Posters have been reimagined to include slogans including 'visit when this is all over' and 'no swimming today'

'Quarantine would not only have a devastating impact on the UK aviation industry, but also on the wider economy,' said Karen Dee, chief executive of the Airport Operators' Association

MALDIVES holidays are on the bucket list of so many Britons thanks to the picture postcard-worthy scenery and year-round sun. Kandima Maldives is one of many hotels in the Indian Ocean nation, so what makes it stand out? This writer headed to the resort to find out.

From classic culture to stylish food, enjoy being pampered in Greece.

The Schengen area comprises of 26 beautiful countries and each of them offers an array of unique and awesome destinations for the travellers looking for a wonderful holiday. There are the popular places like Paris...

The post 5 Tips To Keep In Mind When Planning A Schengen Holiday appeared first on Geeky Traveller.

HOLIDAYS have been put on hold due to the coronavirus pandemic which has killed more than 100,000 people worldwide. When can we go on holiday again?

UK HOLIDAYS and staycations are becoming more sought after since the coronavirus pandemic sent most the world into lockdown back in March. With many planning their next staycation, the Trip Sisters gave their verdict on the best UK destinations for your next trip.

THE GOVERNMENT is to enforce a new rule which will see all travellers arriving into the UK being instructed to go into a 14-day quarantine period. It is not yet known how this rule will be enforced, or for how long, but it has the potential to change the way we experience holidays.

DUBAI hotels are slashing prices by up to 60 percent as part of its wider plans to boost tourism to the country.

UK HOLIDAYMAKERS have been urged not to book a summer holiday abroad following the Government's leaked airport quarantine plan, according to a leading aviation expert.

BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.

INFINITY pools can offer a dreamy escape from the current situation with seamless views over dazzling skylines, land and sea.

A little TLC can create a lovely green oasis in your garden to be proud of

GARDEN CENTRES closed their doors as the UK lockdown began but many are now facing calls to reopen as Brits up and down the country look for new ways to spend their extra hours at home. When will garden centres reopen? Will they be open in bank holiday?

VE DAY is one of the most important anniversaries in British history - and in time for the bank holiday, a huge number of incredible war films are available to watch.

UK HOLIDAYS and staycations are becoming more sought after since the coronavirus pandemic sent most the world into lockdown back in March. With many planning their next staycation, the Trip Sisters gave their verdict on the best UK destinations for your next trip.

UK HOLIDAYS have become even more popular as holidaymakers ditch their summer holiday plans for future staycation breaks. Here's a list of the best hiking destinations in the UK to get you ready for that post-lockdown break.

THE GOVERNMENT is to enforce a new rule which will see all travellers arriving into the UK being instructed to go into a 14-day quarantine period. It is not yet known how this rule will be enforced, or for how long, but it has the potential to change the way we experience holidays.

DUBAI hotels are slashing prices by up to 60 percent as part of its wider plans to boost tourism to the country.

UK HOLIDAYMAKERS have been urged not to book a summer holiday abroad following the Government's leaked airport quarantine plan, according to a leading aviation expert.

NORWEGIAN CRUISES is the latest cruise line to extend its sailing suspension, with holidays now cancelled right up until June 30. Can cruisers get their money back?

CRUISE holidays are on hold for now, however, many cruise enthusiasts continue to hold out hope for future cruises. For those looking to cruise in the future, but faced with a tighter budget, the good news is there are some ways you can save on sailings.

CRUISE ship holidays were a popular vacation choice for many Britons before the coronavirus pandemic struck. The crisis has hit the industry hard, leaving some reluctant to go on a cruise again - but now 12 travel writers have united to reveal why they love cruising so much.

CRUISE holidays are currently on hold, but new plans to implement safety regulations means that travellers must fit certain health criteria in order to sail. What will the new measures entail?

Coffee table picture book tells the 100-year history of the famous race

Justin (the oldest) and Aaron (the youngest) Holiday play for the Indiana Pacers; Jrue Holiday is the best-known of the brothers in the NBA.

Today I read a great post on Travelrants called Ten things that annoy me about booking holidays online. Darren made a list of 10 things that annoy him while booking holidays online. It’s clearly the kind of feedback/information people that work for Online Travel Agencies or Hotel Portals would love to gather from their visitors. That’s [...]

Emergency services and other authorities say travel to beaches and national parks will "cost lives".

It is a one-off holiday in the German capital, but some think it should be marked nationally each year.

Products for the popular character from the Disney Plus hit "The Mandalorian" are about to hit stores.

