As the Central African Republic (CAR) stares into an abyss of potentially appalling proportions, the international community must focus on the quickest, most decisive means of restoring security to its population.

Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum.

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.

A total of 2,283 Salmonella spp. isolates were recovered from 18,334 samples including patients with diarrhea, food of animal origin and pets across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistant to ≥ 1 antimicrobial and 56.4% were multi-drug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), 200 of which were CTX-M-type that were mostly detected from chicken meat and turtle fecal. Overall, eight bla_CTX-M genes were identified, with bla_CTX-M-65, bla_CTX-M-123, bla_CTX-M-14, bla_CTX-M-79, and bla_CTX-M-130 being the most prevalent. Totally, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (and S80I), whilst the PMQR-encoding genes oqxA/B, qepA, and qnrB/S were detected in almost all isolates. Of the fifteen sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in the number of isolates. Our study revealed considerable serovars diversity, high prevalence of co-occurrence of MDR determinants, including CTX-M-type ESBLs, QRDRs mutations and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDRs mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in the health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M Salmonella spp. isolates.

The password-fatigued masses will be pleased to find Keeper's new 30 percent off deal, which brings it down to $20.99 per year from its typical $29.99.

BACKGROUND AND OBJECTIVES:

The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

India, this magical land, has irresistibly captivated crowds of visitors because of definite motives: incredible Indian charms, numerous residues of past ages, and various sacred points for pilgrimage. Tourism in India has always been among the most full-blown spheres of the state's politics. India tourism allows traveling to all the most famous places, you may wish to visit. Among them, there are illustrious palaces and groves, forts built in both oriental and English colonial manners, and...

The march of Marvel off of Netflix continues and this month a few DC films join in, too.

Philip M. Farrell
Jan 1, 2001; 107:1-13
ARTICLES

Douglas K. Richardson
Mar 1, 1993; 91:617-623
ARTICLES

Start your new year off right by getting some new customized items for your business, or just treat yourself to a unique 2020 calendar of your own design, all for a fantastic price.

Google's reverse image search is a breeze on a desktop, but what about when you're on a mobile device? Google, Bing, and others have options.

Payback

A Florida city made the difficult decision to fork over the cash after ransomware hijacked city computers. Everyone needs to make their own choice, but I firmly believe you should never pay the ransom.

The top-rated Kindle Paperwhite, a PCMag Editors' Choice product, is available right now from $84.99 ($45 off) and the new Kindle is on sale starting at $59.99 ($30 off).

Spain's Dani Olmo was man of the match in the final against Germany: see every winner of that honour in 2019.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

Source: www.thegatewaypundit.com - Friday, May 08, 2020
  By Wayne Allyn Root Dear President Trump, here’s an important message from your supporters. First it was “Stormy Daniels.” Then, “Russian Collusion.” Followed by “the Ukrainian Hoax.” Now, it’s “Coronavirus pandemic” and the resulting economic catastophe. “THEY” never give up. But who is “THEY?” “THEY” can’t possibly be Pelosi, Schumer, Schiff, Nadler, Maxine Waters, AOC, et al. Their IQ totaled together and multiplied by 1000 isn’t enough brainpower to take you down, Mr. President. In my opinion “THEY” is a very wealthy, very cunning, globalist, elitist cabal- led by George Soros. Talk about Deep State. Thank God it’s you, as President of the United States, or “THEY” would have already won. There are those who think this pandemic was a planned attack. It wasn’t. It’s not a hoax. It’s very real- as I’ve said from day one. While Coronavirus is a very real pandemic, it was quickly turned into a “target of opportunity.” Likely an off-shoot of the socialist/communist Cloward- Piven plan I learned from my America-hating classmates at Columbia University three decades ago. The goal of Cloward-Piven was to overwhelm the US economic system; bury the economy under a mountain of debt; take down capitalism; bankrupt every business owner in America; and turn America into a socialist basket case like Cuba. Sound familiar? It’s all happening right now. I believe Soros and his socialist, globalist, elitist, America-hating cabal saw the Coron

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

A worker shares the story of one girl who recently took the courageous step to leave her life of prostitution for the freedom Christ offers.

In the 1980s, OM organised large summer campaigns with the huge task of covering every town and village in France with Christian literature.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

Fin24 presenter Moeshfieka Botha talks to Abdulazeez Davids of Kagiso Asset Management about how ratings downgrades affect ordinary South Africans.

As families devastated by the recent fire in a Bangladesh slum rebuild their lives, the team helps, and individuals tell their stories.

The faith of two young Bangladeshi men in 1976 served as a catalyst to OM’s focused outreach and the training of hundreds of new workers.

Buenos Aires, Argentina :: Maintenance crew share Christ's love with local welders helping repair Logos Hope.

Mission-Net welcomes more than 2,500 people and 110 mission organisations from Europe and other parts of the world to Erfurt, Germany, this week.

Leverkusen's tie with Porto hangs in the balance as the German club travel to Portugal defending a 2-1 lead.

Rangers' marathon UEFA Europa League campaign stretches into a 17th fixture as they play host to German heavyweights Bayer Leverkusen.

Bayer Leverkusen appear to be in complete control of this UEFA Europa League round of 16 tie after beating Rangers 3-1 in the Glasgow first leg.

A dream comes true - the first OM recruit from her country sends the next group of recruits to the OM ship.

When a short-term outreach team finds openness among an unreached people group, their church gets motivated to send more people.

“We were strangers, and they called us over to bless us. They didn’t have to give us anything—let alone everything—but they did it with smiles on their faces. They didn’t know us; they didn’t expect anything in return; they just gave,” remembers Nicole.

An OMer shows loves to a young boy at a children's home who finds it easier to connect with animals than with other people.

A man renews his decision to follow Christ after chatting with a volunteer during an OM flash mob in a busy area of Santiago.

When asked to share his testimony, a participant of OM Chile's Adventure Team realises just how much God has worked in his life.

A participant of OM Chile's Adventure Team shares about a man who was deeply affected while they visited the homeless in the streets of Santiago.

Black Friday offers have come from a multitude of brands — high street brands like Vero Moda and Only, smartphone companies like Xiaomi, Sony and Honor, beauty brands like Body Shop, Kiehl’s and Nykaa — infusing much joy among shoppers.

Brands can be broadcasters. Why rely on other media platforms when you can become your own media owner? Create, produce and publish your own content on your own channels.

The chain will be shutting 300-350 stores as part of its global business overhaul.

To effectively reach and engage with this new class of consumers who spend most of their time online, the medical community must explore digital marketing and make strategic patient-centric decisions.

WhatsApp tricks 2020 for iPhone includes some advanced tips such as how to schedule WhatsApp messages, how to hide online status, and how to send WhatsApp message without adding a contact.

The Supreme Court came down hard on Centre and states over the issue of pollution in the national capital. Citing examples of developed nations, the Court questioned why Delhi is choking every year. "Delhi is choking every year and we are not able to do anything.Every year this is

The ECB took to Twitter to share a throwback video of Virat Kohli's dismissal from India's 2018 tour of England.