#Mdr genes

[ask-a-vetblr]

We are switching our dog from regular Simparica to Simparica Trio. If he's already been on one Simparica, he should be ok without the risk of seizures, right? He's never had a bad reaction, but I'm paranoid.

Hi, Sueanoi here

Active Ingredient of Simparica is sarolaner. and TRIO is Sarolaner, moxidectin, and pyrantel.

Sarolaner's toxic dose is 3 times over that of the therapeutic dose. As long as you don't pick the wrong size of the medicine, side effects chances are very low. [cite]

There is a study that states there is more reports of Adverse effects on dogs that are on medications in the isoxazoline group (Sarolaner is in the group) than previously claimed by the manufacturer[cite]. But there is also a report of conflict of interest, where the author of said study is trying to sue the manufacturer [cite]. So take this info as you will.

Pyrantel is antihelminthic drug. It's very poorly absorbed in the gut as its area of desired effect is within the gut. There is very little concern over overdosing as they've tested at 40x therapeutic dose and found no toxicity effects. There's basically no risk if ingested at the correct dose. [cite1, 2]

Moxidectin is a neurological medication aiming to attack the parasites, while sparing the host because of mammalian physiology prevents it from being absorbed to the brain. (Except MDR-1 gene defective dogs, like Collie). This medication is in the same family as ivermectin, but even the dogs with MRD-1 defect, they still tolerate Moxidectin much better then IVM. At 30x of therapeutic dose, there was still no side effects seen in MRD-1 defective dogs. [cite]

For female dogs, there are no studies on pregnancy and nursing safety. There is no evidence of danger (also no evidence of safety). I tell my client to skip it too just in case.

If you are using the CORRECT dose, there shouldn't be any ADDITIONAL concern over neurological side effects.

If your dog gets sick for whatever reason at all, delay the dose until healthy.

I have not personally see any dog gets into neuro trouble over long term of sarolaner. If your dog tolerates the regular formula well, and your dog is not a MDR-1 gene defective dog , I see no reason that your dog would react badly to TRIO version.

I hope this helps!

[worms-in-my-brain]

USAmerican problems in providing healthcare are resulting in the spread of antibacterial-resistant strains.

On top of the overuse of antibiotics contributing to the development of antibacterial-resistant bacteria, people who leave their entire country to access affordable medical care are at a very high risk of spreading resistant bacteria around. This study, for example, found that 30% of international travellers returned with a antimicrobial resistant bacterium. Now consider that that is among completely healthy travellers, and that hospitals tend to be hotbeds for antibiotic and antimicrobial resistant strains of bacteria.

Not only is it dangerous for the individual to leave the country for healthcare (what if you don’t speak the language? Do you have a place to safely recover there? What if you have a complication but you’ve already arrived back at your home country?), not only is it absolutely ludicrous and dystopian that someone in a country with the ability to have good quality medical care would have to LEAVE to actually get such care, it’s also contributing to one of the biggest problems in medical science today.

Universal healthcare is a necessity.

(Additional sources below the cut)

http://www.jstor.org/stable/26690839

[oaresearchpaper]

Antibiotic Resistance in Multidrug-Resistant Bacteria: Bangladesh Study

Abstract

Antibiotic-resistant bacterial strains are widespread in hospitals and intensive care units. This poses a serious threat to human health as the effectiveness of many antibiotics has been diminished by the emergence of resistant strains. The overuse of β-lactam antibiotics has led to the rise of antibiotic-resistant bacteria, including Extended-Spectrum β-Lactamase (ESBL) producing strains. However, ESBL screening is not commonly performed in Bangladesh, despite the growing prevalence of antibiotic resistance. Multidrug-resistant strains, particularly those carrying the Integron integrase 1 gene is responsible for antibiotic resistance. Horizontal integron transfer is one of the key factors that can contribute to the emergence of multidrug-resistant (MDR) bacteria.  In this study, antibiotic sensitivity tests were conducted using 25 antibiotics. It was found that E. coli and Klebsiella both showed resistance to Aztreonam, Ampicillin/Sulbactam, Amoxyclav, Cefepime, Cefepime/Tazobactam, Ampicillin and Cefotaxime antibiotics. Our findings suggest that integron is common among MDR isolates and that they can be used to identify MDR isolates. As a result of the possibility of a widespread outbreak of MDR isolates, molecular surveillance and integron sequencing in other parts of the country is advised. The purpose of this study is innovation to create new antibiotics and alternative treatments to address antibiotic-resistant bacteria.

Introduction

Antimicrobial resistance poses a growing threat to human health and medical treatments and rising multidrug-resistant nosocomial infections in hospitals. Prompt treatment is crucial for vulnerable individuals at risk of bacterial infections. Viral infections are more likely to be the source of localized redness, swelling, and discomfort (Murray et al., 1998).

Antimicrobial resistance in bacteria is a complicated process involving a variety of different mechanisms. Susceptible bacteria can develop resistance through mutations or the transfer of resistance genes found on mobile DNA elements like integron (Barlow et al. 2004, Normak & Normak 2002). This, integron play a crucial role in the spread of antibiotic resistance, especially in Gram-negative bacteria by attaching to mobile genetic elements like transposons and conjugative plasmids, resistance integron transmit antibiotic resistance. (Mazel, 2006). Integron share antibiotic resistance gene cassettes predominantly through convergent evolution. Mobile integron has had a considerable impact on the spread of antibiotic resistance, particularly in Gram-negative bacteria (Davies et al., 2010). From the pool of these environmental genetic elements that is available, Integron has amassed a wide variety of resistance genes. Furthermore, their prevalence has significantly increased, increasing the possibility of interactions with other DNA and the emergence of additional, more complex mobile elements that are resistant to different antibiotic classes, disinfectants, and heavy metals (Gillings & Stokes 2012). 