The Digital Development Group foresees dynamic growth in its industry. “On Nov. 21st we launched our first channel. We are excited to announce 5 more channels coming before year-end. On the heels of those developments we believe it is important to continue to define our mission.”

DigiDev is targeting the revolutionary “OTT” technology arena. “OTT” or Over The Top devices piggyback on existing network services in consumers’ homes or offices; pull content from the Internet and deliver it to their TV or Internet enabled device. DigiDev uses OTT technology to deliver programming to billions of desktops, mobile and smart/Internet enabled TV devices around the world.

“The market for digital distribution to 'smart' (Internet enabled) devices (smart-TV, tablet, smart-phones) continues to grow at an astonishing rate,” states Martin W. Greenwald, Chairman and CEO of DigiDev. “AppleTV, GoogleTV, and Roku sales this Holiday season are running considerably ahead of last year’s tally.”

*Guest Post* Many of my followers ask me how I travel so frequently and how do I manage my budget. I book my flight and hotel through FareoAir deals, I have been using this website for quite some time and I find their deals pretty good and economical. Anyhow, here is a collection of a few destinations which I find the best in terms of cuisine and suggest that you visit them if you are a food lover too.

Morocco

Want to know where you will find the best Berber cuisine? Well go to Morocco as it’s the best place on the planet for Berber cuisine. This means you get to eat your food in ancient medina towns served in tagine fragrant pots with delectable herbal teas. Plus you get to taste some of the North Africa’s freshest sea food.

India

Have you ever tried the spicy veggie Biryani? If no then a visit to India is must in Southern Kerala you will find delicious spicy veggie biryani. In Uttar Pradesh the thali platters of different food will amaze your taste buds and the smoked fish of Nagaland is scrumptious. Indian cuisine is without any doubt the most varied and has the most use of spices in it. It’s the perfect place to tease your taste buds.

Jamaica

We all like fresh food – and honestly speaking who doesn’t like fresh food? If you love fresh food too then Jamaica is the place to be. Stroll down in the Negril early morning an pick fresh plums from the branches of the trees before you settle at a rustic bamboo island hut for some fried salt water fish and ackee with a shot of rum. Delicious isn’t it.

New Zealand

Well the phrase surf and turf is perfect for New Zealand, it’s a strange combination of the finest Oysters from the Pacific Ocean and the highlander lamb cuts in the high-class restaurants of New Zealand with their traditional Maori style cooking. And yes how can I forget their wines, visit the cellars of Otago and you will never want to leave the place again.

Peru

Peruvian food is a true melting pot of multicultural flavors and cultures. In the last few years it has gained a reputation for being one of the finest fares on the culinary list of international favorites. Peruvian food is a little bit chinese, a little bit Japanese, Inca and Spanish thanks to the varied immigrant population of Japanese in this country - even Peru's leader is of Japanese descent. In Peru you can try many dishes like Cuy Asado (guinea pig), Lomo Saltado (the dish below) and Aji de Gallina (a thick testy chicken stew) from our Peruvian Food You Can't Miss on Your Machu Picchu Trip article.

Thailand

No food-lover will forget the food street of Bangkok, with its delicious variety of street food Thailand is another attraction that attracts many food lovers. They sell everything from coconut masaman, to Thai noodle soup and barbequed critters on sticks. Thailand is a place with a very different yet enticing food.

Italy

Yes at last my most favorite destination Italy. There is simply no denying that the Italians gave us the best food in the world Pizza and Pasta. Those crispy cheesy bases from the wooden ovens of Napoli are the best there is no denying in that. The roman kitchens also produce the finest cheese, aromatic coffees, fresh smoked fishes, and ligurian pesto and saffron risottos. All these dishes make Italy one of the best food destinations on the planet.

