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Restaurant Lemon Tree..... The first thing cross my mind is the "Lemon Tree" song 's lyric. da dada de dada da de...... humming along as I walk toward the shop. Gentle breeze accompany me as I walk toward the shop. The sound of leaves rustle and sway as the wind blows. Serenity. Peaceful. This quiet area captures my heart.
Left: Mango Juice Right: Sour Soap
Honey Lemon RM5.50
Main Dishes
Tropical Hawaiian Pizza RM17.80
I prefer this restaurant Hawaiian pizza. It have lots of ingredients. Pineapple, cucumber, ham, capsicum, chicken bites and some chilies. It is a bit spicy.
Island Seafood Pizza RM19.80
Big prawn pieces and lots of tuna meat. However, I prefer thin crust pizza.
Spaghetti Hawaiian RM8.80
The hams are saying "Hi" to me. The sauce is slightly sweet. I like to have some spaghetti on the fork while the ham on the tip of the fork. Yummy, Yummy !!
New Zealand Air Flown Rib Eye Steak RM49.00
The salad is nice as it mixed with vinegar. The steak is medium well cooked. I found it a bit dry. May be cook until 50% will be better taste
Mee Mamak
Our "Mamasan"'s special request dish. She really like mee mamak.
Tuna Bruchetta Cheese Bread RM6.80
Don't the book by it's cover, The bread is evenly spread with tuna before wrapped up by cheese. Cucumber give the extra crunchy ad refresh filling. The sweet and sour tomato is like the catalyst for cheese and tuna. The bread is slightly toast. When I bite into it, I can taste different bread texture. Crunchy crust and warm soft filling.
Mushroom soup RM5.50
The chef used 5 type of mushrooms. The mushroom pieces are very small. Every scoop, I can taste the mushroom.
Mixed Fruit Salad RM5.50
Fresh and juicy fruit pieces. There are watermelon, orange, pineapple, cucumber, honey melon, cherry tomato and lettuce leaves. The salad dressing attract me the most. It is specially made using fresh orange jiuce. The dressing is very refreshing and appetizing.
Spaghetti Seafood Alio-Olio RM12.80
This dish have 4 big prawns. It will tempt you with its fresh seafood. If you like garlic with olive, this will be your dish.
Special Fried Rice RM13.80
Once upon a time, there was a client complained the fried rice portion is too small. He request the chef to add extra side dishes for him. First is fried chicken wing. Second is ham and cheese will some black pepper. Third is a bull eye egg. To ensure, the meal is complete will all the nutrition. A small portion of salad is served too. The client visit the cafe regularly. The chef get the idea and named the dish as "Special Fried Rice". There is an interesting way to taste this dish. Pour some black pepper sauce over the rice. Then taste it. It is very different. The black pepper sauce is not that spicy that will burn off your tongue. However, It add some extra moist and taste to the fried rice. It is very filling dish for girl.
Tiramisu or "Pick me up" is one of the famous dessert in history. The chef used 3 type of coffee to make this dessert. Every bites I taste differently. What capture my attention is the cheese cream? It is very different. The cream is very fluffy yet creamy. It is very light on my taste bud. Usually Tiramisu cream have this very heavy texture. The chef have secret recipe for this.
Creme Brulee
It is very creamy. You can just let the cream play like a child before slowly slide down to the throat. At the bottom of the cup, there are many vanilla seeds. The Chef only use fresh vanilla for this dessert.
Chocolate Lava
70% dark chocolate. No word can express this dish. Allow me to use image to express my feeling.
There are a few girls go over crazy with this dessert. MUST TRY.
Ler's Reviews:
Halal?: No Pork No Lard, No Halal Cert
Halal?: No Pork No Lard, No Halal Cert
Service: 4/5
Delicious: 4/5
Parking: 5/5
(Less / No "saman" or traffic tickets on weekday. Ample of parking lots during night time)
(Less / No "saman" or traffic tickets on weekday. Ample of parking lots during night time)
18, Jalan Bedara,
Taman Melodies
80250 Johor Bahru,
07-335 5688
Operating Hour: 12.00 noon to 11.00 pm
Closed on Monday
Out of Topic
I was more attracted by the floor board. Couple or anyone can just dance on it without renting extra floor board.
Advantages of hosting a small event here
- Ample of parking lots
- No or less "Saman"/ traffic ticket if the event is on weekday (PS: no need to put parking coupon)
- KSL mall or hotel is just a few streets away.
- Good location ( near to Jalan Tebrau Lama or Jalan Kebun Teh)
- A private and cozy place for you to decorate during your events
- Delicious finger food/ food/tapas/canapes by experienced chefs
- Reasonable price
- All ingredients or food preparation have HACCP standard
- Free Wifi for your guests to immediately upload photos
For more information, please visit
Website: http://lemontreerestaurant.yolasite.com/
Facebook: https://www.facebook.com/pages/Restaurant-Lemon-Tree/157181411041060
Photo Credit to Aud and Carinn
Song dedication to everyone.


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- Case report
- Open Access
- Open Peer Review
Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report
- Hari Jayaram1Email author and
- Susan M Downes1
© Jayaram and Downes; licensee BioMed Central Ltd. 2008
- Received: 16 June 2007
- Accepted: 12 March 2008
- Published: 12 March 2008
Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.
Case presentation
We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.
It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.