Class 1 integron are major contributors to antibiotic resistance in Gram-negative bacteria like Klebsiella and E. coli. They evolve due to exposure to selection agents in human-populated areas and natural environments, acquiring advantageous genes. The presence of resistance gene cassettes within class 1 integron is linked to antibiotic resistance. Addressing this problem requires essential research and intervention to combat the spread of antibioticresistant microorganisms. Ongoing development and dissemination of antibiotic resistance in Gramnegative bacteria like Klebsiella and E. coli class 1 integron play a crucial role. Their evolution is fueled by persistent exposure to selection agents in both human-populated areas and natural environments, leading to the acquisition of beneficial genes. The presence of resistance gene cassettes within class 1 integron is closely associated with antibiotic resistance. To effectively combat antibiotic-resistant microorganisms, it is essential to prioritize continuous research and innovation. Class 1 integrons are commonly found in various Gram-negative bacteria such as Acinetobacter, Vibrio, Aeromonas, Proteus, Burkholderia, Alcaligenes, Campylobacter, Enterobacter, Citrobacter, Klebsiella, Mycobacterium, Pseudomonas, Serratia, Salmonella, Shigella, and Escherichia coli (Yu G, Li Y and Liu X. 2013). Several studies have investigated prevalence of integron in MDR Escherichia coli and Klebsiella isolates around the world. These studies have identified a significant link between the presence of integrons and antibiotic resistance. 

The study of integron aims to effectively combat antibiotic resistance by developing precise drugs that can be tailored to individual patients at a low cost, resulting in faster recovery times. With the emergence of antibiotic-resistant bacteria posing a significant threat to public health, there is a growing global interest in exploring integron profiles for the design of novel drugs that can safeguard both human and economically valuable animal populations. By understanding the intricate mechanisms of integron, scientists are hopeful of discovering innovative drugs that can tackle antibiotic resistance, thereby protecting human health and ensuring the well-being of economically important animals. This renewed focus on integron holds the potential to revolutionize the field of medicine and pave the way for personalized and cost-effective antibiotic treatments.

Source : Antibiotic Resistance and Integron Prevalence among Multidrug-Resistant Bacterial in Bangladesh. Molecular Pathology Laboratory, Institute of Biological Sciences, University of Rajshahi, Rajshahi-6205, Bangladesh

[skyovereuropeldkde]

For the first time, German TV MDR covers DNA contamination in Pfizer's mRNA vaccine! We are in a private laboratory in Magdeburg. Professor Brigitte König is examining Corona vaccines here. The result, all samples are contaminated. "With foreign DNA that should not be in the vaccine in this quantity. From my point of view, the alarming result is that all 5 batches had significant foreign DNA in them, which are well above the limit. It's about the BioNTech-Pfizer vaccine. 5 batches were given to the Magdeburg laboratory because there was a suspicion." Foreign DNA could be contained in the vaccine, and beyond the limit. According to WHO, the limit is a total DNA content of 10 nanograms per dose. It is important that this is not exceeded, because there is a risk that foreign DNA could penetrate human cells.

Brigitte König is an external professor at the medical faculty of the University of Magdeburg. She shows us the result of her privately conducted investigation. All 5 examined batches are contaminated. For the lowest concentration, the limit was exceeded by 83 times. The highest concentration found was 354 times the limit to König. This is concerning. The client of the analysis is also a private individual. The biologist Dr. Jürgen Kirchner. He has been one of the vocal critics of mRNA vaccines for years. He operates a website called Gene Vaccines. There he also advertises his books written under a pseudonym. His last one is called "Sullied." He has also appeared on YouTubers like the controversial Corona critic Paul Brandenburg. And discussed with him his theses on vaccines. Also the findings from Magdeburg. When DNA contaminations are found in a vaccine, that are as far above the limits as we have found, then in my view a special paragraph of the Medicines Act automatically applies, that is paragraph 5. It says if a medicinal product is questionable, then it must be taken off the market. And the biologist tries to achieve this. In September, he was at a hearing in the Bundestag's Petitions Committee on the topic of pandemic planning. Here he used the opportunity to present the analysis results from Magdeburg. These are gigantic exceedances of a limit for a really very questionable medicinal product. But do the vaccines actually contain foreign DNA? The accusation is not new.

Already in April 2023, American scientists found foreign DNA above the limit in the vaccines from BioNTech and Moderna. Also in this pre-publication of a Canadian study from the end of October, several scientists come to a similar conclusion. The researchers write, our results extend the existing concerns regarding vaccine safety. But are such traces of foreign DNA actually dangerous?

Humans constantly carry foreign DNA in themselves. This can come from food, but also if bacteria enter the lungs. These floating DNA snippets are digested in the gut by enzymes. But there is a difference with the mRNA vaccination. The vaccine contains so-called lipid nanoparticles. They smuggle the mRNA into the cells. They do not differentiate, however, whether they transport mRNA or DNA. Could foreign DNA thereby directly penetrate the cell nucleus?

That is at least the concern of this American researcher, Prof. Dr. Philip Buckhaults. He is a clear proponent of mRNA technology. Yet he too says he found DNA residues in Pfizer vaccine. Here at a hearing in the South Carolina Senate, he explains the potential consequences of DNA. By email he writes us, at the moment no one knows for sure, whether the foreign DNA has caused damage or will cause damage. But there is clearly a justified theoretical risk of genetic damage to long-lived stem cells. We asked several renowned German scientists about this concern.

