ysabetwordsmith | Poem: "The Purpose of Power"
Poem: "The Purpose of Power"
"The Purpose of Power" won the 2017 Rose and Bay Award in the Poetry category.
This poem is spillover from the July 5, 2016 Poetry Fishbowl. It was inspired by prompts from librarygeek and technoshaman. It also fills the "be here now" square in my 5-1-16 card for the Solo Celebration Bingo fest. This poem has been sponsored by Anthony & Shirley Barrette. It belongs to the Shiv thread of the Polychrome Heroics series, and comes after "Calming the Agitations."
Warning: This poem contains some intense topics. Highlight to read the warnings, some of which are spoilers. It includes introversion, feeling drained and irritated, anxiety over the future, solution-caused problems, deep philosophical discussions which are needful but Shiv is in no way prepared for, confusion, reference to past injuries and almost dying, followed by past medical abuse, cape politics, fate and free will, self-blame, self-hate, discussion of zetetic terror weapons, past traumatic amputation, the difference between legality and morality, purpose, existential angst, and other challenges. On the whole, it's pretty positive, just overwhelming for Shiv. If these are sensitive issues for you, please consider your tastes and headspace before moving onward.
even visiting the social room.
commandeering one of the quiet rooms.
sit quietly for a while?" Rosie asked.
"People," Shiv said as they sat down.
figured out I do better when I'm alone."
hanging out with other people?"
to ramp up the contact for that."
Shiv put his face in his hands.
"You've been in trouble before."
that my control is what it used to be."
supposed to make any kind of sense.
"Shiv, what is your superpower for?"
"No, that's what it does,"
Rosie said. "What is it for?"
Rosie looked at the ceiling.
"All right, we'll come back to that,"
Why do you have it?"
to a regular hospital for a week."
"That's how you got yours,"
something that Shiv wasn't putting out.
does it exist? Why do you have it?
Come on, Shiv, what is it for?"
his words got under Shiv's skin.
then he could push them away.
"Keeping me safe," Shiv said slowly.
wouldn't lock. The staff were ... awful."
almost pulling them out of him.
could figure out what was going on.
stopped the blade, turned it aside."
the hell out of there."
of new skills," Rosie said.
What will you do with them?"
why Rosie kept harping on this.
other jobs now," Rosie said.
Shiv shook his head sharply.
"I'm a supervillain," he said.
"All right," said Rosie. "Why?
Shiv's brain just about bent.
"Think about it," Rosie said.
"I dunno, fate maybe?" Shiv said.
to be a pretty popular opinion.
"No, people have choices," Rosie said.
He opened one hand and then the other.
"There are worse things to be,"
of the Greater Omaha Metropolitan Area.
wasn't that. "So why are you a supervillain?"
"Because I'm nobody's easy meat," Shiv said.
and offered me a job. I was hungry so I took it."
into supervillainy just to get by," he said.
now that you have other options."
enough what a fuckup I am --"
a number of unfortunate choices."
Rosie, I'm just in it for myself, is all."
"Now that I don't believe," Rosie said.
wouldn't have risked your life to save Ragno."
"I'm not a superhero," Shiv said uneasily.
"That's true," Rosie said, looking thoughtful.
"You did something heroic, though. Why?
What's the point of a supervillain doing that?"
"Ragno and me not dying," Shiv said.
the corners until it became a disc.
too much to worry about it running wild."
like dropping things," Shiv said.
everything that isn't nailed down."
kept the edges sharp enough.
he'd seen on a Christmas tree.
"That's useful to know," Rosie said.
to have powers, to be a supervillain?"
The guy was like a dog with one bone.
slipped his mind. "I'm nobody."
"That was very beautiful, Shiv,"
like that play-putty, don't you?"
sometimes or it gave him headaches.
that I can practice more often."
saving someone's life with it?"
the ball in his pocket. "I just was there.
A superhero would've done better."
"You were there, and you chose to act,"
important. Do you know any superheroes?"
have handled the chayne incident?"
It was like ice water sloshing over him.
wouldn't have had the guts for it.
horrible, and he's too nice of a guy."
"What about other people you know?"
random acquaintances -- the field is open."
"I know a few who might," Shiv said.
"Most either wouldn't do it, or couldn't."
"All the same reasons, or different ones?"
he could've figured out a way, but not in time.
That's the hell of it with chayne, there's no time.
doesn't love pain. He would've hesitated."
but neither did he want to talk about it.
what drove you to do it?" Rosie asked.
trying to feel his way through them.
"The first time, I didn't," he admitted.
"I just ... froze. We all did. It was ..."
faced with atrocities," Rose said gently.
"Yeah, right," Shiv said, looking away.
the situation exceeds their training,"
still blames himself for responding badly."
go through that again. I couldn't.
because that was something I could do."
which the superheroes can't or won't do.
so they won't be shocked by it and freeze.
gives you a certain advantage."
he'd never seen it in that light before.
"You mean like ... keeping a lid on it,"
don't make it too high up the ladder."
"If that's how you like to put it,"
other tools in the box for those times."
"But I broke the rules," Shiv said softly.
my superpower, it gets me in trouble."
flicking a hand at the pocket full of metal.
in front of people, especially guards or cops."
Rosie's face fell. "I'm sorry to hear that,"
people who break the rules, too."
Shiv scoffed at him. "Tell that to the judge."
in his eye that made Shiv nervous again.
"Slavery was legal. Colonialism was legal.
places where murdering soups still is legal."
about the bottom-ten countries. Everyone had.
"What's that supposed to mean?" he said.
to follow the rules," Shiv whined.
"Make up your mind already!"
who aren't so susceptible to peer pressure."
let alone anything that felt as ... big as this.
"My brain is full," he said abruptly.
sent it dancing through the shapes.
"Can we just ... stop talking for a while?"
"Any time," Rosie said with a smile.
like a top winding down after it was let go.
For once, Shiv didn't find that creepy.
Introversion and extroversion are two ends of a personality spectrum. Know the signs of being an introvert and how to be a healthy introvert. Shiv is just starting to learn these things about himself, and hasn't really figured out how to meet his own needs yet. Caring for introverts and extroverts requires different techniques. Here's an illustrated guide to introverts.
There are many reasons why someone might feel drained by other people. Happiness requires finding a balance between socializing and solitude.
Fidgets are small objects for manipulation, sold as therapy tools for children or office toys for adults. They have many benefits, including mental focus and hand health. People with superpowers often fidget with their ability. Shiv carries a piece of metal to play with, and has devised a variety of patterns to practice his control, such as the one shown here: hollow circle, hollow square, hollow diamond, solid diamond, solid square with sharp corners, solid square with rounded corners, solid circle, flat star, folded star, bent square, and sphere.
Self-hate and self-blame often come from child abuse, which warps perception of the self. Shiv is just repeating what he's been told over and over again. Recovery requires survivors to remind themselves of positive things that they didn't learn growing up, and turn self-blame into self-compassion. When dealing with someone else's self-blame, you can interrupt negative self-talk and reframe it in more constructive ways.
Quakers have a deep history of activism. You may as well not bother arguing with them, because once God has suggested that they address a particular problem, they will not quit and you will not talk them out of it. Peace activists have observed that many heinous things have been legal, and the government is not a good standard for morality.
Ethics is a set of laudable beliefs and practices. Various theories of ethics have been proposed. Think about how to discover your personal ethics and live by them. Here is a lesson about developing a code of ethics.
A theory of moral development describes a set of stages through which most people progress. Ambrose is talking about post-conventional concepts, which are way of Shiv's head because he barely grasps pre-conventional concepts. But don't blame Ambrose, it was God's idea to ask the poor kid what superpowers are for. I imagine God has the same hard time as other smart people when it comes to figuring out what other folks will understand.
Not all supervillains are necessarily unethical. Examples such as the Noble Demon and Anti-Villain may have their own sense of honor. When organized, they may even have their own laws. Sometimes they'll display valor under the least likely circumstances. It's not that they lack ethics; they just don't share the same set as the hero.
Thinking too hard can deplete energy and cause headaches. Shiv is prone to both of these problems. When your brain is full, you should stop working and take a break. Shiv is slowly learning this part.
Quaker worship centers around silence. It progresses from relaxation through letting go of concerns and expectant waiting to listening to God. If you're not used to the numinous, then suddenly having an open line like that can be very disconcerting, and even hair-raising. Shiv describes it as "creepy" because he is unaccustomed to numinous energy so it feels weird to him. But he has also figured out that Ambrose is good for shutting up unwanted thoughts. There are meditations and steps for practicing silence.
"Please, thank your parents for me. The prompter copy is good for soothing the initial discomfort, but when it's posted, the extra links help for follow-up emotional bandage changes. :-D "
Done. I'm glad I could help.
"One suggestion I have is to have a line in the introduction that this poem follows this, with Ambrose home."
• "I'm listening," Rosie said, and there was something about him that seemed to cup the air, as if the silence was waiting for Shiv to pour words into it, almost pulling them out of him.
> A rich, powerful image. I can *feel* it.
• Quakers have a deep history of activism. You may as well not bother arguing with them, because once God has suggested that they address a particular problem, they will not quit and you will not talk them out of it.
> The second sentence also holds of individuals and subgroups of many other religions; not only rabble-rousers and terrorists, but [insert plural noun here] such as the late unlamented Jack Chick. But I have deep respect for the Friends, for their consistent dedication to doing good peacefully and not evangelizing -- at least, not evangelizing the unwilling.
I'm glad you found this so impressive.
It waaaaaaas. And I may be able to words *why* eventually, but right now ... wowness.
:D I'm always up for more feedback, but "wow" is awesome too.
He is very huggable and cuddly.
Indeed. Shiv actually wants to be useful; it gives people a reason to keep him around and feed him. But the idea of being valued is largely alien to him, let alone being a productive -- if pesky -- member of society.
Ooooh. A Quaker who's not afraid of breaking rules. I *like* him.
Which is to say, if you put Quakers in an ethical society, they will help you make it better; and if you put them in an unethical society, they will do exactly the same thing whether you like it or not. Historic example: the Abolition movement. Personal example: silent vigil for peace during the first Gulf War. It was amusing watching the campus cops try to argue with people who wouldn't argue back, weren't disturbing the peace or disrupting traffic, and would not go away. After a few weeks, the cops gave up. I think it made them uncomfortable trying to break up a peace demonstration when God was standing right there in the middle of the circle. They really didn't have a script for that.
Interestingly, when I looked at Terramagne, I discovered that their Quakers had rather better luck with some applications than ours did, so they're a bit larger and more active group there. Ours tried to launch a progressive penal system way too early, botched horribly, and bailed out. Theirs went to work cleaning up the mess and tried new solutions. So T-America has a better penal system, which is much more suited to reformation, and there's a steady trickle of Friends volunteering or working in it. :D Which is how they came to have one at the forefront of correctional theory, trying to figure out what to do with supervillains. Periodically I look into Quaker culture, beliefs, and practices for inspiration to reflect that.
Yay! My poetry has a way of going where it's needed.
He really does. Of course, he has ulterior resources. When someone is listening to God, he has access to much better ideas than average. :D Hence why it's unwise to argue with Quakers. Out of all the groups who claim to have messages from God, they're the only folks who seem to make a religion out of listening to Him instead of preaching at each other. That makes all the difference in the world.
Yeah, that's a very delicate bit of work.
It is good to re-read this, and to discover its companion.
Heh. One usually thinks of 1 Jan as a day of looking forward, but whose bl---y calendar is it anyway? NOT OURS! It's Winter, and time to reflect... it's a good day.
I'm glad you enjoyed this. Yes, it's a good topic for winter introspection.


