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Address: 2569 Cartwright Road, Honolulu, Oahu, Hawaii, USA
Coordinates: 21.272379, -157.821198 (accuracy not guaranteed)
Waikiki Backpackers Hostel is listed on the following booking sites:Waikiki Backpackers Hostel at Hostelworld Not listed at Booking.com Not listed at HostelsClub
My wonderful days in Oahu
As l travel by myself I was so nervous about everything, but staff members were so nice, friendly and they helped me a lot so I could stay in the hostel comfortably. I was satisfied all the time during my stay here, especially Pizza night on Tuesday and BBQ night on Saturday. Those were so fun cause those parties gave me a chance to make new friends. I really want to revisit this place and if you plan to stay on Oahu for a while, I definitely recommend this comfy, sweet hostel!
Amazing, Clean Hostel!!!
This was a great hostel to stay. Everyone was friendly and helpful, the rooms were really nice and clean, the price is great, and the location is AMAZING!!! If you want to stay at a hostel, choose this one!
Really nice stay, clean, great people
Recommend! Great location!
The whole staff was excellent
This is an excellent hostel to stay. The staff was great. It was very clean. It was affordable. It was conveniently located.
Waikiki Backpackers Hostel is an odd mix of hotel convenience and rooms not wholly adapted for sharing with strangers. In addition, some areas, like the bathrooms and the pool area, are very clean, while the hallway carpets may have not been cleaned since the Clinton administration. There are miniature soaps in the bathrooms, but there are cockroaches in the closets.The LocationThe hostel is located within a five-minute walk from the main drag in Honolulu, and about ten minutes away from Waikiki Beach. It is accessible by bus, and the airport shuttle has a dropoff point in front. It is in a safe and busy area of Honolulu, if not a little too touristic. It is close to restaurants, bars, and a grocery store.Rooms and BathroomsThe hostel was adapted from a hotel, and the result is a little awkward -- some things you'd expect in a hostel are lacking and some you'd never expect are there. One example is the lack of lockers in the rooms -- these are essential in shared rooms; however, most rooms only have one small safe in the closet, if that. So only one lucky guest per room can have their valuables locked up, for a per-day charge. We stayed in two different three-bed dorm rooms equipped with a kitchenette and a small fridge, which was a very nice bonus, but not all rooms have this. The three-bed dorms have been adapted from two-bed hotel rooms with a pull-out couch (which is in fact the third bed; it is not uncomfortable). Another remnant of its hotel history is housekeeping -- beds are made every day, and towels and sheets are changed. A hair dryer and iron are available in the bathroom. The bathroom is clean and well maintained, without any signs of dirt, mold, or peeling paint. The one major problem with this hostel is that it has both bedbugs and cockroaches. The staff explained to us that the cockroaches come from outside and that we should keep our patio door closed if we didn't want them in. This is probably true and we will not hold them responsible for it. As for the bedbugs, unfortunately the staff and ownership don't take the problem seriously and try to pretend that the guests bring them in, or try to convince us that the bites come from mosquitoes. We had our room changed easily after we complained, but staff only believed other guests after they actually brought a bedbug to reception. This is unacceptable, especially since this is a common problem and we heard many complaints during our stay.Common SpacesThe hostel has a nice pool with lounge chairs and also a few tables with umbrellas. There is a well-furnished common area in the penthouse of the adjacent hotel; however hostel guests only have access to it by calling upstairs and having staff come downstairs and let them in. This can get a bit tedious if you want to go to the common room several times a day. The common penthouse has a TV and computer, as well as free Wi-Fi. It also has a kitchen and a balcony. It is clean and nicely furnished, and it is a good place to spend your lazy hours.SummaryOverall, this would be a good hostel if they correct the bedbug problem and clean the carpets (there is unfortunately a lot of variation in the cleanliness of the building -- while the rooms and the pool area are clean, the carpet in the hallways is stained and filthy). However, they don't seem to be in a rush to do it.
It was tough to find and didn't even have a sign, but the location was great, along with the price as compared to the rest of the hotels in the area. The rooms were really nice and were more like a hotel with a bathroom and kitchen.
Hostelworld (3948 Reviews)
HostelsClubNot listed on HostelsClub.
Hostels.com (3 Reviews)
Did not find the hostel you are looking for?See all 10 hostels in Oahu
Wi-Fi in Lobby/Commons
Lockers in Lobby
24 Hour Security
Credit Card Payments
Checkout: 11:00 (11 AM)
Curfew: No Curfew
Minimum Stay: 1 night
Reception Hours: 24 Hours


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Let us help you. Fieger Law is one of the most successful birth injury trial firms in the U.S. We have attorneys in the firm who specialize in infant cephalohematoma and know how to help you and your child. Below, we have outlined information that answers basic questions about infant cephalohematomas and how you can tell when you’re facing a long-term injury.
WHAT IS INFANT CEPHALOHEMATOMA?
A cephalohematoma is a pooling of blood between an infant’s skull and periosteum, or the lining over the bones. This condition is usually due to traumatic labor and delivery, and sometimes through using delivery assistance tools, which can fracture bones on the side of a newborn’s head. Frequently, blood vessels in the periosteum rupture, further complicating the cerebral hemorrhage.
WHAT CAN CAUSE INFANT CEPHALOHEMATOMA?
The use of forceps and/or vacuum during delivery can cause cephalohematoma. However, these surgical tools can help medical staff speed up delivery in the following cases:
- Prolonged labor, high-risk pregnancies or multiple infant pregnancies.
- Infants whose heads are larger than the birth canal.
- Infants in unnatural or distressed birth positions.
Cephalohematoma usually resolves naturally with no damage to brain cells or lasting negative effects. However, it can signal more serious brain injury. It is crucial that you contact Fieger Law and a lawyer that specializes in infant cephalohematoma if you suspect a more severe injury is possible.
HOW DO I KNOW IF MY BABY’S CEPHALOHEMATOMA INDICATES A SERIOUS BRAIN INJURY?
- Are there symptoms of anemia?
- Are there symptoms of infection?
- Has your baby been diagnosed with jaundice?
- Are there any unnatural bulges on your baby’s head?
- Is there bruising on your baby’s head?
- Is your child showing signs of developmental delays?
- Is your child showing signs of motor skill deficiencies?
- Is the cephalohematoma lasting longer than three months, or longer than expected?
If any of these conditions have occurred, your child may have suffered a more serious brain injury that can cause cerebral palsy and other developmental problems. Fieger Law can help you get the answers you need. We don’t just settle cases as quickly as possible, which is what you can expect from many other law firms. We are always prepared to go to trial, and we are not afraid to win.
SECURING THE NATION’S LARGEST VERDICTS FOR BIRTH INJURY VICTIMS SINCE 1983
For over 70 years, the infant cephalohematoma experts and nationally-recognized medical malpractice lawyers at Fieger Law have fought for victims’ rights. If you or your family member suffers from a medical mistake, Geoffrey Fieger and the expert attorneys at Fieger Law can help. Contact Michigan’s top law firm specializing in infant cephalohematoma cases today.