Only a few reply to our request. Among them is Prof. Emanuel Wyler from the Max Delbrück Center for Molecular Medicine, an institute funded by the federal government. He deems it extremely unlikely that the DNA could have negative consequences. Further, he writes, DNA in vaccines is not a new topic and is also tested for, for example, in a flu vaccine. Until now, no one has been interested, or one rightly trusts that the Paul Ehrlich Institute as the responsible authority performs the testing work correctly. In my opinion, this shows that this is not about DNA in vaccines, but either about fundamentally questioning vaccinations, our best weapon against infectious diseases, or about creating a sensation with the issue of Corona.

However, Prof. Gerald Dyker, a chemist at the Ruhr University, does think that negative consequences are conceivable. He writes to us, against the background that one was under extreme time pressure, that the manufacturer decided, either without knowledge or with the acquiescence of supervisory authorities, to release the product with the remaining DNA impurities for mass vaccination. For Prof. Bernd Mühlbauer of the Drug Commission, however, it is still not clear at all, whether the vaccine is actually contaminated to a worrying extent. But he writes that residual amounts of DNA in the case of an mRNA vaccine cannot penetrate the cell nucleus and cause damage. Such experiments, including animal tests over several generations, are necessary and perhaps have already been conducted. And how do the authorities respond to the debate?

The Paul Ehrlich Institute is responsible for the surveillance and safety of vaccines. We want to know, whether they themselves have tested the vaccines for foreign DNA or at least checked the results from Magdeburg. The written response is that parameters such as the residual DNA content in the vaccine are only experimentally tested by the manufacturer. The Institute thus does not test the vaccines themselves for DNA contamination but relies on the manufacturers' test protocols. The fact that the authority neither tests itself nor checks the analysis results from Magdeburg causes surprise to Professor Brigitte König.

"I would have expected, or assumed, that the authorities would at least randomly check the end product for contamination and purity. Depending on the product, or if something else is inside. As I said, the authorities can do that. Especially the Paul Ehrlich Institute has the equipment for it."

The competent Federal Ministry of Health questions the analysis from Magdeburg and points out that some of the tested batches were already expired, according to Dr. Kirchner's notification. However, for the found foreign DNA this is irrelevant, says the scientist. The DNA in these lipid particles does not multiply. And is more likely to be decomposed. That is, if the vaccine is not expired, we might expect even higher values but not lower ones. The DNA does not multiply in a sterile vaccine.

Since the authorities apparently doubt the investigation results from Magdeburg, we want to have various batches tested ourselves. We contacted more than 20 laboratories, some of them at German universities, but also private providers who can conduct such analyses. From all, we received rejections or no response.

So, we failed to have a DNA analysis conducted independently once again. It would indeed be important to conclusively clarify the question of the DNA content. Because one reason for suspected DNA contamination could be the manufacturing process itself, which is different from the one used during the authorization study.

The vaccine used for the clinical studies was manufactured mechanically without the involvement of microorganisms. This production path is named Process 1 in the documents of the European Medicines Agency (EMA). Pfizer then switched to a different production technique, referred to as Process 2. Only very few subjects in the authorization study received this vaccine. Here, the material was supplied by genetically modified bacteria. This process was apparently less complex.

But did it actually pose a higher risk? That there were differences between the batches of the two different manufacturing processes has been a concern. Questions about comparability, characterization, and clinical suitability were raised. We ask BioNTech why the manufacturing process was changed nonetheless, but we do not receive an answer to this question. Regarding the suspected DNA contamination identified by the Magdeburg scientist, the company writes that the Pfizer-BioNTech COVID-19 vaccine is not contaminated with DNA.

Furthermore, it states that the batches were subjected to comprehensive quality control by the manufacturer. The Magdeburg scientist says that she has now examined additional vaccine batches. Here too, she found foreign DNA.

However, we as an editorial team were not able to conclusively answer whether this analysis is indeed accurate and, most importantly, whether the suspected DNA contamination can cause harm. The most recent act in the debate is this official-looking letter from an association called Medical Treatment Association, which warns doctors about the vaccine. However, as informed by the responsible authorities, this is said to be a false report.

[ultrabellasmith55things-blog]

anti abcg2 antibody

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). 

[biomedres]

Distribution of Colistin Resistance Genes Among Clinical Isolate of Gram-Negative Bacteria

Distribution of Colistin Resistance Genes Among Clinical Isolate of Gram-Negative Bacteria in Biomedical Journal of Scientific & Technical Research

