text:
Kora has always been a gift to her parents, starting from the moment of her arrival on December 25th.
In her first few weeks of life, Kora struggled with acid reflux and major spit up. We lived by the five Ss (Swaddle, Side-stomach position, Shush, Swing, Suck) to soothe her somewhat cranky nature. Thankfully, Kora grew out of most of these issues by around three months and was, by all accounts, a normal, healthy baby. She hit milestone after milestone— rolling over, sitting up, crawling around 8 months and pulling herself up on furniture shortly after that.
Some time between six and nine months, we noticed some different eye movements (we now know these to be nystagmus and hand tremors), and were referred to a neurologist. When she hadn’t progressed to walking by 18 months, we finally went in for an MRI.
Following the MRI, we learned that Kora had a delay in myelination in her brain. That was the first time we heard the term leukodystrophy. When googling it, results showed a broad range of disorders all having to do with the white matter of the brain and myelin formation. But none of these seemed to match Kora.
With the MRI results and no real diagnosis, we were sent six hours from our home to the Colorado Children’s Hospital. While there Kora underwent more tests and met with both neurologists and genetic specialists. There were several hypotheses around what she had, including Leigh’s syndrome. At the time, I was also pregnant with our second child, and was fielding questions around whether I would continue my pregnancy if Kora’s diagnosis held serious implications for the health of our second child.
A few days after coming home, we received a call from the neurologist. He had studied under Adeline Vanderver, MD, one of the top researchers in the country for leukodystrophies. This neurologist told us of a clinical study that included a free full genome sequencing, which our insurance had denied. We sent off all of the blood work to the LeukoSEQ program and waited.
As we waited, Kora was evaluated by the local health department to see if she qualified for any state assistance to help pay for medical costs and early intervention programs. At the time, she was on track for most all developmental milestones except for the fact that she couldn’t walk yet on her own. She didn’t qualify for any assistance, but we did start physical therapy around 20 months, and then occupational therapy a few years later.
After 6 months of waiting and just 2 weeks before Kora’s little brother was born, we received the genetic testing results—Kora had a POLR3A gene mutation, causing a lack of myelination. Her formal clinical diagnosis was TACH version of the POL III leukodystrophy, a very rare condition that has only been studied in a handful of people. After the diagnosis and much digging into this condition, I’ve come to learn that every child with POL III Leukodystrophy has a VERY different path.
Kora is now 6 years old. She has never been able to walk on her own, but that does not stop her from being as independent as she can be. She uses a walker, and still crawls a bit while at home. She can dress herself (when motivated), feeds herself, and does a ton independently. She’s in first grade now. Cognitively she needs extra time to learn things, but she works super hard at it. She has a very hard time with writing because of the tremors, but is improving more and more. She absolutely loves school and her friends there. Over the last year or so we have been really battling her over tone in her legs and toe walking, which has really affected her ability to balance and it feels like she has definitely lost some of her walking ability because of the over tone. Her nystagmus also makes it harder to read and do more fine motor activities.
Kora loves to play with her dolls (LOL dolls are her current obsession), builds with Magnatiles and is always extremely happy when she’s in the water. She charms just about everyone she meets, and is a lot of fun to be around. My greatest hope is that we are able to keep her as independent as possible throughout her life, and hopefully make things a little easier for her.


text:
Love's Hope Sample Sunday
Subject to change.
Release Date: August 15, 2022
“Hope, this is unacceptable.”
My fingers froze over the keyboard as my office door slammed open. I watched with annoyance as the angry, bulldog-faced man stalked towards me.
With the same arrogance he displayed in each of our meetings, Mr. Stratford tossed a folder on my desk, watching as several papers skated across the wood before fluttering to the floor.
Adopting a nonchalant expression, I reclined in my chair. “Excuse me?”
“This… this invoice is ridiculous. Do you see the amount of billable hours? You and this company are not only trying to fuck me in this contract, you’re trying to rob me while doing it. It’s bullshit.”
My plan to stay professional with Mr. Stratford wavered each time I was forced to communicate with him.
With crossed legs, I tilted my head and scrutinized him through narrowed lids.
Sometimes, sitting in this office and poring over contracts for hours could get boring. So when moments like these appeared, I looked forward to and enjoyed them.
“Mr. Stratford, as I informed you in our meeting two weeks ago, my time is billed at an hourly rate. Which means, each hour I spend working on your account and fulfilling your demands is billable. Whether that’s reviewing contracts, holding meetings with vendors, or fielding questions and explaining what I do for the hundredth time.” My lips curved when his face reddened because he knew that was a direct jab at him. “Now, that rate, like everything else, was explained to you before any contract was signed. And you still agreed to use our services. Now, if you’re dissatisfied with my performance, I’m willing to schedule a meeting where you, David, and myself can discuss any concerns. But barging in and throwing a tantrum is unacceptable. I’m sure you don’t allow that behavior at your company, so please don’t do it here.”
There were a few moments where he weighed his options, debating on how to respond.
The moment he chose violence over diplomacy was obvious because I’d seen it too many times in the gazes of other men. I was well prepared and had already rolled my chair backwards and stood by the time he’d slammed his palm loudly on the surface of my desk.
“Is there a problem?”
I ignored the jolt low in my gut as I flashed a quick look at Maverick, who stood in the open doorway to the bathroom we shared. “No, we’re fine.”
“No, we’re not, Mr. Martin. Hope,” Mr. Stratford stressed, putting emphasis on my name. “Has repeatedly shown me nothing but disrespect and I…”
Rolling my eyes, I tuned out the rant.
I also hadn’t missed the slight where he referred to me as Hope but addressed Maverick as Mr. Martin. Despite us holding the same title, Mr. Stratford treated him like my boss rather than my equal. It was irritating to bust my ass for years, only to be usurped by a man within a month simply because of what was between his legs.
“... if she can’t show me respect—”
“I don’t think she’s the one lacking respect.”
My eyes bucked, tuning back into the conversation after Maverick interrupted him.
Mr. Stratford’s mouth hung open, probably surprised that a man hadn’t automatically sided with him. I’d seen the way he bullied his assistant and it disgusted me. The woman went well above her duties and he constantly gave her shit, treating her as less than. Many times, I’d been tempted to speak up but had held my tongue, not wanting to overstep.
“From what I’ve seen, the only person in this equation that lacks respect is you, Mr. Stratford. Since I’ve gotten here, you’ve challenged her, done nothing but give pushback, made her job difficult, prolonged the completion of the merger you want… yet you’re complaining about the hours billed? Had you worked with her and not against her, this contract likely would’ve been completed weeks ago and you could’ve saved yourself thousands of dollars.” Maverick’s head tilted, lips flattening as he moved further into the room, keeping his gaze on the man whose hands trembled with anger.
“Since I’ve been here, you’ve refused to agree on one thing. One. Any further delays in this process falls solely on your shoulders. Mr. Gavin has conceded on more than I would have to complete this deal and you’re still not satisfied. And each time, Ms. Givens has busted her ass to meet your unreasonable demands. So in return, that respect you’re demanding? It’s owed to her first, tenfold. Am I clear?”
“Mr. Martin, but sh—”
“Am I clear?”
Mr. Stratford’s jaw clenched and he nodded, flicking his gaze towards me. “I apologize for my earlier behavior, Ho-” He cleared his throat. “Ms. Givens.”
I didn’t accept his halfhearted apology, so I merely nodded.
His entire frame was stiff as spoke through clenched teeth. “From now on, all communication will go through my assistant.”
“That’s probably for the best.” Maverick agreed, tone still painfully neutral.
Mr. Stratford strolled out without the papers he’d tossed my way. The second he was gone, my shoulders sagged from the tension he took with him before inhaling when Maverick rounded the desk, stopping only a foot away.
That damn scent that reminded me of our night invaded my senses and I sucked in a slow breath, hoping he couldn’t tell that it affected me.
An entire month working around this man had me ready to risk it all.
That intense sexual tension was clearly still there. If anything, it had grown stronger.
But unlike me, he seemed completely unfazed, which drove me crazy because how the hell was he able to ignore it?
While I seemed to burn alive every time he stepped into the room, he was fine navigating around me without the temptation.
I nodded, keeping my focus on his neck, refusing to meet his eyes, afraid of what I’d find and how I’d react to it.
“I thought we agreed not to make it weird.”
That statement had my gaze jerking upwards, meeting his head on.
Like he’d expected it, his lips were already curved in a half-grin, eyes lit with amusement. “There she is. The Hope Givens I’ve come to know doesn’t avoid eye contact.”
Rolling my eyes, I turned away, squatting to pick up the papers Mr. Stratford left behind. “You don’t know Hope Givens, Maverick.”
That noncommittal sound had me glancing up, tensing when I found him still standing right behind me, bottom lip tucked between his teeth. His lids were hooded as he looked down with a glare that screamed sex.
“Hmm, what?” I asked, pushing to my feet, stacking the papers neatly before holding them protectively against my chest.
Instead of answering, his gaze trailed over me, leaving a heated path wherever his eyes touched.
For the last month, this man has given me absolutely nothing. So to suddenly be on the receiving end of such blatant interest and attraction left me rattled.
“I’m taking an early lunch, sweetheart.” His eyes still burned my flesh as they made their way back up my body.
He knew calling me that would remind me of that night.
“You want me to bring you something?”
A new pair of panties.
Maybe an orgasm or two?
As if he could sense my internal thoughts, his gaze finally met mine and that half grin spread into a full one, exposing the dimple that creased his cheek, making his already attractive face even more flawless.
“No, no. I’m good.”
He watched me a few moments before nodding and turning, striding with that casual confidence through the bathroom door, closing it behind him.