- Phytanic Acid
- Retinitis Pigmentosa
- Visual Field Loss
- Autosomal Recessive Disease
- Night Blindness
Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations. We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.
Case presentation
Both brothers started a special RD diet and serum phytanic acid levels have been reduced significantly as a consequence. Although their visual impairment is unchanged, the younger sibling reported an improvement in his sense of taste and smell and neither sibling has shown any sign of neurological complications to date.
RP comprises a group of genetic conditions affecting 1 in 3000 to 4000 in the population, leading to progressive photoreceptor degeneration and visual loss [1]. RP is also seen as part of several syndromic conditions, some with severe neurological features. RD, Bassen-Kornsweig syndrome, vitamin E deficiency, and gyrate atrophy are examples of conditions within this group that are amenable to dietary modification that can influence the course of disease.
RD is an autosomal recessive disease with an incidence thought to be less than 1:250000, although the exact incidence and prevalence of the disorder in the general population is not known. Dietary phytanic acid (a branched chain fatty acid) accumulates within the body due to an abnormality in a mitochondrial enzyme phytanic acid α-hydroxylase [2]. The condition shows genetic heterogeneity with one locus on chromosome 10 [3] and a second located on chromosome 6 [4]. Phytanic acid accumulates in retinal pigment epithelium and other tissues and causes cellular death through calcium deregulation, free radical formation and apoptosis [5]. Phytanic acid is not only elevated in RD, but also in other peroxisomal disorders. However, these can be distinguished by molecular genetic analysis and clinical phenotype.
The clinical manifestations of RD affect the eyes, nervous system, bones and skin, and most patients are symptomatic before the age of twenty but may present as late as the fifth decade [6].
Bone spicule retinopathy is a universal and usually early sign in RD. Many patients have noticed night blindness prior to the onset of other symptoms and have constricted visual fields at presentation [6]. Cataract is also a frequent finding in almost 50% of all RD patients [6].
There is a symmetrical mixed motor and sensory polyneuropathy initially affecting the distal lower limbs, which is chronic and progressive in nature and usually preceded by visual symptoms. Many patients also exhibit cochlear hearing loss. Impaired sense of smell presents early in the disease and is thought to be a universal feature [7]. Cerebellar signs tend to develop later.
Bony abnormalities are seen in over a third of patients and tend to be symmetrical and bilateral in nature [8]. The short tubular bones of the hands and feet are most often affected, in particular the terminal phalanx of the thumb and the fourth metatarsal.
The skin can also be affected with rough scaly thickening seen over the extremities (ichthyosis) [9]. Cardiac abnormalities have also been reported, including cardiomyopathy and conduction disturbances, and may be responsible for causes of sudden death in RD [10]. Reports of cardiac arrhythmias, as well as neurological abnormalities indicate that Refsum patients should therefore be managed by a multidisciplinary team.
Treatment for RD is aimed at lowering the serum levels of phytanic acid. Phytanic acid comes exclusively from exogenous sources and hence dietary restriction of products rich in phytanic acid, such as dairy products and ruminant meats and fat, helps to control serum levels. Restriction of green vegetables has found to be unnecessary as chlorophyll bound phytol has poor bioavailability. Diets which are low in phytanic acid are extremely unpalatable and consequently regimens now include poultry, pork, fruit and vegetables [11].
Plasmapheresis [12] or lipopheresis [13] can be used in the event of acute arrhythmias or extreme weakness. Where dietary control has been inadequate, these treatments have been shown to help improve the clinical picture.
Maintenance of normal serum phytanic acid levels has been associated with improvement in motor nerve conduction velocities, ataxia and stabilisation of the progression of RP [14]. Retinal changes are usually irreversible and hence dietary regimens should be implemented as soon as the diagnosis is made.
RD is a potentially lethal and disabling disease, which is amenable to treatment. Brief neurological screening [15] and smell testing [7] of patients with RP have been suggested as possible strategies to identify those who require formal biochemical testing in order to increase the diagnostic yield of RD. Enquiry into the presence of "unusual" feet and hands, as with the cases we have described, may also help distinguish those patients with RD from those with RP alone. However, in view of the severity of the disease, and the fact that it is treatable, phytanic acid testing should be carried out in all cases of autosomal recessive or simplex RP. Early diagnosis of the condition and initiation of an appropriate diet is vital, in order to prevent disease progression and the subsequent development of severe neurological involvement.
Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Anne Bolton, Medical Photographer, Oxford Eye Hospital for acquisition of the clinical photographs.