domain: medical


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Category Archives: Bookends
Since today is Valentine’s Day what better opportunity can there be to talk about how fiction represents romance and love? St Valentine is traditionally associated with courtly and romantic love but authors through the ages have shown different facets of the emotion. So today I’ve picked ten fictional couples whose relationships represent different dimensions of love.
Since the course of true love doesn’t always run smoothly, let’s start with a few examples of troubled relationships.
Pip and Estella
We begin with an example of unrequited love via Charles Dickens’ Great Expectations. Pip, the humble blacksmith who gains wealth from a mysterious benefactor, falls in love with the glamorous Estella though she is aloof and hostile towards him. Dickens’s ending makes it ambiguous whether the two ever marry.
The Butler and the Housekeeper
Kazuo Ishiguro’s Booker prize winning novel The Remains of the Day, gives us an example of love that is never declared. Stevens the butler at Darlington Hall has practiced restraint for so long that he cannot ever allow himself to relax enough to show his true feelings. His relationship with the young housekeeper Miss Kenton at times comes close to blossoming into romance but even when Miss Kenton tries to draw closer to him, his stunted emotional life holds him back.
Sebastian Flyte and Charles Ryder
Love of a different nature is shown in Brideshead Revisited by Evelyn Waugh, where two young men meet as students at Oxford. Charles Ryder, who comes from a sterile, loveless home, is mesmerised by the glamorous and wealthy Flyte family and their stately home at Brideshead. He spends idyllic summers with Sebastian but is powerless when his friend descends into depression and alcoholism. Bruised by the experience, Charles falls into a loveless marriage and then finds temporary solace with Sebastian’s sister Julia. The question readers have to decide for themselves is whether Sebastian was simply the appetiser for the real deal of Charles’ love for Julia or is she second best to Sebastian?
Elizabeth Bennett and Lord Darcy
Sometimes love happens between the most unlikely of individuals. The romantic clash between the opinionated Elizabeth Bennett and the proud Mr Fitzwilliam Darcy is one that has delighted readers since Pride and Prejudice was published in 1813. Jane Austen gets them off to a rocky start however. In their first encounter Darcy thinks Jane”…tolerable, but not handsome enough to tempt me.”
“From the very beginning— from the first moment, I may almost say— of my acquaintance with you, your manners, impressing me with the fullest belief of your arrogance, your conceit, and your selfish disdain of the feelings of others, were such as to form the groundwork of disapprobation on which succeeding events have built so immovable a dislike; and I had not known you a month before I felt that you were the last man in the world whom I could ever be prevailed on to marry.”
Frank Doel and Helene Hanff
You could argue that isn’t strictly a romantic relationship since the author Helene Hanff and the antiquarian bookseller Frank Doel never meet. But I’d challenge anyone to read the letters that fly from New York to London in Hanff’s memoir, 84 Charing Cross Road, and not come to the conclusion that there is something more going on than just a mutual affection for books.
Gabriel Oak and Bathseba Everdene
In Far From the Madding Crowd, Thomas Hardy shows love can endure despite many challenges. Gabriel Oak (his name is a big clue as to his nature) doesn’t give up when the uppity Miss Everdene rejects his marriage proposal. He becomes a servant on her farm while she embarks on a disastrous relationship with a solider. But when she needs him most, he is ready to forgive…. Hardy is careful to show that the love that Gabriel and Bathsheba share is not the passion of a first love but a sadder and wiser connection born out of trials and tribulations.
Sapper Kip and Hana the nurse
I can’t talk about love without mentioning my favourite Booker prize winner, The English Patient by Michael Ondatjee. It shows that sometimes love flourishes in the most unlikely of situations. In this case, in a bomb-damaged Italian villa during the Italian Campaign of World War II, where four people are thrown together unexpectedly. Hana, a troubled young Canadian Army nurse, is caring for a man severely burned in a flying accident. The death of her lover causes her to believe that she is cursed and that all those around her are doomed to die. The arrival at the villa of a Sikh British Army sapper, reawakens her emotions. But their affair is shortlived. Kip is horrified when he learns about the Hiroshima bombing, leaving the villa to return to his native India. He never sees Hana again though he never stops recalling the effect she had on his life.
Dexter and Emma
How long can you be in love with someone and yet never realise it? For the couple in David Nicholls novel One Day, it takes almost 20 years for them to get together after they spend the night together on their graduation from Edinburgh university. The novel visits their lives and their relationship on that date – 15 July – in successive years in each chapter, for 20 years. Does it all end happily? Not quite. But you’ll have to read the book to discover why not.
Benjamin Braddock and Elaine Robinson
I can’t end without an example of what many people would consider to be the ultimate romantic gesture. In The Graduate, Benjamin, a new college graduate with no idea what to do with the rest of his life, is seduced by an older woman, Mrs. Robinson. But then realises it’s her daughter Elaine that he loves. Slight problem: she is about to marry another boy. Queue a desperate race to get to the church before Elaine says I do. If you’ve watched the film starring Dustin Hoffman and Anne Bancroft, you’ll know there is a dramatic ending involving a bride and a bus. I’m not cheating here by the way – the film is in fact based on a novel of the same name written by Charles Webb and published in 1963.
So there you have 10 couples who each, in one way or another, reflect love in many forms. Are there any couples you think of instantly when the subject of love crops up?
Now I’ve managed to close the lid on 2018 (see my wrap up post here), its time to turn my attention to 2019.
I’ve been wrestling with the question of whether to join some of the many challenges that are available. But on balance I decided that last year’s experiment with “Reading Naked” (by which I mean picking my next book randomly) was liberating so I plan to continue using that approach this year.
That doesn’t mean my year will be entirely without structure. But I’ll focus on projects rather than challenges. Challenges usually involve meeting a specific goal – reading a targeted number of books for example, or specified categories of books by a set date. I prefer the more open-ended nature of a project that I create for myself, where I get to decide on the scope and parameters. I want the flexibility to go wherever my mood takes me.
Here’s how the year ahead could pan out.
I’m going for simplicity; largely avoiding specific goals in favour of general directions. Most of these are continuations of existing projects and activities but – just to ring the changes – I’m going to start two new activities.
- Finish the Booker Prize project. This is the only specific goal I’m adopting this year. It should be a piece of cake since I have just two books and then I’m done. Although I have copies of the 2016 and 2018 books I’m not going to count them. If I manage to read them this year, they’ll be considered as bonus.
- Re-connect with the Classics Club project. I’m now 12 books away from the target of 50. But I keep finding new titles to add so this could be a movable feast.
- Travel the world: I stalled last year in my plan to read authors from a broader range of countries. In a year when the UK is supposed to say goodbye to the EU, it feels appropriate to make sure my reading tastes have an international dimension.
- Move through years of my life: I have a feeling that by reading more from my Classics Club list, I will be able to make progress on the Years of My Life project without having to make a special effort.
Booker Talk Team Expands
Booker Talk is approaching its 7th anniversary. I’m marking this milestone by expanding the team. Two new faces will be making an appearance on this site shortly, contributing reviews and articles on reading, authors and books.
Cerian Fishlock is currently studying for an MA in Publishing. She’s an Agatha Christie fan who’s desperate to find a modern author that can match the Queen of Crime . She loves novels with a psychological edge and “if that can be combined with defeating the patriarchy, even better.”
Edward Colley is a retired newspaper editor and graphic designer with an eclectic taste in books. He counts Thomas Hardy among his favourite authors. In between reading fiction he enjoys biographies and travel writing .
Connecting with Welsh authors/publishers
For the past year I’ve been trying to support and promote literature from my home country of Wales, through reviews and the odd feature article on this site. Now I’m going a step further by creating a new series where we get to know some of the authors based in Wales.
I’m calling this new series Cwtch Corner. The idea is to get into a conversation with an author about their favourite authors and books, how and where they get their inspiration and what readers can expect from their own novel/s. This is a spot where authors could pitch their work to potential readers.
Never seen that word Cwtch before? It’s a word used in the Welsh language to describe a physical place – a small cubbyhole for example or a small room in a pub. But it also denotes a form of affection, love and caring. Think of it like a cuddle or a hug. So authors taking part in Cwtch Corner are hopefully going to find the experience a bit like being wrapped in a warm embrace.
I’m reaching out to authors to participate at the moment but if you know someone you think might be interested just ask them to contact me via Twitter using @bookertalk. Please note however that I am not intending to feature self-published authors.
According to Lisa at ANZ LitLovers LitBlog it’s time once more to play A Year in First Lines.
The idea is to:
Take the first line of each month’s post over the past year and see what it tells you about your blogging year.
Let’s recap on the year…
Jan 2018: Reykjavík Nights by Arnaldur Indridason
Sometimes the brain just craves crime.
Feb 2018: Snapshot February 2018
Throughout 2017 I was making a note on the first day of the month of what I was reading and the level of what I call my personal library (otherwise known as the TBR mountain)
March 2018: Books to mark Wales’ special day
March 1 is St David’s Day in Wales —St David being our patron saint — so usually a day for celebration of all things Welsh.
April 2018: Three Things About Elsie by Joanna Cannon
One of the most memorable episodes in Alan Bennett’s series of dramatic monologues Talking Heads features an elderly lady who has taken a tumble in her home while doing a little illicit dusting.
May 2018: WWWednesday 2 May 2018
Currently reading: The Whale Caller by Zakes Mda. This is a book I picked up on my holiday late last year in South Africa when I asked a bookshop owner for recommendations of South African authors.
June 2018: An alternative Golden Booker Prize
2018 marks the 50th anniversary of the Man Booker Prize.
July 2018: New additions to the shelves
After months of admirable self restraint, the flood gates opened in the last few months and all my attempts to whittle down my stack of owned-but-unread books have been thwarted.
August 2018: Classics club spin falls on Mitford
The anticipation is over and the result of the latest Classic Club Spin is in.
September 2018: Six Degrees from film memoir to crime
It’s time for #6degrees which this month begins with a memoir: Where Am I Now? True Stories of Girlhood and Accidental Fame by Mara Wilson.
October 2018: Lullaby by Leïla Slimani
It takes a brave author to begin a novel by revealing the ending.
November 2018: Non-Fiction November: favourite reads
I’ve taken the plunge and joined Nonfiction November which is an annual challenge to read, critique and discuss non-fiction books for a month.
December 2018: Kingdom of the Blind by Louise Penny
How long can a series endure before it runs out of steam?
What does this tell me about my blogging year?
- I tend to write in short sentences
- Like practically every other blogger I’ve come across, I buy far more books than I can possibly read
- Even though I stopped doing the Top Ten Tuesday meme, I still seem to spend a fair amount of time on other memes like Six Degrees of Separation and WWW Wednesday
- I managed to read a few books in translation (though not as many as in previous years)
- I have an interest in literature from my home country of Wales.
- I read crime fiction. I’m actually surprised by how much of this I did read this year genre given it’s not a favourite genre
- I am trying to read more ‘classics’. When I saw the August 2018 first line I remembered that, though I read the spin book, I never managed to write the review.
- I keep an eye on the Booker Prize
- I don’t write reviews very frequently (only 3 of these 12 months are a review post)
What does this mean for 2019?
I’m still mulling over my 2019 plans but this exercise has made me realise that I need to adjust the balance of reviews to other content like memes. I think I’ve been doing more of the latter because I’m slow at writing reviews, spending far too long trying to come up with the ‘perfect’ intro whereas memes etc don’t usually require as deep a thinking process. Consequently I am well behind with my reviews….. I feel a New Year’s Resolution in the wind….
You may have seen this meme doing the rounds recently. It originated as a tag on a book vlog apparently ( I don’t watch these so rely on other people highlighting interesting content).
- The last book I gave up on
Earlier this week I decided to part company with The Librarian by Salley Vickers. It’s the choice for the book club meet up in January. I wasn’t that excited by the selection because I wasn’t very enamoured by her earlier book The Cleaner of Chatres. But I hoped the fact that this plot involves books might prove more interesting. For anyone who doesn’t know this book, it concerns a woman who begins a new job as a children’s librarian and embarks on a mission to get more children enthused about reading. Right from the first few pages I knew I was going to have a problem with this novel. The writing style just jarred on me. In part it read like a synopsis of a story, with lots of telling, and very little showing. It also was very laboured and overly detailed. I lasted to about 60 pages and then decided it was a waste of time to go further when I had many other, greatly superior books awaiting me.
2. The last book I re-read
I’ve done very little re-reading in the past year. The last book I re-read was Peter Pan by J M Barrie – and that was only because it was a set book on a children’s literature course I was pursuing.
3. The last book I bought
The end of 2018 was signalled by a flurry of book purchases. Some were gifts for various family members but I also took the opportunity to acquire a few new items for myself. They included Winter by Ali Smith which is second novel in her Seasonal Quartet collection. I had planned to hold off reading this collection until all four had been published, but this was on offer at the bookshop and seemed too good an opportunity to miss.
4. The last book I said I read but actually didn’t
I’ve never said I’ve read a book when I haven’t. I usually have the reverse problem – always involving a crime novel – where I discover just after starting a new book that I had already read it even if I can’t recall the details of the plot.
5. The last book I wrote in the margins of
I do this only for books I’m studying for a course or where I am trying to get more knowledgeable about a particular topic in order to share the knowledge with other people. interest, as well as ordinary bookmarks.
6. The last book I had signed
This would be Katherine of Arragon by Alison Weir, the first in her Tudor Queens series. I took my copy along when she was in Penarth to talk about the second in the series —about Anne Boleyn. She kindly signed both books for me.
7. The last book I lost
My copy of Voss by Patrick White has disappeared without trace. If anyone finds it please let me know. It’s a rather sad looking paperback edition which I purchased via e-bay.
8. The last book I had to replace
I’ve been trying to think of circumstances in which this would happen and I’ve drawn a blank. I don’t tend to borrow books from other people , I always return books borrowed from the library and I’m not in the habit of losing my own books over a cliff edge or in the bath. If the case arose that the book club chose a book I no longer owned, I’d either get a library copy or go to the meeting relying on my memory.
9. The last book I argued over
I’ve had a few ‘spats’ over the years and a few ‘differences of opinion’ but arguments – never as far as I can recall. The last ‘difference of opinion’ was two days ago when my mum, who was spending Christmas with us, was engrossed in Helen Dunmore’s The Greatcoat. We often chat about the books we’re reading even if we have very different tastes. My mum thought The Greatcoat was superb, whereas I was underwhelmed by it and found the plot implausible beyond belief. We are still on speaking terms though….
10. The last book you couldn’t find
I know without any doubt that I have How Late it Was How Late by James Kelman on my shelves. I started reading it at the beginning of the year so I know it’s in the house somewhere. I can even remember that it’s a bright red cover with just the book title in block letters but no other artwork. Can I remember where I put it though? I can blame no-one other than myself. I have a semi alphabetical system but when I run out of space, books get shoved in anywhere……..