domain: literature


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GRAIL used next-generation sequencing, population-scale clinical studies, and advanced computer science and data science for Galleri
US-based healthcare firm GRAIL has partnered with the UK’s National Health Service (NHS) to offer its multi-cancer early detection blood test Galleri to UK patients starting from 2021.
The company leveraged next-generation sequencing, population-scale clinical studies, and advanced computer science and data science for its multi-cancer early detection test Galleri, to address the challenges in medicine.
Aimed at confirming the clinical and economic performance of Galleri in the NHS system as a precursor to its regular use by the NHS, the partnership programme will include around 165,000 people in the UK, in two groups.
The first group consists of 140,000 people, aged more than 50, not suspected of cancer, and the second includes 25,000 people aged 40 years and above, with signs or symptoms of cancer.
The company intends to expand the access to the test to nearly one million people through 2024 and 2025, based on data from the programme, and offer the test subsequently to a larger population.
UK Health and Social Care Secretary Matt Hancock said: “We are building a world-leading diagnostics industry in the UK — not just for coronavirus, but for other diseases too.
“This exciting and ground-breaking new blood test from GRAIL will give us another tool to give more people the very best chance of survival, demonstrating how the UK continues to lead the way in using the latest innovative treatments to help patients.
“Many of us know a loved one who has battled against cancer and have seen first-hand the impact of this deadly disease.”
Galleri detects more than 50 cancer types with less than 1% false positive rate
According to a clinical validation study conducted in the US, the earlier version of Galleri detected more than 50 types of cancers, with a reduced false positive rate of less than 1% using a single blood draw.
When added to existing standard of care, Galleri has the potential of decreasing nearly half of the cancer cases diagnosed at late stage, which could cut down the total number of cancer deaths in the UK.
GRAIL intends to commercialise Galleri in the US in 2021. The test is currently available under investigational use, and is being used in the first interventional study, dubbed PATHFINDER, to guide clinical care.
GRAIL chief executive officer Hans Bishop said: “The collaboration between GRAIL, NHS England, and the UK Government represents a novel approach to taking on one of the world’s biggest public health challenges.
“We are excited to partner with the UK Government to support the NHS Long Term Plan for earlier cancer diagnoses, and we are eager to bring our technology to patients in the UK, and potentially save many lives.”

domain: medical


text:
March 21, 2013 |
GUWAHATI: Assam has witnessed increase in the number of motor vehicles. The total on road vehicle in Assam has reached 1528269 as on March 2012. According to the state economic survey 2012-13 tabled in the state assembly on Thursday the total number of vehicle in 2011 stood at 1363625. The survey added that growth of total number of registered vehicles recorded a compounded annual growth rate of 16.36 percent during the period 2004-05 to 2011-12.
December 29, 2011 |
Volvo Bus Corporation Auto Expo Volvo Bus Corporation
February 6, 2013 |
NEW DELHI: In an effort to effectively regulate public transport, Delhi Government today issued new guidelines for streamlining registration of public service vehicles and verification of drivers. Delhi Transport Minister Ramakant Goswami said to lessen burden on police, the government has identified certain conditions for purpose of registration of public service vehicle and issuance of public service badges to drivers. The Government has initiated the process for thorough verification of the crew of all public transport vehicles as per directive of the Centre to improve safety of women in the city.
September 19, 2010 |
NEW DELHI: Parking vehicles outside Commonwealth Games venues and iconic buildings have been banned in the wake of firing outside Jama Masjid here this morning. An order was issued in this regard by Lt Governor Tejinder Khanna this evening. "Parking of vehicles outside Games venues and iconic and important buildings have been banned," a senior police official said. Police will also check vehicles passing through these areas.
April 24, 2009 |
The government on Friday extended the time period for availing higher depreciation benefit on commercial vehicles by six months until September-end, a move aimed at boosting demand of such vehicles. The Central Board of direct Taxes has issued a notification to this respect.
August 20, 2010 |
WASHINGTON: Mazda Motor Corp. says its recall of certain Mazda3 and Mazda5 vehicles to fix problems with the power-steering system will include those sold in Europe and parts of Asia. The Japanese automaker said on Thursday the recall will cover more than 500,000 vehicles globally. The automaker had said previously the recall would include more than 300,000 Mazda3 and Mazda5 vehicles in North America from the 2007-2009 model years. Mazda said the vehicles could lose power-steering assist, making it difficult for the driver to steer the vehicle and increase the risk of a crash.
October 26, 2010 |
WASHINGTON: German automaker BMW AG is issuing two recalls involving about 150,000 luxury vehicles to fix faulty fuel pumps that could cause vehicles to lose power while driving. The first recall involves 130,000 vehicles, including the 2007-2010 335i; 2008-2010 135i, 535i and X6 xDrive35i Sports Activity Coupe; and 2009-2010 Z4 Roadster sDrive35i. The vehicles have twin-turbo inline six-cylinder engines featuring BMW's direct fuel injection system.
January 21, 2011 |
NEW DELHI: Automotive components maker Amtek Auto has formed a joint venture with South Korean automaker Autech Corporation to manufacture vehicles for defence, para-medical , fire fighting and waste management sectors to capitalise on the booming demand for specialised vehicles. The Delhi-based company will set up an assembly facility at Daruhera in Haryana with an initial capacity of 10,000 units per year. "We are anticipating a huge market potential as the fast-track Indian economy is bound to create demand for these vehicles.
June 8, 2010 |
WASHINGTON: Auto giant General Motors has recalled more than 1.3 million vehicles in the United States over fears that an electrical fault could cause fire, US government documents showed Tuesday. The problem, linked to the vehicles' windshield wiper fluid system, affects at least 18 models ranging from Chevrolet trucks to Hummers, documents from the National Highway Traffic Safety Administration showed.
April 22, 2013 |
NEW DELHI: Seeking to prevent pilferage of ammonium nitrate and its misuse of by terrorists, the Centre has asked all the state governments to ensure safe transit of vehicles carrying such explosives and monitor the units involved in handling of such substances. In a written reply to the Lok Sabha , Commerce and Industry Minister Anand Sharma today said the Union government has requested Chief Secretaries of all state governments and Union territories to instruct all District Superintendents of Police and Police Commissioners to ensure safe transit of vehicles carrying explosives through their respective districts.

domain: news


text:
Ace designers Ar. Anusha Katoch & Ar. Janesh Jain of arcKala design studio used connecting the dots technique to make sure all the elements in th...
Let us take a look at a set of flattering color palettes, that will suit your mood and liven up your living space.
Khushnuma Patel and Ar. Kartik Patel used earthy materials, a sublime colour scheme and incorporated nature in the interiors to encourage healthy...
Set in a quiet suburban lane in Green Park, South Delhi, this artistically vibrant home is designed by Sanjyt Syngh for a young professional.
The Earth house demonstrates the built environment’s opportunities for addressing the global climate crisis.
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domain: artistic


ANANTNAG: Angered over the littering of garbage on roads and streets allegedly by the Municipal Council Anantnag (MCA), people of various localities of this south Kashmir township Monday took to streets and held a protest demonstration.
Scores of people including youth early morning assembled near busy Mattan chowk after the announcements were made on public address systems of Masjids by the elderly residents of different localities.
Amid a complete shutdown in Kadipora, the protesters blocked the road for nearly three hours causing traffic jamming in different market places.
The protesters alleged that the MCA officials have turned the entire township into a garbage dumping site by allegedly littering the garbage on roads and streets. “It is irony that the MCA officials deposit the garbage on the roads and streets of the town for weeks together causing inconvenience to the people. One cannot afford to come out of the house without covering his or her nose,” President Auqaf committee (Kadipora), Abdul Gani Kiloo said.
He said the town sans proper garbage dumping site. “There is every possibility of the epidemic outbreak in the town if the officials don’t identify the proper dumping site and stop depositing garbage on roads,” said another protester, Zahoor Ahmad Magray.
Executive officer, MCA, Shabir Ahmad admitted the inconvenience to the people in the absence of a garbage dumping site. “Yes, it is true that the garbage has piled up on roads due to the non availability of dumping site.”
“But now we have identified the site in the vicinity of the town and all the garbage will be collected from the town and will be dumped there by Tuesday,” the officer told Kashmir Reader.


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Next Episode of This Farming Life is
A series following the struggles and triumphs of six very different farming families in some of Scotland's most beautiful and remote landscapes.
On Mull, new entrant farmers Janet and Alastair take their lambs to auction, inDumfries and Galloway, three generations of the Roan dairy-farming family enter a cow and a young heifer into competition at the South West Scotland Dairy Show, and in Argyll, hill farmers David and Sandra prepare for autumn by gathering in their sheep for a mineral dose and spreading slurry, while in the far north in the Highlands, crofters Robin and Penny's cattle are tested for bovine TB.
Our old friends newlyweds Mel and Martin Irvine return to the series and introduce their newest member of the family, four-month-old Erin. In Fife, buffalo farmer Stevie must select a new breeding bull from hisherd. Highland crofters Robin and Penny chase a runaway calf and Alastair has to leave Janet alone on Mull while he travels to the mainland to take an important deer-stalking test.
On Mull, Janet and Alastair put Owen, their new young virgin tup, to the test. Stevie risks the wrath of the buffalo mums when he ear-tags four newborn calves, early snow on the Western Highlands helps David gather his sheep and Martin, Mel and Erin hope for a windfall at the Carlisle bull sales.
As winter arrives, Stevie experiments with a radical buffalo feeding idea, David is anxious to find out if his cows are in calf, dairy farmers the Roan family set up a milkshake stand at the Dalbeattie Christmas lights-on event and Robin and Penny's family arrive in the Highlands for the annual festive ceilidh.
Dairy farmers Steven and Tracey Roan turn to technology to increase their chances of female calves, David and Sandra's hefted sheep go back to their homes on the hill, Janet and Alistair's new purchases prove problematic and Stevie and stockman Eddie go all out to save the life of a buffalo calf.
Alone on the farm, Mel must act fast to help a trapped bull, the Holstein Society assessor comes to judge the merits of the Roans' herd, an avian flu scare puts Robin and Penny's hens on lockdown and David is called to the rescue when a cow gets stuck in a bog.
Spring is in the air. On Mull, Highland cow Goldilocks gives Janet and Alastair a fright when a calving goes wrong.
Lambing and calving are in full swing. In Drummuir, Mel tries every trick in the book to help a first-time mum bond with her lambs.
Weaning time at the buffalo farm gives Stevie and his neighbours a sleepless night and a milk fever epidemic puts David and Sandra's cows in peril.
In Appin, David is beset by pests, and out on the hill his lambs are under threat from predators. In the Highlands, Robin and Penny makes use of the fine weather to cut peat, a cow undergoes open stomach surgery at the Roans' dairy farm, and Stevie decides to give his retired bull 007 a new assignment.
The sun is out and in the south of Scotland dairy farmers the Roans are struck down by silage fever; Janet and Alastair take a road trip to the mainland and find something very unusual in a group of young female sheep; crofters Robin and Penny's hopes for making money rest on sales of meat and pies at the biggest local food event of the year; and Stevie test-drives his new burger grill at Perth Races Ladies' Day.
It is midsummer and, in the final episode of the series, David and Sandra have to shear the sheep and start to train a month-old foal. Dairy farmers Stuart and Aylett Roan take a break from the cows to prepare for piglets, Robin and Penny's hay harvest is threatened by the weather, and Stevie reveals big plans for the future of his buffalo business.
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domain: geography


