Glass is the favorite material for parenteral packaging because of its physico-chemical properties. Type I borosilicate glass is worldwide use at this scope, but it may have some issues related to breakage, corrosion and delamination that might compromise the drug quality, safety and efficacy. These issues can be mitigated and avoided starting from the appropriate selection of the most suitable raw material at the early stage of the glass container design. In this study, Type I borosilicate glass vials manufactured using two glass tubes having different chemical compositions, were studied and compared in terms of their resistance to corrosion. Testing design was applied with the aim to select the best practice approach comparing different storage simulation conditions: ageing treatment through autoclaving and stability testing (real-time and accelerated). Clear differences were found between the different glass types in terms of hydrolytic and corrosion resistance that highlighted the relation between chemical composition and glass chemical durability. Non-negligible differences were also observed using different storage conditions.

When nutrients become scarce, bacteria can enter an extended state of quiescence. A major challenge of this state is how to preserve ribosomes for the return to favorable conditions. Here, we show that the ribosome dimerization protein hibernation-promoting factor (HPF) functions to protect essential ribosomal proteins. Ribosomes isolated from strains lacking HPF (hpf) or encoding a mutant allele of HPF that binds the ribosome but does not mediate dimerization were substantially depleted of the small subunit proteins S2 and S3. Strikingly, these proteins are located directly at the ribosome dimer interface. We used single-particle cryo-electron microscopy (cryo-EM) to further characterize these ribosomes and observed that a high percentage of ribosomes were missing S2, S3, or both. These data support a model in which the ribosome dimerization activity of HPF evolved to protect labile proteins that are essential for ribosome function. HPF is almost universally conserved in bacteria, and HPF deletions in diverse species exhibit decreased viability during starvation. Our data provide mechanistic insight into this phenotype and establish a mechanism for how HPF protects ribosomes during quiescence.

IMPORTANCE The formation of ribosome dimers during periods of dormancy is widespread among bacteria. Dimerization is typically mediated by a single protein, hibernation-promoting factor (HPF). Bacteria lacking HPF exhibit strong defects in viability and pathogenesis and, in some species, extreme loss of rRNA. The mechanistic basis of these phenotypes has not been determined. Here, we report that HPF from the Gram-positive bacterium Bacillus subtilis preserves ribosomes by preventing the loss of essential ribosomal proteins at the dimer interface. This protection may explain phenotypes associated with the loss of HPF, since ribosome protection would aid survival during nutrient limitation and impart a strong selective advantage when the bacterial cell rapidly reinitiates growth in the presence of sufficient nutrients.

BACKGROUND

Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes.

OBJECTIVE

Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes.

OBJECTIVE

Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).

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.

Yu Liu, Shuhua Qi, Fridtjof Thomas, Brittany L. Correia, Angela P. Taylor, Roy V. Sillitoe, and Detlef H. Heck

Respiration is controlled by central pattern generating circuits in the brain stem, whose activity can be modulated by inputs from other brain areas to adapt respiration to autonomic and behavioral demands. The cerebellum is known to be part of the neuronal circuitry activated during respiratory challenges, such as hunger for air, but has not been found to be involved in the control of spontaneous, unobstructed breathing (eupnea). Here we applied a measure of intrinsic rhythmicity, the CV2, which evaluates the similarity of subsequent intervals and is thus sensitive to changes in rhythmicity at the temporal resolution of individual respiratory intervals. The variability of intrinsic respiratory rhythmicity was reduced in a mouse model of cerebellar ataxia compared to their healthy littermates. Irrespective of that difference, the average respiratory rate and the average coefficient of variation (CV) were comparable between healthy and ataxic mice. We argue that these findings are consistent with a proposed role of the cerebellum in modulating the duration of individual respiratory intervals, which could serve the purpose of coordinating respiration with other rhythmic orofacial movements, such as fluid licking and swallowing.

PURPOSE

Operational failures are system-level errors in the supply of information, equipment, and materials to health care personnel. We aimed to review and synthesize the research literature to determine how operational failures in primary care affect the work of primary care physicians.

Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.

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.

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.

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.

Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single bacterial species but has expanded to the Burkholderia cepacia complex (Bcc), comprising 24 closely related opportunistic pathogenic species. These bacteria have a widespread environmental distribution, an extraordinary metabolic versatility, a complex genome with three chromosomes, and a high capacity for rapid mutation and adaptation. Additionally, they present an inherent resistance to antibiotics and antiseptics, as well as the abilities to survive under nutrient-limited conditions and to metabolize the organic matter present in oligotrophic aquatic environments, even using certain antimicrobials as carbon sources. These traits constitute the reason that Bcc bacteria are considered feared contaminants of aqueous pharmaceutical and personal care products and the frequent reason behind nonsterile product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in health care facilities, presenting a health threat, particularly for patients with cystic fibrosis and chronic granulomatous disease and for immunocompromised individuals. This review addresses the role of Bcc bacteria as a potential public health problem, the mechanisms behind their success as contaminants of pharmaceutical products, particularly in the presence of biocides, the difficulties encountered in their detection, and the preventive measures applied during manufacturing processes to control contamination with these objectionable microorganisms. A summary of Bcc-related outbreaks in different clinical settings, due to contamination of diverse types of pharmaceutical products, is provided.

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.

Patients with HPV16⁺ cervical cancer and high T-cell responses to an HPV16 vaccine survived longer.

A large international study found that the composition of the intestinal microbiome can predict clinical outcomes in patients undergoing allogenic hematopoietic-cell transplant (HCT) for blood cancers. The findings may help assess patients' transplantation-related mortality risk and aid in developing interventions to prevent or mitigate microbiome changes that affect HCT outcomes.

SUMMARY:

Use of mechanical thrombectomy for stroke has increased since the publication of trials describing outcome improvement when used in the anterior circulation. These results, however, cannot be directly translated to the posterior circulation. While a high NIHSS score has demonstrated an association with poor outcomes in posterior stroke, the NIHSS is weighted toward hemispheric disease, and complex scores potentially delay definitive imaging diagnosis. We performed a retrospective analysis to ascertain whether any rapidly obtainable demographic or clinical and imaging data have a correlation with patient outcome postthrombectomy. Seventy-three cases were audited between September 2010 and October 2017. Presenting with a Glasgow Coma Scale score of >13 meant that the odds of reaching the primary end point of functional independence (defined as a 90-day modified Rankin Scale score of 0–2) were 5.70 times greater; similarly, presenting with a posterior circulation ASPECTS of >9 resulted in the odds of reaching the primary end point being 4.03 times greater. Older age correlated to a lower odds of independence (0.97, p = .04).

The low supply of traditional office space expanding in central districts of Ho Chi Minh City (HCMC) has lead to the growth of coworking spaces, or flexible office spaces there.

The upsurge of land price leads to a real estate bubble, pushing up production costs, creating a virtual tendency and gradually increasing bad debt.

We're bringing you something new: SpeakerChat. This event is both a way to revisit some great eLearning Guild content from a recorded session while also […]

The post SpeakerChat for 05/01/20: Rapid Prototyping for Your eLearning Projects appeared first on e-Learning Feeds.

The UK government has pledged to make smart motorways safer by rolling out a radar detection system within the next three years, but New Scientist can reveal that just 7 per cent of the roads are protected by the measure today

An image-editing program designed by researchers at Abode uses AI to let you quickly transform the shape of objects in images and change the lighting

"This government has failed to show any self-criticism whatsoever, when it is glaringly obvious to everybody that big mistakes have been made."

Earth’s atmosphere thankfully provides air for us to breathe, but when trying to study interesting objects in space it causes all sorts of problems, writes Chanda Prescod-Weinstein

Experts discuss technological inequality and the “reskilling” problem at an MIT conference

