Monday night's game figures to have a big impact on the NFC playoff race.

The Redskins need two more victories to close out the season, including one against the Eagles in the regular-season finale, just to get their playoff chances to 80 percent.

How can you get free things on your next cruise, and get much more bang for your cruising bucks? I discuss the 6 main areas of cruise freebies that are available, if you go and ask for them or seek them out. They are not things that cruise brochures and websites usually reveal, or talk about. I tell you the things to focus on and how to get as many free things as you possibly can, including drinks, special food, gifts, spa treatments, better and improved cabins and more.

** Buy my Cruise T-shirts: http://bit.ly/TFTStore
** USA cruisers get great cruise deals CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise
** UK Cruisers get great cruise deals with CRUISE.CO.UK: http://bit.ly/BookCruiseUK

Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises.

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MacOS Catalina introduced a handy way to tile windows for multitasking, improving upon the split screen multitasking features that were available in previous MacOS releases. These new simple tiling window multitasking options are available from any window, and now you can easily choose to tile a window to the left or right side of the ... Read More

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

Hany Farid talks about fighting fake videos: "Mathematically, there's a lot of linear algebra, multivariate calculus, probability and statistics, and then a lot of techniques from pattern recognition, signal processing, and image processing."

(JAMA Network) This randomized clinical trial looked at the effect of a face-aging mobile app on daily sunscreen use and other skin protection among teens in Brazil. Selfies of students were altered to show UV effects on their future faces and shown to their class, accompanied by information about sun protection. Reducing UV exposure in children and adolescents is important because of the increased risk of skin cancer with cumulative UV exposure and sunburns early in life.

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 

Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.

A TB infection can take two forms, active and latent. Active disease is transmissible, and causes the damage to the lungs which makes TB one of the biggest killers in the world. In the latent form, the bacteria Mycobacterium tuberculosis is quiescent and can stay that way for years until it becomes active and causes those clinical signs. Testing...

One of the best catchers in baseball was available all winter in J.T. Realmuto, and the Reds were very much one of the teams in hot pursuit in trade talks with the Marlins. But on Thursday, it was the Phillies who acquired Realmuto from Miami.

She’s what you’d term the consummate creative – through the sensory ‘dry land tourist’ tales of her ‘Right Roun Di Corna’ blog to the pieces in her JadeLauren eyewear brand, Lauren Campbell is colouring the world with beauty, life, and bomb...

Blood clots, skin rashes and other lesions might be among the symptoms some people experience with COVID-19, according to new research released Thursday.

Originally published in June 1899

-- Read more on ScientificAmerican.com

4 salmon fillets, skin on (175g per portion) 2 tbs soy sauce 1 tbs rice wine vinegar 1 tbs olive oil 1 clove garlic, minced 1 tbs ginger, mined 1 small red chilli 1 lime, juiced

Salmon with a twist.

There's a simple and powerful way to confront the world's most pressing crises, says women's rights activist Yifat Susskind: think like a mother. As she puts it: "When you think like a mother, you prioritize the needs of the many, not the whims of the few." Follow along as she shares moving stories of people around the world who embody this mindset -- and shows how it can also help you see beyond suffering and act to build a better world.

London : Adlard, 1904.

London : J. & A. Churchill, [1874]

London : H.K. Lewis, 1903.

New York : W. Wood, 1887.

London : H. Renshaw, 1849.

Springfield, Virginia : National Technical Information Service, 1974.

The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.

SIGNIFICANCE STATEMENT The transcription factor Nurr1 is ectopically induced in striatal neurons of rats exhibiting levodopa-induced dyskinesia [LID; a side-effect to dopamine replacement strategies in Parkinson's disease (PD)]. Here we asked whether Nurr1 is causing LID. Indeed, rAAV-mediated expression of Nurr1 in striatal neurons was sufficient to overcome LID-resistance, and Nurr1 agonism exacerbated LID severity in dyskinetic rats. Moreover, we found that expression of Nurr1 in l-DOPA naïve hemi-parkinsonian rats resulted in the formation of morphologic and electrophysiological signatures of maladaptive neuronal plasticity; a phenomenon associated with LID. Finally, we determined that ectopic Nurr1 expression can be found in the putamen of l-DOPA-treated PD patients. These data suggest that striatal Nurr1 is an important mediator of the formation of LID.