text:
Cisco executive chairman John Chambers said Thursday that as he prepares to leave the company he’s looking forward to working with start-ups that may have a major impact on the world.
Chambers said in a video broadcast go on Facebook that he meets with around 40 start-ups each month – generally in areas like artificial cleverness, big data, cloud computing and mobility. But he also waxed poetic on the potential of start-up Aspire Meals Group, which operates a robotic farm for edible crickets, and drone analytics business Airware — both of which Chambers invested in.
“I would like to change the globe, and hopefully that’s what I’ve been fortunate enough to become a part of at Cisco, and my intent is to accomplish it another period” with start-ups, Chambers said.
Under Chambers’ leadership, Cisco became a huge of enterprise technology, with annual revenue approaching $50 billion. Today he retains seats on the boards of OpenGov, Pindrop Security and Cisco.
In the next decade, nearly all job creation should come from start-ups, Chambers said. Beyond that, Chambers said start-ups provide opportunities to boost inclusion.
“At my start-ups, each one of them decides simply the basics for each and every start [requisition], requiring at least one female be interviewed,” he said. One start-up he’s caused went from 23 percent female to 34 percent female in 14 months, he said.
Chambers, 68, possesses been on Cisco’s panel since 1993. He was Cisco’s CEO from 1995 to 2015, of which point he was changed by Chuck Robbins. In September he advised the company and its own board that he would not seek to end up being re-elected to the company’s board at the annual shareholder meeting next week, relating to a regulatory filing. The board strategies to make Robbins its new panel chairman, the filing said.
Previous month Cisco stock jumped 5 percent after the company reported earnings for the earliest quarter of its 2018 fiscal year. Chambers owns 712,736 shares of Cisco stock, down from a lot more than 3 million in 2014.
“I want to find Cisco be extremely successful,” Chambers said in feedback directed at employees. “I would like to see you change the globe with digitization. I want Chuck and the leadership team to accomplish great things and wish great dreams.”

domain: finance


text:
The whole family will enjoy this story about a magnificent amusement park where the imagination comes alive.
Set in a Chicago neighborhood nearly a decade after an occupation by an extra-terrestrial force, Captive State explores the lives on both sides of the conflict -- the collaborators and dissidents.
Two teens with cystic fibrosis fall in love yet must remain six feet apart at all times.
Carol Danvers as she becomes one of the universe’s most powerful heroes when Earth is caught in the middle of a galactic war between two alien races.
What began as an unlikely friendship between a Viking and a fearsome dragon has become an epic adventure spanning their lives. In this final chapter, Hiccup and Toothless discover their true destinies.
Two brothers learn what’s possible when you run to—instead of from—the overwhelming love of God.
The heroes of Bricksburg are reunited to save their beloved city in this all-new action-packed adventure.
Just select the showtime with the "lux" button when purchasing tickets.
Never-before-seen footage take you straight into NASA's most celebrated mission as astronauts Neil Armstrong and Buzz Aldrin embark on a historic trip to the moon.

domain: entertainment


text:
Explore Detroit, Michigan
Detroit is a second home to me. It's where I was born, it's where some of my family still lives, it's where some of my friends live. It's where I love to explore. Detroit may have a bad name to some, but it hosts some of the most creative and colorful artwork and buildings that I've seen in Michigan.
I've been to The Heidelberg Project before in the summer, I posted a blog from my first time visiting there. It looked a little different this time, and I wasn't there as long as I was last time, but it was fun to see the changes. I also went to the Packard Plant. I've driven by the abandoned plant a few times, I've always been intrigued by how large and empty it was. The pockets of light you can find inside, if you can find a way inside, are quite beautiful. It's such a quiet place, filled with debris, pieces of clothing, metal and glass, and graffiti on the walls.
As for the upside down houses, I just like them that way.
Film developed and scanned by The Find Lab.


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CFP: Special Issue for The Journal of Medicine and Philosophy: Miscarriage and Spontaneous Abortion
Submission deadline: June 15, 2020
CALL FOR PAPERS
Special issue of The Journal of Medicine and Philosophy
Miscarriage and Spontaneous Abortion: Expanding the Discussion
Issue Editor: Nicholas Colgrove, PhD ([email protected])
Submissions are invited for a special issue of The Journal of Medicine and Philosophy on the theme: “Miscarriage and Spontaneous Abortion.”
Often, contemporary philosophical discussion on miscarriage/spontaneous abortion centers on one debate: whether or not opponents of abortion are “doing enough” to prevent it. The aim of this issue is to provide philosophical analyses and discussions of other aspects of miscarriage and spontaneous abortion.
Potential topics may include (but are not limited to):
· Are there good philosophical reasons for using the term “miscarriage” rather than “spontaneous abortion” (or vice versa)?
· What is miscarriage – what does it involve and how should it be described?
· What philosophical or ethical questions arise when considering miscarriage and the developmental stages of an embryo or fetus? Does twinning or embryo fusion involve miscarriage? Do early and late miscarriage raise different philosophical or ethical questions?
· How do understandings of health, disease, disorders, or conditions inform our understanding of miscarriage?
· Do prospective parents have an obligation to use miscarriage-preventing technologies or treatment (when available)? Do physicians or midwives have an obligation to offer them? Why or why not?
· What are the moral issues associated with miscarriage prevention research?
· What questions arise concerning the phenomenology of miscarriage?
o What is there to be said regarding the experiences and perspectives of prospective parents whose partners experience miscarriage?
o What is there to be said regarding the experiences and perspectives of medical professionals whose patients experience miscarriage?
· How might emerging assisted reproductive technologies (such as artificial womb technology or gene editing) shape our understanding of (or response to) miscarriage and why?
The issue editor welcomes early discussions of brief proposals and/or abstracts by email to: [email protected].
Submissions should be e-mailed to the Managing Editor at [email protected]. Please include a statement that your submission included in Journal of Medicine and Philosophy’s “Special Issue on Miscarriage and Spontaneous Abortion.”
Each manuscript must be accompanied by a statement that it has not been published elsewhere and that it has not been submitted simultaneously for publication elsewhere. Authors are responsible for obtaining permission to reproduce copyrighted material from other sources and are required to sign an agreement for the transfer of copyright to the publisher. All accepted manuscripts, artwork, and photographs become the property of the publisher. Please provide files in MS Word Format.
The Journal of Medicine and Philosophy is a double-blinded, peer reviewed, journal that appears through Oxford University Press. Papers will be submitted to the journal’s usual blinded peer reviewed process prior to acceptance for publication. The Editors and Editorial Board reserve the right to reject the issue in whole or in part, as well as to require significant revisions to particular papers prior to acceptance for publication.
Manuscript preparation instructions are available here: https://academic.oup.com/jmp/pages/Instructions_To_Authors
Submission Deadline: June 15, 2020