https://biomedres.us/fulltexts/BJSTR.MS.ID.006004.php

enes among Gram-negative bacteria isolated from clinical samples at the National Ribat Teaching hospital, in Khartoum, Sudan. A total of 165 Gram-negative isolated pathogens were as follow Klebsiella pneumoniae (73/44.2%), E. coli (53/32.1%), Pseudomonas aeruginosa (33/20%), Proteus vulgaris (6/3.6%), and Citrobacter freundii (2/1.2%), isolated between December 2019 and February 2020 from clinical samples at the National Ribat Teaching hospital in Khartoum, Sudan. Stock of all isolates were stored in 20% Glycerol-broth at -80°C for further subculture for antimicrobial susceptibility profile and resistance genes associated with Colistin resistance were identified. Colistin resistance associated genes (mcr-1, mcr-2, mcr-3, mcr-4, mcr-5) of Gram-negative isolates were determined by polymerase chain reaction (PCR) using appropriate primer sets. Out of 165; 11 isolates (7%) were resistance to Colistin antibiotic with MIC ≥ 9-10 μg/Ml. The majority 67% (4/6) of K. pneumoniae Colistin resistant strains were considered MDR. Three out of the 6 (50%) clinical Colistin-resistant K. pneumoniae isolates were resistant to carbapenems (meropenem ≤ 2 μg/ml). One of these 3 strains was resistant to all tested antibiotics. The remaining K. pneumoniae strains were susceptible to most tested antibiotics (Supplementary material Table A1). The two Colistin resistant P. vulgaris isolates were resistant to all antibiotics including the carbapenems (meropenem ≤ 2 μg/ ml) and were only susceptible to amikacin and ciprofloxacin. One Colistin resistant C. freundii isolate was only susceptible to amikacin, cotrimoxazole, and carbapenems. The Antibiotic resistant patterns were very low among P. aeruginosa isolates, as the majority of the isolates were shown more sensitive to most of the antibiotics. Only one Colistin resistant E. coli isolate was resistant to aminoglycoside and beta-lactam antibiotics. The gene detection by PCR revealed positive mcr-1 gene in 11/165 (7%) of the isolates; 6/73 (8%) were K. pneumoniae with highest mcr-1 gene among Colistin resistant K. pneumoniae 60% (6/10). 2/6 (33%) P. vulgaris, 1/53 E. coli, 1/33 (3%) P. aeruginosa, and 1/2 (50%) C. freundii. While only one (0.6%) K. pneumoniae isolate was found positive for mcr-2 (Table 4). The other Colistin resistant genes were not detected.

For more articles in Journals on Biomedical Sciences click here bjstr

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[silverlab101]

Colloidal Silver Its A Lot More Than Just A Precious Metallic

I found that colloidal silver worked nicely for an eye fixed an infection. I researched it a bit on-line and most of the people stated it was fine. Colloidal silver is an efficient pure remedy for viral conjunctivitis, also called colloidal silver for eye ailments "pink eye." This home therapy is quick and easy and not messy at all. But one downside with silver as a micro organism killer is that silver ions don’t discriminate.

These nanocomposite movie collection may be viewed as a promising candidate for many functions in antimicrobial packaging, biomedicines and sensors. Nanoparticles are included in the PMMA denture resin to achieve an effective antimicrobial materials to assist management widespread infections involving oral mucosal tissues in complete denture wearers. Green synthesis of extremely concentrated aqueous colloidal solutions of enormous starch-stabilised silver nanoplatelets.

The bits of silver are so small they keep afloat within the liquid. Designed, conceived and contributed to the manuscript preparation and wrote the medical paragraphs; D.Ż. With new strategies, ready colloidal silver for eye ailments the dosage type for the patients according to pharmaceutical standards and wrote the chemical and pharmaceutical paragraphs; J.O.

Nanoparticles have been characterised utilizing UV-Visible, X-ray diffraction , scanning electron microscopy (SEM/EDX), and transmission electron microscopy strategies. Furthermore, the possible mechanism of nanoparticles synthesis was also derived using FT-IR analysis. Spectroscopy evaluation revealed that the synthesized nanoparticles had been inside 30 to 75 nm in measurement, whereas XRD results confirmed that nanoparticles formed colloidal silver for eye ailments were crystalline with face centered cubic geometry. Oral toxicity of silver ions, silver nanoparticles and colloidal silver --a evaluation. Durable antibacterial and cross-linking cotton with colloidal silver nanoparticles and butane tetracarboxylic acid with out yellowing. Colloidal silver is widely considered a possible pure various to antibiotic medicine for fighting every kind of infections.

For centuries it has been recognized that silver is a really efficient and highly effective germicide. Silver is an distinctive steel in that it's non-toxic to the human body, however deadly to over 650 disease causing bacteria, viruses, fungi, parasites, and molds. Conventional pharmaceutical antibiotics are sometimes effective against solely 6 or 7 forms of bacteria. Some new strains of bacteria categorized as MDR have confirmed to be proof against all pharmaceutical antibiotics, however to not colloidal silver because of different germicidal mechanisms of deactivation. First off, silver water is extra properly often known as colloidal silver. It is pure, microscopic, elemental silver suspended in pure water.

Health-related information changes regularly and due to this fact data contained on this Web web site could additionally be outdated, incomplete or incorrect. Statements made about products haven't been evaluated by the Food and Drug Administration. Use of this Web site does not create an expressed or implied physician-patient relationship. Our scientists pursue each side of cancer research—from exploring the biology of genes and cells, to developing immune-based therapies, uncovering the causes of metastasis, and more.

[medgenome]

LPA test for MDR TB

The line probe assay (LPA), based on strip technology was used to diagnose TB and detect RIF as well as Isoniazid (INH) resistance due to mutations in rpoβ, and both inhA and katG genes. Click here to know more about  mdr test for tb .

[kiyooooo2]

Beware of growth spurts!

[ultrabellasmith55things-blog]

abcc11 antibody

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White).

[pauvre-lola]

get to know me meme

tagged by @hawkepockets thank chu <3

1. NAME: lola

2. BIRTHDAY: march 15

3. SUN SIGN: pisces

4. HEIGHT: ???? around 1m60 ???? I think ???

5. HOBBIES/INTERESTS: vidya gnomes, drawing, music, litterature, cinema ( esp. peplum from the 50/60/70s and musical sigh gene kelly’s tights.... im thinking about them..........)  arts and cooking lmao god im so boring !!!!!!!!!