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Black Entrepreneur Develops New Hip-Hop and R&B Game Where Players Battle Song Vs. Song
Michael Rousseau, founder of the AUXGOD Music Battle Card Game
Toronto, ON — If you were told to "Play A Song About Your Ex", you could definitely think of more than a few songs to play that relate to your life experience. Did songs start flowing through your head? If so, you're ready for AUXGOD.
AUXGOD is the party game where teams battle against each other using music played from their smartphones in response to AUXGOD's playing cards.
"Now that everyone has a phone in their pocket, we have access to music on demand. AUXGOD gets your whole party together and let's everyone enjoy music with some friendly competition attached," explained Mike Rousseau, Creator of AUXGOD. "Your road trips, cottage weekends and gatherings have just gotten a lot more entertaining."
Players a split into three teams. The judging team will draw a card and read it out loud. The two remaining teams battle against each other in finding the best song that relates to the card. Each team takes turns playing their song for the judges. The goal is to impress the judges with your song selection and to play a better song than the opposing team. That radio hit that everyone loves won't always win.
"The best part is the game creates conversation, a bit of arguing and a lot of dancing. Sometimes people can't believe their song didn't win. When you're appealing to the judges anything can happen. You might have a great song, but if it doesn't hit them in their hearts you won't win the round."
AUXGOD is designed for you to play today's hits and reconnect with yesterday's classics. There are four card categories: Life, Era, Artists and Labels which will allow teams to enjoy music from the 80's to the present.
"Everyone who plays AUXGOD is hooked immediately. As soon as you read the cards your brain starts turning, you're thinking about all the songs you can play. That's the beauty of the game, there are unlimited song options."
AUXGOD is currently creating games for other genres of music, Pop, Rock and Country to be available in the future.
AUXGOD established in 2016 is created by Mike Rousseau, a former financial business analyst who quit his full time job after 7 years and decided to go the creative route. He comments, "I was a photographer on weekends while I was working in finance during the week. One day I decided I was finished. I took a crazy leap and decided creating was where I needed to be…not crunching numbers."
Six months after quitting his job he was at a party playing music on a Bluetooth speaker, a friend asked him to go heads up and play songs back and forth which seemed like a battle. "We split ourselves into two teams and played for an hour. I went home that night and kept thinking about all the songs our team could have played". The next morning, he woke up and started writing questions for AUXGOD.
For more details about the game, visit www.auxgodgame.com or follow the game on social media:
Facebook – www.facebook.com/auxgodgame
Instagram – www.instagram.com/auxgodgame
Mike Rousseau
hello@auxgodgame.com

redpajama_set_name: RedPajamaCommonCrawl


Over 4.6 million students took online courses in fall 2008, a 17 percent increase over the previous year, according to a report from the Sloan Consortium with research undertaken by Babson. This increase is more than 10 times the growth of the entire higher education population, which increased only 1.2 percent during that period. "Online education continues to establish itself as demand remains strong and new applications materialize, such as contingency planning for campus emergencies," said Frank Mayadas, special advisor, Alfred P. Sloan Foundation, which funded the study. "We believe demand will fuel sustained growth especially within public universities and community colleges, raising the need to share research, optimal methods for faculty training, and other best practices to new levels of importance," Mayadas said.
More than one-quarter of college and university students take courses online. In 2002, only 9.6 percent did.
While the economic climate has driven demand for all courses, the demand for online courses greatly outweighs the demand for face-to-face classes.
Budgets are shrinking across the country and schools are finding themselves in the position of having to cut faculty and staff while at the same time facing higher enrollment figures, a situation in which nobody wins. The increased workloads put pressure on the faculty and staff and the increased class sizes lessen the chance of student success.
Online education is obviously one solution. Online courses can lessen teachers' workloads by reducing their preparation and teaching time while increasing students' chance of success with online office hours, reduced travel time and flexible scheduling.
The report also highlights how online courses can be part of a college or university's H1N1 contingency plan. Sixty-seven percent of the schools that have contingency plans include substituting face-to-face courses with online ones.


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Fusion Workouts
Helen Vanderburg
Part I Foundation of Fusion Workouts
Chapter 1 What Are Fusion Workouts?
Benefits of Fusion Workouts
Principles of Fusion Workouts
Fusion Five-Step System
Chapter 2 Getting Started
Understanding Core Conditioning
Preparing for Your Fusion Workout
Gathering Equipment
Practicing Safely
Chapter 3 Mindfulness and Intention
Connecting Thought With Positive Action
Employing Mindful Practices
Setting An Intention
Part II Fusion Exercises
Chapter 4 Warming Up
Planking
Chapter 5 Standing Strength, Balance, and Flexibility Exercises
Single-Leg Balance
Chapter 6 Floor Strength, Balance, and Flexibility Exercises
Front-Lying Position
Tall Seated Position
Side-Lying Position
Abdominal Brace Position
Chapter 7 Calming and Restorative Exercises
Forward Bends
Hip Releases
Chest Releases
Side Bends
Soothing Exercises
Part III Fusion Workout System
Chapter 8 Fusion Workouts by Level
Chapter 9 Fusion Workouts by Time
Chapter 10 Fusion Workouts by Purpose
Core Conditioning
Full-Body Conditioning
Lower-Body Conditioning
Upper-Body Conditioning
Restoration and Relaxation
Chapter 11 Fusion Workouts by Activity
Pilates Core
Yoga-Pilates Blend
Helen Vanderburg, BPE, is owner of Heavens Elevated Fitness, Yoga and Spin Studio and the creator and program developer of Fusion Fitness Training. With a career in fitness beginning in 1982 and experience as a group fitness instructor, yoga teacher, Pilates teacher, personal trainer, and educator, she is an innovator in the fitness industry. She has taught and trained instructors on fusion exercise and Fusion Fitness Training since 2000. Vanderburg is a highly respected leader and conference speaker at regional, national, and international events, presenting at more than 20 conferences annually.
Vanderburg holds a bachelor's degree in kinesiology physical education and is certified in yoga, Pilates, TRX, ACE group fitness, and several CanFitPro fitness disciplines. She has received numerous industry awards, including the IDEA Instructor of the Year in 2005 and CanFitPro Presenter of the Year in 1996, 2006, 2013, and 2015. She's also a consultant, education developer, and spokesperson for some of the world's most influential fitness companies, including Schwinn Cycling, BOSU, and Total Gym. Vanderburg has been a fitness columnist for numerous magazines and newspapers, including Fitness, Self, Chatelaine, Flare, and the Calgary Herald.
Vanderburg has a lifelong passion for fitness and sport. In 1973 she became Canada's junior champion in synchronized swimming. At the 1978 World Aquatics Championships in Berlin she won the gold medal in both the solo and duet categories. In 1978 and 1979 she received the Elaine Tanner Trophy and in 1979 she was named Canadian Female Athlete of the Year. Because of the Canadian boycott of the 1980 Summer Olympics in Moscow, she was unable to compete in the first Olympic Games to include synchronized swimming. She was inducted into the Canada Sports Hall of Fame in 1983 and the International Swimming Hall of Fame in 1985.
Vanderburg lives in Calgary, Alberta.
"Helen Vanderburg is one of the world's leading fitness instructors and educators and has turned her lifelong passion for health and fitness into creating a fitness program that works for all ages and fitness levels. Fusion Workouts is simple to follow and highly effective, combining the best of fitness, Pilates, yoga, and barre into dozens of sequences. It's a must-have for a fun, practical, and easy-to-use workout program."
Jay Blahnik-- Author of Full-Body Flexibility and Fitness Instructor of the Year for IDEA, canfitpro, and FILEX
"As an international presenter, trainer, and leader in the field of fitness and exercise, Helen Vanderburg has educated and trained thousands of professionals and consumers alike. Her engaging teaching style and genuine passion to help people get fit and healthy make Fusion Workouts a must-read for everyone looking for easy-to-follow workouts."
Maureen (Mo) Hagan, BScPT-- Certified Fitness Professional, Vice President of Fitness Innovation for GoodLife Fitness, Education and Events Director for canfitpro
Stress and Weight Gain
How To Overcome The Three Biggest Barriers To Exercise
The Fusion Workouts Book Trailer
Sample Content


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The next 19th October will be celebrated for the first time in Granada the "Noche en Blanco". It is a festival which takes place in the entire city and a series of public events will entertain the public. The aim of this new initiative is to claim the city as the World Capital of the Poetry.
The activities will interest the public in different ways and points of Granada: exhibitions, music performances, and activities for children, city guides and other ones which will be for free from 8 p.m. to 4 a.m. The heart of this festival will be the literature, for that the majority of the events are related with this genre. The central act will take place in the Planetario del Parque de las Ciencias de Granada, here will be a poetry read. There will be many Spanish poets and the Spanish speaking writers who are in the States or in Latin America will be able to participate through videoconferencing.
The 'Noche en Blanco' will catch the attention during the whole week, from the 14th to the 19th October, and people of all the ages will participate. Also the businessmen will be a crucial part in this event. The shop will become exposition gallery and there will be lot of business offers.
On one side the festival wants to promote the cultural creativity and inspire the young artists, from the other side wants to encourage and make more powerful the positive synergy between the cultural and business sectors, which will be quantified by the numbers of commercials that will join in and participate.