Authors' Affiliations
- Haim M, Holm NV, Rosenberg T: Prevalence of retinitis pigmentosa and allied disorders in Denmark. I Main results. Acta Ophthalmol (Copenh). 1992, 70 (2): 178-186.View ArticleGoogle Scholar
- Eldjarn L, Stokke O, Try K: Alpha-oxidation of branched chain fatty acids in man and its failure in patients with Refsum's disease showing phytanic acid accumulation. Scand J Clin Lab Invest. 1966, 18 (6): 694-695. 10.3109/00365516609049057.View ArticlePubMedGoogle Scholar
- Mihalik SJ, Morrell JC, Kim D, Sacksteder KA, Watkins PA, Gould SJ: Identification of PAHX, a Refsum disease gene. Nat Genet. 1997, 17 (2): 185-189. 10.1038/ng1097-185.View ArticlePubMedGoogle Scholar
- van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJ: Identification of PEX7 as the second gene involved in Refsum disease. Am J Hum Genet. 2003, 72 (2): 471-477. 10.1086/346093.View ArticlePubMedPubMed CentralGoogle Scholar
- Kahlert S, Schonfeld P, Reiser G: The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes. Neurobiol Dis. 2005, 18 (1): 110-118. 10.1016/j.nbd.2004.08.010.View ArticlePubMedGoogle Scholar
- Skjeldal OH, Stokke O, Refsum S, Norseth J, Petit H: Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation. J Neurol Sci. 1987, 77 (1): 87-96. 10.1016/0022-510X(87)90209-7.View ArticlePubMedGoogle Scholar
- Gibberd FB, Feher MD, Sidey MC, Wierzbicki AS: Smell testing: an additional tool for identification of adult Refsum's disease. J Neurol Neurosurg Psychiatry. 2004, 75 (9): 1334-1336. 10.1136/jnnp.2003.026690.View ArticlePubMedPubMed CentralGoogle Scholar
- Plant GR, Hansell DM, Gibberd FB, Sidey MC: Skeletal abnormalities in Refsum's disease (heredopathia atactica polyneuritiformis). Br J Radiol. 1990, 63 (751): 537-541.View ArticlePubMedGoogle Scholar
- Ramsay BC, Meeran K, Woodrow D, Judge M, Cream JJ, Clifford Rose F, Gibberd FB: Cutaneous aspects of Refsum's disease. J R Soc Med. 1991, 84 (9): 559-560.PubMedPubMed CentralGoogle Scholar
- Leys D, Petit H, Bonte-Adnet C, Millaire A, Fourrier F, Dubois F, Rosseaux M, Ducloux G: Refsum's disease revealed by cardiac disorders. Lancet. 1989, 1 (8638): 621-10.1016/S0140-6736(89)91654-1.View ArticlePubMedGoogle Scholar
- Brown PJ, Mei G, Gibberd FB: Diet and Refsum's Disease. J Hum Nutr Dietet. 1993, 6: 295-305.View ArticleGoogle Scholar
- Harari D, Gibberd FB, Dick JP, Sidey MC: Plasma exchange in the treatment of Refsum's disease (heredopathia atactica polyneuritiformis). J Neurol Neurosurg Psychiatry. 1991, 54 (7): 614-617.View ArticlePubMedPubMed CentralGoogle Scholar
- Gutsche HU, Siegmund JB, Hoppmann I: Lipapheresis: an immunoglobulin-sparing treatment for Refsum's disease. Acta Neurol Scand. 1996, 94 (3): 190-193.View ArticlePubMedGoogle Scholar
- Gibberd FB, Billimoria JD, Goldman JM, Clemens ME, Evans R, Whitelaw MN, Retsas S, Sherratt RM: Heredopathia atactica polyneuritiformis: Refsum's disease. Acta Neurol Scand. 1985, 72 (1): 1-17.View ArticlePubMedGoogle Scholar
- Goldman JM, Clemens ME, Gibberd FB, Billimoria JD: Screening of patients with retinitis pigmentosa for heredopathia atactica polyneuritiformis (Refsum's disease). Br Med J (Clin Res Ed). 1985, 290 (6475): 1109-1110.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

subset: commoncrawl


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Among various industry events I have attended over the years, both within and beyond the oil and gas sector, marketing and public relations high jinks seen at the World Petroleum Congress can comfortably beat, not just rival, any event on the planet. The 21st round of the once-in-three-years shindig recently held in Moscow was no exception.
Often dubbed the Olympics of the oil and gas business, saw companies ranging from energy majors to services firms, financial advisers to equipment manufacturers, splash out a six or in some cases seven figure dollar spend to keep up the appearances and more for the event that ran from June 15 to 19.
You'd perhaps have to if over 5,000 delegates, 500 CEOs, 50 ministers, government officials, think-tanks, academics and not to mention half the world's press were around, and you wanted attention. Megabucks might be involved, but marketing gurus often begin with the basics. For instance, you couldn't walk 10 yards at the venue without the enticement of a free pen. After being tempted 74 times, alas I succumbed at the 75th when offered one with 'a converged flashlight' in anticipation of that day when I might need to pen my thoughts in a cave.
And of course, there was no shortage of branded erasers, magnets, stickers, coasters, mints, chocolates and my personal favourite – plastic replica rigs bearing the logo of some Middle Eastern oil and gas firm on them, but manufactured in a country that's becoming the prime energy exports destination, viz. China.
For an industry that's largely male, at times scruffy, usually middle aged for better or worse and not known for too much gender diversity, nearly all exhibition stalls had to be hosted by women dressed in a cacophony of colourful outfits, some skimpy, some traditional, some business like and almost always bright with no shortage of crests or logos.
If drinking water was sponsored by one advisory firm, another sponsored something perceptively more crucial – the free charging of smartphones! With everything from drill bits to pipes on display, one company decided to let delegates feast on a shiny Moto GP bike. Not to be outdone, another offered a Formula 1 racing car experience, albeit a virtual one but with some panache.
The accolade of PR strategy master class should surely go to
Away from branding, the usual suspects vied for attention for their respective briefings, with the content in each case nothing short of "exclusive" "groundbreaking" "revolutionary" "the next big thing" and of course, in case that was not enough to convince you, "the briefing would be followed by a cocktail reception."