domain: literature


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A marvelous medley of curves and lines, the Modesto Console Table proves that modern design is anything but mundane. Measuring 28 inches tall, this console table will fit perfectly behind a sofa. The tabletop is crafted from durable engineered wood (engineered wood) with a lively checkered grain pattern. Sleek black metal legs arch inward, creating some cool curves. Some assembly is required, and a matching coffee table and end table complete the Modesto collection.
A Note About Engineered Wood
Often referred to as MDF, which stands for medium density fiberboard, ...
The modern, skinny-mini style of the Southern Enterprises Corman Console Table is going to make the perfect accent for your on-trend space. The frame of the table is made from powder-coated iron with a black finish. The lower shelves are made from shatter-resistant glass, and the wide shelf across the top is crafted from engineered wood. Faux-marble paper veneers give this top shelf a high-end touch with a flowing, dynamic pattern. This console is suitable for anywhere in your home.
A note about wood composite or engineered wood: Often referred ...
Keep your room's contemporary cool with the Black Metal Sofa Table. This sofa table coordinates beautifully with other pieces from Southern Enterprises' Belloza collection. The Belloza collection of tables features glass surfaces and black-finished metal frames to add a touch of elegance to match most any decorative scheme. This particular sofa table features one shelf about 10 inches below the top for a shadowbox effect that allows you creative freedom for decorating or just an extra spot to store your keys.
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A versatile, well-traveled beauty, the Southern Enterprises Drifton Travel Trunk Console Table has vintage steamer trunk style with plenty of storage and display space. This console table stands tall and features a wood case with antique black finish trimmed in antique bronze borders with matching nailheads. Coordinating metal legs and an ornate metal latch add antiqued appeal. This console table has a hinged lid that opens to reveal hidden storage within and a shelf below for display pieces.
The casual and versatile Southern Enterprises Kenton Console Table with 4 Baskets works well with classic or contemporary décor. This console table is made of acacia wood and veneers in a rich mahogany finish. Storage lives in the two top drawers and within the four removable natural seagrass baskets.
Introduce bold color and industrial style into your home with this Southern Enterprises Metal Console Table. It features a vivid red finish that makes it a stand-out behind your sofa or in the entryway. This console table includes a tempered glass top and one display shelf.
Sleek and slender, the Southern Enterprises Darrin 56 in. Console Table is going to provide a dash of glamorous function to any space. The body is made from square-tube metal with a golden finish of baked-on powder-coat. Across the top is a thick mirror with a wide, beveled edge. The mirror is backed by a panel of engineered wood, giving it the body it needs to hold decorative objects, books, or just a bowl for your car keys and loose change. This table is ideal in the foyer, hallway, or ...
With its slim profile, the Southern Enterprises Horten Narrow Console Table works for entryway, dining room, landing, and home office. The clear glass surface and mirrored lower shelf enliven your space and showcase your treasures. The iron frame features a gold finish.
The Southern Enterprises Denise Console Table is the key to a fab foyer, a sexy sofa, or a decidedly delicious dining room. Even though this table has a wide design, the body maintains an open, airy feel with a frame that's inspired by geometric shapes and crafted in rugged iron. A powder-coated, golden finish adds a warm sense of glam to the shape. Across the top is a thick mirror that's backed with engineered wood. The wood gives it the strength to function as a practical, everyday piece. The mirror ...
Keep your space airy, bright, and uncluttered with the Southern Enterprises Paschall Console Table. This glass-topped table features a silvered metal frame for a clean and contemporary feel. Display curiosities that express your style and heritage on the low glass shelf. This versatile console table stands guard anywhere in your home.
Made to be durable, the Mirage Mirrored 2-Drawer Console Table features a tough construction of engineered wood and mirror. You can place this compact, space-efficient console table in an entryway, doorway, or living room. Its mirrored finish allows this table to blend in with virtually any home décor-style. The two roomy drawers provide ample storage space for your belongings. In addition, the faux crystal drawer knobs and painted silver wood trim add to the visual appeal of this table.
The industrial glam Southern Enterprises Lazio Console Table is a perfect addition to your casual, chic space. This slim and tall console table fits behind your sofa or in the entryway. Shimmering mirrors add a modern glimmer to every surface. Nail heads and a matte silver trim finish enhance the look. Two fabric-lined drawers are graced with vegan leather handles and open via smooth metal glides. This console table features an X-shaped base design.
Maintain your minimalist modern design theme with the Southern Enterprises Nordica Faux Marble Console Table. The table has an open, airy quality due to its brushed nickel-plated iron X-frame base. A faux Carrara marble tabletop puts an elegant finishing touch on the console.
The industrial glam Southern Enterprises Glass Console Table updates its turn of the last century styling with a distressed silver finish. This console table stands tall and lean so it's ideal in the foyer, hallway, or behind your sofa. A tempered glass top and shelf offer stylish display space.
Complete your entryway or living room makeover with the Southern Enterprises Magnus Reclaimed Wood Console Table. Perfect for adding mid-century modern design to your home, this piece boasts a powder-coated iron frame finished in gold. The reclaimed elm wood top and bottom shelf have a planked and starburst design which instantly elevates the look of the console table. Asymmetrical legs compete the design.
The Southern Enterprises Youngston Faux Marble Rectangular Console Table - Gray displays what you want, and hides what you don't. With two drawers, oversized table top, and the lower shelf all made from a heavy duty engineered wood and finished in a durable veneer, this will be a forever furnishing in your home. And with the fresh gray and faux white marble colorway, it will revive your living room in a snap.
The Southern Enterprises Rochelle Console Table is going to be a serious statement piece in whatever room becomes lucky enough to have it. This wide console features a curved face and an exterior that's home to dozens of bevel-edged mirrors. The body is crafted from solid pine with engineered wood, then it's finished in a simple shade of matte silver. It's durable enough for regular use, and a pair of drawers at the center make it a practical piece in your foyer, dining room, or living room.
A note about ...
The Southern Enterprises Macen Console Table has a chic simplicity that can land it in your foyer, behind your sofa, or in the dining room. This industrial-inspired piece is made with a frame of metal tube under a powder-coated finish. The simple top is crafted from engineered wood with an exterior of birch veneers. The frame and top are available in a number of different finish combinations, so be sure to take a look and see which one is going become an essential part of your home.
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ORIGINAL RESEARCH article
Sec. Neurocognitive Aging and Behavior
Exosome α-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients
- 1Department of Anesthesiology, Peking University Third Hospital, Beijing, China
- 2Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing, China
- 3Department of Cadre Health Care, Beijing Jishuitan Hospital, Beijing, China
- 4Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
- 5Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
Background: Little is known about the underlying mechanisms of the similarities in the core features of postoperative delirium (POD) and α-synuclein (α-syn)-related cognitive disorders. We herein investigated associations between fluctuated levels of exosomal α-syn in the plasma and POD presentation in geriatric hip fracture patients.
Methods: We conducted an observational, prospective, and 1:1 matched (on age older than 65, hip fracture diagnosis, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative bleeding) case-control study: POD cases and non-POD controls were selected from the overall cohort by using Confusion Assessment Method (CAM). Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). Plasma exosome levels of α-syn were examined preoperatively and at the time that POD was diagnosed, by using an established immunocapture technology based on a putative brain-cell-specific marker. Circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also determined. The relationship between α-syn levels and POD risk, as well as the association between α-syn and MDAS scores and plasma cytokines, were assessed.
Results: POD incidence was 8.4% (17/202). Postoperative α-syn were either elevated or lowered. As primary outcome variables, the change of α-syn in POD patients was significantly higher than non-POD ones (21.0 ± 29.3 pg.ml−1 vs.1.9 ± 20.0, P = 0.047). The α-syn alteration was positively correlated to MDAS (r = 0.436, P = 0.010) and the change of IL-6 (r = 0.383, P = 0.025).
Conclusions: Exosome α-syn release in plasma may be associated with the POD development which might be due to systemic inflammation.
Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR-IPR-17012301.
Prior Presentation: The abstract of this work has been selected for presentation in the 2019 ANESTHESIOLOGY Journal Symposium “What’s New with the old,” and it has been present in the ASA 2019 annual meeting October 21st, 2019 in Florida.
Delirium is an acute and fluctuating brain dysfunction characterized by cognitive impairment and disturbance of consciousness. Postoperative delirium (POD) is commonly observed among older adult surgical patients during the postoperative period. It is associated with prolonged hospitalization, poor surgical outcomes, and greater healthcare costs (Whitlock et al., 2011). Despite the prevalence and clinical importance of POD, its pathophysiology is poorly understood, and no reliable biomarkers have been reported in previous studies.
α-synuclein (α-syn) is a neuronal protein of 140 residues that localizes predominantly to presynaptic terminals (Burre, 2015). There are several similarities in the core features of POD and α-syn-related cognitive disorders, including Parkinson’s disease (PD) dementia and dementia with Lewy bodies; these include fluctuating attention, visual hallucinations, and disorganized thoughts (Sunwoo et al., 2013; Gore et al., 2015; Vardy et al., 2015). A previous clinical study demonstrated that α-syn pathologies in the stomach are associated with POD after gastrectomy (Sunwoo et al., 2013). More recently, the same research group reported a significant correlation between POD and PD-related non-motor symptoms (Kim et al., 2018). Given that non-motor symptoms may represent the burden of α-syn deposit, POD is thus hypothesized to be a series of α-syn-related cognitive disorders, and maybe a preclinical stage of α-synucleinopathy (Sunwoo et al., 2013; Gore et al., 2015; Kim et al., 2018).
α-syn is abundant and self-propagates throughout the brain, and can also be transferred to peripheral tissues through exosomes, which are small membranous vesicles secreted by virtually all cell types (Danzer et al., 2012). Moreover, α-syn is not restricted to the brain, but can also be detected in peripheral tissues and in several body fluids, including plasma and saliva (Malek et al., 2014). In the plasma, α-syn can be found in its free form or in association with exosomes (Matsumoto et al., 2017). Exosomes carry disease-specific cargos and reflect changes that occur during several neurodegenerative diseases, and the involvement of exosomes in transmitting α-syn pathology has been clearly demonstrated (Vella et al., 2016; Wu et al., 2017). In a previous study, it is reported that plasma exosomal α-syn is likely brain-derived [i.e., it is L1 cell adhesion molecular (L1CAM)-positive] and is increased in PD compared with healthy controls (Shi et al., 2014). However, to the best of our knowledge, no previous study has investigated the association between plasma exosomal α-syn and POD.
Elderly patients with hip fractures are prone to developing delirium after surgery for their injury, with the prevalence of POD ranging between 38% and 61% (Yoon et al., 2017). POD occurs more often in an early period postoperatively with arbitrary time courses ranging from postoperative day 0–1–5–30 days (Safavynia et al., 2018). Both trauma and surgical stress may contribute to neuroinflammation and the resultant POD occurrence. The inflammation cascade may be implicated in α-syn pathology and synaptic disruption (Alam et al., 2018). Since the plasma exosomal α-syn level was highly correlated to the a-syn content within the neuron, we hypothesized that patients with greater change amount of exosomal a-syn levels in plasma from a preoperative non-delirium state to an occurrence of POD would likely to be vulnerable to developing POD, accompanied by a more severe systemic inflammation. Accordingly, the present study was undertaken with the primary aim of exploring the association of the change of plasma α-syn in L1CAM-carrying exosomes and POD occurrence, and secondarily, to determine whether aforementioned exosome a-syn changed parallel to circulating inflammatory mediators in older adult hip fracture surgery patients.
Materials and Methods
A prospective observational, single-center, 1:1 matched case-control preliminary study was conducted in Beijing Jishuitan Hospital. The study was approved by the Beijing Jishuitan Hospital ethics committee (Institutional Review Board: JLKS201705-04; Registration number: ChiCTR-IPR-17012301). Written informed consent was obtained from each enrolled patient accompanied by at least a family member or proxy.
Patients and Controls