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CAST: Koch, Howard W., Boris Karloff, Don Red Barry, Jana Lund, Tom Duggan, Charlotte Austin DIRECTED BY: Koch,
Bop Girl
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CAST: Howard W. Koch, Lex Barker, Anne Bancroft, Mamie Van Doren, Ron Randell, Marie Windsor, John Dehner, John Holland,
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CAST: Otto Preminger, Dyan Cannon, James Coco, Jennifer ONeill, Ken Howard, Nina Foch DIRECTED BY: Preminger,
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CAST: Howard W. Koch, Brian Keith, Dick Foran, Efrem Zimbalist Jr., Merry Anders, Sean Garrison, Joanna Barnes, Perry Lopez, Arthur Batanides, Ed Prentiss, Ann Doran,
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CAST: Alfred E. Green, Allyn Joslyn, Evelyn Keyes, Marguerite Chapman, Edgar Buchanan, Nina Foch, Hugo Haas, Shemp Howard, Frank Jenks, Erwin Kalser, Tonio Selwart, John Wengraf, Hugh Beaumont, Eugene Borden, Jack Carr, Lane Chandler, Tom Coleman, Dean Collins, James Conaty, Kernan Cripps,
Andy Hardy Comes Home
CAST: Howard W. Koch, Mickey Rooney, Patricia Breslin, Fay Holden, Cecilia Parker,
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text:
Выборы в Европейский парламент в Хорватии были проведены в связи с вступлением 1 июля 2013 года Хорватии в Европейский союз. Срок полномочий избранных депутатов — 1 год, с 1 июля 2013 по 1 июля 2014 года. Хорваты избрали 12 депутатов. Выборы прошли 14 апреля 2013 года.

Основные участники
Социал-демократическая партия Хорватии, Хорватская народная партия-Либералы, Хорватские пенсионеры

Хорватское демократическое содружество, Хорватская партия права, Пенсионеры вместе

Хорватские лейбористы, Партия Труда и

Хорватская крестьянская партия, Хорватская социал-либеральная партия и

Хорватский демократический союз славонии ибараньи, демократический свободный союз Далмации, Хорватские зелёные.

Независимый список

Хорватская партия права

Рейтинги (21 марта 2013)
Блок Социал-демократической партии, Хорватской народной партии-Либеральные демократы и Хорватской партии пенсионеров — 31,4 % (Ipsos Puls) / 29,6 % (CRO Demoskop).
Блок Хорватского демократического содружества, Хорватской партии права А.Старчевича и Блока «Пенсионеры вместе» — 27,4 (Ipsos Puls) / 21,4 % (CRO Demoskop).
«Хорватские лейбористы — Партия труда» — 9,1 (Ipsos Puls) / 9,7 % (CRO Demoskop).
Блок Хорватской крестьянской партии и Хорватской социально-либеральной партии — 4,7 % (Ipsos Puls) / 4,4 % (CRO Demoskop).
Блок Хорватского демократического союза Славонии и Бараньи, Демократического свободного союза Далмации и «Хорватских Зелёных» — 4,3 % (Ipsos Puls) / 3,1 % (CRO Demoskop).
Независимый список И.Грубишича — 3,5 % (Ipsos Puls) / 2,0 % (CRO Demoskop).
Хорватская партия права — 2,8 % (Ipsos Puls) / 1,8 % (CRO Demoskop).

Выборы
 Блок Социал-демократической партии, Хорватской народной партии-Либеральные демократы и Хорватской партии пенсионеров −5
 Блок Хорватского демократического содружества, Хорватской партии права А.Старчевича и Блока «Пенсионеры вместе» −6 (ХДС −5 мест, Партия правых- 1 место)
 «Хорватские лейбористы — Партия труда» — 1

Примечания

Ссылки
 Выборы в Хорватии

Выборы в Хорватии
Хорватия
Хорватия

redpajama_set_name: RedPajamaWikipedia


Miche Bag Set Review + Giveaway CLOSED!
I love my purses, and I love to accessorize with what I am wearing. So when I go out everything has to coordinate. But when you are on a budget and have a husband like mine, who dreads it when I go shopping, and has to tell me his thoughts on how many purses I may have, you have to find other ways to style. That is what I love about the Miche Bag. You get a awesome purse that you can dress up to coordinate with your wardrobe. So instead of going out and buying numerous purses, and having to switch your stuff over constantly, you just buy one purse with numerous shells that you can change out. Since I received my Miche Bag to sample and review, courtesy of the wonderful people from Miche Bag, I can stick to my husbands savvy ways when it comes to accessorizing with my wardrobe. I can change the look with out having to change my bag!! I love it!!! So awesome, and when my husband tries to say something and pester me about having too many bags, I can show him how awesome I am. With all the great selection of shells to choose from, I can show off my awesomeness to all of my friends too!! The Miche Bag shells are unbelievably amazing, they keep the concept of designer styles you love and want. They look just like designer bags that you would pay big money for, but at a very affordable price. Perfect for the Momma Divas, students and other styling ladies out there, that love to style but also love to save money as well!!!! When I was asked to choose a couple of the shells that Miche Bag has to offer, I knew that I would have to go with the Hope shell. I am a huge advocate for the fight against Breast Cancer and Breast Cancer awareness, and when I find companies that feel the same and are contributing by making products that not only advertise Breast Cancer awareness, but also contribute by donating a portion of their profits of certain items to Breast Cancer research, I feel the need to let others know about it as well. The Hope shells not only support Breast Cancer research, but the design is one that you can coordinate your wardrobe easily to. I also find the design to be very fashionable!
The other shell that I went with is the Whitney. The Whitney shell from Miche Bag is awesome. It has the pewter ostrich leather look, and can coordinate with so many outfits that I own!!! I am officially hooked on the Miche Bag and with my birthday coming up I have been dropping hints on which shells I would like to go with next to my husband!!! To purchase your own Miche Bag head on over to www.Michebag.com and check out the endless possibilities that they have to offer!!!
The concept behind the Miche Bag is simple. You choose your Miche Bag, then you choose your shells. When you are ready to change out your shells, its very easy to do. You take off the shell you want to change out, put the new shell on, then you have a whole new looking bag!!! Another great plus is the fact that the magnets that Miche Bag uses, are earth magnets, which are magnets that do not damage your credit cards, cell phones or any other electronic devices!!!
I love my Miche Bag and that is why I thought that the Miche Bag would be great to put in with my Valentines Day Event. Also another thing that I dont just think I love, something that I think you will love too is, the wonderful people from Miche Bag are going to give one of my amazing readers a Miche Bag and 2 shells!
Like Miche Bag on Facebook! Then come back here and let me know you have done this, also leave me your email with this entry.
Tweet about this giveaway daily!!
This giveaway is open to US residents. This giveaway will end at midnight on March 1 ,2011. Winner will be chosen at random.org and will be given 48 hours before another winner will be chosen. All products for reviews and giveaways are given as a sample from the companies. All opinions in reviews I conduct are my own. I was not paid to say anthing or review any products.
Previous Post Princess Party: Personalized Kids Book Review + Giveaway CLOSED!


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Otero County COVID-19 vaccine tracker: 32% of people fully vaccinated
Chastity Laskey, USA TODAY NETWORK
Some 32% of people living in Otero County are fully vaccinated as of June 7, according to data from the New Mexico Department of Health.
The Centers for Disease Control and Prevention considers someone fully vaccinated two weeks after they've been given a single-dose shot (Johnson & Johnson) or a second shot (either Pfizer or Moderna).
New Mexico reported 203,686 total cases of coronavirus, an increase of 0.43% from the week before.
The five counties with the highest percentage of their population fully vaccinated in New Mexico as of June 7 are Los Alamos County (67%), Taos County (57%), Santa Fe County (55%), Harding County (55%) and McKinley County (54%).
Here are the latest numbers on COVID-19 vaccinations in Otero County as of June 7:
How many people in Otero County have received a COVID-19 vaccine?
40% of people in Otero County have received at least one dose of the vaccine, for a total of 25,980 people
32% of people in Otero County are fully vaccinated, for a total of 21,094 people
For a county-by-county look at the vaccination rollout, see our COVID-19 vaccine tracker, which is updated daily.
How many people in New Mexico have been vaccinated so far?
59% of people in New Mexico have received at least one dose of the vaccine, for a total of 1,227,490 people
49% of people in New Mexico are fully vaccinated, for a total of 1,023,353 people
We pull data on local vaccine distribution on a weekly basis. Check back for our next weekly update mid-week for the latest numbers.


My first GOALS post. This is how much I NEED to be writing down goals…..I had a "Goal" to blog about "GOALS" since January 1st…. and now it's January 25th and I'm just now getting around to it! Get my point?? I think blogging about some monthly goals may be extremely beneficial for me for many reasons. 1. It will hold me accountable. 2. It will hold me accountable and 3. It will really hold me accountable. That's what I need! My to-do lists are wonderful but there are always a few things that I really need to just get accomplished and I keep re-writing them on my daily to-do lists and before I know it, they disappear and never get done. So!
is really unnecessary… I realize this. Michael and I are trying to cut back on the unnecessary purchases, not eating out as much, etc. etc. So when this personalized stamper came in the mail a few days ago, I really felt the need to exclaim that "This will save us money in the long run! It will! And look how awesome it is!". I immediately began stamping every envelope that had come in the mail that day (wasting our precious ink). He agreed that is was pretty sweet (and I don't normally use the word "sweet" so you know it's really cool:). I love it and it makes me want to crank out some thank you cards!


