Probiotics might provide an alternative approach for the control of oral candidiasis. However, studies on the antifungal activity of probiotics in the oral cavity are based on the consumption of yogurt or other dietary products, and there is a necessary to use appropriate biomaterials and specific strains to obtain probiotic formulations targeting local oral administration. In this study, we impregnated gellan gum, a natural biopolymer used as a food-additive, with a probiotic and investigated its antifungal activity against Candida albicans. Lactobacillus paracasei 28.4, a strain recently isolated from the oral cavity of a caries-free individual, was incorporated in several concentrations of gellan gum (0.6% to 1%). All tested concentrations could incorporate L. paracasei cells while maintaining bacterial viability. Probiotic/gellan formulations were stable for 7 days when stored at room temperature or 4°C. Long-term storage of bacteria-impregnated gellan gum was achieved when L. paracasei 28.4 was lyophilized. The probiotic/gellan formulations provided a release of L. paracasei cells over 24 hours that was sufficient to inhibit the growth of C. albicans with effects dependent on the cell concentrations incorporated into gellan gum. The probiotic/gellan formulations also had inhibitory activity against Candida spp. biofilms by reducing the number of Candida spp. cells (p < 0.0001), decreasing the total biomass (p = 0.0003), and impairing hyphae formation (p = 0.0002), compared to the control group which received no treatment. Interestingly, probiotic formulation of 1% w/v gellan gum provided an oral colonization of L. paracasei in mice with approximately 6 log of CFU/mL after 10 days. This formulation inhibited the C. albicans growth (p < 0.0001), prevented the development of candidiasis lesions (p = 0.0013), and suppressed inflammation (p = 0.0006) when compared to the mice not treated in the microscopic analysis of the tongue dorsum. These results indicate that gellan gum is a promising biomaterial and can be used as a carrier system to promote oral colonization for probiotics that prevent oral candidiasis.

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.

Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.

The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.

Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate.

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

The off-label use of third generation cephalosporin (3GC) during in ovo vaccination or vaccination of newly hatched chicks, was a common practice worldwide. CMY-2-producing Escherichia coli have been disseminated among broiler production. The objectives of this study were to determine the epidemiological linkage of bla_CMY-2-positive plasmids among broilers both within and outside Japan because grandparent stock and parent stock were imported in Japan. We examined the whole genome sequences of 132 3GC-resistant E. coli isolates collected from healthy broilers during 2002-2014. The predominant 3GC-resistance gene was bla_CMY-2, which was detected in the plasmids of 87 (65.9%) isolates. The main plasmid replicon types were IncI1-I (n=21; 24.1%), IncI (n=12; 13.8%), IncB/O/K/Z (n=28; 32.2%), and IncC (n=22; 25.3%). Those plasmids were subjected to gene clustering and network analyses and plasmid multi-locus sequence typing (pMLST). The chromosomal DNA of isolates was subjected to MLST and single nucleotide variant (SNV)-based phylogenetic analysis.

MLST and SNV-based phylogenetic analysis revealed high diversity of E. coli isolates. ST429 harboring bla_CMY-2-positive IncB/O/K/Z was closely related to isolates from broiler in Germany harboring bla_CMY-2-positive IncB/O/K/Z. pST55-IncI and pST12-IncI1-I and pST3-IncC were prevalent in western Japan. pST12-IncI1-I and pST3-IncC were closely related to those detected in E. coli isolates from chicken in American continent, whereas 26 IncB/O/K/Z were related to those in Europe. These data will be useful to reveal the whole picture of transmission of CMY-2-producing bacteria in and out of Japan.

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

BACKGROUND AND OBJECTIVES:

Children with medical complexity (CMC) comprise only 6% of the pediatric population, account for ~40% of pediatric health care spending, and provide an important opportunity for cost saving. Savings in this group can have an important impact on pediatric health care costs. The objective of this study was to assess the impact of a multicenter care management program on spending and use in CMC.

France beat Croatia to earn a final tournament debut, as they joined Serbia, Romania and Poland in qualifying for UEFA Futsal EURO 2018 via the play-offs.

School boards are well positioned to push back against so much of the influences of the "progressive" left on our schools and our society, write Michael J. Petrilli and Chester E. Finn Jr.

There are plenty of ways to transfer large files between Windows, Mac, iOS, and Android devices, including AirDrop, Google Photos, Bluetooth transfer, and third-party programs.

The world's largest education research group said it will work to convert much of the annual meeting into a virtual experience for attendees and presenters.

G. C. Liggins
Oct 1, 1972; 50:515-525
ARTICLES

Yong Y. Han
Dec 1, 2005; 116:1506-1512
ARTICLES

G. J. Schwartz
Aug 1, 1976; 58:259-263
ARTICLES

All Classroom Q&A posts offering advice on Science Instruction (from the past eight years!) are described and linked to in this compilation post.

Rio de Janeiro, Brazil, Apr 20, 2020 / 09:25 am (CNA).- On Friday, Brazil’s Federal Supreme Court will hold a virtual hearing to consider whether to decriminalize abortion for pregnant women infected with the Zika virus.