We enrolled patients aged 65 or older who experienced POD after an emergency or planned hip fracture surgery, under either general or regional anesthesia, between September 2017 and February 2018. All the patients were admitted to the orthogeriatric unit. Exclusion criteria were: preoperative delirium, Parkinson disease, all-cause dementia (including PD related dementia, AD-related dementia, and Lewy’s body dementia) alcohol-related disorders, multiple trauma or multiple fractures, acute or chronic infectious diseases, anti-inflammatory drug treatment, a stroke in the prior 6 months or any other central nervous system (CNS) disease, severe deafness or vision problems, linguistic barriers, illiteracy, and/or communication difficulties, patients who received blood transfusion perioperatively, transferred to ICU postoperatively and refusal or unexpected discharge.
POD cases and non-POD controls were frequency matched (1:1) on five variables using incidence density sampling. Specifically, one non-delirium control was randomly selected for each POD case from the source population according to the five matched variables, including age, diagnosis, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative blood loss. These variables shown in Supplementary Table S1 were listed in the European Society of Anesthesiology’s evidence- and consensus-based guidelines on POD and were considered to be risk factors for POD incidence after hip fracture (Aldecoa et al., 2017) surgery. A patient recruitment flow chart is shown in Figure 1.
Figure 1. Flow diagram showed selection of eligible patients and the enrollment process. Abbreviations: POD, postoperative delirium.
We interviewed all patients the day before surgery and collected baseline data, including age, sex, gender, body mass index (BMI), ASA physical status, education history, and Mini-Mental State Examination (MMSE) score. Other information including comorbidities, past medical history, fracture classification, types of anesthesia and surgery, and time from injury to operation were also collected according to the patients’ medical records. All the history collection, physical evaluation and cognitive assessment related to dementia were conducted by the geriatrician (JXJ). Additionally, after cognitive assessment, written informed consent was signed with each patient accompanied by a family member or proxy.
Anesthesia and Analgesia
All patients received ultrasound-guided fascia iliac block immediately after admission. For the block, a single injection of 30 mL of 0.33% ropivacaine was used. On the operating day, patients did not receive sedatives or anticholinergics before anesthesia. The eventual choice of anesthetic regimen (general anesthesia or neuraxial block) was based on the preference and experience of the anesthesiologist alongside discussion with the patient and their family. A uniform anesthetic regimen was conducted based on previous studies of orthopedic operations in older adults (Zhang et al., 2018). In order to minimize postoperative pain, a second fascia iliac block with the aforementioned protocol was provided right before anesthesia regardless of the anesthetic regimen. Furthermore, all patients received intravenous patient-controlled analgesia (PCA) postoperatively with the same analgesic regimen (sufentanil 100 μg and ondansetron 8 mg in 100 ml).
Cognitive Scanner and Delirium Assessment
We interviewed all patients the day before surgery. The aforementioned MMSE test was used for dementia screening without any functional assessment. We followed the cut off by data from a Chinese cohort. Specifically, the cut-off points for dementia screening were 16/17 for illiterate (sensitivity 87.6% and specificity 80.8%), 19/20 for individuals with 1–6 years of education (sensitivity 93.6% and specificity 92.7%), and 23/24 for individuals with 7 or more years of education (sensitivity 94.3% and specificity 94.3%; Li et al., 2016).
The Confusion Assessment Method (CAM; a widely used, standardized method for the identification of delirium with a sensitivity of 94%, specificity of 89% and high interrater reliability) was used to exclude patients who had experienced preoperative delirium (Inouye et al., 2014). To be specific, four items (acute onset and fluctuating course, inattention, disorganized thinking, altered level of consciousness) were included in CAM, and if the first two were checked and at least one item of the last two was checked, a diagnosis of delirium was suggested. All participants were followed in the first two postoperative days, a period in which POD is usually diagnosed after hip fracture surgery in older adult patients (Scholtens et al., 2016). Surveillance included twice-daily visits (8:00 and 20:00) performed by a trained geriatrician (XJJ). POD patients were diagnosed using the CAM, and the severity of POD was determined by the Memorial Delirium Assessment Scale (MDAS) test (Marcantonio et al., 2002). Postoperative pain intensity was assessed using a 0–10-point Numerical rating scale (NRS; 0: no pain and 10: worst imaginable pain; Jensen et al., 1986).
Blood Specimen Processing
Two venous blood samples (4 ml each) were collected from all the patients before the induction of anesthesia preoperatively. Postoperative blood samples (4 ml) were also collected either when delirium was diagnosed for POD cases or at the last visit on postoperative day 2 for non-POD controls. Blood samples were stored at 4°C immediately after collection and sent to centrifuge (at 3,000× g for 10 min) within 4 h to separate the plasma and blood cells. All the plasma samples were stored at −80°C before being sent to the Department of Pathology, Peking university third Hospital, for further processing.
Exosome Isolation and α-syn Quantification
The primary outcome variable of this study was the change in exosomal α-syn concentration after a hip surgery. We evaluated plasma exosome levels of α-syn preoperatively and at the time that POD was diagnosed for cases or at a postoperative visit on day 2 for non-POD controls. Based on the preliminary study data and sample size estimation, we, therefore, chose the blood samples from 17 POD patients and 17 non-POD controls for further investigation with the method described in detail in the “Statistical Analysis” section and shown again in Figure 1.
Current strategies for purifying exosomes from blood or plasma differ significantly. There are basically three methods including ultracentrifugation-based isolation techniques, size-based isolation techniques, and immunoaffinity capture-based techniques. A recent study has demonstrated that immunoaffinity capture enriched for exosome and exosome-associated proteins by at least 2-fold more than the other two methods (Li et al., 2017). We, therefore, isolated the exosomes from plasma by using an immunoaffinity-based capture method as previously described (Li et al., 2017). As the founding member of subfamily of cell adhesion molecules, L1CAM was primarily expressed in the nervous system and was proved to be a high-affinity marker on the surface of exosomes derived from CNS (Shi et al., 2014). Therefore, anti-L1CAM antibodies were used for immunocapture of exosomes. Briefly, the method involves introducing anti-L1CAM antibodies to plasma to form an immunocomplex, binding the exosomes in the plasma to a solid phase through the immunocomplex, and then separating the solid phase and enriching the exosomes. Specific details refer as follows: 10 μg of L1CAM antibodies (clone UJ 127.11, Abcam, Cambridge, MA, USA) or normal mouse IgGs (Santa Cruz Biotechnology, Dallas, TX, USA) as negative controls were coated onto one set (1 mg) of M-270 Epoxy beads using a Dynabeads® Antibody Coupling Kit (Life Technologies, Grand Island, NY, USA) according to the manufacturer’s instructions. After thawing quickly (within 2 min) at 37°C, plasma samples (>300 μl) were centrifuged at 2,000× g for 15 min followed by 12,000× g for 30 min, and then the supernatant was diluted 1:3 with phosphate buffered saline (PBS; pH 7.4). One set of antibody-coated beads and 900 μl of diluted plasma were incubated for ~24 h at 4°C with gentle rotation. The beads were then washed four times with 1 ml of 0.1% bovine serum albumin (BSA)/PBS (pH 7.4) and transferred into a new tube. Exosomes were eluted from the beads with 60 μl of a 1:1 mixture of 0.1% BSA/PBS (pH 7.4) and a fixing buffer (4% paraformaldehyde/5% glutaraldehyde) for electron microscopy imaging or lysed by incubating the beads in 110 μl of 1% Triton X-100 plus 10% of a protease inhibitor cocktail (P2714, Sigma-Aldrich; prepared in 10 ml of H2O) in 0.1% BSA/PBS (pH 7.4) for 1 h at room temperature with gentle shaking. The exosomal preparations were stored at −80°C until α-syn levels were measured using Luminex assays (Luminex, Austin, TX, USA) according to a previously published protocol (Hong et al., 2010).
Determination of Plasma Cytokines
Concentrations of the plasma inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α were determined in duplicate using a commercially available, sensitive enzyme-linked immunosorbent assay (#ab214025, #ab178013, and #ab181421, respectively; Abcam) according to the manufacturers’ instructions. All determinations were performed by laboratory technicians with no access to the clinical data.
The risk of POD was presented using odds ratios (OR) and 95% confidence intervals (CI) which was calculated by the Clopper-Pearson method. All selected risk factors and their associations with POD development were examined using univariate logistic regression analyses first. We also performed a multivariate analysis of factors related to POD onset by using a logistic regression model. Variables in the final model were selected according to a stepwise method and those deemed to have potential clinical importance (P < 0.2 in univariate logistic regression analyses) were included.
A power analysis was based on results from preliminary data comparing changes in plasma exosomal α-syn after surgery for hip fracture between groups. In our preliminary study, 5 of 50 patients experienced POD after surgery. Five non-POD controls were frequency-matched on age, diagnosis, ASA physical status, duration of surgery, and intraoperative blood loss. POD cases had greater increases in blood levels of α-syn in L1CAM-carrying exosomes from preoperative to postoperative compared with non-POD controls (Mean ± SD were 31.3 ± 13.8 pg.ml−1 and 15.8 ± 9.4 pg.ml−1, respectively). Sample-size calculations showed that a Student’s t-test with a type I error (two-sided) of α = 0.05 would have 95% power to detect the aforementioned difference in change of plasma exosomal α-syn between the two groups if the sample size in each group was 15. To account for a possible loss in the follow-up period, we enrolled 17 cases per group. All statistical analyses were performed using SPSS for Windows (version 14.0, SPSS, Chicago, IL, USA). Statistical significance was considered as P < 0.05.
A total of 263 consecutive patients underwent hip surgery from April 2017 to February 2018; of these, the majority were over the age of 65. Two-hundred and two older adult patients (age range: 65–89 years) were enrolled in our study. Of the enrolled patients, 17 subjects experienced POD during the first two postoperative days. The incidence of POD was 8.4%. Another 17 patients that did not experience POD over the first 2 postoperative days were also enrolled in this study (Figure 1).
The sample characteristics of the match variables stratified by POD cases and non-POD controls are illustrated in Supplementary Table S1. There were no significant differences between cases and controls for any of the five matched variables (age, diagnosis, ASA physical status, duration of surgery, and intraoperative blood loss), suggesting a successful matching procedure.
Risk Factors of POD
Patient characteristics are shown in Table 1. Univariate logistic analysis of the potential risk factors for POD in older adult hip fracture patients demonstrated that there were no significant differences in a series of preoperative risk factors (all P > 0.05). However, univariate logistic analysis identified that a greater increase in exosomal α-syn from preoperative to postoperative was a risk factor for POD in older adult hip fracture patients (crude OR = 1.033, 95% CI 1.001–1.066, P = 0.047). Besides, it was also worth mentioning that the MDAS scores were significantly different between two groups, which not only confirmed that two groups were correctly classified by CAM but also added suitability of MDAS to be used for subsequent correlation analysis between MDAS scores and α-syn change. Furthermore, factors that remained statistically significant in the multivariate analysis are shown in (Table 2). Both the change in exosomal α-syn from preoperative to postoperative (adjusted OR = 1.044, 95% CI 1.003–1.087, P = 0.034) and preoperative MMSE (adjusted OR = 0.857, 95% CI 0.752–0.978, P = 0.022) were significantly different between the groups, which implied that patients with a higher increase in α-syn level and a lower preoperative MMSE score were more likely to develop POD.
Table 1. Univariate logistic analysis of potential factors for POD in geriatric hip fracture patients.
For postoperative pain intensity (Supplementary Table S2), univariate logistic analysis revealed significant differences in pain at rest (crude OR = 2.499, 95% CI 1.164–5.367, P = 0.019) and movement-evoked pain (crude OR = 1.727, 95% CI 1.102–2.707, P = 0.017) on postoperative day 2, but not on postoperative day 1 (pain at rest: crude OR = 1.102, 95% CI 0.713–1.704; movement-evoked pain: crude OR = 1.181, 95% CI 0.846–1.649, p > 0.05). However, it is important to note that some patients experienced delirium on postoperative day 1; this means that POD occurred before postoperative pain assessment in these patients. The pain intensity score during the first 48 h after surgery should therefore not be crudely treated as a potential risk factor for POD during statistical analysis in this study. For this reason, we have presented these data separately in Supplementary Table S2.
Plasma Concentrations of Exosomal α-syn