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The comparison used to create a P value is indicated by horizontal lines (*; 0.05, **; 0.01, ***; 0.001). 3. GS115, ATCC20864) by electroporation and inoculated to BMGY moderate (1% yeast remove, 2% peptone, 1.34% YNB, 1% glycerol, 100 mM potassium phosphate, 6 pH. 0) incubated in 30 C for 48 h then. The culture moderate was transformed with 0.5% methanol containing BMGY, referred to as BMMY moderate and methanol was added. Histidine-tagged 5xM2e proteins was purified by affinity chromatography using the nickel-nitrilotriacetic acidity (Ni2+-NTA) column. Soluble 5xM2e proteins vaccines had been characterized using mouse anti-M2e monoclonal antibody (mAb) 14C2 (Abcam, Cambridge, MA, USA) by Traditional western blot and enzyme-linked immunosorbent assay (ELISA) respectively. How big is the 5xM2e proteins(s) was noticed with multiple higher rings, which are larger than the anticipated molecular fat (~17C18 kDa). It really is speculated that oligomers surfaced because of the GCN4-oligomer stabilizing domains fused towards the 5xM2e proteins (Appendix Amount A1b). Influenza A/Philippines/2/82 (H3N2) and A/Vietnam/1203/2004 infections had been grown up in embryonated poultry eggs and purified from hen egg embryonic liquid. Inactivated trojan was made by treatment with formalin (1:4000, = 10, Charles River Laboratories, Inc., Wilmington, MA, USA) had been intramuscularly (we.m.) best immunized with 25 g of 5xM2e proteins (Pro) or 10 g of 5xM2e VLP (VLP) and increase immunized with 25 g 5xM2e proteins (Pro) or 10 g of 5xM2e VLP at weeks (weeks) 0 and 4 respectively. Bloodstream examples were collected in 3 weeks after getting immunized twice. Immunized mice had been anesthetized by isoflurane (Baxter, Deerfield, IL, USA) and intranasally (i.n.) contaminated with 4 50% mouse lethal dosage (4 LD50) of A/Philippines/2/82 (H3N2) in 50 L of PBS per mouse 11 weeks after increase immunization. Mice had been daily monitored for two weeks to record bodyweight changes and success rates if not sacrificed at 6 DHRS12 times post-infection (dpi). All pet studies had been approved and executed based on the suggestions of Georgia Condition University Institutional Pet Care and Make use of Committee (IACUC). This scholarly research was included in IACUC protocols A14025, october 2014 accepted on 20, and A18001, september 2017 approved on 18. 2.3. Lung Viral Titers Lung viral titers had been driven using PK68 fertilized poultry eggs, PK68 that have been incubated for 10 times at 37 C. Lung homogenates were diluted in PBS and inoculated in to the allantoic sacs serially. Inoculated embryonated eggs had been additional incubated for 3 times and chilled within a frosty room right away. The allantoic fluids were transferred and harvested into 96-well V-bottom plates containing chicken red blood cells. The plates had been left at area temperature for 30 min to determine viral titers avoiding the crimson blood cell precipitation. 2.4. Test Planning and Antibody Replies Bronchoalveolar lavage liquids (BALF), lung ingredients, and mediastinal lymph node (MLN) had been collected time 6 post contamination. BALF were obtained by infusing 1 mL of PBS into the lung via the trachea using a 25-gauge PK68 catheter (Exelint International Co., Los Angeles, CA, USA). MLN cells were cultured in plates pre-coated with M2e peptides for 1 or 5 days at 37 C. Antibody titers in immune sera, BALF, and lung specific for influenza computer virus were PK68 determined by enzyme-linked immunosorbent assay (ELISA) using human M2e peptide and inactivated influenza A/Philippines/2/82 computer virus (H3N2, iPhil) as covering antigens. Briefly, M2e peptide or iPhil (4 g/mL) antigens were coated onto 96-well microtiter plates (Nunc, Rochester, NY, USA), followed by incubation overnight at 4 C. The plates were washed with PBS made up of 0.05% Tween 20 (PBST) and blocked with 1% bovine serum albumin in PBST. Samples were added to the M2e-coated plates and incubated for 1.5 h (immune sera, BALF, lung homogenates), 1 or 5 days (MLN cells). Horseradish peroxidase-conjugated goat anti-mouse IgG, IgG1, and IgG2a (Southern Biotech, Birmingham, AL, USA) were used as secondary antibodies, and then tetramethylbenzidine (TMB) (Sigma-Aldrich, St. Louis, MO, USA) was used as a substrate. The optical density at 450 nm (OD450) was measured using an optical spectrophotometer reader. The total antibody concentration was determined with respect to the quantitative standard curve by using purified IgG, IgG1, IgG2a antibodies. 2.5. Bone Marrow-Derived Dendritic Cell (BMDC) Culture and Cytokine ELISA Bone marrow (BM) cells were harvested from your femur and tibia of BALB/c and reddish blood cells (RBC) removed using RBC lysis buffer (Sigma Aldrich, St. Louis, MO, USA). BM cells were cultured in completed RPMI 1640 with 20.
The illness of diabetic foot syndrome was known for 10 years and the patient had previously undergone amputation of a toe due to this condition. healthy volunteers. (PDF) pone.0212023.s014.pdf (103K) GUID:?69891B51-20B8-4B8F-ABB9-D023C7CCEEEA S8 Table: Free Hepcidin CKD patients. (PDF) pone.0212023.s015.pdf (129K) GUID:?A2DF0417-A6FA-4EC8-9649-CB945EC179C1 S9 Table: Slow response parameters/switch from baseline for healthy volunteers and CKD patients. (PDF) pone.0212023.s016.pdf (43K) GUID:?7C88FF5C-1110-49FB-B486-2E3FA63A3B76 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract In chronic kidney disease both renal insufficiency and chronic inflammation trigger elevated hepcidin levels, which impairs iron uptake, availability. and erythropoiesis. Here we report the two first-in-human phase 1 trials of PRS-080#22, a novel, rationally designed Anticalin protein that targets and antagonizes hepcidin. A single intravenous infusion of placebo or PRS-080#22 was administered to 48 healthy volunteers (phase 1a) and 24 patients with end stage chronic kidney disease (CKD) on hemodialysis (phase 1b) at different doses (0.08-16mg/kg for the phase 1a study and 2-8mg/kg for the phase 1b study) in successive dosing cohorts. The primary endpoint for both randomized, double-blind, phase 1 trials was security and tolerability. Following treatment, all subjects were evaluable, with none experiencing dose limiting toxicities. Most adverse events were mild. One severe adverse event occurred in the phase 1b (CKD patient) study. There were no clinically significant changes in safety laboratory values or vital indicators. PRS-080#22 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately three days in healthy volunteers and 10 to 12 days in CKD patients. Serum hepcidin levels were suppressed in a dose dependent manner and remained low for up to 48 hours after dosing. PRS-080#22 dose-dependently mobilized serum iron with increases in both serum iron concentration and transferrin saturation. No consistent changes were observed with regard to ferritin, reticulocytes, hemoglobin, and reticulocyte hemoglobin. Low titer anti-drug-antibodies were detected in five healthy volunteers but in none of the CKD patients. PRS-080#22, ML418 a novel Anticalin protein with picomolar affinity for hepcidin, was safe and well-tolerated when administered to healthy volunteers and CKD patients at all doses tested. The drug exhibited linear pharmacokinetics, longer half-life in CKD patients in comparison to healthy volunteers as well as expected pharmacodynamic ML418 effects which hold promise for further clinical studies. Introduction Anemia is usually a frequent complication of chronic kidney Mouse monoclonal to CD9.TB9a reacts with CD9 ( p24), a member of the tetraspan ( TM4SF ) family with 24 kDa MW, expressed on platelets and weakly on B-cells. It also expressed on eosinophils, basophils, endothelial and epithelial cells. CD9 antigen modulates cell adhesion, migration and platelet activation. GM1CD9 triggers platelet activation resulted in platelet aggregation, but it is blocked by anti-Fc receptor CD32. This clone is cross reactive with non-human primate disease (CKD). The incidence and prevalence of anemia increases in patients with more advanced stages of CKD, as kidney function declines [1, 2]. The most common causes are iron deficiency and insufficient erythropoietin (EPO) ML418 production . Consequently, current treatment regimens consist of iron (oral or intravenous (IV)), erythropoietin stimulating brokers (ESAs), or a combination of both. Adequate iron stores are essential for achieving maximum benefit from ESAs; therefore, most end-stage CKD patients also receive IV ML418 iron supplementation. However, IV iron may cause infrequent but severe adverse reactions and issues about long-term security have been raised [3,4]. A clear relationship between iron therapy and hepatic iron overload has been exhibited by hepatic MRI . ESA therapy, particularly at high doses, has been associated with an increased risk of cardiovascular complications and mortality . Finally, a significant number of patients remain anemic despite combination therapy with ESAs and IV iron. In this light, there is a significant need for novel therapeutic approaches to address ESA/iron resistant anemia in CKD patients. Hepcidin, a liver-derived 25 amino acid peptide hormone, is usually a central regulator of iron homeostasis. Many disorders of iron imbalance can be attributed to aberrant hepcidin production . Hepcidin binds to and degrades the iron export channel ferroportin in both the gut and the plasma.
Finally, three trials performed on casein and gluten in children during GFCFD, randomly receiving gluten or casein placebo foods, demonstrated no difference in behavior and intestinal symptoms between the two groups [173,174,175]. learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the suggested romantic relationship between ASD and Compact disc and the feasible usefulness of the gluten-free diet plan in ASD individuals. and also to percentage . Notably, different metabolite degrees of bacterial source, such as brief chain essential fatty acids (SCFAs), indoles and lipopolysaccharides (LPS), had been seen in the bloodstream and urine of autistic kids . Thus, improved gut permeability in colaboration with dysbiosis in people with Compact disc might favour the passing of poisonous substances, aswell as bacterial metabolite, through the intestinal hurdle, which promote swelling affecting the mind. Figure 1 identifies the foundation of opioid hypothesis correlating Compact disc with ASD. Open up in another window Shape 1 Opioid hypothesis. In celiac individuals, the incomplete digestive function of proteins produced by whole wheat and milk generates peptides known as gliadinomorphin-7 and exorphins (gliadorphin, rubiscolin, Sitravatinib casomorphin). Having less protease DPP-IV mementos the transformation of gliadinomorphin-7 in exorphins. Exorphins mix gut bloodCbrain and hurdle hurdle and so are in a position to bind and stimulate opioid receptors in mind. These events could possibly be in charge of disorders of interest, public and learning relations, normal of ASD. GFCFD: gluten free of charge casein free diet plan. 5. Oxidative Tension Hypothesis Another interesting subject is displayed by the Sitravatinib countless different research that pinpointed a good relationship between oxidative tension, CD and ASD. The build up of reactive air species (ROS), aswell as the impairment of protecting antioxidant systems, can result in oxidative injury in lots of different circumstances, influencing extra and intestinal intestinal areas , in order that some authors speculated about the usage of oxidative tension biomarkers for the administration of Compact disc. Alternatively, waligora et al recently. took into consideration that neurological adjustments happening in ASD, such as for example strength of behavioral and psychological symptoms, may be ascribed to oxidative harm  and regarded as ROS Sitravatinib and biomarkers of oxidative tension mainly because potential metabolic signals for the introduction of appropriate applications of pharmacological therapy. Oxidative tension is thought as some events leading to an imbalance between your creation of oxidative varieties and the experience of antioxidants . Reactive air varieties (ROS) and reactive nitrogen varieties (RNS) era represent the primary causal occasions of oxidative tension in the cells. ROS are reactive substances and free of charge radicals produced from molecular air . The primary varieties consist of unpredictable air free of charge radicals extremely, such as for example superoxide anion (O2?C), and hydroxyl radical (?OH), and even more stable, diffusible non-radicals freely, including hydrogen peroxide (H2O2). Superoxide anion can respond with nitric oxide (NO), which Sitravatinib can be made by nitric oxide synthase (NOS), to create the peroxynitrite anion (ONOO-), a reactive nitrogen entity with nitrosative and oxidative potential . ROS are produced inside the cells physiologically. The major mobile resources of ROS Rabbit polyclonal to PDGF C are mitochondria, where electrons which have escaped through the respiratory string can respond with O2 substances to create O2?C . ROS could be created by the experience of different enzymes also, such as for example NADPH oxidase, xanthine oxidase, lipoxygenases, and cyclooxygenases  or through the activities of different exterior factors, including contaminants, tobacco smokes, carcinogens and food [125,126,127,128]. ROS produced in the cells exert physiological tasks or cause poisonous effects in romantic relationship with their amounts . At low dosages ROS can function in the cells as signaling substances by regulating different procedures, including cell proliferation, gene activation and angiogenesis . Nevertheless, under oxidative tension circumstances, overproduction of ROS could cause irreversible harm of macromolecules, including RNA and DNA, lipid peroxidation and amino acidity oxidation.