The promise of a beverage extended well beyond the briefings. Occasionally, an old marketing contact would slip in an embossed card just before lunchtime. That crucial ticket was the difference between a mundane salmon sandwich on the Congress floor and a three course meal accompanied by something bubbly. Or to quote a new Russian acquaintance, "a choice between a VIP lunch or common man food". Surely, some sentiments got lost in translation there but you get the idea.
With many VIPs were around, there was the matter of conversational etiquette, and you can always count on PR personnel to help whether you want it or not. As the Russians were the hosts, the common PR request was not to "digress towards Ukraine". Being an insolent scribe, if you digressed there anyway like I did, the near-standard reply would be: "The Congress is a global event being held in Russia, not a Russian event."
Some 'inconsiderate folks' still didn't buy it. For instance, President Barack Obama made sure not a single high ranking US official turned up. The Canadian province of Alberta, stars of the last Congress in Doha, didn't "meaningfully participate in deliberations" while familiar faces from British, German and French policymaking circles were missing too.
However, PRs quickly and correctly, pointed out that the Chinese delegation was quite large. Make that very large, in fact the largest after the locals. Furthermore, senior ministers from Algeria, Angola, Cuba, Columbia, India, Israel, Kazakhstan, Kuwait, Nigeria, Norway, Pakistan, Saudi Arabia, Serbia, Uruguay, Columbia and Turkey (hosts of the next Congress) turned up. Surely, that's enough to be getting on with.
Should that not be enough, not a single boss or senior executive of any oil and gas heavyweight on the Forbes list of 500 biggest public listed companies was missing. In a 'needs must' geopolitically troubled sector, that was no surprise. Neither was the marketing and PR overdrive.


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The Little Blonde TruckBlondie's mobile unit brings freshly baked treats and made to order indulgences to you. Grilled Mac&Cheese Sandwich, anyone?
Book the Blonde Truck for a special event, private party, wedding, or corporate event.
Email: firstname.lastname@example.com
Or... check the events page or Blondie's Facebook feed to find out what local fairs and festivals the truck will be attending!
Event Calendar


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I am personally looking for two types of domains. I am looking for a few choice 5 letter dot coms and a few coloranimal.coms ie bluehorse.com or yellowmonkey.com. Remember I am a reseller not an enduser. If you are hoping to make big money on them I am not your person. I also am not looking to take advantage of anyone. If you're in love with the name, don't send it, I don't have enough money to break up your relationship. I am restocking my portfolio on the former and need the latter for a buyer that I am working with. There are few rules AND DO NOT POST YOUR NAMES IN THE COMMENTS only send them via email. I don't want the comments to turn into a classified section. Please send your asking price. My email is in the contacts or you can send them to [email protected] Take out the thisismyemailfor and ILovetoEatCake. Don't be upset if I don't respond to your email. Thank you in advance for taking the time to send me your names. If I am interested I will email you back. Or if I think your price is absolutely ridiculous in relation to your price I will email as well.
On the 5 letter here are my requirements
1. Don't send me more than 10 names. If you have more only send me your best.
2. They have to be easy to say and spell.
3. No domains that end in "I"
4. No acronyms.
5. examples of what I have and am looking for. Weeba, Bleeb, Dumpo,Fazzy, Happa, Hooku, Jukio, Ploob.
6. If it has three consonants in a row don't send it
For the color animal its pretty simple
Don't send animal then color and make sure it's an animal a 5 year old has heard of.


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It seems as though every new development nowadays is on the nano-scale, and this is no exception. Professors from the University of Munich and the University of Dresden have improved a method for the synthesis of polymer carpets.
|A Polymer Carpet
Polymer carpets are made by grafting styrene polymers onto copper supported graphene and these scientists have discovered that the carpet density and thickness depends on the hydrogenation of the graphene. Graphene is an incredible material, due to its versatility, but what makes it so useful as a support for making polymer carpets is how stable it is to mechanical and chemical influences. The team working on these carpets say that the 'Polymer carpets exhibit remarkable and unprecedented properties combining extreme thinness, mechanical and chemical stability, robustness, flexibility, and (chemical) sensitivity'. The chemical sensitivity mentioned by the team may sound like a flaw, but this actually means that the nature of the carpet (effectively its thickness, fluffiness or tangled-ness) can be fine-tuned with changes in conditions like the solvent quality, wetting and pH.
|Natural (left) and artificial (right) nacre
Polymer carpets are one of those materials that seem to be good at everything. They are similar to biological membranes, such as the outside layer of cells, but have the significant advantage of stability and the ability to withstand considerable pressure. This feature means they have been applied to use in water purification and desalination. Any developments in these fields are of huge importance globally and more research and discoveries in this field could make these polymer carpets a viable solution to the cleanliness of drinking water.
Another unsuspected use of these is in the synthesis of artificial nacre. If, like me, you don't know what nacre is, it is mother of pearl, the shiny inside coating of some seashells and the outer surface of pearls. Pearls have had many uses over the years, but these tend to be mostly decorative, in jewellery or furniture, but are beginning to be applied in more areas. The pearl is originally made as a surface to protect the molluscs' soft material from damage through bombardment and protection from parasites. Nacre is now being used as a novel material in medical surgery, as it has been shown to stimulate the growth of cartilage when injected into bones. The ability to make a Nacre alternative in the labs could prove to be advantageous, over having to source it from the sea.
