Title: CDC Draft Guidelines For Reopening U.S. Being Reviewed by White House
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

You can now search for Open Access articles that have certain types of licenses, by using special filters in both PMC and PubMed. These filters are based on license information that is provided to PMC by publishers and other content providers, as encoded by machine-readable identifiers in the source XML of each article. For more information, see our updated Open Access Subset page.

Collaboration with publishers and funders to ensure the openness and preservation of the scientific record is one of PMC’s core principles. Open Access Week offers an opportunity to celebrate some of the recent outcomes of these collaborations:

• In July 2018, the PMC corpus of publicly accessible articles hit 5 million articles.
• In May 2018, the PMC Open Access Subset surpassed the 2 million article mark.
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• The PMC and Research Funder Policy page underwent an update in September 2018 to increase transparency around funder support in PMC for publishers, authors, and the public.
• Funder policy support in PMC has been extended to the US Department of Homeland Security, in addition to several new US private research funders via the Health Research Alliance.

In FY2018 more than 200 new journals committed to archiving their complete contents in PMC, to be made publicly accessible in 12 months or less.

On March 18, 2019, PMC will no longer provide bulk packages of Open Access (OA) Subset text and XML at the top level directory of the FTP Service. These files were superseded in August 2016 by the Commercial Use and Non-Commercial Use bulk packages located in the oa_bulk subdirectory. One set comprises articles that may be used for commercial purposes (the Commercial Use Collection); the other contains articles that can be used only for non-commercial purposes. Anyone planning to use OA subset content for non-commercial purposes will need to download both “non_comm_use.*.tar.gz” and “comm_use.*.tar.gz” to access the complete collection. See the Open Access Subset page for additional details. Questions should be directed to pubmedcentral@ncbi.nlm.nih.gov.

ABSTRACT

Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB'-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met.

IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.

The selection and firing of DNA replication origins play key roles in ensuring that eukaryotes accurately replicate their genomes. This process is not well documented in plants due in large measure to difficulties in working with plant systems. We developed a new functional assay to label and map very early replicating loci that must, by definition, include at least a subset of replication origins. Arabidopsis (Arabidopsis thaliana) cells were briefly labeled with 5-ethynyl-2'-deoxy-uridine, and nuclei were subjected to two-parameter flow sorting. We identified more than 5500 loci as initiation regions (IRs), the first regions to replicate in very early S phase. These were classified as strong or weak IRs based on the strength of their replication signals. Strong initiation regions were evenly spaced along chromosomal arms and depleted in centromeres, while weak initiation regions were enriched in centromeric regions. IRs are AT-rich sequences flanked by more GC-rich regions and located predominantly in intergenic regions. Nuclease sensitivity assays indicated that IRs are associated with accessible chromatin. Based on these observations, initiation of plant DNA replication shows some similarity to, but is also distinct from, initiation in other well-studied eukaryotic systems.

OBJECTIVE

We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture.

Tlarge granular lymphocyte leukemia (T-LGLL) is characterized by the expansion of several large granular lymphocyte clones, among which a subset of large granular lymphocytes showing constitutively activated STAT3, a specific CD8⁺/CD4^– phenotype and the presence of neutropenia has been identified. Although STAT3 is an inducer of transcription of a large number of oncogenes, so far its relationship with miRNAs has not been evaluated in T-LGLL patients. Here, we investigated whether STAT3 could carry out its pathogenetic role in T-LGLL through an altered expression of miRNAs. The expression level of 756 mature miRNA was assessed on purified T large granular lymphocytes (T-LGLs) by using a TaqMan Human microRNA Array. Hierarchical Clustering Analysis of miRNA array data shows that the global miRNome clusters with CD8 T-LGLs. Remarkably, CD8 T-LGLs exhibit a selective and STAT3-dependent repression of miR-146b expression, that significantly correlated with the absolute neutrophil counts and inversely correlated with the expression of Fas ligand (FasL), that is regarded as the most relevant factor in the pathogenesis of neutropenia. Experimental evidence demonstrates that the STAT3-dependent reduction of miR-146b expression in CD8 T-LGLs occurs as a consequence of miR-146b promoter hypermethylation and results in the disruption of the HuR-mediated post-transcriptional machinery controlling FasL mRNA stabilization. Restoring miR-146b expression in CD8 T-LGLs lead to a reduction of HuR protein and, in turn, of FasL mRNA expression, thus providing mechanistic insights for the existence of a STAT3-miR146b-FasL axis and neutropenia in T-LGLL.

Some years ago, I entered a completely unfamiliar world. This was a landscape that clinicians deal with every day but for the individual suspected of having lung cancer, it can appear hostile and scary, often misrepresented by outdated imagery, information and television portrayal. Lung cancer is not awash with celebrities admitting to having it or grand fundraising campaigns like other conditions. Despite many changes in the treatment landscape, it's still generally much more stigmatised than other cancers.

The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of B. mandrillaris in vitro. Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.

Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].)