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Chris Christie Says Republicans Must Put Election Fraud 'Fantasies' to Rest
By Darragh Roche On 11/13/21 at 7:28 AM EST
Politics Chris Christie Donald Trump 2020 Election Republicans
Former New Jersey Governor Chris Christie has suggested claims of voter fraud in the 2020 presidential election are "fantasies" and Republicans need to move on if they hope to win over voters.
Christie, a former Republican presidential hopeful, made the comments in his forthcoming book, Republican Revival, which will be published on Tuesday.
Excerpts from the book were published by The Guardian on Saturday.
Once a close ally of former President Donald Trump, Christie has rejected the idea that the 2020 election was stolen from him and received strong criticism from the former president as a result.
Donald Trump Supporters Didn't Appreciate Barack Obama's "So-Called Wisdom"
In Republican Revival, Christie wrote that members of his party "need to renounce the conspiracy theories and truth deniers, the ones who know better and the ones who are just plain nuts."
Christie did not say which category the former president falls into.
"We need to give our supporters facts that will help put all these fantasies to rest, so everyone can focus with clear minds on the issues that really matter," Christie wrote
"We need to quit wasting our time, our energy and our credibility on claims that won't ever convince anyone or bring fresh converts onboard."
The former governor reportedly criticized Republican Representative Marjorie Taylor Greene of Georgia's 14th district - a strong supporter of Trump who has frequently been embroiled in controversy - and said Trump likes "anyone who says nice things about him."
Addressing the QAnon conspiracy theory, Christie said believing in it would "ridiculous" if it weren't "so sad." QAnon posits, among other things, that Trump is waging a secret war against an international cabal of Satanic pedophiles.
Rittenhouse Trial Judge's Phone Rang With Lee Greenwood Trump Rally Theme
Eric Swalwell Expects Mark Meadows to Comply With 1/6 Committee Subpoena
Ex-'Apprentice' Contestant Summer Zervos Drops Defamation Suit Vs. Trump
"Many in our society use these wild, untrue conspiracy theories to advance their political agendas," Christie wrote.
Christie and Trump have clashed amid speculation that the former governor may launch another bid for the Republican presidential nomination in 2024. During a speech at a Republican Jewish Coalition conference on November 6, Christie said the party needed to move on from 2020.
"We can no longer talk about the past and the past elections - no matter where you stand on that issue, no matter where you stand, it is over," he said.
"Every minute that we spend talking about 2020 - while we're wasting time doing that, Joe Biden, Kamala Harris, Nancy Pelosi and Chuck Schumer are laying ruin to this country. We better focus on that and take our eyes off the rearview mirror and start looking through the windshield again," Christie said.
Those comments earned a stern rebuke from Trump, who said in a statement that Christie "was just absolutely massacred by his statements that Republicans have to move on from the past, meaning the 2020 Election Fraud."
"Everybody remembers that Chris left New Jersey with a less than 9% approval rating — a record low, and they didn't want to hear this from him!" Trump said.
Christie's approval rating stood at 19 percent in the Rutgers-Eagleton poll published in January 2018. He left office that same month.
Speaking to CNN following his comments in Las Vegas, Christie said Trump could be a positive for GOP candidates if he is "talking about the future and tell the truth about the election and move on."
In an interview with Axios on HBO conducted on Tuesday, Christie said: "I'm not gonna get into a back-and-forth with Donald Trump."
"But what I will say is this: When I ran for reelection in 2013, I got 60 percent of the vote. When he ran for reelection, he lost to Joe Biden," the former governor said.
Former New Jersey Governor Chris Christie participates in a discussion about his new book at the Washington Post January 31, 2019 in Washington, DC. Another book by Christie, Republican Revival, will be published on Tuesday. Chip Somodevilla/Getty Images


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OpEdNews Op Eds 5/30/2012 at 12:42:27 H3'ed 5/30/12
Pentagon Consolidates Control Over Balkans
By Rick Rozoff (Page 1 of 2 pages) (# of views) No comments
by Rick Rozoff
Ahead of, during and after the North Atlantic Treaty Organization's 25th summit in Chicago on May 20-21, the Pentagon has continued expanding its permanent military presence in the former Yugoslavia and the rest of the Balkan region.
The military bloc's two-day conclave in Chicago formalized, among several other initiatives including the initial activation of its U.S.-dominated interceptor missile system and Global Hawk-equipped Alliance Ground Surveillance operations, a new category of what NATO calls aspirant countries next in line for full Alliance membership. Three of them are former Yugoslav federal republics - Bosnia, Macedonia and Montenegro - and the fourth is Georgia, conflicts involving which could be the most immediate cause of a confrontation between the world's two major nuclear powers.
This year new NATO partnership formats have sprung up like poisonous toadstools after a summer rain: Aspirants countries, the Partnership Cooperation Menu, the Individual Partnership and Cooperation Program, the Connected Forces Initiative and partners across the globe among them.
The military bloc's inauguration as an active, aggressive military force in Bosnia and the Federal Republic of Yugoslavia in the 1990s laid the groundwork for the U.S.'s already unmatched military to move troops, hardware and bases into Southeast Europe for actions there and to points east and south: The Middle East, the Caucasus, North Africa and Central and South Asia.
Since 2004 several nations in the east and west Balkans - Bulgaria, Romania, Slovenia, Croatia and Albania - have been incorporated into the alliance as full members and the remainder - Bosnia, Macedonia, Montenegro, Serbia and the generally unrecognized Republic of Kosovo - have in the first four instances joined NATO's Partnership for Peace program and in the last had its nascent armed forces, the Kosovo Security Force, built from scratch by the leading alliance powers.
Macedonia, which would have become a full member in 2009 except for the lingering name dispute with Greece, and Montenegro have been granted the Membership Action Plan, the final stage before full accession, and Bosnia will be accorded the same once the quasi-autonomous Republika Srpska is deemed properly stripped of the last vestige of self-governance.
NATO and the wars waged under its command, not only in the Balkans but in Afghanistan and all but officially in Iraq, have provided the Pentagon the mammoth Camp Bondsteel in Kosovo and three major air bases in Bulgaria and Romania as well as headquarters for new military task forces and jumping-off points for "downrange" operations outside Europe. The U.S. Department of Defense has also acquired subservient legionaries for wars in Asia and Africa and training grounds for American and multinational expeditionary units employed in 21st century neo-colonial wars far beyond the Euro-Atlantic area. Romania will host 24 U.S. Standard Missile-3 interceptors starting in three years.
NATO's Cooperative Longbow and Cooperative Lancer 2012 command and field exercises started in Macedonia on the second day of the Chicago NATO summit, May 21, and ended on May 29. The largest of four such exercises held within the framework of the Partnership for Peace program - "to train, exercise, and promote the interoperability of Partnership for Peace forces using NATO standards" - to date, this year's Longbow/Lancer drills included 2,200 troops from several NATO and a dozen Partnership for Peace nations, a total of 25 countries including the U.S.
On May 26 U.S. Army Europe and U.S. Air Forces in Europe launched the Immediate Response 2012 exercise in Croatia with military personnel from the host country, Albania, Bosnia, Montenegro and Slovenia. Macedonia and Serbia sent observers.
A report on the opening of the exercise posted on the website of U.S. European Command appended this paragraph:
<blockquote>"U.S. Army Europe is uniquely positioned to advance American strategic interests across Eurasia, building teams, assuring allies and deterring enemies. The relationships we build during more than 1,000 theater security cooperation events in more than 40 countries each year lead directly to support for U.S. actions such as in Kosovo, Iraq, Afghanistan, and Libya."<\blockquote>
Balkan states Albania, Bosnia, Bulgaria, Croatia, Macedonia, Romania and Slovenia deployed troops to Iraq after 2003 and all those nations as well as Montenegro (which became independent in 2006) have troops under NATO command in Afghanistan currently.
NATO's Allied Joint Force Command Naples has military missions in Bosnia, Macedonia and Serbia.
On May 28 the U.S. Joint Chiefs of Staff began a two-week disaster management and crisis response exercise, Shared Resilience 2012, in Bosnia. In addition to the U.S. and Bosnia, participating nations include Albania, Bulgaria, Croatia, Montenegro, Norway, Serbia and Slovenia.
Immediately before the NATO summit, the U.S. Marines Corps' Black Sea Rotational Force 2012 held multinational exercises near Constanta, Romania from May 7-18. The Black Sea Rotational Force was established in 2010 and last year doubled the duration of its training exercises in the Balkans, the Black Sea region and the South Caucasus from three to six months annually.
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Rick Rozoff has been involved in anti-war and anti-interventionist work in various capacities for forty years. He lives in Chicago, Illinois. Is the manager of the Stop NATO international email list at: http://groups.yahoo.com/group/stopnato/
Related Topic(s): 2012; Afghanistan; Ambassador; Army; Conflict; Iran; Military; NATO; NATO; NATO; (more...) Pentagon; Pentagon; Pentagon Propaganda; Pentagon War Strategy; Russia; Wars, Add Tags (less...)
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"Rob explores the difference between a natural, organic, bottom-up connection consciousness and our corporately imposed top-down hierarchical collective consciousness. What Rob is speaking about is the difference between an artificial and ultimately stagnate way of organizing the world and a natural, organic growth, which starts with a seed, sends downs roots and sends up shoots which blossom. By returning to a Nature-based theory of connection, the Bottom-Up revolution brings us back into alignment with Earth's laws, returning humanity to its place in creation. Like a good gardener, Rob works into the soil of his thesis different voices that exemplify how this Bottom-Up revolution is expanding in politics, business, religion, personal self-awareness and story. And he places technology where it belongs—as a tool to further our connection consciousness, not an end in itself. The bottom-up revolution is about democracy finally living up to its original ideals, where we the people decide what we need from our society."
Cathy Pagano, author of Wisdom's Daughters: How Women Can Change the World