Any improvements in the understanding of the mechanism or the synthesis of polymer carpets is useful, and allows a large step to be taken towards applications such as these, however the greatest use of these diverse materials could yet to be discovered.


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The best service provider:
Well, if you are going through this kind of problem and don't know where you find professional service then let you know we offer the best Sewer Pump Replacement service. We are one of the best leading service providers of recent times. We know how it feels when your pump does not work properly. And for this reason, we always strive to offer quality service that would leave you speechless. But still if you are thinking why you should hire us then let us explain.
- Professional tips & advice:
The first and foremost reason to hire us because you can get more than a simple fix or replacement. Our professional team will perform a thorough inspection to diagnose the main problem and replace your sump or sewer pump effectively. They will give you necessary advice as well as tips that would aid you in future. Thus, now you can not only avail sewer pump replacement service with us but also can have valuable tips of the professionals.
- A job well- performed:
To get quality service you should definitely hire us. Today's sump pump can be intricate, with wide electric systems and other components which mean for most homeowners, Sump Pump Replacement is not any DIY project. You will have to spend several hours or a whole day to determine the main issue. But we know how to fix it or replace it with efficiency. So, it will be better for you to trust on us because we offer the best replacement service that would make you feel happy.
So, whenever you need our assistance and guidance in matter of sewer ejector pumps then without hesitation call us. For more details, visit our official page.


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The relentless beatings in Europe have taken a break for the day, as major indices surge to their highs of the morning.
Germany is up about 3.7%.
France is up 2.8%.
Italy is up 3.1%.
The only big "news" of the day is the German high-court ruling about the legality of bailouts, along with Merkel's insistence on defending the Eurozone, even if that means amending the Treaty.
Meanwhile, gold is tanking, and is down to $1820. That's about $100/oz lower than it was yesterday morning.
A little more that might be helping things right now: The Bank of Canada just came out sounding dovish, saying the need to withdraw monetary stimulus had clearly diminished.
Get the latest Gold price here.


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an unfinished quilt
a few months ago, i turned 40. it was like most birthdays, no revelation. i felt good about it. as i do on most birthdays (yay, another year alive!). a little nostalgic, a little hopeful. i consider birthdays my personal new year, and 40 feels really good to me.
so. i don't even know how to get into this. or honestly where to take it. it was going to be a post about finishing a quilt. but i feel like you deserve some back story. i guess the start of it is, i don't speak with my father. it's a long drawn out thing, that mostly has to do with my questioning his humanity (too dramatic?). i didn't grow up with him. he has another family. he treated my mother questionably (when they were mere children) and when i moved up to the northwest to get to know him, there wasn't much of that happening, and then he said some not nice things. it's never how you imagine it- people are who they are. it was no happy reunion, gushing about life, and catching up. we didn't all click, and i've put it aside. it's… as it is, and how it will be for the foreseeable future.
10 years ago, my grandmother died. she had alzheimer's. i don't remember how i felt at the time. a little relieved for her, upset, of course. but i was going through a lot personally, and the idea of traveling to her funeral felt overwhelming. i felt numb about a lot of things at that time. i was working a job i hated, i had migraines 24/7, and a doctor had just told me i potentially had an aneurism in my brain that was in a mostly inoperable place. it wasn't my best year.
my grandmother holds a vast amount of my childhood memories. my parents were divorced a year after my birth- my mother, the ripe age of 18 (dude.). she worked, and was probably trying to finish her ged? having kids now, and having some perspective, she probably just needed a break now and then, and my father's parents lived in our town. i spent a lot of time with them. i adored them. i have amazing memories of the two of them indulging a 3-4 year old little girl with her (mostly modest) heart's desires. my grandpa took me on his errands, and i was always allowed some indulgence. i had the run of my grandma's closet, clothes, jewelry- i'm sure it's why i'm the clothes hoarder i am present day. and fabric! my grandma had had her own sewing store as a business, in our very small town, and she had a room dedicated to sewing and fabric, and making. another direct influence, surely.
she was a quilter. i have several blankets she made me. one a baby quilt, that although much worn, is a treasure. i remember being small and seeing her quilts, and being amazed. they were big. voluminous. warm. and above all… colorful. i don't know if it was the time, or her taste, but she didn't shy away from color. i don't remember her house being that way. but her quilts were…on the verge of bold, even.
anyway- all of this to get to this snippet of the tale. on my 40th birthday, my stepmother texted. she said she was going to send me something. which seemed…unexpected.
it came and i opened this… box. it's an unfinished quilt. and as i opened the ziplock bag, that holds the entire thing, this smell, my grandma, came at me. i sat in my car with my face buried in this bag, and cried. 10 years. i miss her like she died last week. i miss her from 20 years ago, when her sharp mind started failing. her letters from that time that i've read, and reread, that i wish i would have been older to write back to. to cherish them for what they were… lovely words from this woman who loved me beyond reason. i sat there, staring into this bag of fabric. and i slowly started putting together that this quilt… is of poppies. it's a poppy quilt.
a woman (named pansy) probably over 40 years ago, started making a poppy quilt- cut, pieced, basted, ready to start assembly. her grand daughter was born (me). she made zillions of other quilts. baby quilts for her grand children. wedding quilts for people getting married. she sewed until she couldn't any longer. she became sick when i was a teenager, into my 20's. to die when i was 29. she left a deep mark on my heart and mind. the only consideration when naming my daughter was that she would have a flower name, for my grandma. and we chose poppy. two years later, ten years after her death, i receive a quilt that she started but didn't finish all those years ago… a poppy quilt.