6. FAVORITE COLOR: pink and yellow

7. FAVORITE BOOKS: on empêche pas un petit coeur d’aimer by claire castillon, antigone by anouilh, and le mal court by audiberti !oh i had to read the last one some years ago when I was studying litchacha and i was shooketh i spend all of my year thinking about it and simping for princess Alarica every single minutes of my miserable student life. Also Audiberti is a really interesting french author and if you’re a nerd like me I recommand him 10/10 oh anything by petrarch too but that’s because he was a fucking loser and i like to make fun of him ( man really went like I Am A Role Model In Love................. never got laid and the woman he loved left him on read................. bisous champion mdr )

8. LAST SONG: instant cytron - la marcia dei bambini

9. LAST FILM/SHOW: oh i finally watched La La Land and !!!! I mean I liked it and I cried a little bit at the end lol but that was so ??? basic ??? Maybe my expectations were Too High ??? wait no i realize i just have problem with movies that play the “tribute to another movies ahah i love cinema :) ”  card or whatever bc honey thats not a tribute its being a little snob and I AM CACKLING bc most of the time whos behind that type of movies ??? a sad little old man im getting angry !!!

10. INSPIRATION: Marjorie Miller, Aubrey Beardsley, Arthur Rackham, Mary Blair, Eyvind Earle

11. STORY BEHIND THE URL: it’s a song by serge gainsbourg because i was Obsessed by his music when I was younger and I didnt know better sad i know !!! But I grew attached to it and I cannot dissociate myself from this stupid song + it has lola in it

TAGGING: @wonderlandcrows @tk-duveraun @kissingagrumpygiant @shrimpnest @eledhrim if ya want smek smek

[lupinepublishers]

Lupine Publishers | Carbapenem-Resistant Bacteria in Oncology Clinic

Lupine Publishers | Open Access Journal of Oncology and Medicine (OAJOM)

Abstract

The present study was objected to check the awareness about SARS among scholars of university. The pupil of Bahauddin Zakariya university Multan acted as the subjects for this research. Total of 109 subjects showed consent to be the part of this study. Severe acute respiratory syndrome (SARS) is considered a deadly animal virus which, perhaps originated from bats and then it was spread to other animals. According to a report, the humans were affected by SARS very firstly in 2002 in Guangdong, china. a report by World health organization states that 8098 people were affected by SARS in an outbreak during 2003, out of which 774 died. It was first observed as an influenza like disease with headache, fever leading to failure of respiratory system and sometimes death of the patient. The early symptoms of SARS are headache, body ache, high fever, coughing and sneezing, feeling difficulty in breathing leading to asthma sometimes. Treatment of SARS includes taking antibiotics (to prevent pneumonia) and some antiviral medicines. Present research helped in knowing about the knowledge of SARS in university students. This study helped in estimating that 84.40% pupil consider SARS as a viral disease, 12.84% students think it’s a genetic problem while 9.17% suppose it’s a metabolic error.

Keywords: SARS (severe acute respiratory syndrome); Pupil; Ailment; Viral; Metabolic; Pandemics; Steroids

Introduction

Go to

The occurrence of carbapenem-resistant (CarR) bacteria is a serious problem for the treatment of potentially fatal infections. According to estimates of most authors the mortality rate for infections caused by the CarR microorganisms is 24%-70% [1-4]. They are a growing concern in global public-health due to their associative resistance to all or almost all β-lactams and other classes of antibiotics, such as aminoglycosides, fluoroquinolones and cotrimoxazole. Treatment options are limited and there is still no consensus on optimal treatment regimens [5-7]. Therefore, regular monitoring of carbapenem-resistant strains of microorganisms and followed by the determination of the molecular mechanism of resistance is extremely important to prevent the spread of such bacteria and to select the optimal antibiotic therapy in any clinics. The purpose of this study was to determine the species composition of the carbapenem-resistant strains of microorganisms isolated from the biological materials of patients at an oncology clinic, to identify strains producing carbapenemases and to determine the types of carbapenemases.

Materials and Methods

Studies were conducted in the period 2017-2018. Sources of bacterial isolates were biological materials from patients of the oncological clinic. The study took strains of gram-negative bacteria resistant (R) or intermediate resistant (I) to carbapenems. Microorganisms were identified by the method of matrixassociated laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) and software MALDI Biotyper v.3.0 (Bruker Daltonics, Germany). Genes encoding carbapenemases of the VIM, OXA-48, OXA-40, OXA-23, NDM groups were detected by real-time polymerase chain reaction using the AmpliSense® MDR MBL-FL and AmpliSense® MDR KPC/OXA-commercial kits 48-FL” (developed by FBUN Central Research Institute of Epidemiology, Russia) and the Rotor-Gene 6000 system (Corbett Research, Australia). The strains of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii from the RIACh collection (n= 14), producing known carbapenemases of the listed types, were used as positive controls. P.aeruginosa isolates tested for MBL of the VIM, IMP, NDM and Class A carbapenemases groups (GES-5-like). The strains of A.baumannii were tested for the above-mentioned metal beta-lactamase and class A carbapenemases, as well as the presence of OXA-carbapenemases of class D typical of this type (groups OXA-23, -24/40,-51, -58). Bacteria of the Enterobacteriaceae family were examined for the presence of MBL and OXA-carbapenemases (group OXA-48).

Results

The Gram-negative bacteria resistant to carbapenems were studied in the laboratory of microbiological diagnostics and treatment of infections in oncology N.N. Blokhin National Medical Research Cancer Center, Russia in conjunction with the Microbiology Laboratory of the Research Institute of Antimicrobial Chemotherapy, Russia, in 2017-2018. A total of 123 strains of the most frequently isolated microorganisms were studied (A. baumannii-35 (28.5%), P. aeruginosa-26 (21.1%), E. coli-11 (8.9%), K.рneumoniaе-37 (30.1%)). Also, the study took strains of such microorganisms as: Enterobacter cloacae, Serratia marcescens, Enterobacter asburiae, Burkholderia cepacia the relative amount of which was 10.6%. All test isolates were obtained from biological materials of oncological clinic patients. The ratio of carbapenemresistant microorganisms from different biological materials of cancer patients is presented in Figure 1.

