurodevelopment/mental health.
Background: Timely preparation and presentation of the annual cumulative antibiogram play an important role in the dissemination of an updated susceptibility pattern to clinicians and thus aid in the ...appropriate choice of antimicrobials for empirical therapy while minimizing adverse effects and resistance. The study aimed to present and analyze the annual AMR data that may be helpful in designing antibiotic policy. Methods: All clinical specimens routinely submitted to the Department of Microbiology from January to December 2021 for bacteriological culture and antimicrobial susceptibility testing (AST) were included. AST was performed for pathogenic isolates by disc diffusion/agar dilution/broth microdilution methods/VITEK® 2 compact system. All data were entered and analyzed using WHONET 2020 software. Results: A total of 46,629 routine specimens were processed, yielding 5792 non-repeat bacterial isolates. Relatively fewer specimens were received during the first few months when the hospital catered exclusively to COVID-19 patients. The most common bacterial isolates were Escherichia coli (30%), Staphylococcus aureus (21%), Klebsiella sp. (18%), Pseudomonas sp. (10%), Acinetobacter sp. (8%) and Enterococcus sp. (5%). Analysis showed low susceptibility to 3rd generation cephalosporins, fluroquinolones, and cotrimoxazole among Gram negative bacteria. Less than 50% Acinetobacter sp. were carbapenem susceptible. We report high rate of methicillin resistance in S. aureus (74%). Overall susceptibility was much lower in specimens from ICU followed by in-patients and out-patients. Conclusion: Antimicrobial resistance is rapidly assuming the proportions of a pandemic, with several authors calling it “invisible” pandemic. As is evident from the present study, low susceptibilities to all but a few last-resort drugs are leaving few choices for treatment. This mandates effective preparation, distribution, and presentation of annual antibiograms, which will help in formulating hospital antibiotic policy.
Throughout the world multi drug resistant nosocomial infections are one of the leading causes of death and morbidity among hospitalized patients. Antimicrobial resistance AMR has become a major ...problem in treatment of such infections. High consumption of antimicrobials particularly in ICUs is often described as the most important factor leading to AMR.
The aim of the study was to study the magnitude of antimicrobial resistance amongst nosocomial pathogens and the antimicrobial prescription patterns of patients admitted in intensive care unit.
The study was conducted in I.C.U of a tertiary care government hospital in Delhi over a period of 4 months, on 100 patients admitted in I.C.U. Depending on clinical suspicion laboratory samples were collected and subjected to antimicrobial sensitivity testing. Antimicrobial prescription of these patients were collected from I.C.U records and analyzed.
Staphylococcus aureus and Klebsiella species were the most common organism 23%. Among patients where causative organism was isolated, two or more organisms were isolated from 50% of the samples. Most of the Klebsiella species and Acinetobacter species were resistant to beta lactam group of antibiotics such as cephalosporins and piperacillin-tazobactam. 60% of isolates of S. aureus were found to be MRSA while none of the S. aureus were resistant to linezolid and vancomycin. All patients were prescribed two or more antimicrobials while 66% patients were prescribed 3–5 antimicrobials. Commonest combination was beta lactam with metronidazole followed by levofloxacin with metronidazole with addition of aminoglycosides or linezolid as third drug. Total 20 antimicrobial agents were used in the treatment of the patients. Among these consumption in DDD/100bed days of metronidazole was highest 100.9 followed by fluconazole 76.6 and levofloxacin 62.7.
High usage of antimicrobial consumption has been noted in this study, prompting institution of measures to formulate and adherence to antimicrobial policy strictly.
An immunization experiment was conducted in specific pathogen-free chickens with the inactivated Newcastle disease virus (NDV) vaccine encapsulated in the poly-(lactic-co-glycolic) acid (PLGA) ...nanoparticles (NP) to evaluate its immunogenicity and protective efficacy. The NDV vaccine was prepared by inactivating one virulent Indian strain of NDV belonging to Genotype VII by using beta-propiolactone. PLGA nanoparticles encapsulating inactivated NDV were prepared by the solvent evaporation method. Scanning electron microscopy and zeta sizer analysis revealed that the (PLGA+NDV) NP were spherical, with an average size of 300 nm, having a zeta potential of -6 mV. The encapsulation efficiency and loading efficiency were 72% and 2.4%, respectively. On immunization trial in chicken, the (PLGA+NDV) NP induced significantly (P < 0.0001) higher levels of HI and IgY antibodies with the peak HI titer of 28 and higher expression of IL-4 mRNA. The consistency of higher antibody levels suggests slow and pulsatile release of the antigens from the (PLGA+NDV) NP. The nano-NDV vaccine also induced cell mediated immunity with higher expression of IFN-γ indicating strong Th1 mediated immune responses in contrast to the commercial oil adjuvanted inactivated NDV vaccine. Further, the (PLGA+NDV) NP afforded 100% protection against the virulent NDV challenge. Our results suggested that PLGA NP have adjuvant potential on induction of humoral as well as Th1 biased cell mediated immune responses and also enhanced protective efficacy of the inactivated NDV vaccine. This study provides an insight for development of PLGA NP based inactivated NDV vaccine using the same genotype circulating in the field as well as for other avian diseases at exigencies.