As shown in Figure 2; there were no significant differences in preoperative and postoperative plasma concentrations of exosomal α-syn between POD patients and controls (P = 0.70 and 0.17, respectively; Figures 2A,B). Similarly, there were no statistical differences between preoperative and postoperative plasma concentrations of exosomal α-syn in patients who experienced POD (P = 0.49) or in those who did not develop POD (P = 0.14; Figures 2C,D). However, univariate logistic analysis showed that the changes in exosomal α-syn concentration from preoperative to postoperative (delirium detection for POD cases and at a postoperative visit on day 2 for non-POD controls) were significantly higher in non-POD controls than in POD patients (1.9 ± 20.0 pg.ml−1 vs. 21.0 ± 29.3 pg.ml−1, P = 0.047; Figure 2E). By calculating the difference between the two groups (non-POD controls minus POD cases), the effect size is −19.1 pg.ml−1 (−36.7 pg.ml−1, −1.6 pg.ml−1). This implies that there is a greater alteration in plasma concentrations of exosomal α-syn in patients with POD. Furthermore, there was a positive correlation between the changes in plasma exosomal α-syn concentration and MDAS (a measure of delirium severity) scores (Figure 2F), however, this correlation was not significant in neither POD group nor non-POD one (data not shown).
Figure 2. The changes in plasma exosomal α-syn concentration after hip fracture surgery in controls and POD patients. Data of preoperative and postoperative α-syn for controls and POD patients were nonnormally distributed and were described in Box-and-Whiskerr plots, presenting the minimum, maximum, and all points (A,B). Before-after plots showing the trend of exosomal α-syn concentration before and after surgery in POD cases and non-POD controls (C,D). The changes of plasma exosomal α-syn concentration from preoperative to postoperative (delirium detection for POD cases and a postoperative visit on day 2 for non-POD controls) were shown as mean and SD with all scatter points (E). The changes of α-syn were positively correlated with MDAS scores (r = 0.436, P = 0.010), solid spots (black) represented POD cases and hollow spots (white) represented non-POD controls (F). Abbreviations: POD, postoperative delirium; MDAS, memorial delirium assessment scale; α-syn, α-synuclein. n.s., non significant.
Plasma Concentration of Inflammatory Cytokines
Neuroinflammation after surgery and anesthesia is thought to play a crucial role in POD development. There were no significant differences in preoperative IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) between POD cases and non-POD controls (P > 0.05; Figures 3A–C). However, the postoperative levels of IL-1β and IL-6, but not TNF-α, were much higher in POD cases than in controls (P < 0.05; Figures 3D,E,F). We also compared the changes in concentration of the three cytokines from preoperative to postoperative, and there were no significant differences in IL-1β and TNF-α changes (P > 0.05; Figures 3G,I). However, the POD cases had a higher elevation in IL-6 concentrations than the non-POD controls (P < 0.05; Figure 3H). In addition, the relationship between changes in plasma exosomal α-syn and changes in inflammatory cytokines was examined using correlation analysis conducted with Prism 6. The changes in IL-6, but not in IL-1β or TNF-α, were positively correlated with changes in α-syn (r = 0.383, P = 0.025; Figures 3J–L).
Figure 3. Plasma concentration of inflammatory cytokines. Data were shown as mean and SD with all scatter points. There were no significant difference in preoperative IL-1β, IL-6, and TNF-α between cases and controls (A–C). Postoperative levels of IL-1β and IL-6, but, not TNF-α, were much higher in POD cases than those in non-POD controls (D–F). The changes of plasma inflammatory cytokines from preoperative to the time that POD was diagnosed for cases or a postoperative visit on day 2 for non-POD controls (G–I). Compared with non-POD patients, increases of plasma IL-6 concentration were much higher (P = 0.014); similarly, the changes of IL-6 (r = 0.383, P = 0.025), but not IL-1β and TNF-α, were positively correlated with postoperative increases in plasma exosomal α-syn (J–L). Abbreviations: IL-1β, Interleukin-1β; IL-6, Interleukin-6; TNF-α, tumor necrosis factor-α; POD, postoperative delirium; α-syn, α-synuclein. n.s., non significant.
Our results revealed for the first time that fluctuated (either increase or decrease) plasma exosomal α-syn level was an independent risk factor for POD. However, there is still no direct evidence that α-syn is involved in POD. An earlier study reported that α-syn pathologies and phosphorylation in the stomach are associated with POD after gastrectomy (Sunwoo et al., 2013), and this study group also reported a significant correlation between POD and PD-related non-motor symptoms, which may represent the burden of α-syn deposit (Kim et al., 2018). These indirect pieces of evidence strongly implied that POD represents a preclinical stage of α-syn-related cognitive disorders. In agreement with these, we observed a considerably higher alteration in plasma exosomal α-syn in POD cases when compared with non-POD controls. In addition, there was a positive correlation between the changes in plasma exosomal α-syn and MDAS score, which is a measure of delirium severity.
Many researches indicated that preoperative brain dysfunction (frail brain) of elderly patients is the predisposing factor for POD (Inouye et al., 2014). In our study, the multivariable analysis indicated that patients with lower preoperative MMSE were more vulnerable to POD (adjusted OR = 0.857, 95% CI 0.752–0.978, P = 0.022). Our finding is consistent with several previous studies that demonstrated that baseline cognitive deficits, even subtle ones, have been associated with an increased risk of developing delirium and the presence of dementia more than doubled the risk for POD (Maldonado, 2018). Therefore, it is essential to evaluate the baseline cognitive condition for elderly patients with hip fracture and communicate with the proxy the risk of delirium and the importance of early distinguish.
As one of the precipitating factors, inflammatory cytokines play a pivotal role during POD (Beloosesky et al., 2007; Whitlock et al., 2011; Liu et al., 2018). In the current study, both postoperative plasma concentration and elevation of IL-6 were significantly higher in POD cases than in non-POD controls. In contrast, the changes in IL-1β and TNF-α concentrations did not differ between POD cases and controls. Our results are consistent with a previously published meta-analysis, in which elevated peripheral levels of IL-6, but not IL-1β and TNF-α were detected in association with a POD (Liu et al., 2018). Although the exact mechanism of the correlation of a-syn change and delirium was not clear at present, the a-syn change might just be a bystander that confounded to the increase of IL-6, a marker of systemic inflammation. The detection of IL-6 may, therefore, be a good choice for inflammatory evaluation in future POD studies. We also found that the changes in peripheral IL-6 levels were positively correlated to the changes in α-syn, which demonstrated that there could be mutual regulation between neuroinflammation and α-synucleinopathy in the development of POD. Although few studies have investigated their association in POD, previous studies had shown their mutual association in neurodegeneration, including in PD and multiple system atrophy (Qin et al., 2016; Wong and Krainc, 2017; Gordon et al., 2018). The interesting finding of our study could be explained by this possible mechanism that it was the systemic inflammation that strong enough to cause POD to alter the dynamics of a-syn in the brain, that would be potentially initiated or exacerbate alpha synucleinopathies. Further investigations into the role of neuroinflammation in α-syn toxicity would thus be important for understanding α-syn pathophysiology in POD and may contribute to the development of future therapies to treat POD.
In our study, only 8.9% of patients experienced POD. This incidence was much lower than the overall incidence of POD of 23.3% (Yoon et al., 2017). We believe the most important reason lies in the orthogeriatric unit, a new model of care for our participants (González-Montalvo et al., 2010). The systematic organization of an orthogeriatric unit in our hospital allowed all participants to receive immediate regional nerve block analgesia, earlier geriatric assessment, coordinated daily clinical care, joint planning of the surgical schedule and discharge date and destination. Currently, this comprehensive intervention is thought to improve efficiency in perioperative management and reduce the incidence of delirium after hip fracture (González-Montalvo et al., 2010; Shields et al., 2017). Specifically, it is worth mentioning that the vast majority of participants in our study were discharged home or to a rehabilitation center on postoperative day 2, and delirium screening was then not available in our study. In fact, however, POD can occur up to 7 days after surgery. Furthermore, a number of previous studies have confirmed that pain is a risk factor for POD in older patients (Nie et al., 2012; Lin et al., 2016) and that effective pain management reduces the incidence and severity of POD (Lynch et al., 1998; Vaurio et al., 2006). We speculate the effective perioperative pain management, including twice preoperative fascia iliac blocks and postoperative intravenous PCA administration, may also partially account for the lower POD incidence in our study.
Our investigation had two limitations. First, two traumas, hip fracture, and surgery were in the patient population being studied, however, which one of them played an important role of the POD development remain largely unknown (Alam et al., 2018). Second, plasma total α-syn levels were not determined in our study. Although blood is more readily accessible, changes in α-syn concentrations in the blood of PD patients have been less consistent (Atik et al., 2016; Wang et al., 2018). Considering the abundance of α-syn in red blood cells and platelets that can substantially influence plasma α-syn levels, we, therefore, adopted a well-established immunocapture technology to isolate exosomes, and then examined brain-derived α-syn in the blood (Shi et al., 2014). Nevertheless, the patterns of change in plasma total and exosome-associated α-syn in POD patients need to be further investigated.
Conclusions and Implications
In summary, our study indicates that fluctuated in plasma exosomal α-syn levels during the perioperative period might be associated with POD in older patients following hip fracture surgery. The change of α-syn level in L1CAM-carrying exosomes in the plasma was correlated with both IL-6 concentrations and POD severity, implying that an alteration in plasma exosomal α-syn may be implicated in the inflammatory process. Clinical determination of α-syn content in exosomes in plasma may, therefore, be helpful to differentiate older patients at risk of POD after hip fracture surgery.
Data Availability Statement
All datasets generated for this study are included in the article/Supplementary Material.
The studies involving human participants were reviewed and approved by Beijing Jishuitan Hospital ethics committee. The patients/participants provided their written informed consent to participate in this study.
YY, ZL and NY were the co-first authors of this article, responsible for the design and implementation of this project, data collection, data statistics, and article writing. XJ conducted neuropsychological tests. DH, YuL, TL and FY were responsible for exosome isolation and α-syn quantification. XW and CN participated in the analysis and interpretation of data. YY, YH, JH, and YaL were responsible for the patient data collection. YZ designed the project and modified the manuscript. XG was responsible for the expenses. PZ and GW also modified the manuscript. All authors read and approved the final manuscript.
This work was supported by the National Natural Science Foundation of China (81873726, 81600933 and 81701052) and the Interdisciplinary Medicine Seed Fund of Peking University (BMU2017MC006).
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
α-syn, α-synuclein; ASA, American Society of Anesthesiologists’; BMI, Body Mass Index; BSA, Bovine Serum Albumin; CAM, Confusion Assessment Method; CI, Confidence Intervals; CNS, Central Nervous System; CSF, Cerebrospinal Fluid; IL-1β, Interleukin-1β; IL-6, Interleukin-6; IQR, Inter Quartile Range; L1CAM, L1-Cell Adhesion Molecular; MDAS, Memorial Delirium Assessment Scale; MMSE, Mini-Mental State Examination; NRS, Numerical Rating Scale; OR, Odds Ratios; PBS, Phosphate Buffered Saline; PCA, Patient Control Analgesia; PD, Parkinson’s disease; POD, Postoperative delirium; TICS, Telephone Interview for Cognitive Status; TNF-α, Tumor Necrosis Factor-α.
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnagi.2020.00067/full#supplementary-material.
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Scholtens, R. M., de Rooij, S. E., Vellekoop, A. E., Vrouenraets, B. C., and van Munster, B. C. (2016). Preoperative CSF melatonin concentrations and the occurrence of delirium in older hip fracture patients: a preliminary study. PLoS One 11:e0167621. doi: 10.1371/journal.pone.0167621
Shi, M., Liu, C., Cook, T. J., Bullock, K. M., Zhao, Y., Ginghina, C., et al. (2014). Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson’s disease. Acta Neuropathol. 128, 639–650. doi: 10.1007/s00401-014-1314-y
Shields, L., Henderson, V., and Caslake, R. (2017). Comprehensive geriatric assessment for prevention of delirium after hip fracture: a systematic review of randomized controlled trials. J. Am. Geriatr. Soc. 65, 1559–1565. doi: 10.1111/jgs.14846
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Yoon, B.-H., Yoo, J.-I., Youn, Y. C., and Ha, Y.-C. (2017). Cholinergic enhancers for preventing postoperative delirium among elderly patients after hip fracture surgery: a meta-analysis. Eur. Geriatr. Med. 8, 486–491. doi: 10.1016/j.eurger.2017.07.023
Zhang, M., Zhang, Y. H., Fu, H. Q., Zhang, Q. M., and Wang, T. L. (2018). Ulinastatin may significantly improve postoperative cognitive function of elderly patients undergoing spinal surgery by reducing the translocation of lipopolysaccharide and systemic inflammation. Front. Pharmacol. 9:1007. doi: 10.3389/fphar.2018.01007
Keywords: postoperative delirium, α-synuclein, exosome, hip fracture, geriatric (aging)
Citation: Yuan Y, Li Z, Yang N, Han Y, Ji X, Han D, Wang X, Li Y, Liu T, Yuan F, He J, Liu Y, Ni C, Zou P, Wang G, Guo X and Zhou Y (2020) Exosome α-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients. Front. Aging Neurosci. 12:67. doi: 10.3389/fnagi.2020.00067
Received: 29 November 2019; Accepted: 25 February 2020;
Published: 13 March 2020.
Edited by:Niccolo Terrando, Duke University, United States
Reviewed by:Catherine C. Price, University of Florida, United States
Kensuke Ikenaka, Osaka University, Japan
Copyright © 2020 Yuan, Li, Yang, Han, Ji, Han, Wang, Li, Liu, Yuan, He, Liu, Ni, Zou, Wang, Guo and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
† These authors have contributed equally to this work