it's an odd thing. i don't have many of her belongings, not being that close with the rest of that family. i have a couple trinkets that i took, mostly without asking. i have a few of her sewing things that my grandpa offered- they are treasured, and used almost daily. i have some clothes that a cousin bestowed, and i have a necklace that means very little to me. my aunt, another broken person, in ways i didn't understand, had treasure that i would have sold my arm for. quilts, i'm sure. photos. jewelry. my grandmother's engagement ring maybe. all of those things lost, due to her sickness. gone. my grandmother's quilts. and when i found out everything was gone, i was bereft. inconsolable. mostly about blankets. that one would never come to me. made by her hands.
and suddenly, unexpectedly, one shows up to my door. it's funny how what you ask you for, you get in ways you never expected. i wanted more than anything one of her quilts. to have in my home, to use. to think of her, and think of her making it. and now we'll have one that we worked on together. i love that. and i love her for bringing it to me all these years later. xoxo- k.


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Start: Wednesday, July 3
Hand in: Friday, July 12
Group Project
Counts for 15% of final grade.
In this assignment, you will practice using the Contextual Inquiry and Design techniques. Unfortunately, we won't be able to do a "real" contextual inquiry of someone performing a real task. As a stand-in, you will perform a contextual inquiry of one of your classmates performing a task that is similar to ones for your project.
Check list of what to turn in:
Please turn in a hardcopy printout of the report, and email a copy to the TA.
Back to Homework overview
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As waves of German-American settlers moved into the Piedmont of North Carolina in the early 1800's, they began to form congregations of worship. St. Stephens was the fifth Lutheran church in Catawba County when it was organized in 1837. Originally called Miller's Lutheran (for the land benefactor), the congregation went thru two splits before the church evolved into the three churches that are now located on the original church land: St. Stephens ELCA, Miller's NALC, and St. Stephens Missouri Synod.
The timeline going forward for our congregation includes:
1909 - One hundred members dedicated a sanctuary.
1935 - Our first full time pastor was hired (prior pastors were shared with other parishes).
1952 - Our Scout Hut was constructed for the Boy Scouts.
1955 - Our current sanctuary was dedicated.
1962 - Our current educational/recreation building was dedicated.
1980 - Our current chapel was dedicated.
1994 - Our church vans were purchased.
1997 - Our picnic shelter was completed.
We have deep connections with the founding of the Trinity Village Assisted Living / Skilled Care Facility (which sits west of our property). The Via de Cristo renewal movement has a strong presence in the lives of our members. In addition, our parish has a strong outreach to both our local Hickory community and to world-wide relief efforts.
We have two Sunday worship services: A Contemporary Worship service in our chapel at 8 am and Traditional Worship service in our sanctuary at 10:30 am. Our major emphasis on Christian Education continues with Sunday School for all ages at 9:15 each Sunday.
God has continued to richly bless our efforts and our ministries; forging strong bonds of friendship and community among our members as we continue God's work in the Hickory area. God is good!


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Anne Glancey didn't have the money to repair her deteriorating house, nor did she have the family or friends to help her do it – until one day her neighbors decided to fix it themselves.
MORE: Beloved Town Dog Has Made 4-Mile Trek Every Day For 10 Years Just to Visit Neighbors
Anne's neighbors, Adam and Kristin Polhemus, were the first people in the community to reach out to the hermit. When they learned of her financial dilemma, they took matters into their own hands.
Every summer weekend, Kristin and Adam would recruit their family, friends, and neighbors to join them in fixing Anne's house.
In lieu of the constant stream of helpers, Anne even came out of her shell to serve orange juice and homemade carrot cake to the volunteers.
RELATED: Neighbors Clean Up Vandalism Before Family Returns From Vacation
By the end of the August, the home was completely transformed and the code violations were dropped.
"To see the joy on our neighbor's face, I think the biggest thing is Anne's happiness and her kind of restored life," Adam told People. "Her outgoingness to other neighbors is based on her house being improved."
Don't Be Shy: Click To Share – Photo by Kristin Polhemus


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Friday Updates
*I'm told that Cuban defector Reinier Alcantara will begin workouts with Chivas USA next week. He previously had trained with Kansas City.
*Alexi Lalas speaks out about Becks, Arena and the Galaxy.
*D.C. United midfielder Ivan Guerrero has been recalled by Honduras for its crucial World Cup qualifier against Mexico Nov. 19 in San Pedro Sula.
*Russian superstar Andrei Arshavin wants out of St. Petersburg.
*USA defender Carlos Bocanegra chats with FIFA.com.
*Virginia and Virginia Tech meet in the ACC women's semifinals at 7:30 tonight.
*The USSF is accepting nominations for America's best soccer bar, store, video, blog and fan photo.
Back later with the weekend TV listings.....
Steve Goff
November 7, 2008; 2:02 PM ET
Categories: Beckham , College Soccer , MLS , U.S. men's national team , World
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I'm putting out the lawn signs right now:
Vote for Soccer Insider. A Blog We Need
I'm working on the campaign speech:
Who is this Ives Ahmadinejad Chavez Jong-Il Galarcep. He doesn't see soccer the way you and I see soccer.