Antimicrobial peptides (AMPs) offer a novel alternative to present day antibiotics which are becoming ineffective due to development of resistance in microbes. In this study, a short synthetic β ...sheet forming antimicrobial peptide-IRK (IRIKIRIK) was synthesized and we studied the effect of multimerization of peptides on its antimicrobial activity. The activity of linear, dimeric and tetrameric forms of IRK peptide was evaluated against reference strain of
Staphylococcus aureus
(ATCC 29,213) and Methicillin Resistant
Staphylococcus aureus
(MRSA) clinical isolates (n = 25). It was observed that the linear IRK peptide showed a minimum inhibitory concentration (MIC) of 16 µM, whereas the dimeric IRK showed 65% and 76% inhibition of bacterial growth at 16 µM and 32 µM respectively. However, tetrameric form of IRK peptide showed only 60% inhibition at both 16 µM and 32 µM concentration. At higher concentration, i.e., 64 µM (equivalent to 4 X MIC for linear IRK), all forms of IRK peptide inhibited the growth of more than 92% of MRSA isolates. While antibacterial activity decreased with the branching of IRK peptide, the haemolytic activity increased with the degree of branching. Structural changes arising due to multimerization may have attributed to this change in biological activity. We can conclude that linear and branched forms of IRK peptide have immense potential to inhibit the growth of MRSA and can be used as an alternative to antibiotics, especially in formulations for topical applications.
IntroductionInfections are a common cause of paediatric morbidity. Antibiotics are vital in treating them. Erratic prescribing practices are an important cause for the development of antibiotic ...resistance. Our objective was to estimate the effectiveness of educational interventions to improve empirical antibiotic prescribing practices among paediatric trainees. We aimed to improve the compliance to antibiotic protocols and to sustain it over 6 months.MethodsIt is a time interrupted non-randomised trial conducted in a tertiary hospital in India. Initially, 200 admitted children were selected randomly. Their antibiotic prescriptions, adherence of prescriptions to the then existing antibiotics guidelines, course during hospital stay and the final outcome were noted. The existing antibiotic policy and its use were reviewed. It was then considered essential to prepare a fresh antibiotic policy based on national guidelines, local sensitivity patterns and with inputs from microbiologists. This was distributed to the residents through seminars, posters and cellphone friendly documents. Compliance to the policy was also tracked twice a week. The adherence to guideline was recorded in the subsequent 6 months.ResultsThe adherence of empirical antibiotic prescriptions was 59% before intervention which improved to 72% in the first month, 90% in the second month, 86% and 78% in the third and sixth months, respectively. There was no significant difference in duration of stay and the outcome at discharge in the patients in adherent and non-adherent groups.ConclusionEducational interventions and frequent monitoring improved antibiotic prescribing practices among residents with no negative impact on patient outcomes. Quality improvements need persistent reinforcement and frequent monitoring to be sustainable.
Introduction: Empirical antimicrobial therapy is the mainstay of antimicrobial stewardship. The gram stain can be used to guide initial empiric antimicrobial therapy in cases where culture report is ...not available. This rapid test can therefore be helpful in preventing the initiation of inappropriate therapy and its adverse outcomes. Aim: To determine the effectiveness of gram stain of tracheal aspirate samples in order to predict the causative microorganism and starting appropriate initial antimicrobial therapy. Materials and Methods: This cross-sectional study was done for 208 tracheal aspirate samples that were sent to Department of Microbiology, Lady Hardinge Medical College, New Delhi, India, with a request for bacterial culture and Antibiotic Susceptibility Testing (AST) from January 2019 to June 2019. Each sample was inoculated on 5% Sheep blood agar, Chocolate agar and MacConkey agar followed by gram stain preparation and smears. The culture plates were checked after 24 hours for any bacterial growth and further identification was done by gram stain, motility and biochemical tests. The AST was performed as per Clinical and Laboratory Standards Institute (CLSI) 2019 guidelines. All data entry was done on MS excel software and appropriate statistical tests were applied. Results: Out of total 208 samples significant gram stain findings were seen in 90 cases (43.2%). Out of 208 samples 132 (63.5%) cases grew significant pathogens on culture. Out of these 90 cases, 68 (75.5%) of gram stain finding matched with culture results. The correlation between gram stain and culture was found to be 75.5%. Conclusion: Gram stain is not only a quick and cost-effective method but also easily available in most laboratories and is highly reproducible. Gram stain, a rapid diagnostic tool, can thus be very useful in antimicrobial stewardship especially for the critically ill patients.