4 out of 5 Stars!
Because of its power-trio line-up and the era of its brief existence, not to mention the occasional hard-driving and often funky rhythms showcased on its debut album, this U.K. band always reminded me of the legendary Trapeze, only with a more “metal” edge.
Featuring underappreciated guitarist John Cann (Atomic Rooster), lauded bassist (RIP) Johnny Gustafson (Ian Gillan Band/Roxy Music/Quatermass), and drummer Paul Hammond (Atomic Rooster), Hard Stuff started in 1970 (along with vocalist Al Shaw) under the name Daemon, then (for whatever the reason) dropped Shaw to forge onward as a threesome.
And that’s what I originally viewed as a detriment—the fact that Trapeze possessed an extraordinary and recognizable vocalist in bassist Glenn Hughes, whereas Hard Stuff did not. So, to be perfectly frank, I originally never embraced this album due to its “only average” vocals.
But thankfully, with hindsight being 20/20, I reexamined Bulletproof in the past decade, paying closer attention to the stellar musicianship involved, and have since grown quite fond of it. Indeed, it’s heavy as hell, with occasionally Blues-influenced tracks such as “Sinister Minister,” “Taken Alive,” “Millionaire,” “Mr. Longevity,” “Time Gambler (Rodney)”,” “The Provider,” and “No Witch at All,” blaring out of the speakers. One other track in particular, “Monster in Paradise”—which I vividly remembered through the many years before once again revisiting this release—was a collaboration between Gustafson and Ian Gillan/Roger Glover of Deep Purple fame, and (to me) sounds as if it could have easily fit into the other band’s repertoire—or at least, I can easily imagine Gillan singing it.
Regardless, before finally disbanding, Hard Stuff went on to create a second platter (Bolex Dementia), but also altered its style a bit, thus leaving Bulletproof as the group’s unrivaled masterpiece. Therefore, fans of other Proto-Metal groups of the era such as Dust, May Blitz, Sir Lord Baltimore, Three Man Army, etc. who are unfamiliar with this group would likely find this debut album of interest.