And my friends at ACORN are working on voter frau... ummm registration.
Posted by: I-270Exit1 | November 7, 2008 2:29 PM | Report abuse
I think that Lalas' comments are probably the first he's said in a very long time that I can somewhat agree with.
Posted by: TCompton | November 7, 2008 2:54 PM | Report abuse
Lala probably had a shut-up clause in his contract that lasted until the end of the season, which for the Gala ended early.
Posted by: IamAM | November 7, 2008 5:22 PM | Report abuse
UVA has an early 1-0 lead over the Hokies.
Posted by: sitruc | November 7, 2008 7:57 PM | Report abuse
UVa has controlled much of the match and hit the posts, but it is 1-1 right now.
Posted by: sitruc | November 7, 2008 9:03 PM | Report abuse
Carden and the Hokies won another match after PKs. Carden saved four of the PKs.
Posted by: sitruc | November 7, 2008 10:05 PM | Report abuse
It will be interesting to see how the Hokies do against the Albicelestes on Sunday. (As someone noted in a separate thread, it will be shown live on CSN.)
In other NCAA women's action, Navy got by Colgate. They have to beat Army on Sunday, period. There is no way the Patriot League will get a second berth. W&M and JMU were both upset in the CAA semis, so the winner of Hofstra-Northeastern gets the automatic bid. The CAA may get a second invite, or possibly even a third, so W&M and JMU are on the bubble. WVU got knocked out of the Big East tournament at the semifinal stage, but they should get a bid, as should Georgetown.
In area NCAA men's action, GWU and GMU won, probably putting them in the middle of the seeds for their respective conference tournaments next weekend. And of course, Maryland beat the other Albicelestes, while Virgina lost to Wake Forest.
Posted by: universityandpark | November 8, 2008 11:07 AM | Report abuse
I'm confused by all these Albicelestes. ho's playing Argentina and who's playing the New Jersey WPL team?
Posted by: I-270Exit1 | November 8, 2008 6:14 PM | Report abuse
The comments to this entry are closed.


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16 April, 2011
1 Comments:
- shrutanne said...
write a poem about an overused word.
Anyways. This poem
is about Anyways.
Anyways is such a cliche
Let's write a poem about Anyways
Anyways to drop the subject
and anyways to change the topic
of Anyways.
Anyways is my boredom
Anyways is incomprehension
Anyways is anticipation
of rejection. Anyways.
Anyways expresses everything
without needing expression.
Anyways is not a lexical word anyways.
But who cares? Anyways is "our" word
Anyways so I decided to write a poem
about the delightfulness of Anyways. Anyways


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- Review
- Open Access
Peripheral mechanisms of neuropathic pain – involvement of lysophosphatidic acid receptor-mediated demyelination
- Hiroshi Ueda1Email author
© Ueda; licensee BioMed Central Ltd. 2008
- Received: 18 February 2008
- Accepted: 01 April 2008
- Published: 01 April 2008
Recent advances in pain research provide a clear picture for the molecular mechanisms of acute pain; substantial information concerning plasticity that occurs during neuropathic pain has also become available. The peripheral mechanisms responsible for neuropathic pain are found in the altered gene/protein expression of primary sensory neurons. With damage to peripheral sensory fibers, a variety of changes in pain-related gene expression take place in dorsal root ganglion neurons. These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications – decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions. Another characteristic change is observed in allodynia, the functional change of tactile to nociceptive perception. Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms. Because neuropathic pain in peripheral and central demyelinating diseases develops as a result of aberrant myelination in experimental animals, demyelination seems to be a key mechanism of plasticity in neuropathic pain. More recently, we discovered that lysophosphatidic acid receptor activation initiates neuropathic pain, as well as possible peripheral mechanims of demyelination after nerve injury. These results lead to further hypotheses of physical communication between innocuous Aβ- and noxious C- or Aδ-fibers to influence the molecular mechanisms of allodynia.
- Neuropathic Pain
- Myelin Basic Protein
- Dorsal Root Ganglion Neuron
- Mechanical Allodynia
- Spinal Dorsal Horn
Chronic pain should be considered to be a disease rather than just a symptom, because it is one of most common reasons for hospital visits. Although recent advances in molecular biology techniques, and the subsequent discoveries of key molecules involved in pain production, have clearly contributed to better understanding acute pain [1–4], the molecular mechanisms underlying chronic pain remain to be fully clarified.
Chronic pain, or specifically neuropathic pain, is quite different from other types of pain, such as nociceptive (or physiological) or inflammatory pain, because it is irreversible, even when the underlying cause has been rectified [2]. For this reason, the proper diagnosis and early treatment are often difficult. Moreover, neuropathic pain commonly occurs as a secondary symptom in diseases, such as diabetes, cancer, and herpes zoster infection, or as a side effect of chemotherapeutic treatments [3, 5–7]. Neuropathic pain is often characterized by stimulus-independent persistent pain or abnormal sensory perception of pain, such as allodynia (pain perception upon the innocuous tactile stimuli) and hyperalgesia (exaggerated pain sensations by mildly noxious stimuli) [3, 8]. To treat chronic pain, we must first understand the initial and sustained molecular events in experimental animal models. Because the central mechanisms of sustained molecular events, which are closely related to memory in the brain, have been described in elsewhere in detail [9, 10], this review focuses on peripheral mechanisms of initial events from nociceptors to the spinal dorsal horn.