Peripheral blood was the stem cell source in 42 patients, BM was used in 12 and CB in 1. Cancrologie de Marseille, Institut Paoli Calmettes, Programme de Transplantation &Therapie Cellulaire, Marseille, France; 10Nottingham University or college Private hospitals NHS Trust, Nottingham, United Kingdom; 11Queen Elizabeth Medical Centre, University Hospital Birmingham NHS Trust, Division of Haematology, Birmingham, United Kingdom; 12Erasmus MC Malignancy Institute, University Medical Center Rotterdam, Division of Haematology, Rotterdam, Netherlands; 13Tor Vergata ARP 101 University or college of Rome, Policlinico Universitario Tor Vergata, Stem Cell Transplant Unit, Rome, Italy; 14CHU Bordeaux H?pital Haut-leveque, Pessac, Bourdeaux, France; 15Addenbrookes Hospital, Division of Haematology, Cambridge, United Kingdom; 16Asweet Leukemia Working Party, Western Society for Blood and Marrow Transplantation Paris Study Office/Western Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France; 17Vanderbilt University or college Medical Center, Division of Hematology/Oncology, Division of Internal Medicine, Nashville, TN, United States; 18Chaim Sheba Medical Center, Tel-Hashomer, Israel, Hematology Division BMT and Wire Blood Standard bank, Ramat Gan, Israel; 19Tel Aviv ARP 101 University or college, Tel Aviv, Israel Background: Allogeneic haematopoietic cell transplant (allo-HCT) is the only therapeutic modality to offer cure to individuals with relapsed acute myeloid leukaemia (AML) achieving second total remission (CR2). Few studies have focused on allo-HCT results in AML CR2 concerning the effect of myeloablative (Mac pc) versus reduced intensity (RIC) conditioning. Methods: This is a multicentre, retrospective registry study from the Acute Leukemia Working Party of the Western Society for Blood & Bone Marrow Transplantation in a large cohort of AML CR2 individuals. Eligibility: Age 18y, 1st allo-HCT 2007C16, analysis AML CR2, cytogenetic profile at analysis, peripheral blood stem cells (PBSC) or bone marrow (BM) from a matched related (MRD), volunteer unrelated with HLA match 10/10 (VUD) or 9/10 (MMVUD), or haplo-identical (haplo) donor. Univariate and Cox Regression multivariate analyses (MVA) were undertaken. Measured results included ARP 101 2y OS, leukemia free success (LFS), non-relapse mortality (NRM), graft vs web host disease (GVHD), chronic GVHD (cGVHD) and GVHD-free/relapse-free success (GRFS). Outcomes: A complete of 1879 sufferers, 1013 male, had been entitled and 1010 (54%) received Macintosh allo-HCT. Donors had been MRD (36%), VUD (39%), MMVUD (15%) or haplo (10%). Allocation to Macintosh allo-HCT was 37% MRD, 36% VUD, 14% MMVUD and 13% haplo (P? ?10?3). Macintosh ARP 101 versus RIC allo-HCT groupings were similar for de novo AML (95%), calendar year of HCT, median follow-up (24.8 vs 30.53m), reported FLT3 mutations (25.63 vs 24.4%), NPM1 Rabbit Polyclonal to CDON mutations (48.67 vs 50.16%) and confirmed measurable residual disease at HCT (33%). Recipient-donor pairs were equivalent for CMV and sex-matching sero-status. Karnofsky performance position was 80% in 97.21% Macintosh and 93.07% RIC allo-HCT recipients (P? ?10?3). At 2y, general final results had been LFS 52% (CI: 49.5C54.5), OS 58.7% (CI: 56.2C61.2), RI 28.9% (CI: 26.7C31.2), NRM 19% (CI: 17.2C21), GRFS 38.7% (CI: 36.2C41.1), acute GVHD II-IV 24.3% (CI: 22.3C26.3), cGVHD 37.2% (CI: 34.7C39.7) and extensive cGVHD 15.9% (CI: 14.1C17.8). In MVA, in 50y, RIC vs Macintosh were equivalent for everyone final results. In 50y, RIC vs Macintosh reduced NRM (HR 0.535, CI 0.378C0.758) with worse cGVHD (HR 1.377, CI 1.027C1.845) but no effect on RI, OS or LFS. Indie of conditioning strength, adverse and intermediate cytogenetics increased RI ( 50y HR 1.52 CI 1.115C2.071, HR 3.347 CI 2.26C4.958; 50y HR1.436 CI 1.006C2.049, HR 1.79 CI 1.035C3.096) with concomitant results on OS ( 50y HR 1.318 CI 1.026C1.692, HR 2.417 CI 1.708C3.421; 50y HR 1.202 CI 0.903C1.6, HR 1.607 CI 1.042C2.479). Conclusions: Allo-HCT rescues a lot more than 50% of AML sufferers attaining CR2 post-relapse. Outcomes of allo-HCT for the go for band of relapsed AML sufferers achieving CR2 show up comparable to those reported in the books for AML sufferers who received allo-HCT in CR1. In sufferers with AML CR2, RIC allo-HCT decreases procedural mortality in sufferers 50y without raising RI and equivalent final results to Macintosh allo-HCT in sufferers 50y. Standard methods to Macintosh allo-HCT in the 50y require prospective reappraisal. Issue appealing: The authors possess nothing to reveal O010 Abstract previously released O011 Superior Final results with Myeloablative versus Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Supplementary Acute Myeloid Leukemia with Prior Solid Tumor: An ALWP of EBMT Research Catherine Lee1, Myriam Labopin2, Dietrich Beelen3, Jrgen Finke4, Didier Blaise5, Arnold Ganser6,.
Hoffmann-La Roche Ltd. The author is employed by F. oseltamivir-treated sufferers enrolled onto Roche-sponsored scientific studies of oseltamivir treatment through the oseltamivir advancement programme). Nevertheless, an oseltamivir-resistant influenza A (H1N1) trojan emerged in European countries through the 2007C08 period and circulated in the southern and north hemispheres in 2008C09. No hyperlink with oseltamivir use could be discovered, as well as the scientific impact of the infections was limited. Oseltamivir-susceptible pandemic (H1N1) 2009 infections now predominate in lots of countries. Oseltamivir is certainly well tolerated generally, with an identical undesirable event profile to placebo. valueand CNS tolerability profile of oseltamivir continues to be revisited within the extensive basic safety review. No medically relevant distinctions in plasma pharmacokinetics of oseltamivir and its own energetic metabolite oseltamivir carboxylate (OC) had been observed between Japanese and Caucasian adults89 or kids.90 Penetration in to the CNS of both oseltamivir and OC was lower in Japan and Caucasian adults (CSF/plasma maximum concentration and AUC ratios of 0.03; Statistics?4 and ?and55),91 and the capability for converting oseltamivir into OC in rat and mind was low.85 In animal autoradiography research, brain/plasma radioactivity ratios had been generally 20% or lower, and animal research showed no particular CNS/behavioural results after administration of doses corresponding to 100 times the clinical dose.85 Oseltamivir and OC didn’t connect to human neuraminidase or with 155 known molecular focuses on in radioligand binding and functional assays. A books review of useful variants of genes highly relevant to oseltamivir pharmacokinetics and pharmacodynamics and simulated gene knock-out situations have not discovered any plausible hereditary explanations for the noticed NPAEs.85 A literature critique indicated that influenza itself may be associated with a number of neurological sequelae. 92 Predicated on this provided details as well as the results from the basic safety review, a disease-mediated pathogenesis for the noticed NPAEs appears most likely. Lately published retrospective studies possess confirmed too little association between NPAEs and oseltamivir. Open in another window Body 4 (a) Mean (SD) concentrationCtime profile for oseltamivir in plasma after an individual oral dosage of 150 mg of oseltamivir phosphate in Caucasian ( em n /em ?=?4) and Japan ( em n /em ?=?4) topics and the entire people ( em n /em ?=?8). (b) Mean (SD) concentrationCtime profile for oseltamivir in CSF after an individual oral dosage of 150 mg of oseltamivir phosphate in Caucasian ( em n /em ?=?4) and Japan ( em n /em ?=?4) topics and the entire people ( em n /em ?=?8). Reproduced from Jhee em et al. /em 91 with authorization. Open in another window Body 5 (a) Mean (SD) concentrationCtime profile for oseltamivir carboxylate in plasma after an individual oral dosage of 150 mg of oseltamivir phosphate in Caucasian ( em n /em ?=?4) and Japan ( em n /em ?=?4) topics and the entire people ( em n /em ?=?8). (b) Mean (SD) concentrationCtime profile for oseltamivir carboxylate in CSF after an individual oral dosage of 150 mg of oseltamivir phosphate in Caucasian ( em n /em ?=?4) and Japan ( em n /em ?=?4) Hyodeoxycholic acid topics and the entire people ( em n /em ?=?8). Reproduced from Jhee em et al. /em 91 with authorization. General basic safety: treatment Pooled basic safety data in the oseltamivir scientific treatment programme have already been reported at duration previously.93 In kids and adults, oseltamivir ENO2 treatment was well tolerated generally, with a standard occurrence of adverse occasions comparable to placebo. In treatment research in adults, just throwing up and nausea had been reported with an increased regularity in the oseltamivir hands, and these occasions happened in the initial or second time generally, were minor in strength and solved without discontinuation. The occurrence of adverse occasions was equivalent between oseltamivir and placebo and was equivalent in youthful ( 65 years) and older adults (65 years).93 Small data in immunocompromised sufferers claim that oseltamivir treatment is well tolerated also. 31 Because from the known association between fatalities and influenza from cardiac disorders, a thorough overview of the obtainable data on cardiac basic safety in patients subjected to oseltamivir was executed.93 No influence on QTc T or intervals wave morphology was noticeable, and pre-clinical research demonstrated that oseltamivir acquired no prospect of results on cardiac repolarization. In kids, vomiting and stomach pain had been the only occasions that occurred more often with oseltamivir; generally, these occurred in the beginning of treatment and resolved without resulting in problems such as for example dehydration rapidly. In the pooled evaluation, fifty percent of these 6 years had asthma around. 93 Oseltamivir had no undesireable effects on pulmonary function in these small children. Similarly, in the procedure research of asthmatic Hyodeoxycholic acid kids described earlier, the entire occurrence of undesirable occasions was equivalent in Hyodeoxycholic acid the placebo and oseltamivir hands, with gastrointestinal disorders one of the most reported events frequently.20 Vomiting and stomach pain had been slightly more frequent in the oseltamivir group compared to the placebo group (15.9% versus Hyodeoxycholic acid 11.0% and 6.5%.
INS-1 cells were incubated with THAP (0.5 M), with (A) exendin-4 or (B) FSK at indicated concentration for 24 h, then the cellular viability was analyzed by MTT assay (n = 5). Ser307 and Ser308 positions, resulting in Cyclo(RGDyK) its degradation activation of mobile proteasome pathway. In keeping with this observation, TXNIP (S307/308A) mutant resisted the degradation ramifications of PKA C. Nevertheless, exendin-4 neither affected TXNIP level in TXNIP (S307/308A) mutant overexpressed -cells nor in PKA C-KO -cells. Furthermore, exendin-4 treatment decreased the irritation gene appearance in TXNIP overexpressed -cells, but exendin-4 treatment does not have any influence on the irritation gene appearance in TXNIP (S307/308A) overexpressed -cells. To conclude, our study unveils the integral function of PKA C/TXNIP signaling in pancreatic -cells and shows that PKA C-mediated TXNIP degradation is essential in -cell defensive ramifications of exendin-4. PKA activation in pancreatic -cells (Kim et al., 2010). To be able to confirm these total outcomes, we hence treated INS-1 cells with thapsigargin Cyclo(RGDyK) (THAP), an ER tension inducer, to see the result of FSK or exendin-4 on -cell viability, because FSK or exendin-4 both could activate PKA. Like the prior outcomes, exendin-4 ( Amount 1A ) or FSK ( Amount 1B ) treatment could statistically considerably improve ER stress-induced -cell loss of life. Taking into consideration ER stress-induced irritation is the reason behind -cell loss Cyclo(RGDyK) of life (Oslowski et al., 2012), we evaluated Rabbit Polyclonal to ZNF682 the consequences of FSK in IL1- known level. As proven in Amount 1C , Generally improved IL1- transcription THAP, which was low in the current presence of FSK or exendin-4. Therefore, we wished to know if the anti-inflammation impact was reliant on PKA. After PKA activation was inhibited by H89, a PKA inhibitor, IL1-, was in the same level under ER tension condition with or without FSK or exendin-4 treatment. Moreover, H89 cannot Cyclo(RGDyK) induce even more IL-1 appearance under ER tension, which excluded the chance that the inhibition of PKA provides other downstream results that raise the IL-1 appearance. The results indicated that PKA played an integral role in the protective aftereffect of FSK or exendin-4. Open up in another screen Amount 1 FSK or Exendin-4 treatment reduces ER stress-induced -cell viability. INS-1 cells had been incubated with THAP (0.5 M), with (A) exendin-4 or (B) FSK at indicated concentration for 24 h, then your cellular viability was analyzed by MTT assay (n = 5). INS-1 cells had been incubated with THAP (0.5 M), H89, with (C) exendin-4 or (D) FSK at indicated concentration Cyclo(RGDyK) for 24 h, then your IL-1 level was analyzed by qRT-PCR (n = 3). Pubs represent the indicate SEM of unbiased samples. Factor in appearance between un-treated group as well as the medications group as tagged was analyzed by one-way ANOVA, corrected for multiple evaluations using the Bonferroni check. *** signifies P worth < 0.001). Taking into consideration ER stress-induced TXNIP locates on the upstream of IL1-, we as a result explored whether PKA activation could regulate TXNIP level under ER tension condition in -cells. THAP statistically induced TXNIP expression as soon as 0 significantly.5 h post-treatment, which lasted for 8 h ( Amount 2A ). This observation was in keeping with a prior survey (Oslowski et al., 2012). Nevertheless, FSK treatment reduced TXNIP protein level induced by ER Tension generally, as soon as 0.5 h ( Figure 2B ). These total results inspired us to learn whether TXNIP transcriptional level was also inhibited by FSK. As proven in Amount 2C , FSK (10 M) acquired no influence on the mRNA degree of TXNIP induced by THAP after 0.5-4 h treatment, except 8 h. Furthermore, it wasfound that FSK decreased TXNIP mRNA level at 12, 24 and 48 h treatment inside our laboratory (data not proven). In the above, these outcomes indicated that FSK generally marketed TXNIP degradation apart from on the transcriptional level at small amount of time incubation. Open up in another window Amount 2 FSK treatment decreases TXNIP level. (A) INS-1 cells had been incubated with THAP (0.5 M), and TXNIP protein was discovered using WB.