The most frequently carbapenem-resistant strains of microorganisms were isolated from wound discharge (24%), from urine (18%), in equal amounts from the discharge of the lower respiratory tract and from bile (16%). In the discharge drainage and in the blood, CarR strains were found in 12% and 8% respectively. When conducting research, the types of carbapenemases produced by microorganism strains isolated from biological materials of cancer patients were determined. Types of carbapenemases CarR strains of microorganisms circulating in the oncological clinic are presented in Table 1. As a result of the research, it was revealed that out of 123 strains of microorganisms resistant to carbapenems, 88(71.5%) strains of bacteria were producers of carbapenemases. The carbapenemase-producing of type OXA-48 were: K.pneumoniae (86.5%), E.coli (9.1%), Enterobacter asburiae (100%) and Serratia marcescens (50.0%). The producers of NDM-type carbapenemases were also identified - this is Enterobacter cloacae (40.0%) and K.pneumoniae (2.7%). A. baumannii produced carbapenemases OXA-23 (97.1%) and OXA-40 (2.8%). Among the P.aeruginosa strains studied 46.1% produced VIM-type carbapenemases and 11.5% GES-5-like.

Conclusion

The species composition of gram-negative carbapenemresistant microorganisms isolated from the biological materials of cancer patients is presented as the most frequently isolated hospitals pathogens (A. baumannii, P. aeruginosa, E. coli, K.pneumoniae) and microorganisms, the relative amount of which as infectious complications pathogens not large (Enterobacter cloacae, Enterobacter asburiae, Serratia marcescens, etc.). Endemic strains of bacteria producers of globally common carbapenemases: OXA- 48, OXA-23, NDM, VIM - types are circulate in the oncological clinic. Obviously, regular monitoring of CarR strains of microorganisms, determination of resistance genes by molecular-genetic methods, well thought-out antimicrobial therapy and effective infection control strategy are necessary to effectively inhibit the spread of carbapenem-resistant bacteria.

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[tinyshe]

First in the EU: Vienna to vaccinate pregnant women from mid-May

The city of Vienna wants to be the first city in the EU to have pregnant women vaccinated from mid-May. This was announced by the office of the Vienna City Councilor for Health. Experts are alarmed.

Published: May 5, 2021, 8:25 am  Vienna

Read more

Breaking: High number of side effects expected for Covid vaccine

Could new mRNA coronavirus vaccines lead to infertility, miscarriage, birth defects?

A gene vaccine with nanoparticles? Many are starting to have doubts

An 89-year-old vaccinated against Corona — dead an hour later

Bremen considering easing vaccination sequence for AstraZeneca

From mid-May, Vienna will be the first city in the European Union to also have pregnant women vaccinated against the Coronavirus. The office of City Councilor for Health Peter Hacker (SPÖ) announced this on Sunday, reported the Austrian portal oe24.

At the initiative of the Vienna Health Association, the National Vaccination Committee included pregnant women as a priority group in the vaccination plan at the end of April. The City of Vienna will thus have pregnant women vaccinated against Covid-19 from the 13th week of pregnancy.

Depending on how many expectant mothers are interested in an anti-Corona vaccination, the vaccination dates for pregnant women are activated without restriction or vaccinations are given according to prioritization. In the latter case, heavily pregnant women will have their turn first, and the next candidates will be considered based on the respective week of pregnancy.

It has been found that pregnant women who become infected, often suffer a more severe form of the illness than non-pregnant women in the same age group, the portal reported.

Martin Hesse from the professional association of Thuringian gynecologists, on the other hand, warned against general Corona vaccinations for pregnant women, according to the MDR Thuringia. The Thuringian state chairman told the broadcaster that vaccination of pregnant women is not desirable as long as sufficient data has not been generated yet.

According to the gynecologist, Thuringian gynecologists have been involved in the vaccination campaign since last week, but they adhere to the requirements of the Standing Vaccination Commission in Germany (STIKO). It stipulates that the vaccination may only be offered to pregnant women after an individual risk-benefit assessment, for example if they have had previous illnesses.

In Thuringian special care units, however, pregnant women with severe courses are a rarity. The majority of the so-called Level 1 clinics that care for patients with severe courses in the Free State of Thuringia have not had to treat any infected pregnant women in intensive care since the beginning of the pandemic.

According to a spokeswoman, the number of pregnant women infected with Covid-19 at the Altenburger Land clinic has been “manageable” since the beginning of the pandemic and all cases have been mild. The Wald-Klinikum Gera painted a similar picture; pregnant infected women are isolated cases, their number has not increased. At the St. Georg Klinikum Eisenach, an increasing number of Covid-19-positive women have given birth in the past few months, but there were no intensive inpatient cases there either.

In countries outside the EU, including the USA, Great Britain, Israel, pregnant women are already regularly vaccinated. As a rule, mRNA vaccines are used for this.

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Huge Genetic Inclusion during Conversion of R-Plasmids into MDR Conjugative Plasmids in Multidrug-Resistant Bacteria: Crimson Publishers

Huge Genetic Inclusion during Conversion of R-Plasmids into MDR Conjugative Plasmids in Multidrug-Resistant Bacteria by Asit Kumar Chakraborty in Cohesive Journal of Microbiology & Infectious Disease: Crimson Publishers_Open Access High Impact Articles

High rate infections and deaths due to multidrug-resistant pathogens have created a horror worldwide. Because MDR bacteria are present in river, sea and air as well as in all household matters, such infections are ubiquitous. Most dangerous step occurred when R-plasmids and integrons (2-9kb) were combined with F’-conjugative plasmid (50-500kb) creating MDR conjugative plasmids that highly donated the mdr genes into household pathogens in the environment. Now 40% of household Escherichia coli and Staphylococcus aureus like Gram (+) and Gram (-) bacteria are ampicillin resistant and also to some extent tetracycline, chloramphenicol, streptomycin, erythromycin, ciprofloxacin, sulfamethoxazole and neomycin resistant.