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Plastic bag ban passes in Cohasset
By Abigail Adams aadams@wickedlocal.com
Cohasset now joins nearly 70 Massachusetts municipalities that have banned the distribution of single-use plastic bags.
The citizen�s petition proposed by Katie Dunn of 751 Jerusalem Road and Martha Gangemi of 24 Rust Way received overwhelming support both ahead of the town�s Annual Town Meeting and on Town Meeting floor Monday evening (April 30). The goal, the two said, was to help contribute to an ongoing international effort to ban plastic bags.
�By using reusable, recyclable, and compostable bags, we can be a part of the solution,� Dunn said.
Although some residents questioned whether the ban would truly have an impact on the environment, the article easily earned the 2/3 majority required for the article to pass. Jack Buckley of 272 North Main Street applauded the petitioners and urged voters to �act for the next generation.�
�Although I am not familiar with some of the research that may have been cited or some of the suggestions that there is a trade-off with which we are not familiar, I think that this is an incredibly important time and I think the symbolism of the vote is definitely important,� Buckley said.
The ban will go into effect on November 1. Stores will have six months to distribute their remaining stock.
Paragraph body
Cohasset Mariner ~ 600 Cordwainer Drive, Norwell, MA 02061 ~ Do Not Sell My Personal Information ~ Cookie Policy ~ Do Not Sell My Personal Information ~ Privacy Policy ~ Terms Of Service ~ Your California Privacy Rights / Privacy Policy


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NYC Parks
Hart Island's conversion into public park is back on the table
A Manhattan City Council member is looking to open the Potter's Field to the public as a park
By Tanay Warerkar@TanayWarerkar Updated May 24, 2018, 10:30am EDT
A Manhattan City Council member is looking to restart the conversation on opening Hart Island as a public park, the New York Post reports. Earlier this month, Council member Ydanis Rodriguez introduced a couple of bills in the City Council that would allow for the transfer of the Potter's Field from the city's Department of Corrections to the Parks Department, and also create a ferry service that would allow more people to commute to the island.
In early 2016, the Parks Department rejected a similar proposal put forward by a different City Council member. At that time, the Department said it would be too costly to convert the island into a park, and representatives from the Department of Corrections said they were happy maintaining the island as a mass burial ground.
This time around, Council member Rodriguez is also calling for the allocation for $10 million in funds that would allow for the conversion of the island into a park.
"Open Hart Island, give the dignity and respect to the men and women, more than 1 million that have been buried in this location for 150 years," he told a group of reporters who had a chance to tour the island recently, according to the Post.
Hart Island is the largest publicly-funded cemetery in the United States, but it wasn't until 2015 that family members of those who are interred on the island, were allowed to visit. Those hoping to visit the island now must go through the Department of Corrections, and make an appointment months in advance. On the island, they are escorted by a corrections officer at all times. At present, about 1,000 bodies are interred on the island every year—usually for New Yorkers who can't afford a burial or when a body is unidentified.
If Council member Rodriguez's bill is approved, families and other New Yorkers would be able to visit the island more freely.
Councilman resurrects plan to turn graveyard to park [NYP]
Hart Island Won't Become a Park Anytime Soon [Curbed]
Get a Drone's-Eye View of Hart Island, Manhattan's Off-Limits Potter's Field [Curbed]
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Dixons Carphone has made a strong start to its financial year, with UK and Ireland like-for-like revenues rising 10 per cent during its Q1 2015/2016 period.
For the 13 weeks ended August 1st 2015, the Currys/PC World/Carphone Warehouse owner saw group like-for-like revenues increase eight per cent across the board.
The retail giant posted good performance in the Nordics with like-for-like revenues up four per cent, while recording flat like-for-like revenues in Southern Europe. Trading improved in Spain and the company saw growth in Greece despite it remaining a challenging market.
The news comes ahead of Dixons Carphone opening its first US stores next week, in partnership with Sprint.
Sebastian James, Group Chief Executive, said: "This is a very encouraging first quarter with excellent growth for the Group overall, showing strong like-for-like revenues in the UK driven principally by significant market share gain in phone sales. Against the World Cup last year I was also pleased to see growth in UK electricals.
"At the same time, we have continued to see improvements in customer satisfaction and price competitiveness through the period and across all our major territories. Our Nordic business has also experienced decent growth overall against a slightly less buoyant market backdrop.
"Our multi-channel proposition continues to make good headway against our competitors, both on and offline, and we continue to invest in those areas that will ensure our long term profitability: service, delivery options, expansion of free warranty, digital marketing and Norwegian price competitiveness.
"Work has started well on our new venture with Sprint in the US and we are opening our first stores next week. The integration is also going smoothly with our UK head-office move on track and the new management structures in place and working well.
James added: "Overall, a very good start to the trading year but I am aware that there is plenty of the year left to go. In the next quarter we will anniversary the startlingly successful iPhone 6 launch, the consolidation of the mobile market and, later in the year, an extraordinary Black Friday.
Back in July Dixons Carphone posted its first financial results as a merged company, and told PCR it was hoping to increase its PC gaming offering.


I think we can all agree our lives would be better if they were an 80s movie.
The look Bender gives Claire still melts my heart.
I don't think anyone's proms were actually this memorable. All I remember from it was a sweaty gym with awkward dancing, definitely not crushes proclaiming their love for anyone.
I had the time of my life rewatching this scene 30 times in a row. Also, why did I never meet a boy that could dance like that/look at me like that?
This has to be the number one scene from the 80s. It would have been my dream to have a boy show that he loves me by standing outside of my house holding a boombox. John Cusack, you raised my expectation for boys in high school, an expectation which was never met.
Okay, again with The Breakfast Club, but this movie has too many scenes to pick from. I think we all wish we had the courage to kiss a bad boy right in front of our parents to make them mad. Also, I wanted a boy to throw his fist in the air because he was so happy he had me.
After having an abusive ex-boyfriend, Ren shows her what love looks like. I think we all dreamed about that kiss they had after she gave him the music-box.
When Jake is waiting for Samantha outside of the church, after the wedding. All we ever wanted was a good-looking boy in a nice car to fall in love with on our 16th birthday.
We all secretly want to ride off in the sunset on a lawn mower.


How do I completely reset my server and start over?
A fresh start may be just what you need!
Starting over can be desirable if you've made some mistakes and just want a clean slate, or even if you just want to begin anew. No matter what your reason, we've made it simple to do!
Using the reset feature will delete all of your files, though your "Server Type", internal "Server Name", and world name (not the world folder itself) will remain.
Once you have logged in, select the server you wish to reset.
Navigate to "ADVANCED" > "RESET".
A window will appear warning you that resetting the server will result in all files being deleted.
You will be asked to verify your Prisma password before the "Reset Server" button will unlock.
Once your password is entered, another pop-up may appear confirming, again, that you wish to reset your server. You'll need to click "OK" before you can continue.
If you've clicked "OK" or the pop-up did not appear and you've clicked "Reset Server", your server should be successfully reset.
Before starting the server, you may adjust your server type and world name as you please, then start the server when ready.
Once started, a new world will be generated and the server type selected will be installed.
Note: This feature is restricted to the owner of the server only.