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While responding to questions concerning the recently concluded Kenya Elections, Kizza Besigye was angry and not happy about Ugandans who are spreading false allegations that he will always be a loser like his Kenyan counterpart.
He added that it is a matter of time and he will take over Uganda government as he busy planning a new strategy to avoid elections malpractices.
“All Ugandan who think like that have shallow brains and can't think well. We normally lose the elections because of irregularities in the electoral processes,” he said.
What do you think?

domain: politics


text:
By Paul Goble
“The key to understanding” Moscow’s decision to go to war in Ukraine lies in “the corporatist character of the Russian elite” and the increasing ritualization of power at the top, Pavel Luzin says. Today, “the only corporation Putin speaks for is the FSB,” which increasingly dominates what the Kremlin does at home and abroad.
“However insane the words of the Russian president seem to us,” the Russian commentator says, “these are the words and this is the language of the way of thinking which is characteristic for almost any officer of any regional administration” of the Russian successor to the KGB out of which Putin sprung (theins.ru/opinions/pavel-luzin/248984).
The distrust of rationality and the belief in a special historical mission are characteristic of all these present and former Soviet and Russian special services because “only such an ideological construction allows the representatives of this corporation to explain, justify and preserve their place in the Russian political hierarchy,” Luzin continues.
And the ritualization of thought and action among these people has allowed them to transform at least in their own minds this war as “a unique ritual which unites the elite together and also guarantees an absolute monopoly on political and economic power” by its officers, according to the Russian analyst.
Such people see as a triumph what almost everyone else, including members of the Russian economic elite, views as a disaster, the de-globalization of Russia which means that the FSB cadres can rule the roost even if the rest of the Russian elite and the Russian people suffer a major defeat.
Putin and his FSB colleagues are betting that they can mobilize the patriotism of Russians sufficiently to keep their power beyond challenge; but Russian society and the Russian economy given the willingness of the West to impose increasingly draconian sanctions may make that ever more difficult the longer the war goes on.
That in turn could lead to radical shifts either within Russia or between Russia and the rest of the world but whether these would move toward some kind of reconciliation or even sharper breaks between the Kremlin and Russia or between Russia and the West remains “impossible to say” for the time being, Luzin concludes.