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Mechanisms of AMR: Mdr Genes and Antibiotics Decoys Retard the New Antibiotic Discovery against Superbugs-Open Access Publishers Many microorganisms cause lethal diseases in human causing loss of lives and property worldwide. Many antibiotics are used to cure deadly infections for the past 75 years with no difficulty. Recent outbreaks of multi-drug resistant bacteria have caused millions of death every year and physicians do not know how to cure KPC2 Klebsiella kneumoniae, NDM1 Escherichia coli or MRSA Staphylococcus aureus and XDR Acinetobacter baumannii infections. Sadly once used ampicillin, streptomycin, azithromycin, tetracycline, and chlormphenicol are useless against those bacteria. Combination therapy using colistin, imipenem, amakacin, ceftizidime and investigation drug ovibactam sometime are giving good clinical efficacy but not sure. In such a situation, heterogeneous phyto-antibiotics and gene medicines have been welcome by medical authorities but AMR calamity remains as mdr genes (amp, bla, tet, cat, aac, aad, aph,sul etc) moved to conjugative plasmids and chromosome of bacteria with target specific alterations in rRNA and porins genes. Keywords: Mdr genes; Anti-microbial resistant; Gene medicine; Phyto-antibiotics Introduction Past 75 years are the golden era of drug development and several types of antibiotics are in centre stage of such discoveries since the discovery of penicillin drug by Alexander Flaming from slime mold Penicillium notatam in 1928 targeting peptidoglycan cell wall biosynthesis of most Gram (+) and Gram (-) bacteria [1]. Since then 1000 derivatives were made alone for penicillins (ampicillin, cefotaxime and imipenem) for better drug usually called penicillinases resistant drug. A professor of biochemistry and microbiology at Rutgers University, Dr. Selman A. Waksman discovered over twenty antibiotics (a word he coined) and introduced procedures of antibiotic production (streptomycin) that led to Nobel Prize in Physiology or Medicine in 1952. However, such dream could not last long as more potent penicillinases called, oxacillinases, cefotaximases, carbapenemases were appeared in bacterial plasmids [2]. New era of biology was begun in 1953 with the discovery of structure of DNA, gene structure, regulation of gene expression and advancement of DNA sequencing, chromosomal structure and RDT work (Figure 1). Profound impact was found by biomolecules separation by ultra centrifugation and HPLC with chemical structure analysis by Mass, NMR and FTIR. Invitebly we got many life saving drugs with known target site although basic DNA, RNA and protein composition in virus to bacteria to human were same [3]. [Click here to view Large Figure 1] Semi-synthetic drugs and anti-microbial resistance Naturally, semi-synthetic drugs were made without choice to overcome the action of multi-drug resistant class located in bacterial plasmids that inactivate the antibiotics by different mode of actions. As for example, ampR cell extract was discovered as early as 1940 and amp gene which produces an enzyme, Beta- lactamase was sequenced in 1965. Now one in three bacteria in river and sea water contained amp gene in large conjugative plasmids that also carry 5-10 other mdr genes and 10-15 Tra and Tnp genes [4]. So journey from 1940-1960, described the isolation of tetracycline, streptomycin, sulfa-drug, ampicillin, amoxicillin, cefoxitin, cefotaxime, erythromycin, nalidixic acid, ciprofloxacin, neomycin, polymyxin, enoxacin, norfloxacin (Figure 2). However, at the almost same time, resistant bacteria to all these antibiotics were developed creating pressure to drug industry for more and more new drug development. However, it is not very easy to develop a drug for human use because it needed at least one billion dollar to develop a drug. What happen to investor if a developed drug is good for few years and then drug resistant microbes appeared when no one want to prescribe that antibiotic because uncertainty of cure of such infections and also delay in treatment and also taken of repeated different antibiotics surely toxic to health and time and monetary loss [5]. [Click here to view Large Figure 2] Drug screening from bacteria against bacteria-a wrong message In fact, now R & D Industry screening new drugs everyday and also computer-guided graphics design and stimulate artificial drug-target interactions have accelerating the new drug development. Screening of new drug from fungi was favourable in sense that in soil and water there is a battle between bacteria and fungi and so fungi will produce anti-bacterial to kill bacteria. That type of selection is good having different genus but what we did that we introduced the battle between actinomycetes and bacteria like neomycin (1946) and actinomycin (1940). And then we introduced the battle between bacteria against bacteria as for example streptomycin is produced from soil bacteria, Streptomyces griseus and also chloramphenicol that eradicate typhoid disease in early decades. What has happened in life of bacteria that all want to destroy it and as a result bacteria are forced to re-arrange its genes to save its life, Hypothesis is not so easy as its own counterpart is enemy and bacteria created many new entity like transposons, integrons, R-plasmids and many DNA rearrangement enzymes like transposes, resolves and integrases and also many topoisomerases and restriction end nucleases [6]. In 1960-1980, we produced 1000 tons of antibiotics in industry and 7000 millions of global peoples now taken antibiotics almost every day or every month to remove the bacteria from intestine and blood to keep healthy. Doctors have forgotten that bacteria needed for human development and intestine should stay (10)12 bacteria for normal synthesis of vitamins which human could not synthesize itself . When such discrepancy was noticed, then probiotic bacteria were used as supplement after each antibiotic therapy. In other word, we used many unnecessary doses of antibiotics as for example, for viral infection, for pain and