Copyright: © Sang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+. We hypothesized that the apoptotic pathway may be blocked through the inhibition of T-type Ca2+ channels in cochlear cells in NOD/LtJ mice. NOD/LtJ mice were divided into 2 groups as follows: the ethosuximide-treated and untreated (control) groups. Ethosuximide was administered by intraperitoneal injection every other day from post-natal day seven (P7) until the mice were 8 weeks of age. Following treatment, auditory-evoked brainstem response (ABR) thresholds and distortion product oto-acoustic emission (DPOAE) of the mice in the 2 groups were measured at different time points. Morphometric analysis and the expression of genes involved in the T-type Ca2+-mediated apoptotic pathway were monitored. The ABR and DPOAE results revealed that the NOD/LtJ mice exhibited early-onset and rapidly progressive AHL. A histological examination revealed that hair cell degeneration coincided with the progression of hearing loss. Hair cell and SGN was were significantly lower and auditory function was significantly improved in the ethosuximide-treated group compared to the untreated group. Our data thus indicate that ethosuximide prevents the degeneration of cochlear cells by regulating the expression of genes in apoptotic pathways. Our findings suggest that activating the T-type Ca2+ channel and downstream genes may be key pathological mechanisms responsible for AHL in NOD/LtJ mice.
Presbycusis or age-related hearing loss (AHL) is a common sensory functional disturbance (1,2), which negatively affects the quality of life of affected individuals (3). AHL decreases a person's ability to communicate with a spoken language and has been implicated in various somatopsychic illnesses, including depression, social isolation and a lower self-esteem. Despite extensive research efforts, our understanding of the mechanisms responsible for AHL remains limited, and there are currenlty no available effective medications to prevent or treat this condition. Environmental and other factors, such as endocrine disease and ototoxic drugs may contribute to the development of AHL. In the United States, approximately two-thirds of all adults older than 70 years have clinically significant hearing loss (4). Globally, the incidence of AHL has continued to increase due to the aging population, and it has become a major burden to families and society.
Sensorineural hearing loss is characterized by a difficulty in hearing high frequencies and is caused by the degeneration of hair cells and spiral ganglion neurons (SGNs). The organ of Corti is located in the cochlea. It is composed of mechanosensory cells known as hair cells, and is responsible for the sensations of sound. SGNs establish connections between hair cells and central auditory system neurons in the brainstem. Unfortunately, hair cells and SGNs are non-renewable; hence, their impairment results in decreased hearing sensitivity (5,27).
The normal lifespan and fecundity of NOD/LtJ mice provide a complementary model to facilitate the genetic basis of human presbycusis. Inbred strains of NOD/LtJ mice are susceptible to early-onset AHL (6). This phenotype has been traced to the hypomorphic Cdh23 (753A) allele in the cadherin 23 gene (Cdh23). In addition, the corresponding cadherin 23 (CDH23) is a component of the tip link in hair-cell stereocilia (7). The major contributor to the difference in hearing loss onset time between NOD/LtJ and C57BL/6J mice is the Ahl2 locus on mouse chromosome (Chr)5 in NOD/LtJ mice (6). NOD/LtJ mice exhibit hearing loss before 3 months, and this is much earlier than C57BL/6J mice, which do not exhibit hearing loss until 10 months of age or older (6). Thus, these features established an appropriate therapeutic time frame for AHL-associated genetic mechanisms, and may be used to provide new insight as to the treatment of AHL.
Calcium channel blockers has been demonstrated to improve hearing thresholds in females during aging, suggesting that calcium disorders are an important factor underlying human AHL (8). Furthermore, Ca2+ ions can activate the apoptotic signaling pathway. Apoptosis plays a key role in the age-related decline of physiological function in multiple organs, including the cochlea (9–11). Thus, in this study, we selected ethosuximide, which is used as a first-line treatment for the absence seizures, and which its primary mechanism is to selectively inhibit T-type Ca2+ channels in the neuronal cell membrane (12). This study aimed to evaluate the otoprotective effects of ethosuximide as a Ca2+ channel blocker in NOD/LtJ mice with AHL.
The pan-caspase inhibitor, Z-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK), can attenuate the progression of AHL in Cdh23erl/erl mice and reduce age-related outer hair cell (OHC) degeneration, and prevent apoptotic cell death by inhibiting the calpain signaling pathway (13). Calpain is a cysteine protease, and alterations in intracellular Ca2+ can activate calpain and the caspase family (14,15). In addition, erythropoietin (EPO) can protect against hearing loss in Cdh23erl/erl mice through apoptosis-related pathways (16).
In the present study, NOD/LtJ mice were treated with ethosuximide from post-natal day 7 (P7). We hypothesized that ethosuximide could block T-type Ca2+ channels, suppress apoptotic factors, and thus prevent hair cell degeneration and preserve auditory function.
NOD/LtJ mice (age range, P7 to 5 months) obtained from the Jackson Laboratory (Bar Harbor, ME, USA), were housed at 24°C with a 12-h light/dark cycle in a standard animal house. A total of 95 NOD/LtJ mice were used in this study. Food and water were available ad libitum. The Animal Care and Use Committee of Binzhou Medical University, Yantai, China approved the care and use of mice for this study.
In the experiment shown in Fig. 1, we tested ABR and DPOAE at 3, 4, 6, 8, 10 and 14 weeks of age for the NOD/Shi LtJ mice (n=5/time point) and the mice were anesthetized and sacrificed for phalloidin staining after testing. In order to determine the tendency for cell loss, the mice were anesthetized at 18 weeks (n=5) and sacrificed for phalloidin staining after testing. The key time points are shown. As mouse hearing can be tested at 3 weeks of age by ABR and we did not observe any loss of hair cells, this was not shown (total mice used = 35). In the experiment shown in Fig. 2, the ABR and DPOAE of the untreated mice and ethosuximide-treated mice were assessed at 4, 6 and 8 weeks of age (n=5/group). After testing at 4 weeks, the mice were then allowed to grow 6 weeks for testing and then to 8 weeks for testing (total mice used = 10). In the experiment shown in Fig. 3, the mice in the ethosuximide-treated and untreated groups were sacrificed at 4 and 8 weeks of age (n=5/group/time point), and the Corti were isolated, OHC and IHC hair bundles were visualized with phalloidin staining (total mice used = 20, 10 at each time point in both groups). In the experiment shown in Fig. 4, at 4 and 8 weeks of age, the mice in the ethosuximide-treated and untreated groups were sacrificed (n=5/group/time point) (total mice used = 20, 10 at each time point in both groups). In the experiment shown in Fig. 5, we examined expression differences between the ethosuximide-treated and untreated mice (n=5/group) at the age of 8 weeks (total mice used = 10).
Auditory function tests in NOD/LtJ mice at different time points. (A) Mean auditory-evoked brainstem response (ABR) thresholds for mice aged between 3 and 14 weeks, exhibiting early hearing loss (at 3 weeks of age) progressing to severe hearing loss by 14 weeks of age. (B) Distortion product oto-acoustic emission (DPOAE) amplitudes decreased in mice aged between 3 and 14 weeks. W, week. (C–H) Hair cells in the basal turn of the organ of Corti in 4-, 8-, 10-, 14- and 18-week-old mice were stained to reveal stereocilia bundles. At 18 weeks of age, normal hair cells in the basal turn had almost disappeared. Dark areas indicate outer hair cell (OHC) degeneration. Arrows indicate sites of OHC loss, and triangles indicate sites of inner hair cell (IHC) loss (scale bar, 20 μm). (H) Cytocochleograms showing the mean percentage of total hair cell loss (y-axis) at various time-points (x-axis) in the basal turn. Error bars indicate the standard error of the mean.
Effects of ethosuximide treatment in different frequencies at different time points (n=5/group). (A–E and G–I) In 4-week-old mice, auditory-evoked brainstem response (ABR) thresholds in the ethosuximide-treated group (red line) were significantly lower compared to the untreated group (blue line) at a stimulus frequency of 8 kHz (P<0.01). In 6-week-old mice, ABR thresholds in the ethosuximide-treated group (red line) were significantly lower compared to the untreated group (blue line) at a stimulus frequency of 16 kHz (P<0.01). In 8-week-old mice, ABR thresholds in the ethosuximide-treated group (red 2 groups during the period (4–8 weeks) of drug application. (F) There were no significant differences in body weight (8-week-old) in ethosuximide-treated mice compared to untreated mice after drug application. Comparison of distortion product oto-acoustic emission (DPOAE) amplitudes between the 2 mouse groups in 4-week-old mice (G), 6-week-old mice (H) and 8-week-old (I) mice. (G) In 4-week-old mice, mean DPOAE amplitudes in the ethosuximide-treated group (red line) at 8,844 and 12,503 Hz were significantly higher compared to the untreated group (blue line). (H) In 6-week-old mice, mean DPOAE amplitudes in the ethosuximide-treated group (red line) at 4,422, 17,672 and 24,990 Hz were significantly higher compared to the untreated group (blue line). (I) In 8-week-old mice, mean DPOAE amplitudes in the ethosuximide-treated group (red line) at 8,844, 12,503 and 35,344 Hz were significantly higher compared to the untreated group (blue line). Error bars indicate the standard error of the mean. *P<0.05 and **P<0.01.
Morphological observations of effects of ethosuximide treatment compared to the untreated group. (A–B and C–D) In untreated mice, outer hair cell (OHC) morphology and arrangement appeared abnormal (A and C) compared to ethosuximide-treated mice (B and D). Arrows indicate sites of OHC loss, and triangles indicate sites of inner hair cell (IHC) loss (scale bar, 20 μm). (E and F) OHCs and IHCs in the apical-basal cochlear location in 4- and 8-week-old mice are shown. Mean OHC loss (%) in the middle and basal turns were significantly lower in ethosuximide-treated mice compared to untreated mice. Error bars indicate the standard error of the mean. *P<0.05, **P<0.01 and ***P<0.001.
Ethosuximide treatment reduces cochlear cell degeneration. Spiral ganglion neurons (SGNs) (A and B) and hair cells (C and D) in the basal turn of the cochleae from ethosuximide-treated and untreated NOD/LtJ mice. Arrows indicate regions of hair cells (scale bar, 25 μm). (A and C) Photomicrograph of the basal turn of the cochleae in 8-week-old mice in the untreated group shows degeneration of SGNs and hair cells. (B and D) Photomicrograph of the basal turn of the cochleae in 8-week-old mice in the ethosuximide-treated group shows less degeneration of SGNs and hair cells. (E and F) Photomicrograph of the SGN of ethosuximide-treated and untreated mice demonstrates apoptotic features in the untreated group at a 100X oil immersion objective lens; scale bar, 1 mm). (E) In the untreated group, SGNs revealed apoptotic features: shrunken cytoplasm, condensed chromatin and pyknosis, and decreased neuronal number compared to the ethosuximide-treated group (F). (G) In 8-week-old mice in the ethosuximide-treated group, SGN survival was increased compared to the untreated group. Error bars indicate the standard error of the mean. *P<0.05.
T-type calcium-mediated apoptotic pathway was downregulated in ethosuximide-treated 8-week-old NOD/LtJ mice. (A) Mean expression levels of α1G, α1H and α1I subunits were determined by RT-qPCR. There was a significant decrease in α1H and α1I gene expression in the ethosuximide-treated group compared to the untreated group. (B) Mean mRNA levels of μ-calpain and m-calpain were significantly decreased in the ethosuximide-treated group, indicating that the intrinsic apoptotic pathways was involved in hearing loss in NOD/LtJ mice. (C) Mean mRNA levels of caspase-3, -9 and -12 in inner ear tissues of the ethosuximide-treated group were lower compared to the untreated group. Error bars indicate the standard error of the mean. *P<0.05 and **P<0.01.
Auditory-evoked brainstem response (ABR) was tested to identify the lowest level at which an ABR pattern can be recognized. Distortion product oto-acoustic emission (DPOAE) represented the function of OHCs. They were measured at various intervals at 3, 4, 6, 8, 10 and 14 weeks of age for the NOD/Shi LtJ mice (n=5/time point). The computer-aided evoked potential system (Intelligent Hearing Systems, Miami, FL, USA) was used to test for ABR thresholds (17,18). Briefly, the mice were anesthetized with 3% chloral hydrate (10 mg/kg) and body temperature was maintained at 37±1°C. Platinum needle electrodes were inserted subcutaneously at the vertex (active), and ventrolateral to the right ear (reference) and left ear (ground). ABR thresholds were detected by reducing the sound pressure level (SPL) at 10-dB steps, and subsequently at 5-dB steps. Following the ABR test, we measured DPOAE using the IHS Smart EP 3.30 and USB ez Software (Intelligent Hearing Systems, Miami, FL, USA) (19). Stimuli (ranging from 4,422 to 35,344 Hz) were presented from lowest to highest frequency. Amplitudes were recorded automatically.
For morphometric observation, at 4, 8, 10, 14 and 18 weeks, the mice were anesthetized and sacrificed (n=5/time-point). The inner ears were removed, fixed in 4% paraformaldehyde, and decalcified in Cal-Ex solution. Cochleae were isolated and divided into 3 turns (apex, middle turn and base turn). Finally, the organ of Corti was exposed in each turn and specimens were mounted on glass slides. OHC and inner hair cell (IHC) hair bundles were visualized with Alexa Fluor® 488-conjugated phalloidin staining and a confocal laser scanning microscope (Leica TCS SPE; Leica Microsystems GmbH, Wetzlar Germany). The number of missing hair cells was counted per view using a x40 oil immersion objective lens (13); counts of continuous views for each turn were recorded for statistical analyses. Cytocochleograms were generated.
Seven-day-old mice were divided into 2 groups as follows: ethosuximide-treated group and untreated group (n=5/group). Ethosuximide (Sigma Chemical Co., St. Louis, MO, USA) was dissolved in ddH2O and stored at 4°C in dark bottles until use. Ethosuximide was administered by intraperitoneal injection (10 mg/kg of body weight) every other day from P7 to 8 weeks of age. A higher dosage 14 mg/kg injection of ethosuximide every other day resulted in the death of 2 litters of mice (not the mice used in these experiments) after 2 weeks initial treatment. We measured body weight prior to injection. Body weight was also used for monitoring the animal health status.
The ABR and DPOAE of the untreated mice and ethosuximide-treated mice were assessed at 4, 6 and 8 weeks of age (n=5/group/time point).
The mice in the ethosuximide-treated and untreated groups were sacrificed at 4 and 8 weeks of age (n=5/group/time point), and the Corti were isolated, OHC and IHC hair bundles were visualized with phalloidin staining as described previously. Hair cells in the ethosuximide-treated and untreated groups were observed and counted, and these were reported as the percentage of missing OHCs and IHCs.