MIT conference considers companies that have implemented job-friendly AI

For weeks after Ahmaud Arbery was killed while running down a road in coastal southern Georgia, there were few public developments in the case of a 25-year-old unarmed black man who was shot while being pursued by two white men with weapons in February.Then a graphic video of the shooting surfaced online, spurring widespread outrage.Within days, the Georgia Bureau of Investigation had taken over the case. The video was criticized by celebrities and politicians alike, including President Donald Trump, who called the footage "very, very disturbing," and former Vice President Joe Biden, the presumptive Democratic presidential nominee, who said Arbery had essentially been "lynched before our very eyes."And in a major turn, the authorities announced Thursday night that they had arrested two suspects in the case and charged them with murder and aggravated assault.The video -- which by Friday officials had described as "a very important piece" of evidence in moving forward with criminal charges -- was first posted by WGIG, a radio station in Brunswick, Georgia, which said it had obtained the footage from an anonymous source.But in a twist emblematic of the small-town politics that have defined the case, that source turned out to be a criminal defense lawyer in town who had informally consulted with the suspects.The lawyer, Alan Tucker, said in an interview Friday that the video had come from the cellphone of a man who had filmed the episode and that he later gave the footage to the radio station. Tucker's role was confirmed by Scott Ryfun, who oversees the station's programming.Asked why he had leaked the video, Tucker said he had wanted to dispel rumors that he said had fueled tension in the community. "It wasn't two men with a Confederate flag in the back of a truck going down the road and shooting a jogger in the back," Tucker said."It got the truth out there as to what you could see," he added. "My purpose was not to exonerate them or convict them."The video, taken from inside a vehicle, shows Arbery running when he comes upon a white truck, with one man standing next to its open driver's-side door and another in the bed of the pickup. Arbery runs around the truck and disappears briefly from view. Then the man standing outside the truck tussles with him, and three gunshots are heard.The authorities identified Travis McMichael, 34, as the person who shot Arbery. His father, Gregory McMichael, 64, a retired investigator at the local district attorney's office, was also charged.Before the charges were filed this week, two prosecutors had recused themselves from handling the case, citing professional ties to Gregory McMichael. Tucker, too, said he had been an acquaintance of McMichael's from their work in legal circles.Reports suggest Tucker had consulted with the McMichael family in some capacity during the investigation, although it is not clear to what extent. Reached by The Washington Post before his arrest Thursday, Gregory McMichael referred questions to Tucker.Tucker declined to comment on his conversations with the McMichaels on Friday, citing attorney-client privilege."I'm not going to tell you what I told them or what they told me," he said, using profanity to say that any conversations -- had they occurred, he said -- were none of the public's business.At times during the interview, a woman could be heard in the background whispering suggested answers to Tucker.By Friday afternoon, Tucker said that it had been decided that he would not be retained as the lawyer for either of the McMichaels, and it was unclear who was representing them.Tucker said he would not be representing anyone else involved in the case, as the authorities announced Friday that they were pursuing a number of leads, including investigating the man who took the video.The man, Roddie Bryan, lives in the neighborhood. He had shared the video with the police before sharing it with Tucker and was cooperating with the authorities, his lawyer, Kevin Gough, said in an interview Friday evening."Mr. Bryan has never tried to hide anything from anybody," Gough said. "If anybody wanted a copy of the video, he would give it to them."But he said the added attention, including the scrutiny from the authorities, had come as a shock to his client, a mechanic who had since lost his job and received threats. "The atmosphere down here is very volatile," Gough said. "People are in fear. That's all a result of the last few days."The latest developments in the case on Friday fell on Arbery's birthday, when he would have turned 26. Thousands of people commemorated the occasion by running 2.23 miles, a nod to Feb. 23, the date he was killed.This article originally appeared in The New York Times.(C) 2020 The New York Times Company

It’s that time of the year in the WHL. News of player signings are a daily occurrence and the Winnipeg Ice’s management team has been busy. On Monday, the club announced ...

The U.S. government reported more catastrophic economic fallout from the coronavirus crisis on Friday as the pandemic pierced the very walls of the White House and California gave the green light for its factories to restart after a seven-week lockdown.

Neil Ferguson, whose modelling has informed the UK's coronavirus strategy, says that the need for intensive care beds will come close to, but not exceed, national capacity

Children will face many hidden negative effects from the new coronavirus, but it's not too late to avert them, says Paul Ramchandani

Asos has been making more use of augmented reality (AR)...

The post Coronavirus: Asos Scales Up Usage Of AR Technology To Model Products appeared first on Man's World India.

Plan would help Trump administration advance projects held up over global heating concerns such as the Keystone XL oil pipeline

The Trump administration on Thursday unveiled a plan to speed permitting for major infrastructure projects like oil pipelines, road expansions and bridges.

Related: How the oil industry has spent billions to control the climate change conversation

Lendbreen, a pass high in the Norwegian mountains, was an important route from the Roman era until the late Middle Ages

While the virus seems capable of infecting some pets and wild animals, these cases probably aren’t occurring often

A new title from Smithsonian Books highlights the diversity of Earth's 10 to 100 million insect species

Some plants, like soybean, are known to possess an innate defense machinery that helps them develop resistance against insects trying to feed on them. However, exactly how these plants recognize signals from insects has been unknown until now. Scientists have now uncovered the cellular pathway that helps these plants to sense danger signals and elicit a response, opening doors to a myriad of agricultural applications.

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.

((This April 30 story has been corrected to say Starship can carry more than 100 metric tonnes of cargo, not 100 pounds in paragraph 9. The error occurred in a previous version as well.))

The Australian government on Monday set aside A$300 million ($191 million) to jumpstart hydrogen projects with the help of low-cost financing as the country aims to build the industry by 2030, the country's energy minister said on Monday.

Read our live updates on coronavirus HERE Coronavirus: The symptoms