Supplementary Materialscells-10-00698-s001. migration with time-lapse imaging and quantitative morphodynamic methods, were combined to investigate ALLO actions on microglia. BV-2 cells communicate subunits of GABA-A receptor that mediates ALLO activity. ALLO (10M) induced microglial cell process extension and decreased migratory capacity. Interestingly, ALLO modulated the phagocytic activity of BV-2 cells and main microglia. Our results, which show a direct effect of ALLO on microglial morphology and phagocytic function, suggest that the natural neurosteroid-based approach may contribute to developing effective strategies against neurological disorders that are evoked by microglia-related abnormalities. = 3C4 self-employed experiments, * 0.05, ** 0.01. 3.2. The BV-2 Cell Collection Expresses Transcripts of GABA-A Receptors ALLO Fosfosal seems to play a crucial part during cerebral diseases, notably thanks to TLN1 its immunomodulatory activity. Most of the known effects exerted by this neurosteroid are mediated through the GABA-A receptors. To detect possible transcriptional regulations due to the serum concentrations used to cultivate BV-2 cells, the level of manifestation of specific GABA-A receptor mRNAs was investigated by quantitative PCR. We analyzed the manifestation of the following subunits normalized to Ppia manifestation: 1, 2, 4, 3, and . In our samples, the subunit 4 was not recognized, whereas the additional subunits were all found. The manifestation of the subunit 1 was Fosfosal unchanged between BV-2 cells cultivated with 1% FCS or 10% FCS (Number 2A). On the contrary, there was a significant reduction in the manifestation of transcripts for the subunit 2, 3, and (Number 2BCD). Similar results were acquired using other research genes Hmbs and Pgk1 (data not shown). Open in a separate window Number 2 Gene manifestation of -aminobutyric acid-A (GABA-A) receptor Fosfosal subunits in BV-2 cells. Manifestation level of GABA-A receptor (A) 1, (B) 2, (C) 3, and (D) subunits in BV-2 cell collection are determined by quantitative PCR. The experimental results represent the fold induction of mRNA indicated by BV-2 cultivated in presence of 10% FCS in comparison to BV-2 cultivated with 1% FCS after normalization to Ppia manifestation. Mean ideals SEM are demonstrated, from = 4 self-employed experiments, * 0.05. 3.3. Effect of ALLO within the Viability of BV-2 Cells BV-2 cells that were cultivated in presence of 1% FCS exhibited a significant reduction of their viability only after incubation with 10 M ALLO (Number 3A). In contrast, none of the tested doses affected the viability of BV-2 cells cultured in the presence of 10% FCS (Number 3B). Open in a separate window Number 3 Effect of allopregnanolone (ALLO) within the viability and proliferation of BV-2 cells. (A,B) The viability of BV-2 cells was investigated by circulation cytometry following incubation with graded concentrations of ALLO. (C,D) The dilution of CFSE showed that proliferation of BV-2 cells cultivated with 1% or 10% FCS is not modified in presence of ALLO. Mean ideals SEM are demonstrated, from = 4 self-employed experiments, * 0.05. 3.4. ALLO Does Not Modulate Proliferation of the BV-2 Cell Collection Neurosteroid ALLO has been reported to induce the proliferation of different cell types [37,38]. This parameter is definitely important in the context of autoimmune diseases, where an uncontrolled proliferation of immune cells could exacerbate the swelling. Thus, we analyzed the CFSE dilution in BV-2 cells by circulation cytometry after four days of treatment with graded concentrations of ALLO. Regardless of the dose of neurosteroid applied to BV-2 cells cultured in the presence of 1% FCS, the pace of cell division was unchanged (Number 3C). A similar observation was carried out if BV-2 cells were cultivated with 10% FCS (Number 3D). 3.5. ALLO Favors the Elongation of Microglial Processes To date, the effects of ALLO on microglia have not been deeply investigated. When cultivated in the presence of 1% FCS, BV-2 cells become adherent and develop processes (Number 4A). In control conditions, among the BV-2 cells bearing processes, 69% were bipolar and 31% were Fosfosal multipolar exhibiting at least three extensions (Number 4B). One day after the addition of ALLO, none of the tested doses was able to affect the proportion of bipolar vs. multipolar cells (Number 4B). However, after treatment with 10 M ALLO, BV-2 cells seemed to show longer extensions (Number 4A). The measurement of the processes borne by each cell exposed that the application of 10 M ALLO led to an increase of 22% of their mean size (Number 4C). This extension is found mainly in bipolar cells (Supplementary Number S1). Open in a separate window Number 4 ALLO increases the length of microglial cells. (A) BV-2 cells cultivated in 1% FCS exhibited processes in both control and.
Rev. increased tumor size = 8.819, = 0.012), advanced differentiation (= 14.249, = UK-383367 0.001) and higher AJCC stage (= 4.99, = 0.025) (Table ?(Table2).2). No significant association was found between Lgr5 expression and age or gender (all > 0.05). Kaplan-Meier analysis suggested that prognosis was poor for patients with high Lgr5 expression (Figure ?(Figure1D1D). Table 1 The expression of Lgr5 in esophageal squamous cell carcinoma tissues and normal esophageal squamous epithelial tissues = 98, 400, scale bar, 20 m), (B) three different high-grade ESCC tissues (= 93, 400, scale bar, 20 m) and (C) three different low-grade ESCC UK-383367 UK-383367 tissues (= 95, 400, scale bar, 20 m). (D) Kaplan-Meier survival analysis indicated a correlation between high expression of Lgr5 and poorer overall survival in ESCC patients. Table 2 Lgr5 expression and clinicopathological characteristics in ESCC patients as non-adherent spheres under serum-free culture conditions [27, 28]. Using ultra low attachment surface plates and serum-free culture conditions supplemented with B27, bFGF, EGF and heparin, ESCC KYSE450 cells grew IL12B as non-adherent, three-dimensional spheroid bodies after seven days (Figure ?(Figure2).2). These spheroid body cells could be dissociated into single cells, which indicated they have the capacity of self-renewing. Open in a separate window Figure 2 Spheroid formation is evident in ESCC KYSE 450 cells(A) Morphology of cells grown in RMPI 1640 medium supplemented with 10% FBS (200). (B, C) Cells cultured in stem cell specific culture media. Cell morphology shows formation of spheroids (400). Lgr5, CSCs-related genes and RSPO2 are overexpressed in ESCC KYSE450 spheroid body cells A growing body of evidence demonstrates that SOX2, ALDH1A1 and NANOG are important stemness genes for many CSCs and play crucial roles in self-renewing, differentiation and tumorigenicity of CSCs [29, 30]. RSPO2 is a member of the R-spondin UK-383367 family proteins that are secreted agonists of the canonical Wnt pathway, which act through binding with LGRs. qRT-PCR and western blot analyses were performed on spheroid body cells and parental cells. We found that ESCC KYSE450 spheroid body cells overexpressed, ALDH1A1, NANOG and the specific ligand of Lgr5, RSPO2, compared to ESCC KYSE450 parental cells (Figure 3A, 3B). To further examine the expression of Lgr5 in ESCC KYSE450 spheroid body cells, qRT-PCR, western blot and flow cytometric analyses were performed on the spheroid body cells UK-383367 and parental cells (Figure 3C, 3D). The results of qRT-PCR and western blot indicated that the protein and mRNA levels of Lgr5 were elevated in ESCC KYSE450 spheroid body cells, compared with ESCC KYSE450 parental cells. Flow cytometric analysis revealed that KYSE450 spheroid body cells contained a high proportion of Lgr5+ cells, while parental cells had a smaller Lgr5+ fraction. These results indicate that ESCC KYSE450 spheroid body cells have an increased expression of CSC-related genes. Moreover, in these spheroid body cells, the expression of Lgr5 and its specific ligand, RSPO2, were increased. Open in a separate window Figure 3 Lgr5, CSC-related genes, and RSPO2 are overexpressed in ESCC KYSE450 spheroid body cells(A) mRNA and protein levels of SOX2, ALDH1A1, and NANOG are up-regulated in spheroid body cells *< 0.05, **< 0.01, vs the parental cells group). (B) qRT-PCR and western blot analysis demonstrated elevated mRNA and protein levels of RSPO2 in KYSE450 spheroid body cells compared with parental cells (*< 0.05). (C) qRT-PCR and western blot analysis demonstrated elevated mRNA and protein levels of Lgr5 in KYSE450 spheroid body cells compared with parental cells (*< 0.05). (D) Flow cytometric analysis of the Lgr5+ cell subpopulation in KYSE450 spheroid body cells (67.2%) and parental cells (12.8%). Spheroid body cells display high tumorigenic potential = 5/group). Xenograft tumors developed 4 weeks post cell injection. Tumor size was measured every three days. Tumor volume was calculated as length width depth. (A) The average of tumor volumes was plotted. (B) Xenograft tumors were resected from mice at 4 weeks post cells injection. Silencing of Lgr5 inhibits the proliferation,.
Hepatitis C disease (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). found that the activation and ABX-464 DNA binding ability of Y220C p53 were strongly suppressed by FBP1 but significantly triggered upon knockdown of FBP1. Transient manifestation of FBP1 in FBP1 knockdown ABX-464 cells fully restored the control phenotype in which the DNA binding ability of p53 was strongly suppressed. Using electrophoretic mobility shift assay (EMSA) and isothermal titration calorimetry (ITC), we found no significant difference in target DNA binding affinity of recombinant wild-type p53 and its Y220C mutant p53. However, in the presence of recombinant FBP1, the DNA binding ability of p53 is definitely strongly inhibited. We confirmed that FBP1 downregulates BCCIP, p21, and p53 and upregulates TCTP under radiation-induced stress. ABX-464 Since FBP1 is definitely overexpressed in most HCC tumors with an HCV background, it may possess a role in promoting prolonged disease illness and tumorigenesis. IMPORTANCE It is our novel finding that FUSE binding protein 1 (FBP1) strongly inhibits the function of tumor suppressor p53 and is an essential sponsor cell factor required for HCV replication. Oncomine data analysis of a large number of samples has exposed that overexpression of FBP1 in most HCC tumors with chronic hepatitis C is definitely significantly linked with the decreased expression level of p53. The most significant finding is definitely that FBP1 not only literally interacts with p53 and interferes with its binding to the prospective DNA but also functions as a negative regulator of p53 under cellular stress. FBP1 is definitely barely detectable in normal differentiated cells; its overexpression in HCC tumors with the CHC background suggests that FBP1 has an important role in promoting HCV illness and HCC tumors by suppressing p53. Intro Hepatitis C disease (HCV) infection is definitely a leading cause of chronic liver diseases. More than a decade after the recognition of HCV ABX-464 as the major causative agent of non-A, non-B hepatitis (1), molecular strategies for total eradication of HCV infection are actively ABX-464 pursued. HCV is the major cause of chronic liver disease. Relating to new findings from your U.S. Centers for Disease Control and Prevention (CDC), the number of individuals in the U.S. living with chronic hepatitis C disease infection is about 2.7 million (2). Globally, the number of people with HCV is definitely greater than 185 million (3). During the past 3 years, the U.S. Food and Drug Administration has authorized four new medications (boceprevir, telaprevir, sofosbuvir, and simeprevir) for treatment of HCV illness, and many fresh medicines are under development. There has been a renewed effort from the CDC to prevent HCV-associated complications by improving treatment. However, the cost of HCV treatment is definitely highly prohibitive; it costs $80,000 for any three-month treatment program with the recently authorized sofosbuvir (Gilead Sciences, CA). Although the majority of HCV-infected persons are unaware of their illness (4), 15 to 25% of them clear the disease without treatment, while the majority of infections Alox5 persist, leading to chronic hepatitis C (CHC), which is definitely closely linked with the risk of liver cirrhosis (LC) (5) and hepatocellular carcinoma (HCC). The molecular mechanisms that set up prolonged HCV illness and its progression to LC and HCC are poorly recognized. The HCV genome is definitely a positive-strand RNA comprising highly organized 5 and 3 nontranslated areas (NTRs) with multiple regulatory elements essential for viral replication and translation. We have identified many sponsor cell factors associated with the viral RNA genome (6, 7); many of them were shown to be essential for HCV replication. One of the sponsor factors essential for HCV replication was FBP1 (6), which is known to interact with the far-upstream element (FUSE) of.
Organic killer (NK) cells were so named because of their uniqueness in killing specific tumor and virus-infected cells without preceding sensitization. occasions for NK cell priming, we analyzed IL-15 results on NK cells where the pathways emanating from IL-15 receptor activation had been blocked with particular inhibitors. Our outcomes demonstrate which Rabbit polyclonal to TNNI1 the PI3KCAKTCmTOR pathway is critical for cytokine reactions in IL-15 primed NK cells. Furthermore, this pathway is also implicated in a broad range of IL-15-induced NK cell effector functions such as proliferation and cytotoxicity. Similarly, NK cells from mice treated with rapamycin to block the mTOR pathway displayed problems in proliferation, and IFN- and granzyme B productions resulting in elevated viral burdens upon murine cytomegalovirus illness. Taken collectively, our data demonstrate the requirement of PI3KCmTOR pathway for enhanced NK cell functions by IL-15, therefore coupling the metabolic sensor mTOR to NK cell anti-viral reactions. knock-out and NK cell-specific knock-out mice showed that NK cells are absent in peripheral lymphoid organs, suggesting a critical importance of the IL-15CSTAT5 pathway in NK cell development (17C19). In addition, similar to STAT5 knock-out mice, a severe reduction in NK cell figures has been found in a patient comprising the mutation (20). Studies have shown that IL-15 activates NK cells to become equipped with cytotoxic granules and sensitize them to secondary stimuli. This priming has been previously shown with respect SD 1008 to IL-12 and IL-15 co-stimulation, which induces an exaggerated IFN- response in NK cells (8, 21, 22). However, it is mainly unknown if one of three major signaling pathways is responsible for NK cell priming or it is achieved by a collaborative effort of multiple pathways. In this study, we set out to investigate the signaling pathway downstream of IL-15 activation responsible for sensitizing NK cells to subsequent stimulations. We hypothesized that IL-15-mediated priming of NK cells is not restricted to IL-12 activation, but can be prolonged to additional cytokines. Our data indicated that prior exposure to IL-15 dramatically SD 1008 improved NK cell reactions to stimulations though Ly49H activation receptor in addition to a myriad of cytokine receptors that employ the JAKCSTAT pathway. Furthermore, we display that PI3KCmTOR pathway is vital for major effector functions as well as the IL-15-mediated priming procedure for cytokine replies in NK cells. To translate the significance of PI3KCmTOR pathway for NK cell features rapamycin remedies WT B6 and C57BL/6.SJL (C57BL/6 congenic mice with Compact disc45.1 allotype marker) mice from Charles River had been housed in SPF environment and useful SD 1008 for tests at 7C12?weeks old. All procedures had been accepted by and executed relative to the institutions pet guidelines from the School of Ottawa. Smith stress MCMV stocks had been generated inside our lab from contaminated salivary glands of BALB/c mice and viral titers dependant on regular plaque assays. WT C57BL/6 mice had been contaminated with 5,000 plaque developing device (PFU) of MCMV intraperitoneally 4?h after initial rapamycin shot. Rapamycin (3?mg/kg/time) or DMSO seeing that vesicle control was administered through intraperitoneal shots once per time until sacrificed. Reagents and antibodies The next monoclonal antibodies had been utilized: -Compact disc16/32 (clone 2.4G2) from Bioexpress, -individual/mouse Granzyme B (clone GB12) and SD 1008 fixable much red live/deceased from Invitrogen. -Ly49H (clone 3D10), -TCR- (clone H57-597), -NK1.1 (clone PK136), -Compact disc49b (clone DX5), -Compact disc8a (clone 53-6.7), and -IFN- (clone XMG1.2) from eBiosciences, -BrdU (clone B44), -Compact disc4 (clone RM4-5), and mouse isotype IgG- from BD Biosciences. For recognition of phosphorylated indicators, BD PhosFlow antibodies against pSTAT1 (clone 49), pSTAT3 (clone 4), pSTAT4 (clone 38), pSTAT5 (clone 47), and pSTAT6 (clone 18) SD 1008 had been utilized except -pS6 ribosomal proteins (Ser235/236) (clone D57.2.2E) from Cell Signaling. Cytokines, recombinant murine (rm) IL-2, rmIL-4, rmIL-12, rmIL-15/IL-15R complicated, and rmIL-21, are from eBiosciences except rmIFN- from Miltenyi Biotec. To physiologically imitate trans-presentation of IL-15 to NK cells by DCs lab tests (*(one-tenth level of a 96-well) towards the cells, 2?h to intracellular staining for BrdU prior. Histograms depict BrdU incorporation.