Mohamad Navab
Jun 1, 2004; 45:993-1007
Thematic Reviews

JF Oram
Dec 1, 1996; 37:2473-2491
Reviews

Purpose: To evaluate ¹¹C-choline PET/CT detection performance for biochemically recurrent prostate cancer (PCa) in a large non-European cohort in the context of emerging evidence for PSMA PET in this setting, and to map patterns of PCa recurrence. Methods: We retrospectively analyzed ¹¹C-choline PET/CT scans from 287 patients who were enrolled onto an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean:3.43 ng/mL, median:0.94 ng/mL, range:0.15–89.91) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP; 79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy (RT), and 70 had persistent PSA elevation after receiving initial treatment (69 post-RP, 1 post-RT). The level of suspicion for recurrence on ¹¹C-choline PET/CT was scored (0:negative, 1:equivocal, 2:positive) by two readers. The correlation between ¹¹C-choline PET/CT positivity and initial treatment, Gleason score, NCCN stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map ¹¹C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the two readers deemed 66% of the ¹¹C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with PSA<0.5 ng/mL, 56% of patients with PSA 0.5–0.99 ng/mL, 70% of patients with PSA 1.0–1.99 ng/mL, and 90% of patients with PSA ≥2.0 ng/mL scored either 1 or 2 on ¹¹C-choline PET/CT scans. When considering scores of 2 only, ¹¹C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA <0.5 ng/mL, 0.5–0.99 ng/mL, 1.0–1.99 ng/mL, and ≥2.0 ng/mL). In multivariate analysis, only the PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had ¹¹C-choline-positive suspected recurrences outside the initial treatment field. Conclusion: ¹¹C-choline PET/CT can detect PCa recurrence even among patients with low PSA levels when interpretation accounts for the clinical context, providing a certain pre-test probability. Until PSMA agents are fully approved for PCa, choline PET/CT may provide clinical utility.

Edward A Dennis
Apr 28, 2020; 0:jlr.T120000868v1-jlr.T120000868
Tribute

Inga Nilsson
Mar 10, 2020; 0:jlr.RA120000654v1-jlr.RA120000654
Research Articles

This week host Matt Egan is joined by first time podder and editor of PC Advisor Jim Martin to chat Microsoft Windows 10 anniversary updates and the impact on Microsoft Surface devices. Producer Chris then comes on to chat about Sky's two big NOW TV announcements, and the future of television and broadband (16:00). Finally, UKTW podcast regular David Price chats about the impact technology is having on our holidays (26:30).  

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Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport.

Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate (N-retinylidene-PE, NRPE) through a Schiff base linkage with phosphatidylethanolamine (PE). The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial (RPE) cells, their fluorescence characters and new findings related to light and iron-associated oxidation of bisretinoids.

Phospholipases A₂ (PLA₂s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca²⁺-independent phospholipase A₂ (PLA₂)β (iPLA₂β). Here, we assessed the link between iPLA₂β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA₂β–/–) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA₂β.Tg mice with selective iPLA₂β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA₂β^–/–, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA₂β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF₁α, PGE₂, leukotriene B₄) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA₂ or cytosolic PLA₂α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA₂β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA₂β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10^–6) with replication at Bonferroni-corrected P < 8.6 x 10^–4. Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10^–4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood–derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat–associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.

Nonalcoholic steatohepatitis has emerged as a major cause of liver diseases with no effective therapies. Here, we evaluate the efficacies and pharmacokinetics of B1344, a long-acting PEGylated FGF21 analog, in a nongenetically modified nonhuman primate species that underwent liver biopsy, and demonstrate the potential for efficacies in humans. B1344 is sufficient to selectively activate signaling from the βKlotho/FGFR1c receptor complex. In cynomolgus monkeys with nonalcoholic fatty liver disease, administration of B1344 via subcutaneous injection for eleven weeks caused a profound reduction of hepatic steatosis, inflammation and fibrosis, and amelioration of liver injury and hepatocyte death as evidenced by liver biopsy and biochemical analysis. Moreover, improvement of metabolic parameters was observed in the monkey, including reduction of body weight and improvement of lipid profiles and glycemic control. To determine the role of B1344 in the progression of murine NAFLD independent of obesity, administration of B1344 were performed in mice fed with methionine and choline deficiency diet. Consistently, B1344 administration prevented the mice from lipotoxicity damage and nonalcoholic steatohepatitis at a dose-dependent manner. These results provide preclinical validation for an innovative therapeutics to NAFLD, and support further clinical testing of B1344 for treating nonalcoholic steatohepatitis and other metabolic diseases in humans.

VOLUME 295 (2020) PAGES 4079–4092There was an error in the abstract. “The pyridinium cation hampers uptake of OPs into the central nervous system (CNS)” should read as “The pyridinium cation hampers uptake into the central nervous system (CNS).”

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.

Giulio Marchesini
Aug 1, 2001; 50:1844-1850
Pathophysiology

We aimed to assess the value of ¹¹C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on ^99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUV_max and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the ¹¹C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUV_max was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that ¹¹C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and ^99mTc-sestamibi imaging yield negative or discordant results.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging ¹⁸F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with ¹⁸F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of ^99mTc-sestamibi SPECT/CT, ^99mTc-sestamibi/pertechnetate subtraction imaging, and ^99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of ¹⁸F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: ¹⁸F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.