Diabetic keratopathy occurs in ~70% of all people with diabetes. This study was designed to examine the effects of vitamin D receptor knockout (VDR^–/–) and vitamin D deficiency (VDD) on corneal epithelial wound healing and nerve density in diabetic mice. Diabetes was induced using the low-dose streptozotocin method. Corneal epithelial wounds were created using an Algerbrush, and wound healing was monitored over time. Corneal nerve density was measured in unwounded mice. VDR^–/– and VDD diabetic mice (diabetic for 8 and 20 weeks, respectively) had slower healing ratios than wild-type diabetic mice. VDR^–/– and VDD diabetic mice also showed significantly decreased nerve density. Reduced wound healing ratios and nerve densities were not fully rescued by a supplemental diet rich in calcium, lactose, and phosphate. We conclude that VDR^–/– and VDD significantly reduce both corneal epithelial wound healing and nerve density in diabetic mice. Because the supplemental diet did not rescue wound healing or nerve density, these effects are likely not specifically related to hypocalcemia. This work supports the hypothesis that low vitamin D levels can exacerbate preexisting ophthalmic conditions, such as diabetes.

PURPOSE

Most real-world studies on anticoagulants have been based on health insurance databases or performed in secondary care. The aim of this study was to compare safety and effectiveness between patients treated with vitamin K antagonists (VKAs) and patients treated with direct oral anticoagulants (DOACs) in a general practice setting.

PURPOSE

Online programs may help to engage patients in advance care planning in outpatient settings. We sought to implement an online advance care planning program, PREPARE (Prepare for Your Care; http://www.prepareforyourcare.org), at home and evaluate the changes in advance care planning engagement among patients attending outpatient clinics.

This study investigated the effects of long-term soil fertilization on the composition and potential for phosphorus (P) and nitrogen (N) cycling of bacterial communities associated with hyphae of the P-solubilizing fungus Penicillium canescens. Using a baiting approach, hyphosphere bacterial communities were recovered from three soils that had received long-term amendment in the field with mineral or mineral plus organic fertilizers. P. canescens hyphae recruited bacterial communities with a decreased diversity and an increased abundance of Proteobacteria relative to what was observed in soil communities. As core bacterial taxa, Delftia and Pseudomonas spp. were present in all hyphosphere samples irrespective of soil fertilization. However, the type of fertilization showed significant impacts on the diversity, composition, and distinctive taxa/operational taxonomic units (OTUs) of hyphosphere communities. The soil factors P (Olsen method), exchangeable Mg, exchangeable K, and pH were important for shaping soil and hyphosphere bacterial community compositions. An increased relative abundance of organic P metabolism genes was found in hyphosphere communities from soil that had not received P fertilizers, which could indicate P limitation near the fungal hyphae. Additionally, P. canescens hyphae recruited bacterial communities with a higher abundance of N fixation genes than found in soil communities, which might imply a role of hyphosphere communities for fungal N nutrition. Furthermore, the relative abundances of denitrification genes were greater in several hyphosphere communities, indicating an at least partly anoxic microenvironment with a high carbon-to-N ratio around the hyphae. In conclusion, soil fertilization legacy shapes P. canescens hyphosphere microbiomes and their functional potential related to P and N cycling.

IMPORTANCE P-solubilizing Penicillium strains are introduced as biofertilizers to agricultural soils to improve plant P nutrition. Currently, little is known about the ecology of these biofertilizers, including their interactions with other soil microorganisms. This study shows that communities dominated by Betaproteobacteria and Gammaproteobacteria colonize P. canescens hyphae in soil and that the compositions of these communities depend on the soil conditions. The potential of these communities for N and organic P cycling is generally higher than that of soil communities. The high potential for organic P metabolism might complement the ability of the fungus to solubilize inorganic P, and it points to the hyphosphere as a hot spot for P metabolism. Furthermore, the high potential for N fixation could indicate that P. canescens recruits bacteria that are able to improve its N nutrition. Hence, this community study identifies functional groups relevant for the future optimization of next-generation biofertilizer consortia for applications in soil.

Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.

Plazomicin was active against 97.0% of 8,783 Enterobacterales isolates collected in the United States (2016 and 2017), and only 6 isolates carried 16S rRNA methyltransferases conferring resistance to virtually all aminoglycosides. Plazomicin (89.2% to 95.9% susceptible) displayed greater activity than amikacin (72.5% to 78.6%), gentamicin (30.4% to 45.9%), and tobramycin (7.8% to 22.4%) against carbapenem-resistant and extensively drug-resistant isolates. The discrepancies among the susceptibility rates for these agents was greater when applying breakpoints generated using the same stringent contemporary methods applied to determine plazomicin breakpoints.