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Gap CreekDownloadable Audiobook - 2011 | Unabridged
Julie Harmon is a hard worker living a hard life. Only a teenager, she has already witnessed the deaths of her brother and father when she loses herself in the work of a new marriage. The trials she faces in early 20th century Appalachia gradually build into an examination of the ways the human spirit can triumph.
Publisher: Prince Frederick, Md. :, Recorded Books ;,
Copyright Date: phonogram 2000
Branch Call Number: DOWNLOADABLE AUDIOBOOK RBdigital
Characteristics: 1 sound file (11 hr., 15 min.) : digital analog,Digital recording,rda data file,rda

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ELK Home 66955/1 One Light Wall Sconce, Oil Rubbed Bronze Finish Sconce
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As Singapore’s annual pinnacle performing arts festival, the Singapore International Festival of Arts (SIFA) presents captivating and diverse works across theatre, music, dance, film and visual arts. First launched as the Singapore Festival of Arts in 1977, the festival has gone through several evolutions and inspired generations of arts lovers and practitioners. Today, the highly anticipated festival is a high point on Singapore’s arts and cultural calendar. Under the helm of Festival Director Gaurav Kripalani, SIFA continues its festival mission to champion the creation and presentation of Singaporean and international works. From May 2020, the Singapore International Festival of Arts goes virtual with the launch of SIFA v2.020. Featuring a line-up of virtual talks, workshops, vodcasts, performances and more, please visit sifa.sg for details.
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The lovable robot cat has arrived at the National Museum of Singapore (NMS) for Doraemon’s Time-Travelling Adventures in Singapore from 31 October to 27 December 2020! Visitors can look forward to rediscovering Singapore and meeting Doraemon, a beloved character many of us grew up with, through photo opportunities within the museum’s grounds and specially-designed collectibles. Easily one of the most famous doors in Japanese manga and anime, the Anywhere Door can be found alongside lovable Doraemon statues across the museum’s front lawn. Another of Doraemon’s classic gadgets, the Time Machine, invites you to travel through both time and space. Don’t forget to look out for Doraemon’s Gadgets of the Future, where visitors can view some of his fascinating gadgets including the Doc-in-a-Box and Shrink Ray. Visitors will also be able to discover some Gadgets of the Past in a temporary showcase towards the end of the Singapore History Gallery. Visitors can try their hand at designing their own gadget in the Redesign an Artefact activity, based on real artefacts displayed at the museum. You can explore stories of Singapore through fascinating artefacts in the museum’s galleries and our National Collection. A fully online trail by the museum, Let’s jalan-jalan!, allows you to rediscover fun facts about 14 neighbourhoods around Singapore through an “island-wide” hunt, through a microsite https://go.gov.sg/timetravelwithnms. Stand to win exclusive Doraemon Singapore-themed collectibles The National Museum is also presenting a series of programmes in conjunction with the ongoing Children’s Season. This includes the Get Curious trail, which features a fun tic-tac-toe game in the museum’s galleries. Participants will stand a chance to win a specially-curated range of the museum’s merchandise with Doraemon Singapore-themed collectibles designed by homegrown design-led lifestyle goods brand Supermama! Selected designs from the NMS Doraemon Singapore-themed Collection by Supermama Safety at the Museum To ensure a safe environment for everyone, the installations are applied with self-disinfecting coating and cleaned regularly. We would like to remind visitors to refrain from touching the installations and to continue to observe safe management measures as well as good personal hygiene during their visit.