At 4 and 8 weeks of age, the mice in the ethosuximide-treated and untreated groups were sacrificed (n=5/group/time point) and the bullae (including both the middle and inner ears) were isolated, and immersed in 4% paraformaldehyde, decalcified with Cal-Ex solution, and embedded in paraffin. Subsequently, 5-mm-thick sections of cochleae were cut, mounted on glass slides, counterstained with hematoxylin and eosin (H&E), and observed under a microscope using a 40× objective lens and 100× oil immersion objective lens (Leica DM4000 B; Leica Microsystems GmbH).
The experiment were assessed between the ethosuximide-treated and untreated mice (n=5/group) at the age of 8 weeks. The entire inner ears were dissected, and total RNA was extracted using TRIzol reagent (Invitrogen, Carlsbad, CA, USA). For each sample, a reverse transcriptase reaction was performed with 1 μg of total RNA using the ReverTra Ace qPCR RT kit (Toyobo, Osaka, Japan). The resulting cDNA was diluted for use as template for the real-time PCR reaction. Primer3 was used to design the primers (http://primer3.sourceforge.net/) (Table I). The PCR reaction was carried out using the FastStart Universal SYBR-Green Master kit (Roche, Mannheim, Germany) and specific primers in a Bio-Rad iCycler iQ5 peltier thermal cycler. The process was as follows: one cycle at 95°C for 10 min; 40 cycles at 95°C for 15 sec, 58°C for 30 sec and 72°C for 10 sec; and 71 cycles at 60–95°C. PCR cycles were continued until the fluorescence intensity exceeded a predetermined threshold, and he cycle number was measured automatically. The relative quantification of the initial amount of template for each sample was achieved by determining the number of cycles. The ΔCt value was calculated using the comparative Ct threshold method. The difference in the initial amount of total RNA among samples was normalized using the housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The relative levels of target gene mRNA were analyzed using the 2-ΔΔCt method (20).
Primers used for RT-qPCR for the detection of apoptosis- related genes.
[i] GAPDH, glyceraldehyde 3-phosphate dehydrogenase.
Statistical comparisons of differences between groups were conducted using the Student's t-test. A P-value <0.05 was considered to indicate a statistically significant difference. All statistical analyses were performed using the statistical package SPSS for Windows (version 16.0; SPSS, Inc., Chicago, IL, USA).
To investigate hearing loss during the lifespan of NOD/LtJ mice, we detected ABR and DPOAE at 6 time points (in mice aged between 3 and 14 weeks, n=5/group/time point) (Fig. 1A). The 3-week-old mice exhibited hearing loss with average ABR thresholds >60 dB above normal, which is considered to be a profound impairment (6). The ABR thresholds increased after 8 weeks of age, particularly at high frequencies (16 and 32 kHz). From 3 to 8 weeks of age, the average shift in the ABR threshold was approximately 15 dB; while from 8 to 14 weeks of age, the average shift in the ABR threshold was >25 dB (Fig. 1A). In the 12-week-old mice, the average ABR thresholds were >90 dB SPL, and the 14-week-old mice exhibited almost complete deafness. DPOAE was measured to determine OHC function over time (Fig. 1B). The 3-week-old mice exhibited decreased DPOAE amplitudes, which deteriorated with age.
To investigate changes in cochleae morphology during the course of hearing loss to the status of complete deafness in NOD/LtJ mice, the organ of Corti was examined in all 3 turns of the cochleae (Fig. 1C–G). To quantify hair cell loss, cytocochleograms were generated from mice aged between 4 and 14 weeks (Fig. 1H). From post-natal day zero (P0) to 3 weeks of age, the mice exhibited no evidence of OHC loss. However, in the 4-week-old mice, evidence of OHC degeneration began at the basal turn and OHC loss was 6% in all 3 turns totally (Fig. 1C and H). At 8 and 14 weeks of age, OHC loss was 25 and 45%, respectively, in all 3 turns (Fig. 1D and H). The loss of OHCs coincided with increased ABR thresholds. In the 18-week-old mice, no normal OHCs were visible (Fig. 1G). In the 10-week-old mice, evidence of IHC degeneration was observed (Fig. 1H). IHC loss was 9% in the 10-week-old mice, which increased with age.
To investigate whether ethosuximide protects against hearing loss in NOD/LtJ mice, we conducted hearing tests in 4-, 6- and 8-week-old ethosuximide-treated and untreated mice (n=5/group).
ABR thresholds were lower in the ethosuximide-treated group than in the untreated group at stimulus frequencies of 8 kHz in the 4-week-old mice (P<0.01), 16 kHz in the 6-week-old mice (P<0.01), and at click, 8 and 32 kHz in the 8-week-old mice (P<0.05) (Fig. 2A–D). ABR threshold shifts in the 2 groups during the period (4–8 weeks) of drug application were also measured to determine whether ethosuximide can alter or attenuate the progression of hearing loss. The ethosuximide-treated group displayed lower ABR threshold shifts compared to the untreated group (Fig. 2E).
The mean amplitude of DPOAE was significantly higher in the ethosuximide-treated group than in the untreated group at 8,844 and 12,503 Hz in the 4-week-old mice (P<0.01), at 4,422, 17,672 and 24,990 Hz in the 6-week-old mice (P<0.05), and at 8,844, 35,344 Hz (P<0.01) and 12,503 Hz (P<0.05) in the 8-week-old mice (Fig. 2G–I). As DPOAE reflects OHC function, these data suggest that ethosuximide protects auditory function in NOD/LtJ mice.
Fluorescence images of the OHCs and IHCs characterized the progression of hair cell degeneration in the cochleae in the 4- and 8-week-old untreated mice (Fig. 3A and C). OHC survival was increased in the ethosuximide-treated group compared to the untreated group (Fig. 3B and D). Cytocochleograms indicated that the mean percentage of OHC loss was significantly lower in the ethosuximide-treated group than in the untreated group at all 3 cochlear turns. IHC loss was not substantially altered by ethosuximide treatment (Fig. 3E and F) (n=5/group/time point).
H&E staining demonstrated that the ethosuximide-treated group (Fig. 4B and D) experienced minor SGN and hair cell degeneration in the basal turn compared to the untreated group (Fig. 4A and C) in the 8-week-old mice (n=5/group/time point). In the untreated group, the SGNs did not exhibit apoptotic features in the basal turn until the mice were 8 weeks old (Fig. 4A). At this time poinr, auditory nerve fibers became loosened and the neurons exhibited a shrunken cytoplasm, condensed chromatin and pyknosis (Fig. 4A and E). In the basal turn, the neuronal population was decreased in the untreated group compared to the ethosuximide-treated group (Fig. 4G). However, the SGN in the apical turn was normal at this time point. Cell counting demonstrated that ethosuximide treatment increased SGN survival (Fig. 4G) in the 8-week-old mice, and increased OHC survival in both the 4- and 8-week-old mice (Fig. 3E and F).
Ethosuximide treatment was not associated with any noticeable side-effects in the 4- and 8-week-old mice. There were no significant differences in body weight in the ethosuximide-treated mice compared to the untreated mice (Fig. 2F).
We then determined whether the blocking of T-type Ca2+ channels can downregulate cochlear cell gene expression. The family of T-type Ca2+ channels is comprised of 3 main pore-forming α subunits: α1G, α1H and α1I (21). The mean mRNA expression levels of the α1G, α1H and α1I subunits were decreased in the cochleae of the ethosuximide-treated 8-week-old NOD/LtJ mice; a significant difference was observed between the ethosuximide-treated group and the untreated group for the α1H and α1I genes (P<0.01) (Fig. 5A).
There are 2 major intracellular apoptotic pathways. Extracellular stimuli can initiate an extrinsic pathway (caspase-8) that activates the caspase family. Alternatively, the intrinsic pathway involves intracellular calpain, which ultimately triggers apoptosis by activating caspase-3 (Fig. 6) (22,23). Calpains (m-calpain and μ-calpain) are activated by Ca2+(24). Our results suggested that ethosuximide treatment downregulated the intrinsic apoptotic pathway (Fig. 5B and C).
Conceptual graphic of targeted sites of ethosuximide inhibition and associated molecules mechanism in NOD/LtJ mice. Calpains are activated by Ca2+, which subsequently activates caspase-12, -9 and -3; and finally initiates cell death. Ethosuximide treatment blocks this T-type Ca2+ channel, and associated genes are downregulated. Ethosuximide treatment has no effect on extrinsic caspase-8. Dashed lines are proposed links indicating that that Ca2+ may influence the efficiency of CDH23.
This study included NOD/LtJ mice with a Cdh23 and Ahl2 background, and this strain experienced progressive hearing loss starting at approximately 3 weeks after birth. AHL began in the high frequency region and progressed to the low frequency region with increasing age. The phenotype is similar to that observed in some humans with presbycusis, in which the basal turn of the cochlea first degenerates (25). These functional deficits were accompanied by the loss of hair cells and SGNs that began at the base of the cochlea, which spread toward the apex. NOD/LtJ mice were deaf by 14 weeks of age.
AHL is characterized by the widespread structural and functional degeneration of hair cells and SGNs in the cochleae (26). Hair cells are responsible for collecting acoustic signals and transducing them to SGNs. SGNs transform acoustic signals into nerve impulses that are received by the auditory cortex. Finally, information is interpreted in the brain (27). Hair cells promote neurotrophin release; and 93% of SGNs innervate IHCs (28), which suggests that the degeneration of SGNs may be a secondary phenomenon associated with the loss of IHCs. However, in NOD/LtJ mice, SGN degeneration occurred earlier than the loss of IHCs, suggesting the occurrence of early-stage SGN degeneration, which is independent of the age-related loss of hair cells.
As NOD/LtJ mice exhibit rapid and progressive hearing loss, associated genetic mechanisms may provide new insight into the development of AHL and may aid in prevention and treatment. AHL is a genetically complex quantitative trait in common inbred mouse strains, including NOD/LtJ mice. Based on our observations, auditory functional deficiencies occurred before cochlear cell degeneration in the NOD/LtJ mice. We hypothesize that synergistic interactions of Cdh23 and Ahl2 variants are responsible for the AHL phenotype. Interactions between Cdh23 and Ahl2 have not been characterized, as Ahl2 has not been identified at the gene level. In NOD/LtJ mice, exon 7 in Cdh23 has a single nucleotide polymorphism that displays an important association with AHL. AHL may be caused by homozygosity in Cdh23 (753A) in association with the effects of heterogeneous secondary factors (7). Cadherins mediate Ca2+-dependent cell-cell adhesion, migration and compaction (29). CDH23 is encoded by the Cdh23 gene, which is a transmembrane protein and a component of the tip-link in hair cells in the organ of Corti (29–31). CDH23 is involved in regulating the activity of mechanically gated ion channels in hair cells (6,32,33). Evidence suggests that Ca2+-dependent cell-cell adhesion deficiency significantly influences cochlear cell integrity (34).
Population-based studies have linked the use of Ca2+ channel blockers to improved hearing thresholds in elderly females. T-type Ca2+ channels are voltage-gated Ca2+ channels (VGCCs) that can regulate intracellular Ca2+ levels (35–38). In this study, we demonstrated that a blocker of T-type Ca2+ channels, ethosuximide, significantly reduced the increase in age-related ABR thresholds, as well as OHC and SGN loss, in NOD/LtJ mice; this most likely mediated through the effects of the downstream apoptotic pathway. Ethosuximide is a relatively selective inhibitor of T-type Ca2+ channels. In accordance with our findings, it has been demonstrated that the blocking of T-type Ca2+ channels with ethosuximide can prevent epileptogenesis (39). In a study on glutamate-induced injury in stroke, the blocking of Ca2+ channels effectively prevented Ca2+ entry and delayed neuronal death (40). In addition, as shown in another study, the protective effect of hydrogen sulfide on colonic mucosa relied on T-type Ca2+ channel-dependent neuronal excitation in rats (41). In a noise-induced C57BL/6J mouse model, ethosuximide delayed age-related SGN loss and preserved ABR thresholds (42). However, Ca2+ was not the sole mediator in ferutinin-mediated eryptosis/erythroptosis, as the wastage of external Ca2+ did not prevent the apoptotic effect of ferutinin (43).
The mechanisms responsible for AHL in NOD/LtJ mice include structural alterations of the tip-links in hair cells and cochlear cell apoptosis. CDH23 protein is located near the Ca2+-binding site. We speculate that Ca2+ may influence the efficiency of CDH23 interactions with proteins, affect Ca2+-dependent cell adhesions, and ultimately lead to apoptosis in NOD/LtJ mice. Thus we suggest that blocking the Ca2+ channel with ethosuximide may inhibit the calpain-mediated (intrinsic) apoptotic pathway that activates the caspase family and a cascade that leads to cell death. This is supported by data indicating that leupeptin, which is a calpain inhibitor, protects the cochlear and vestibular hair cells against gentamicin (GM) ototoxicity (44). Furthermore, conventional Ca2+ entry antagonists prevent neuronal death when administered before and during the injury phase of glutamate excitotoxicity (45,46). However, following excitotoxic insults, these Ca2+ entry antagonists are no longer effective. Thus, our results demonstrate that the prophylactic use of ethosuximide may prevent neuronal death.
The debate of determining which component of the cochlea is involved in the aging process and which part of the inner ear is involved if affected by ethosuximide continues. It should be noted that the elevation of hearing thresholds in AHL detected by traditional audiograms is primarily based on OHC and not SGNs. Further studies are required in order to further understand the subtle structural changes in AHL and also following the application of ethosuximide.
In conclusion, the NOD/LtJ mouse provides a valuable model for the study of AHL-associated genetic mechanisms. In particular, the role of cadherins in the tip-link of hair cells can be investigated. The effects of mutation in Ahl2 remain unclear, and warrant further investigation. This study confirmed that blocking T-type Ca2+ channels plays a crucial role in the maintenance of cochlear cells. Additional research is required in order to explore the clinical significance of ethosuximide in AHL in humans.
We would like to thank Fengchan Han, Qingzhu Wang and Hui Wang for breeding the NOD/LtJ mice. The present study was supported by grants from National Natural Science Foundation of China (no. 81271085, 81530030 and 81500797), the Natural Science Foundation of Shandong Province (ZR2012HL30, ZR2012HL31 and ZR2014HL050), the Foundation of Taishan Scholar.
Sang, L., Zheng, T., Min, L., Zhang, X., Ma, X., Entenman, S., Su, Y., Zheng, Q."Otoprotective effects of ethosuximide in NOD/LtJ mice with age-related hearing loss". International Journal of Molecular Medicine 40.1 (2017): 146-154.