domain: news


text:
At DWDC, we defend human rights by advocating for assisted dying laws that respect the Canadian Constitution and the Charter of Rights and Freedoms.
You can help.
This toolkit and action guide provides you with the resources needed to engage with your Member of Parliament and request a meeting. In doing so, you are setting the groundwork to influence policy on issues – like medical assistance in dying – that are important to you.
Dying With Dignity Canada is currently advocating for much-needed changes to Canada’s assisted dying law, namely:
- Removing the clause that “natural death has become reasonably foreseeable” (NDRF) as an eligibility requirement.
- Allowing waiver of the requirement for final consent for those patients who are eligible but who may lose capacity in advance of their scheduled date.
- Proposing that only one independent witness be required to sign the formal request for MAID, and that this witness may be a paid personal care or healthcare worker.
- Removing the explicit exclusion of those with mental illness as the sole underlying condition from accessing MAID.
- Lifting the ban on advance requests for assisted dying.
- Allowing MAID for mature minors who meet all other eligibility criteria.
Let your local Member of Parliament (MP) know that you care about end-of-life choice and the constitutionally protected right to MAID. Download the 2020 Toolkit and Action Guide.
Already scheduled a meeting?
DWDC has developed a backgrounder on the right to medical assistance in dying that you can share with your MP. It has been included in the 2020 Toolkit and Action Guide, but you can click here to download and print the backgrounder (or email it) as a separate PDF for your MP.
Cliquez ici pour télécharger le document en français.


text:
Would you like a nice french kiss?
With the big carb craze going around there is no wonder someone made a...
This is one Dumb Ass Bass!
Now this is just the cutest little kitten.
Can you imagine if cows had guns!
You are a Fucking Moron Courtney Love
Here is a funny flash movie about the ancient art of Chinese Torture.
Great remake of the song Cats in the Cradle. In this flash movie, The Cat...
Butterfield makes fun of Brittney Spears in this animation.
A Prank call that was turned into an animation about butt plugs.

domain: entertainment


text:
More about Choiseul Quarter
Discovering the Hidden Gems of Choiseul, Saint Lucia
Choiseul, Saint Lucia is a hidden gem that is often overlooked by tourists visiting the Caribbean. Located on the southwestern coast of the island, this charming town offers a unique blend of natural beauty, rich culture, and warm hospitality. Choiseul is known for its lush rainforests, pristine beaches, and stunning waterfalls that are sure to take your breath away. The town is also famous for its thriving arts and crafts scene, which showcases the talents of local artisans who create beautiful pottery, wood carvings, and woven baskets. If you're looking for an authentic Caribbean experience, Choiseul is the perfect destination.
Top Reasons to Visit Choiseul, Saint Lucia
There are many reasons why Choiseul should be on your travel bucket list. One of the top reasons is the town's natural beauty. Choiseul is home to some of the most picturesque beaches on the island, including Anse L'Ivrogne, Anse Citron, and Anse Chastanet. These beaches are perfect for swimming, sunbathing, and snorkeling. Choiseul is also known for its lush rainforests, which offer a wide range of hiking trails and nature walks. The town is home to several stunning waterfalls, including the Diamond Falls and the Toraille Waterfall, both of which are popular tourist attractions.
Another reason to visit Choiseul is its rich culture. The town is home to a vibrant arts and crafts scene, which showcases the talents of local artisans. Visitors can shop for handmade pottery, wood carvings, and woven baskets at the Choiseul Craft Centre, which is located in the heart of the town. Choiseul is also known for its lively street parties and festivals, which celebrate the town's rich cultural heritage.
Exploring the Best Things to Do in Choiseul
Choiseul offers a wide range of activities for visitors of all ages. One of the best things to do in Choiseul is to explore the town's natural beauty. Visitors can hike through the lush rainforests, swim in the crystal-clear waters of the Caribbean Sea, or simply relax on one of the town's beautiful beaches. Choiseul is also home to several stunning waterfalls, which are a must-see for any nature lover.
For those interested in culture, Choiseul offers a variety of activities that showcase the town's rich heritage. Visitors can shop for handmade crafts at the Choiseul Craft Centre, attend a traditional street party, or visit the Choiseul Heritage Park, which features exhibits on the town's history and culture.
Traveling to Choiseul: A Comprehensive Guide
Getting to Choiseul is easy, thanks to the town's proximity to Hewanorra International Airport. The airport is located just 30 minutes away by car, and visitors can hire a taxi or rent a car to get to Choiseul. The town is also accessible by bus, with several daily services running between Choiseul and other parts of the island.
Once you arrive in Choiseul, there are several transportation options available. Visitors can hire a car, take a taxi, or use the local bus service to get around the town and explore the surrounding area. Walking is also a great way to see the sights of Choiseul, as the town is small and easy to navigate.
Where to Stay in Choiseul: The Best Accommodations
Choiseul offers a variety of accommodation options to suit every budget and preference. One of the best places to stay in Choiseul is Tranquility Suites- Feels like home. This charming hotel offers spacious and comfortable suites that are perfect for couples and families. The hotel is located just a short walk from the beach and offers stunning views of the Caribbean Sea.
Another great option is the Tet Rouge Resort St. Lucia. This luxurious resort is situated on a hilltop overlooking the town and offers breathtaking views of the surrounding area. The resort features a range of amenities, including a swimming pool, spa, and restaurant, and is perfect for those looking for a relaxing and indulgent vacation.
Tasting Choiseul: A Culinary Journey Through Saint Lucia
Choiseul is known for its delicious and authentic Caribbean cuisine. Visitors can sample a variety of local dishes, including grilled fish, jerk chicken, and callaloo soup. One of the best places to try these dishes is at the town's street vendors, who offer a wide range of tasty and affordable options.
For those looking for a more upscale dining experience, there are several restaurants in Choiseul that offer a fusion of Caribbean and international cuisine. One of the best is the Mango Tree Restaurant, which is located in the Tet Rouge Resort St. Lucia. The restaurant offers stunning views of the Caribbean Sea and features a menu that showcases the best of local and international cuisine.
The Best Time to Visit Choiseul for Your Dream Vacation
The best time to visit Choiseul is between December and April, when the weather is dry and sunny. This is also the peak tourist season, so visitors should book their accommodation well in advance. May to November is the rainy season in Choiseul, but this is also the time when the town is at its most lush and green. The rainy season is also a great time to visit for those looking for a quieter and more affordable vacation.
Expert Tips for Travelers Visiting Choiseul, Saint Lucia
When visiting Choiseul, it's important to pack light and bring comfortable clothing and shoes. The town is very casual, so there's no need to bring formal attire. Visitors should also bring sunscreen, insect repellent, and a hat, as the sun can be strong and there are mosquitoes in the area.
It's also a good idea to bring cash, as many of the local shops and restaurants do not accept credit cards. Visitors should also be prepared to haggle when shopping at the street vendors, as this is a common practice in the Caribbean.
Getting Around Choiseul: A Transportation Guide
Getting around Choiseul is easy, thanks to the town's small size and excellent transportation options. Visitors can hire a car, take a taxi, or use the local bus service to get around the town and explore the surrounding area. Walking is also a great way to see the sights of Choiseul, as the town is small and easy to navigate.
For those looking to explore the island, there are several tour operators in Choiseul that offer a variety of excursions and activities. These include hiking tours, snorkeling trips, and visits to nearby towns and attractions. Visitors can also rent a car and explore the island on their own, but should be aware that driving in Saint Lucia can be challenging due to the narrow and winding roads.

domain: geography


Call 267 279 9477 to make your appointment today—
New reports from the US suggest that Volkswagen may have developed several types of its infamous " defeat device ," which may even be equipped on its newest range of vehicles. Previously, the defeat device used to achieve " targeted results " in official emissions tests was confirmed only to be fitted to the brand’s vehicles equipped with the EA189 2.0 litre EU5-compliant diesel engine.
from Volkswagen News http://ift.tt/1jybngY
via IFTTT Doylestown Audi repair specialist. 241 Harvey Ave Doylestown pa 18901


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Oct. 10--The Academy Awards' documentary short subject category is often one of the trickier Oscar races to predict. On Thursday, the Academy of Motion Picture Arts and Sciences released a shortlist narrowing the field of contenders down to eight films. That should allow office pollsters and prognosticators to get a jump on the race.
Three to five films will be announced as the final nominees along with all the other Oscar nominations on Jan. 16, 2014.
In alphabetical order, with their production companies, the eight films are:
"Facing Fear," Jason Cohen Productions
"Jujitsu-ing Reality," Sobini Films
"Karama Has No Walls," Hot Spot Films
"The Lady in Number 6: Music Saved My Life," Reed Entertainment
"Prison Terminal: The Last Days of Private Jack Hall," Prison Terminal
"Recollections," Notrac productions
"SLOMO," Big Young Films and Runaway Films
Malcolm Clarke, director of "The Lady in Number 6," won in the same category in 1989 for "You Don't Have to Die."
The 86th Academy Awards will take place on Sunday, March 2.
Follow Mark Olsen on Twitter: @IndieFocus
(c)2013 the Los Angeles Times
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- Morgan Stanley Ponies Up $275 Million to Settle SEC Charges
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Fall is an upcoming American survival movie directed by way of Scott Mann and starring Grace Caroline Currey, Virginia Gardner, Mason Gooding, and Jeffrey Dean Morgan. It’s scheduled to be launched in the US on August 12, 2022, by way of Lionsgate Motion pictures.
WHAT FONT WAS USED IN POSTER?
“Boheld Six” is the font used in Fall poster. Boheld was designed by Teuku Deky Firnanda and published by Graptail. Boheld contains 6 styles and family package options.

domain: artistic