The legal intervention, called “Direct Action on Unconstitutionality-ADI 5581,” was filed with Brazil’s highest court by the National Association of Public Defenders. Supreme Court Justice Cármen Lúcia Antunes Rocha will present the legal action to the court, whose 11 members will have until April 30 to vote on the issue.

Several pro-life organizations have come out strongly against efforts to expand abortion, which is illegal in Brazil but is considered a “non-punishable crime” in cases of rape, a proven risk to life of the mother and, as of 2012, babies diagnosed with anencephaly.

“It’s a usurpation of powers because the Supreme Court does not have competency to rule on this matter,” said jurist José Miranda de Siqueira, president of the National Association of Citizens for Life. “This is a crime against the Federal Constitution of Brazil which in Article V guarantees the inviolability of the right to life.”

“We’re working with the Union of Catholic Jurists of Rio de Janeiro and will soon issue a strong statement on the issue,” continued Miranda, who is also a bioethics professor and authored a book on euthanasia, “O Poder sobre a Vida” (The Power over Life), which specifically addresses ADI 5581.

“Life is a preeminent right in the legal world. I’m asking people to pray and publicize this serious situation which is going on,” the lawyer added.

In an open letter to all Brazilians, the National Network for the Defense of Life and Family argued that the court challenge is “part of a strategy to introduce abortion in case of disabilities in general, or even abortion on demand, with the weak justification that the pregnant woman would be in a state of distress.”

“Eugenic abortion carries an enormous burden of prejudice and discrimination towards people with disabilities, sending an unseemly message that it would be better if they did not exist,” the pro-life organization added.

The Zika virus garnered international attention in 2015 after areas of Brazil noted a spike in cases of the birth defect microcephaly – a condition marked by abnormally small heads, brains, and developmental delays – following a recent outbreak of the virus in areas of northeastern Brazil.

Research on the virus suggested a link between Zika virus infection during pregnancy and severe neurological birth defects, including microcephaly and incomplete brain development.

A CitizenGo petition addressed to the Supreme Court justices called for the case to be removed from the docket and for the lives of the unborn to be respected. The petition was launched April 16. Within 24 hours, it had garnered 35,000 signatures and as of April 20 has 85,000.
 

Rio de Janeiro, Brazil, Apr 27, 2020 / 04:35 pm (CNA).- A majority of Brazil’s Supreme Federal Tribunal has voted against an intervention seeking to decriminalize abortion for expectant mothers diagnosed with the Zika virus.

The judges convened a virtual plenary session April 24 to hear arguments for and against the “Direct Action on Unconstitutionality-ADI 5581,” a legal intervention filed with the court by the National Association of Public Defenders.

While the court has until April 30 to vote on the matter, 7 of its 11 members have already voted in opposition, effectively rejecting the measure.

Abortion is illegal in Brazil but previous Supreme Court rulings have declared it a “non-punishable crime” in cases of rape, a proven risk to life of the mother and, as of 2012, babies diagnosed with anencephaly.

The Zika virus garnered international attention in 2015 after areas of Brazil noted a spike in cases of the birth defect microcephaly – a condition marked by abnormally small heads, brains, and developmental delays – following a recent outbreak of the virus in areas of northeastern Brazil.

Research on the virus suggested a link between Zika virus infection during pregnancy and severe neurological birth defects, including microcephaly and incomplete brain development.

However, some experts criticized what they described as technical and scientific flaws of the premise behind ADI 5581.
The Union of Catholic Jurists of Rio de Janeiro issued an official statement arguing that a causal relationship was never established between Zika virus and the microcephaly outbreak that occurred in Brazil.

Raphael Câmara, an obstetrician at the Federal University of Rio de Janeiro, said that when an attempt was made in 2016 to allow abortion in Zika cases, little was known about the virus.

“Since then, we have answers to many of the issues raised in ADI-5581 in support of allowing abortion,” Câmara said. “The first fact is that recent studies show that fetuses of infected mothers are affected only 5 to 14% of the time, with the majority having mild problems, as shown by research from the Centers for Disease Control and Prevention.”

“In addition, a study recently released by the CDC showed that 73% of Brazilian labs have a low accuracy rate for diagnosing the Zika virus, so the request is meaningless because we cannot talk about someone 'infected with Zika', but rather 'maybe infected by Zika.’ Is it based on this inaccuracy that we will kill fetuses?” the obstetrician continued.

Ahead of the Supreme Court ruling, pro-life groups in Brazil had spoken out against efforts to expand abortion in the country. A CitizenGo petition against the legal action drew more than 184,000 online signatures.

The Brazilian Bishops’ Conference had also opposed the attempt, calling on Catholics to defend life and oppose abortion. The conference wrote an open letter and also wrote privately to the Supreme Court, reiterating the duty to value the inviolable gift of life.

In 2017, the conference stated, “It does not belong to any public authority to selectively recognize the right to life or who will live or die. This discrimination is evil and exclusionary.”