The Getty Museum hopes its social media challenge will spark inspiration amid the COVID-19 pandemic

Called "Social Distancing, Haiku and You," Alan Nakagawa's project will result in a sound collage that interweaves a multitude of voices

Are we really going to bet that we can go back to life as normal without proper coronavirus tracking in place?

To try and make life a little easier for you when trying to navigate the minefield of skincare, we’ve compiled a list of some of the companies out there making an effort to have cruelty-free products.

SPENDING less on skin care products can be tempting. Aren’t all the products the same? Don’t they all just use the same ingredients? You’re basically just paying for the brand name, right? It’s far too easy to fall into this trap – the trap which leads us to try and convince ourselves that the dollar store brand stuff is just as good as high-end beauty products.

Prudence Wade chats to self-confessed 'skincare junkie' Dominic Skinner, one of MAC's top make-up artists.

WITH the usual proviso that nothing, but nothing, in sport is in any way important when human lives are at stake due to coronavirus, nevertheless I do think it is time for some realism to surface in rugby – and other sports I could name.

Skin and soft tissue infections (SSTIs) are a common pediatric condition often requiring inpatient management. Several studies describe recent increases in hospitalizations due to SSTIs.

In addition to rising hospitalizations, analysis of pediatric SSTI resource utilization trends revealed a twofold increase in incisions and drainages over a 13-year period. A growing number of incisions and drainages were performed in younger children. (Read the full article)

Blood cultures are a common investigation in children admitted to the hospital with skin and soft tissue infections. The yield of blood cultures in this condition is unknown.

Blood cultures are not useful in children admitted to the hospital with uncomplicated skin and soft tissue infections, and they may be associated with increased length of hospital stay. (Read the full article)

Primary ciliary dyskinesia presents in infancy with unexplained neonatal respiratory distress, yet diagnosis is often delayed until late childhood. Earlier diagnosis facilitates earlier onset of therapy, which may help to reduce long-term pulmonary morbidity and mortality.

A diagnostic workup for primary ciliary dyskinesia should be considered in a term infant presenting with unexplained respiratory distress and either lobar collapse, situs inversus, or a prolonged oxygen therapy requirement (>2 days). (Read the full article)

Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US-FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), β-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC_50/90, 0.5/1 mg/L; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [lsqb]MRSA[rsqb]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [lsqb]ESBL[rsqb]-phenotype). A total of 74.4% of P. aeruginosa, 100% of β-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/L. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016–2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for the potential ABSSSI indication.

Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the Accessory Gene Regulator (agr) system, which is ubiquitous among staphylococci. Common and rare CoNS make autoinducing peptides (AIPs) that function as MRSA agr inhibitors, protecting the host from invasive infection. In a screen of CoNS spent media we found that Staphylococcus simulans, a rare human skin colonizer and frequent livestock colonizer, released potent inhibitors of all classes of MRSA agr signaling. We identified three S. simulans agr classes, and have shown intraspecies cross-talk between non-cognate S. simulans agr types for the first time. The S. simulans AIP-I structure was confirmed, and the novel AIP-II and AIP-III structures were solved via mass spectrometry. Synthetic S. simulans AIPs inhibited MRSA agr signaling with nanomolar potency. S. simulans in competition with MRSA reduced dermonecrotic and epicutaneous skin injury in murine models. Addition of synthetic AIP-I also effectively reduced MRSA dermonecrosis and epicutaneous skin injury in murine models. These results demonstrate potent anti-MRSA quorum sensing inhibition by a rare human skin commensal, and suggest that cross-talk between CoNS and MRSA may be important in maintaining healthy skin homeostasis and preventing MRSA skin damage during colonization or acute infection.

Many of education's most common questions skip a logical step or two, warns Alfie Kohn.

Dover, Del. (October 23, 2017) – The state of Delaware wants to hear from small business owners, community leaders and interested citizens as the new Division of Small Business, Development & Tourism charts a path forward. There will be three listening sessions this week – one in each county – to allow the public to […]

About 95 percent of watermelon is just water, which helps nourish your skin and make it radiant from within

  The earliest computers were often pushed to the limit performing even a single task, between hammering the hard drive, swapping memory frantically, and crunching through computations. With Microsoft W...

It's true that our skin needs regular breaks from makeup and repetitive layers of creams and moisturisers, more so for those with inflamed skin.