Bacterial persisters are phenotypic variants that temporarily demonstrate an extraordinary tolerance toward antibiotics. Persisters have been linked to the recalcitrance of biofilm-related infections; hence, a complete understanding of their physiology can lead to improvement of therapeutic strategies for such infections. Mechanisms pertaining to persister formation are thought to be associated with stress response pathways triggered by intra- or extracellular stress factors. Unfortunately, studies demonstrating the effects of osmolyte- and/or pH-induced stresses on bacterial persistence are largely missing. To fill this knowledge gap within the field, we studied the effects of various osmolytes and pH conditions on Escherichia coli persistence with the use of phenotype microarrays and antibiotic tolerance assays. Although we found that a number of chemicals and pH environments, including urea, sodium nitrite, and acidic pH, significantly reduced persister formation in E. coli compared to no-osmolyte/no-buffer controls, this reduction in persister levels was less pronounced in late-stationary-phase cultures. Our results further demonstrated a positive correlation between cell growth and persister formation, which challenges the general notion in the field that slow-growing cultures have more persister cells than fast-growing cultures.

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

Antituberculosis (anti-TB) drug development is dependent on informative trials to secure the development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamide (PZA) are important components of recommended standard multidrug treatments of TB. Paradoxically, in a phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant drug effect was demonstrated for the two drugs using traditional statistical analysis. Using a model-based analysis, we characterized the statistically significant exposure-response relationships for both drugs that could explain the original findings of an increase in the numbers of CFU with CLO treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make the right decisions for advancement to further development. We propose that this quantitative semimechanistic approach provides a rational framework for analyzing phase IIa EBA studies and can accelerate anti-TB drug development.

Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N = 33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800–81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance, and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective.

Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10–78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment.Significance:Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib.

In the third quarter of 2019, condotel and resort villa market saw both supply and consumption falling by double digits since the ‘Ghost month’ made investors hesitate.

Signs of deceleration of the real estate market have appeared quite clearly in many segments since the beginning of this year, according to Tran Khanh Quang, General Director of Viet An Hoa Real Estate Company.

Electronic Arts in their fiscal year Q4 2020 results said they plan to release 14 titles in the 2021 fiscal year, which ends on March 31, 2021. Electronic Arts labeled one of the game as "an HD remake of an EA game."

VentureBeat is reporting this HD remake is an HD remaster of the Mass Effect Trilogy.

"We are planning to launch 14 new titles to players this fiscal year," said EA CEO Andrew Wilson. "hat includes four new EA Sports titles — FIFA, Madden, NHL, and one more unannounced sports game — all of which deliver on the mix of creativity, authenticity, and quality that sets EA Sports apart.

"Our FY21 plans also include four more games drawing on the breadth of our IP, from Command & Conquer Remastered to unannounced games for our console and PC players. We’ll have more games from indie developers launching this year through EA Partners, and two new mobile titles leveraging top IP that we’ll bring to players worldwide."

Read EA's full lineup for the 2021 fiscal year below:

1. Burnout Paradise Remastered (Nintendo Switch)
2. Command & Conquer Remastered (PC)
3. Medal of Honor VR
4. FIFA 21
5. Madden NFL 21
6. NHL 21
7. Unannounced sports game
8. An HD remake of an EA game
9. EA Partner game
10. EA Partner game
11. EA Partner game
12. EA Partner game
13. EA Mobile game
14. EA Mobile game

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443409/rumor-mass-effect-trilogy-hd-remaster-to-launch-by-march-31-2021/

Martha Wells's action-packed novel Network Effect puts you inside the head of a Murderbot. It raises fascinating questions you will think about for a long time, says Sally Adee

The UK government will begin trials of its coronavirus contact-tracing app this week, but what impact it will have on slowing the spread of covid-19 is unclear

This week we figure out BioWare’s next title. Then we settle the great question of Persona 4 vs. Nocturne. Finally, we give our list of...

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Scientists are working hard to understand how age changes the immune system so that they can better protect seniors against current and future infectious diseases

Chief junior national coach Sanjay Mishra tells his wards to try and control the negative thoughts which would also help them deal with tough match situations.