 

This article was originally published by our sister agency, ACI Digital. It has been translated and adapted by CNA.

 

Many of Penn State Behrend's student clubs and organizations have moved online due to COVID-19 restrictions. One benefit of the new model: It's easier to bring in guest speakers.

Selected poems of Rachelle Bowser, Rachel Mennies, Erin Murphy and Eleanor Stanford have been chosen to represent the Pennsylvania Center for the Book’s 2020 Public Poetry Project, with poetry interpreted into art posters for the annual event.

The cable is capable of delivering 72Tbps of bandwidth to South America and will be reserved for Gmail, YouTube, Search, and Google Cloud data transmission.

If you're looking for an economical and fuel-efficient hybrid vehicle for safe, reliable commuting, it's hard to beat the no-frills 2020 Toyota Corolla Hybrid.

The 'accelerator suppression function' is a new safety feature which ignores accelerator pedal input if the car thinks the driver pressed it by mistake.

Italian referee Nicola Rizzoli to officiate at Wembley

029 - Six clubs fulfil conditions set out by CFCB

Gibraltar becomes UEFA’s 54th member association

Draws for qualifying rounds to be held at UEFA Headquarters on 24 June

038 - Romanian club handed deferred sanction

041 - Draws to be held at UEFA headquarters in Nyon on 19 July

042 - Decisions made after Beşiktaş JK and Fenerbahçe SK appeal initial decision

043 - Draws to be held at UEFA headquarters on 9 August

The app failed for the same reason that every tech rollout struggles: bugs, user training, and the known unknowns.

Making sure the social and mental well-being of students is tended to is essential to getting young people through this period of chaos and uncertainty.

Next-generation sequencing has revolutionized the diagnostic process, making broadscale testing affordable and applicable to almost all specialties; however, there remain several challenges in its widespread implementation. Barriers such as lack of infrastructure or expertise within local health systems and complex result interpretation or counseling make it harder for frontline clinicians to incorporate genomic testing in their existing workflow. The general population is more informed and interested in pursuing genetic testing, and this has been coupled with the increasing accessibility of direct-to-consumer testing. As a result of these changes, primary care physicians and nongenetics specialty providers find themselves seeing patients for whom genetic testing would be beneficial but managing genetic test results that are out of their scope of practice. In this report, we present a practical and centralized approach to providing genomic services through an independent, enterprise-wide clinical service model. We present 4 years of clinical experience, with >3400 referrals, toward designing and implementing the clinical service, maximizing resources, identifying barriers, and improving patient care. We provide a framework that can be implemented at other institutions to support and integrate genomic services across the enterprise.

South Africa’s chloroquine supplies were temporarily depleted amid speculation that the drug could be used to treat the coronavirus and additional supplies to treat lupus sufferers had to be procured from India.

The Naples processor is designed to compete with Intel's Xeon offerings for the data center.

An Epyc server can contain up to 4TB of memory and 128 lanes of PCIe, making it a worthy Intel Xeon competitor.

The deal will help Marvell generate $3.4 billion in annual revenue, Marvell says.

Originally announced in February 2015, Apple is giving up on trying to build the new facility.

Microsoft realizes you can use the sea as a giant heatsink and save a small fortune in cooling costs.

While it won't be ready until 2022, it will create hundreds of jobs, run on 100 percent renewable energy, and be the first data center to take advantage of a new StatePoint Liquid Cooling system that promises a 50 percent reduction in water use.

The old NATO bunker in Germany was acquired in 2013 and then turned into a heavily-secured data processing center for illegal activities linked to organized crime and the dark web.

I'm a bit of a boat paddling enthusiast, as you might have guessed from some of my previous paddling blog posts. The amount of exertion in race-paddling is similar to running - the longest race I've paddled in a race so far was 13 miles (half-marathon distance). But in the [...]

The post How long does it take to paddle a canoe 100 miles? appeared first on Graphically Speaking.

The Delaware State Housing Authority (DSHA) honored students in the DSHA housing community for achieving academic excellence by making the honor roll and having perfect attendance, with a luncheon and awards ceremony at Polytech High School in Woodside, Delaware.

Wilmington, DE – Highlighting ongoing efforts to revitalize Delaware’s downtowns, Governor Jack Markell and Delaware State Housing Authority Director Anas Ben Addi presented a grant check on Monday to the owners of Tonic Bar and Grille, money that helped Tonic fund extensive renovations throughout the restaurant. Tonic’s grant rebate was funded by Delaware’s Downtown Development […]

DOVER – Delaware State Housing Authority (DSHA) held an event today marking the completion of renovations at Liberty Court, a public housing site in Dover, and recognizing the authority’s 20th year participating in Moving to Work (MTW), a U.S. Department of Housing and Urban Development (HUD) program. Many of the residents at Liberty Court participate […]

The Nebula Capsule II by Anker is an unusual entertainment projector: It runs the Android TV operating system, and can double as a Bluetooth speaker.