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By Deb Haines
Recently, veterinarians discovered that grapes, raisins and currants (fruits from Vitis species) can cause kidney failure in dogs. It is unclear whether this is a new problem, or if the toxic nature of grapes and raisins became recognized after the establishment of a computerized animal toxicity database about 25 years ago. Whatever the case, the number of identified cases of illness or death in dogs after they have eaten raisins or grapes is on the rise.
What types of grapes and raisins are toxic to dogs?
Poisoning has occurred in dogs following ingestion of seedless or seeded grape varieties, commercial or homegrown fruits, red or green grapes/raisins, organic or non-organic fruits, and grape pressings from wineries. Foods containing grapes, raisins, and currants (such as raisin bran cereal, trail mix, granola mix, baked goods) are all potential sources of poison.
What is the toxic dose?
Unfortunately, there is no well-established toxic dose for any of these fruits but two principles seem to prevail: 1) Dogs are more likely to become poisoned if they ingest large amounts of fruit and, 2) there is significant individual sensitivity amongst dogs. Some dogs appear to tolerate small doses of the fruit without consequence while other dogs may develop poisoning after the ingestion of just a few grapes or raisins. There is no way to predict which dogs may be more sensitive.
Why are raisins, grapes, and currants toxic?
Currently, it is not known why these fruits are toxic. Some researchers suspect that a mycotoxin (a toxic substance produced by a fungus or mold) may be the cause. Some suspect a salicylate (aspirin-like) drug may be naturally found in the grape, resulting in decreased blood flow to the kidneys. However, so far no toxic agent has been identified. Since it is currently unknown why these fruits are toxic, any exposure should be a cause for concern.
What should I do if my dog eats grapes or raisins?
If you suspect that your pet has eaten any of these fruits, please contact your veterinarian or Pet Poison Helpline, an animal poison control service, immediately. Do not waste any time. Since there are still many unknowns associated with this poisoning, it is better not to take any chances when it comes to your dog’s health. As with any toxin, the sooner the poisoning is diagnosed and treated, the less dangerous for your pet, and the less expensive therapy will be for you.
What are the symptoms of grape or raisin toxicity?
The most common early symptom of grape or raisin toxicity is vomiting, which is generally seen within 24 hours following ingestion. Lack of appetite, lethargy, and possibly diarrhea can be also seen within the next 12-24 hours. More severe signs are not seen for 24-48 hours after ingestion – often after acute kidney failure has already begun. Signs of acute kidney failure include nausea, lack of appetite, vomiting, uremic breath, diarrhea, abdominal pain, excessive thirst, and excessive urination.As the poisoning progresses, the kidneys may shut down and the dog will not produce any urine. Following this, the dog’s blood pressure will increase dramatically and the dog will usually lapse into a coma. Once the kidneys have shut down and urine output has dropped, the prognosis is poor
How is grape/raisin poisoning diagnosed?
Unfortunately, the symptoms of grape or raisin poisoning are non-specific and are similar to kidney failure from many other causes. Your veterinarian will base a presumptive diagnosis of this poisoning on a history of eating grapes, raisins, currants, or the presence of pieces of grapes or raisins in the dog’s vomit.Your veterinarian will also recommend diagnostic tests such as a complete blood count (CBC), a serum biochemistry profile, and a urinalysis to assess the amount of damage to the kidneys.
The test results will help determine the dog’s likelihood of recovery.Is there an antidote?
No. How is this poisoning treated?
The goal of treatment is to block absorption of the toxins and prevent or minimize damage to the kidneys.The best treatment is to decontaminate a patient right away via the induction of vomiting and administration of activated charcoal. This helps to prevent absorption of the toxin from the stomach or intestines. As grapes and raisins stay in the stomach for a prolonged period of time, inducing vomiting is of the utmost importance (even up to 4-6 hours after ingestion). Following decontamination, more treatment might be necessary including aggressive intravenous fluids to flush any absorbed toxins out of the body as quickly as possible and to help maintain kidney function. Drugs to control nausea or vomiting, to help maintain blood flow to the kidneys, and to control blood pressure will be administered as indicated.”The goal of treatment is to block absorption of the toxins and prevent
or minimize damage to the kidneys.”Ideally, dogs should be hospitalized on intravenous fluids for 24 to 48 hours following ingestion. Affected animals may need to be hospitalized for 2-7 days. During the course of treatment, your veterinarian will monitor the patient’s kidney values daily to assess the response to treatment and determine whether the treatment needs to become more aggressive. Blood work should also be repeated 2-3 days after going home; this is to make sure the kidney blood values have not increased.
What is the prognosis following poisoning from grapes or raisins?
Prognosis depends on many factors, including how severe the poisoning was, how soon the patient was decontaminated, whether or not the patient has already developed kidney failure, how soon treatment was initiated, and whether the clinical signs and kidney values improved once treatment was started.If a dog only ate a few grapes or raisins (depending on the size of the patient) and received immediate treatment, the prognosis is excellent. If the kidneys are damaged and no urine is produced, the prognosis is poor and fatality is likely. The kidneys have very little capacity to regenerate or repair themselves so once they are damaged, they will not function as well as they did before the episode. When in doubt, seek treatment right away by contacting your veterinarian or Pet Poison Helpline for advice. Your veterinarian will estimate the prognosis for your dog based on symptoms, individual situation, and response to treatment.
How can I prevent this problem?
Keep all grapes, raisins, currants, or foods containing these fruits, out of reach of your pets. Do not share any food that may contain grapes or raisins with your dog, and especially do not use grapes as treats for your dog. Some misinformed dog trainers still recommend this.What other common foods are toxic to dogs?
Onions, garlic, alcohol, chocolate, cocoa, macadamia nuts, fattening foods, and foods containing the sweetener xylitol can also be fatal.Are other animals at risk?
So far, grape and raisin poisoning has only been identified as a problem in dogs. That said, there have been anecdotal reports of cats and ferrets being potentially affected. Since there are still many unknowns associated with this poisoning, it would be prudent to avoid giving ANY grapes and raisins to your pet dog or any other pet.
This article is written by Ahna Brutlag, DVM, MS, DABT, DABVT, Associate Director of Veterinary Services, Pet Poison Helpline
*Pet Poison Helpline, is an animal poison control service available 24 hours, seven days a week for pet owners and veterinary professionals who require assistance treating a potentially poisoned pet – including birds! Pet Poison Helpline is available in North America by calling 800-213-6680. Additional information can be found online at www.petpoisonhelpline.com.
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Kristen Stewart strikes a pose here during Paris Fashion Week. What do you think of her look?
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She's lovely. And hope she and Pattinson would be back together again.
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