Antimicrobial peptides (AMPs) offer a potent and effective alternative for treatment of antibiotic resistant microbes. Mastoparans or mastoparan like peptides are the most abundant peptides reported ...in vespid/social wasp venoms with potent antimicrobial activity. Polybia MP-1 is an amphipathic tetradecapeptide isolated from the venom of the vespid wasp
Polybia paulista
with potent antimicrobial activity and high selectivity for bacterial membranes. In the present study, the antimicrobial activity of Polybia MP-1 was evaluated against antibiotic resistant
Pseudomonas aeruginosa
isolated from mastitic cow milk samples. The isolates (n = 20) were obtained from mastitic milk samples and screened for sensitivity to antibiotics (Amikacin, Ciprofloxacin, Gentamycin, Imipenem, Ceftazidime, Colistin, Ceftriaxone and Aztreonam) by disc diffusion assay. The isolates were also characterized for the presence of different genes (n = 27) by polymerase chain reaction (PCR). These genes encoded for virulence factors, biofilm formation and antibiotic resistance. A correlation study was carried out to establish the significance of presence of antibiotic resistant genes i.e.
bla
TEM
,
bla
CTX−M
,
bla
SHV
and
bla
OXA
and resistance against different antibiotics for the bacterial isolates. Out of twenty, 7 isolates were found to be multiple drug resistant (MDR). We determined the minimum inhibitory concentration (MIC) of synthetic peptide, Polybia MP-1 against
P. aeruginosa
(ATCC 27853) and it was found to be 75 µM (124 µg/mL) whereas its minimum bactericidal concentration (MBC) was found to be 150 µM (2 X MIC). The Polybia MP-1 was able to effectively inhibit the growth of 5 out of 7 (71 %) MDR isolates at 6 X MIC (450 µM). The Polybia MP-1 was highly membrane selective and hence showed very low to moderate haemolytic activity against cattle, buffalo and goat red blood cells (RBCs). It further showed potent anti-biofilm activity against
P. aeruginosa
ATCC 27853 at 8 X MIC (600 µM). Thus, synthetic Polybia MP-1 has potent antimicrobial activity against antibiotic resistant
P. aeruginosa
and can be explored as an alternative to antibiotics for the management of disease conditions like mastitis in cattle.
Spontaneously occurring canine mammary tumours (CMTs) are the most common neoplasms of unspayed female dogs leading to thrice higher mortality rates than human breast cancer. These are also ...attractive models for human breast cancer studies owing to clinical and molecular similarities. Thus, they are important candidates for biomarker studies and understanding cancer pathobiology. The study was designed to explore underlying molecular networks and pathways in CMTs for deciphering new prognostic factors and therapeutic targets. To gain an insight into various pathways and networks associated with the development and pathogenesis of CMTs, comparative cDNA microarray expression profiling was performed using CMT tissues and healthy mammary gland tissues. Upon analysis, 1700 and 1287 differentially expressed genes (DEGs, P ≤ 0.05) were identified in malignant and benign tissues, respectively. DEGs identified from microarray analysis were further annotated using the Ingenuity Systems Pathway Analysis (IPA) tool for detection of deregulated canonical pathways, upstream regulators, and networks associated with malignant, as well as, benign disease. Top scoring key networks in benign and malignant mammary tumours were having central nodes of VEGF and BUB1B, respectively. Cyclins & cell cycle regulation and TREM1 signalling were amongst the top activated canonical pathways in CMTs. Other cancer related significant pathways like apoptosis signalling, dendritic cell maturation, DNA recombination and repair, Wnt/β-catenin signalling, etc. were also found to be altered. Furthermore, seven proteins (ANXA2, APOCII, CDK6, GATC, GDI2, GNAQ and MYH9) highly up-regulated in malignant tissues were identified by two-dimensional gel electrophoresis (2DE) and MALDI-TOF PMF studies which were in concordance with microarray data. Thus, the study has uncovered ample number of candidate genes associated with CMTs which need to be further validated as therapeutic targets and prognostic markers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antibody testing is often used for serosurveillance of coronavirus disease 2019 (COVID-19). Enzyme-linked immunosorbent assay and chemiluminescence-based antibody tests are quite sensitive and ...specific for such serological testing. Rapid antibody tests against different antigens are developed and effectively used for this purpose. However, their diagnostic efficiency, especially in real-life hospital setting, needs to be evaluated. Thus, the present study was conducted in a dedicated COVID-19 hospital in New Delhi, India, to evaluate the diagnostic efficacy of a rapid antibody kit against the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Sixty COVID-19 confirmed cases by reverse transcriptase-polymerase chain reaction (RT-PCR) were recruited and categorized as early, intermediate, and late cases based on the days passed after their first RT-PCR-positive test report, with 20 subjects in each category. Twenty samples from pre-COVID era and 20 RT-PCR-negative collected during the study period were taken as controls. immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the RBD of the spike (S) protein of SARS-CoV-2 virus were detected by rapid antibody test and compared with the total antibody against the nucleocapsid (N) antigen of SARS-CoV-2 by electrochemiluminescence-based immunoassay (ECLIA).
The detection of IgM against the RBD of the spike protein by rapid kit was less sensitive and less specific for the diagnosis of SARS-CoV-2 infection. However, diagnostic efficacy of IgG by rapid kit was highly sensitive and specific when compared with the total antibody against N antigen measured by ECLIA.
It can be concluded that detection of IgM against the RBD of S protein by rapid kit is less effective, but IgG detection can be used as an effective diagnostic tool for SARS-CoV-2 infection in real-life hospital setting.
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