The official Star Wars Youtube channel has recently updated with a new trailer for the next episode of Star Wars Rebels. The next episode titled ", Holocrons of Fate," will feature the return of Darth Maul. Holocrons of Fate will premiere this Saturday on Disney XD at8:30 p.m. ET/PT.
In anticipation for their upcoming movie release, Marvel today released an Exclusive First Look trailer for Dr. Strange.
TF Con Chicago Sept Guest List!


This month has been a rough one for fires on the Colorado frontier. Every night as I watch the news I wonder if there is going to be much left of the Colorado forest by the time winter comes. The West Fork Fire was started by lightening and is quickly taking over the forest near me, a forest that I spent last weekend 4-wheeling in.
The West Fork Fire is burning less than 60 miles from me and the pictures below are taken from various locations around my town and neighboring towns. The fire does make for the most amazing sunsets that we have been all in awe of, but at the same time it's very sad knowing that the forests we love are quickly disappearing.
West Fork Fire June 2013 taken by a dear friend and neighbor Anna.


About me: Academic staff member at the state university for 26 years, Mugla Vocational School, Electric and Energy Department. I am an open mind person who enjoys natural and cultural life, analytical thinking, using my bike for transport (which I have done so for over 30 years), teaching energy management and PV system, environmental protection, and seeking project funding. I am a long distance cyclist, certified bicycle policy auditor, the National Eurovelo Coordinator for Turkey, a charter member of ENVERCEVKO – Energy Efficiency and Environment Protection Association (head of the board), and a member of S4C – Scientists for Cycling of ECF. ENVERCEVKO is a member of ECF and an advisory board of a regional development agency. I have a keen interest in cycling tourism models, eco tourism and natural energy. Among the cycling tours I have completed is a trip from Munich, Germany, to Mugla, Turkey.
My daily exercise: Cycling from home to work. I live in a small town named Gulagzı near Mugla (10 km) and have cycled 5600 km from Gulagzı to the city centre of Mugla since September 2013 (approx 30 km daily). I rarely use my car.
My MOVE Week story: I first learned about MOVE Week last year. We organised two cycling events at Bodrum/Mugla and Uzundere/Erzurum with the Bodrum Cycling Club and Caglayan Culture, Science and Art Association. Bodrum is in southern Aegean region of Turkey. Uzundere/Erzurum is in eastern North of Turkey. We were almost 100 cyclists at each event. I followed the project and kept in contact with ISCA staff and now I am a national coordinator of MOVE Week. I think that this project is very influential and efficient.


text:
Jaques Joseph
6. September 1865 Jakob Lewin Joseph was born in Koenigsberg on the 6th September 1865 as the third child of Rabbi Israel Joseph and his wife Sara.
From 1885 to 1889 he was a student of medicine at the Friedrich-Wilhelm University in Berlin.
In 1892 he joined the staff of the Berlin University Clinic for Orthopaedic Surgery. In the same year he married his wife Leonore.
In 1904 Jacques Joseph published his first report on the simultaneous, intranasal correction of a hump nose with the correction of the front septum.
In 1916 he was appointed head of the newly founded Department of Facial Plastic Surgery at the Ear, Nose and Throat Clinic at the Charité by the Prussian Ministry of Education and Cultural Affairs.
1919 appointed professor despite not having habilitated; awarded the Iron Cross.
1922 Joseph set up his own practice where he dedicated himself to work in several fields of plastic surgery.
In 1922 a report on Jacques Joseph was published by "raving reporter" Egon Erwin Kisch.
In 1928 and 1929 the first two sections of Jacques Joseph's book on 'nasal plastic surgery' were published at Curt Kabitzsch Publishers, Wuerzburg / Leipzig.
1931 the publication of the book presented here as a reprographic reprint, 'Nasal Plastic Surgery and Other Facial Reconstructive Procedures, With an Appendix on Reconstructive Breast Surgery and Some Other Procedures in the Area of External Plastic Surgery. An Atlas and Text Book' [Nasenplastik und sonstige Gesichtsplastik nebst einem Anhang ueber die Mammaplastik und einige weitere Operationen aus dem Gebiete der aeusseren Koerperplastik. Ein Atlas und Lehrbuch]
On 12th February 1934 Jacques Joseph died of a heart attack in the hallway of his house on his way to his practice.