in food animal growth as well as in agricultural land [7]. Conjugation plasmid-a safe guard of bacteria to transmit genes without failure However that is too late, as bacteria developed another armour against antibiotics by using its very urgent plasmids used in conjugation (marriage) that means bacteria could form a sex pilus using Tra proteins coded by 62kb plasmid called F'- plasmid which usually did not carry MDR genes. What bacteria did that combined R-plasmid with F'-plasmid and such plasmid is known today as conjugative MDR plasmid which could be large as 100-500kb and such plasmids are hard to purify by plasmid purification method for molecular biological study being contaminated with bacteria chromosome (2000-5000kb) [8]. Never the less CsCl density gradient centrifugation and Pulse Field Gel Electrophoresis have help to isolate such plasmids with purity and also fully sequenced. What we see that such plasmids carry most Tra and Tnp genes including localized mdr genes. What is the advantage of bacteria then? Very advantage for life because such plasmids are very stable in bacteria during cell division and also could donate the non-MDR bacteria of mdr genes to save from deleterious effects of antibiotics and toxic chemicals in water. What is a toxic chemical? Well large industry like mineral Industry, Paint industry, drug industry, paper industry, petroleum industry and excreta from 100 million peoples in many big cities (New York) releases tons of chemicals, antibiotics and heavy metals into sea water that are very harmful to bacterial central dogma enzymes like those involved in replication, transcription and translation. What exactly bacteria did Bacteria simply made 100 different enzymes that destroy antibiotics once it entered into bacteria. But that is not sure as 100 chemicals and detergent in sewage water and bacteria made drug efflux genes (known as tetA, acrAB, mexAB/CD/EF, and ABC genes) that could remove drugs and chemicals from cytoplasm into outside keeping save its cellular enzymes and nucleic acids (Figure 3). That mean whatever the high concentration of pollutants and antibiotics outside water where bacteria live no toxicity because once a chemical enter into bacteria acrAB/C proteins pump it back into environment keeping bacteria safe. What is the consequence? Well bacteria in our body stay alive and divide most to cause sepsis and trauma but condition not likely going to improve by taking prescription drugs because no achievable concentration of the drug would be happen in bacterial cytoplasm (to stop protein synthesis) due to bacterial drug efflux pumps (Figure 4). [Click here to view Large Figure 3] [Click here to view Large Figure 4] Bacteria moved mdr genes into chromosome to increase gene dose further Did any other genetic changes happen that we should be worry? Yes, bacteria also made safe guard by combing mdr genes into their chromosome and few bacteria like Staphylococus aureus and Acinetobacter baumannii and also household bacteria like Escherichia coli genome-MDR-islands were sequenced confirming the calamity (Figure 4). That is not the end, porin membrane proteins are also mutated in such a way that antibiotics receptors altered and no drug could enter into bacteria at low drug concentration giving MDR. Further, ribosomal ribonucleic acids (23S, 16S rRNAs) gathered few mutations (usually very conserved) and many ribosomal proteins and drugs interactions did altered causing MDR. On one word, bacteria have achieved many shrouds against antibiotics and drug companies did not know where to start [9]. As for example, we discovered at least twenty types' bacterial beta-lactamases (mdr genes) that were sequenced. Again in each type beta-lactamase gene, hundreds of mutations were discovered that sometime gave high drug resistance increasing drug MIC or totally resistant. Gen Bank analysis clearly showed that each conjugative plasmid in Pseudomonas aeruginosa, Klebsiella kneumoniae, Escherichia coli and Salmonella typhi have many mdr genes giving resistant to 5-10 antibiotics from different groups with different mode of ations (Table 1). Interestingly such plasmids carry mdr genes in one locus with activation by transposon promoter-enhancers and Tra genes are located in clusters (Figure 5). It is very easy to isolate MDR bacteria in water by adding antibiotics in media at 50μg/ml and then isolate plasmid DNA by alkaline lyses method and then do PCR reactions in presence of mar gene specific primers as shown (Figure 6) where Escherichia coli KT-1_mdr bacterial plasmids were amplified with mcr, tet, bla VIM and acrAB mdr genes specific primers. Such PCR product could be confirmed by di- deoxy DNA sequencing as shown in (Figure 7) where blaTEM gene was found in every ampicillin resistant bacteria we have isolated from Ganga River water of Kolkata [3,10]. [Click here to view Large Figure 5] [Click here to view Large Figure 6] [Click here to view Large Figure 7] [Click here to view Large Table 1] Conclusion It is very evident that superbugs were highly contaminated in water resources of India similar to other Asian and American countries [11,12]. WHO warned that if alternative to antibiotics were not discovered, very fatal human loss might be occurring in the future? Likely herbal antibiotics research has given priority in India as there is enough medicinal plants and spices available as described in Sanskrit books Charaka Samhita and Veda [8]. However, gene medicines (ribozymes, miRNA, antisencse RNA, and DNA nanotechnology have benn welcome to stop the horror of MDR bacterial pathogenesis. MDR phenomenon is ancient and also universally have detected in viral pathogenesis, cancer cells and parasitic diseases [13,14]. More sadly, bacteria have acquired promoter induction system by antibiotics and many transcription factor repressors (tetR, acrR) have been accumulated in conjugative plasmid. What it mean that if you take imipenem then it will activate MDR genes causing more AMR and simply patient will die on antibiotic treatment [15].

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