Competition ushers in new era to recognise the country’s standout real estate projects and senior leaders.

A temporary coronavirus hospital ward in China is being staffed entirely by robots. Around 200 patients with mild symptoms will be fed and treated by machines, while medical staff issue commands from outside

Inside a mountain in the Arctic, Microsoft is building a backup of open-source software that it says will keep the code safe for 1000 years

This could be a trial run for the rest of Disney’s parks in the US, Japan, France, and Hong Kong.

Don't analyse them too closely, they didn't have HD in the 1970s.

No going out to buy ingredients you don't already have, though. Crumpets are treats.

The country faces the same problem today it did two months ago: There are not enough tests to contain the virus.

Using reinforcement learning and randomized simulations, researchers taught this robot how to solve a Rubik's cube one-handed

OpenAI’s GPT-2 program churns out natural language that’s remarkably coherent—and that’s a problem

We learn how to run a sports league. Then we cover the big new Final Fantasy announcement. Then we’ve got exciting news for the new...

Focused ultrasound, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors -- and even help repair the devastating damage caused by stroke.

The UK Cinema Association aims to resume business before July release of Christopher Nolan’s blockbuster Tenet, as studios and distributors scramble to protect theatrical business model

The UK cinema industry is understood to be lobbying the government to approve a proposed reopening scheme that would see venues welcome customers by the end of June.

Phil Clapp, the chief executive of the UK Cinema Association said: “We’ve made representations to government on the safeguards which UK cinemas would look to have in place for audiences and staff alike upon re-opening, and have asked that consideration be given – with these in mind – to allow cinemas to open by the end of June.”

The White House is making "contingency plans" for a second wave of coronavirus after emails reportedly contradict their claims that Centers for Disease Control and Prevention guidelines to safely reopen the economy were set aside because medical experts did not approve of them.

Restaurants and drive-in movie theatres are allowed to reopen in Las Vegas today, with casinos hoping to reopen by Memorial Day.

Out of 200 employees tested at a German meat processing plant, 151 tested positive Thursday for coronavirus, triggering an "emergency mechanism" to delay the easing of social distancing restrictions.

College sports will not resume until all students are back on campus, NCAA president Mark Emmert said Friday.

Many studies suggest coronavirus has low transmission rates among children, but there are still risks to reopening schools that were closed due to social distancing policies

"Right now it is a concern, but they're taking measures ... we'll be up and running again shortly."

BEIJING - Grunts, groans and the sound of pulsing music and crashing weights have returned to some of Beijing's gyms after being closed for nearly three months due to the coronavirus outbreak.

Macy’s is planning to reopen its stores in the United...

The post Macy’s To Reopen 68 Stores In USA appeared first on Man's World India.

"People get so emotional when you give them communion for the first time in seven weeks," one religious leader said.

Pennsylvania Gov. Tom Wolf has a brewing rebellion on his hands as counties set out to defy his plans.

America can take its next steps toward reopening by placing an emphasis on emerging health data and closely examining how early states are performing, Housing and Urban Development Secretary Dr. Ben Carson asserted Saturday.

Lawsuits are pending from groups who have challenged the constitutionality of shrinking Bears Ears and Grand Staircase-Escalante

Plans finalized on Thursday for two national monuments in Utah downsized by Donald Trump would ensure that lands previously off-limits to energy development will be open to mining and drilling.

The move comes despite pending lawsuits from conservation, tribal and paleontology groups, who have challenged the constitutionality of the president’s action. The Trump administration slashed the size of Bears Ears national monument by 85% and Grand Staircase-Escalante national monument by nearly half in December 2017, in what represented the largest elimination of public lands protections in US history.

Conservation groups criticized the Trump administration on Thursday for spending time on management plans they believe will become moot when the court sides with their assertion that Trump misused the Antiquities Act to reverse decisions by previous presidents.

Planned sale of land to fossil fuel, mining and and timber concerns mirrors rollback of Obama-era pollution regulations

The Trump administration has ratcheted up its efforts amid the coronavirus pandemic to overhaul and overturn Obama-era environmental regulations and increase industry access to public lands.

The secretary of the interior, David Bernhardt, has sped efforts to drill, mine and cut timber on fragile western landscapes. Meanwhile, the EPA, headed by the former coal lobbyist Andrew Wheeler, has weakened critical environmental laws and announced in March that it would cease oversight of the nation’s polluters during the Covid-19 crisis.

While NBA teams are slowly gearing up to return to training facilities this week, the league has reportedly issued a memo prohibiting those with elevated temperatures from participating.  

Dallas Mavericks owner Mark Cuban has been the most outspoken figure in the NBA to push for the season to resume but he made it clear on Thursday that he won’t even consider opening the team’s training facility until everyone is able to get tested for coronavirus. 

The direction of ocean currents can determine the direction of gene flow in rafting species, but this depends on species traits that allow for rafting propensity. This is according to a study focusing on seahorse and pipefish species. And it could explain how high genetic diversity can contribute to extinction in small populations.