Remember that time Mrs Carter aka Beyonce aka the reigning...

The post The Beyonce Effect: OnlyFans Sees Massive Traffic Surge After Diva Drops Name appeared first on Man's World India.

As interest in the application of plasma medicine -- the use of low-temperature plasma (LTP) created by an electrical discharge to address medical problems -- continues to grow, so does the need for research advancements proving its capabilities and potential impacts on the health care industry. Across the world, many research groups are investigating plasma medicine for applications including cancer treatment and the accelerated healing of chronic wounds, among others.

What hasn't changed much in the past two month and may not change by the fall is the political fortunes of the NDP and Sask. Party.

The record is filled with soaring vocals, melodic guitar work, stomping grooves and more

The post Nagaland Pop-Rockers Trance Effect Release Smashing EP ‘Clowns’ appeared first on My Site.

Being discriminated against in the health-care system is one factor, but not the only one. 

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One study suggests one in three people from 16 to 64 have been victims of image-based abuse. But most will never step foot in a police station

When Laura* was 14, she was convinced that her boyfriend was the love of her life. So, when several girls messaged her to say he had sent them a video of her drunk and engaging in a sexual act, she told herself they were lying.

“I was just like, ‘Oh, you don’t know anything about our relationship. I don’t believe you,’” she says. “But after we broke up, he pretty much sent it to everyone that I knew.

The actress and her husband, Tom Hanks, were both hospitalised with the deadly virus

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As interest in the application of plasma medicine -- the use of low-temperature plasma (LTP) created by an electrical discharge to address medical problems -- continues to grow, so does the need for research advancements proving its capabilities and potential impacts on the health care industry. Across the world, many research groups are investigating plasma medicine for applications including cancer treatment and the accelerated healing of chronic wounds, among others.

Questions remain over the viability of the coronavirus contact tracing app that has been developed by the NHS's digital department, NHSX.

The impressive clinical response to ibrutinib seen in mantle cell lymphoma clinical trials can be achieved in the National Health Service, say UK clinicians, although progression rates remain high.
Medscape News UK

The future of Australian aviation is crucial for the wider tourism sector, which is already bleeding because of recent travel bans initiated to stop the spread of COVID19.

Click to view a price quote on TLRY.

The Department has reached a settlement agreement with the Alameda County, Calif., Sheriff’s Office, under which it will provide sign language interpreters and other auxiliary aids and services to arrestees, detainees, suspects, victims, witnesses, complainants and visitors who are deaf, hard of hearing or deaf-blind at two jails.

Revised regulations implementing the Americans with Disabilities Act (ADA) will take effect tomorrow, March 15, 2011.

“All individuals have a right to go to the hospital and communicate with medical staff without having to sign a waiver of liability, and hospitals have a responsibility to ensure that individuals get effective communication,” said Thomas E. Perez, Assistant Attorney General for the Civil Rights Division.

The Justice Department today announced a settlement agreement with the Alexandria Country Day School in Alexandria, La., to resolve allegations that the school denied a six-year-old girl with Type I diabetes admission to the school after her parents requested that the school supervise her in daily diabetes care practices.

As part of Attorney General Eric Holder’s call for cost-cutting measures to streamline operations and reduce spending during a time of constrained funding, the Department of Justice today announced that it will realign functions in various offices, lower lease costs by consolidating or reducing office space and continue to look for ways to more effectively utilize the department’s resources.

The Justice Department announced that the 2010 ADA Standards for Accessible Design go into effect today.

"Although there is still much work to be done, the United States has made significant strides in developing effective community responses to intimate partner violence that has stolen far too many promising futures – and shattered far too many lives," said Deputy Attorney General Cole.

Kathryn Keneally, Assistant Attorney General for the Tax Division, will leave her post at the Department of Justice effective June 5, 2014, she announced today.

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More than 2 million Americans suffer from opioid use disorder, but only about 25% of people receive any sort of care. For many, inpatient treatment often means leaving a job and loved ones behind to seek recovery.

Adults with non-valvular atrial fibrillation prescribed apixaban have a lower rate of ischaemic stroke and systemic blood clots compared with those prescribed rivaroxaban, according to a retrospective cohort study in Annals of Internal Medicine.

To read the whole article click on the headline

A recent study looking at the effects of caffeine on brief, high intensity exercise found the substance improved performance, regardless of genetic variations in how subjects metabolized caffeine.

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