Approaches to study plasticity in nociceptor endings
Neuropathic pain occurs as a consequence of complex sensory dysfunction and may differ depending on the type of insult and the individual patient. Furthermore, due to the dynamic nature of the pain system, signs and symptoms of neuropathic pain change over time. Injury to peripheral nerves causes functional and biochemical changes at the site of injury, as well as to other areas of the affected nerve, and later to higher order neurons in the spinal cord and brain [3, 8–12]. Nociceptor endings cause a generator potential, which leads to an action potential in polymodal C and mechanothermal Aδ fibers [1, 13]. These action potentials are then conducted to higher centers in the central nervous system (CNS) via neurotransmitter release and are accompanied by a variety of responses, including withdrawal reflexes, conscious perception of pain, and emotional effects. The pain signal, on the other hand, drives the descending noradrenergic and serotonergic pain-inhibitory systems from the lower brain stem to the spinal dorsal horn [14]. Therefore, chronic neuropathic pain is a result of problems in ascending pain transmission or descending pain-inhibitory system.
The identification of mechanisms or key molecules related to hyperalgesia and allodynia in neuropathic pain could be elucidated by studies using antisense oligos, RNA interference (RNAi), or transgenic (KO) mice lacking specific genes. However, these approaches present difficulties, such as: 1) intrathecal treatments with antisense oligo or RNAi cannot specify whether the action site is on sensory fibers or the spinal cord, although some studies have demonstrated dorsal root ganglion (DRG)-specific down-regulation [15, 16]; 2) the availability of specific KO mice is limited, and functional compensation during development and growth may modify the roles of the genes involved; and 3) the availability of conditional KO mice is even more limited. Considering this, as an initial attempt to survey key molecules responsible for neuropathic pain, we have developed novel nociception tests to measure algogenic-induced paw flexion (APF) [3].
Pharmacological plasticity in neuropathic hyperalgesia
Our laboratory has developed a highly sensitive and minimally stressful nociception test (APF test) in mice [3]. In this test, the mouse is held in a hammock-type cloth sling, which is suspended from a bar, and nociceptive responses (in force) that are induced by intraplantar injection of a receptor ligand or algogenic substance can be measured. The APF test has proven to be advantageous for the study of in vivo pain signal transduction at peripheral nerve endings and has enabled the characterization of pain induction through nociceptors on C- or Aδ-fibers. In vivo signal transduction can be studied through the use of pharmacological methods using intraplantar treatments with various inhibitors and intrathecal pretreatments with antisense oligodeoxynucleotide (AS-ODN). The AS-ODN treatments are intended to determine whether the action site of compounds (i.pl.) reside on nociceptor endings or on non-neuronal peripheral cells.
Pharmacological studies have shown that the nociceptive fibers are responsible for various algogenics actions, which can be divided into three groups [17]. Neonatal pretreatment of capsaicin degenerates unmyelinated C fibers, polymodal nociceptive fibers [18–20]. Spinal antagonism, using receptor antagonists for substance P (SP) or glutamate, is another way to characterize nociceptive fibers. The use of neonatal capsaicin-sensitivity and spinal antagonism enabled us to pharmacologically categorize algogenic-induced nociceptive flexor responses into three groups [17]: 1) subcutaneous (s.c.) capsaicin-pretreatment and/or intrathecal (i.t.) pretreatment with NK1-type SP receptor antagonist abolished nociceptive responses to bradykinin (BK), SP, and histamine (His), which are representative chemical mediators; 2) ATP-induced responses were abolished with pretreatments of neonatal capsaicin (s.c.) or NMDA receptor antagonist (i.t.), but not by NK1 antagonist (i.t.); 3) PGI2 receptor agonist-induced responses were not affected by neonatal capsaicin, but were abolished by the NMDA antagonist. Therefore, we proposed that C-fibers could be further divided into two groups: peptidergic type 1 (SP-containing) and non-peptidergic type 2 (P2X3 receptor-expressing) C-fibers. This proposal is similar to the schematic model proposed by Snider & McMahon [21], who report two groups of C-fibers with differential gene (or protein) expression. This sub-classification of C-fibers is anatomically supported elsewhere [22]; only 3% of P2X3 receptor-positive neurons co-existed with SP in rat DRG neurons. Our proposal suggested a third group (type 3) of nociceptive fibers that may be related to myelinated A(δ) fibers, as opposed to C fibers [3].
Partial injury to peripheral nerves has been used to generate representative experimental animal models for neuropathic pain [23], where remarkable functional and molecular changes are observed. The injury-induced expression of Nav1.3 in large (A-fiber) DRG neurons [24] is thought to be one of the mechanisms underlying the hypersensitivity. We have also observed injury-induced appearance of TRPV1 and B1-type BK receptors in N52 (an A-fiber marker)-positive DRG neurons [15, 25]. Neuropeptides, such as galanin, neuropeptide Y (NPY), and pituitary adenylyl cyclase activating polypeptide (PACAP), which are normally expressed at low levels in sensory neurons, are dramatically increased in DRG neurons, including medium to large size neurons (A-fibers) [26–29]. Recently, a paper described reduced neuropathic pain in mice lacking PACAP [27]. Nevertheless, the up-regulation of these neuropeptides is not always the mechanism intrinsic to neuropathic pain. NPY-null mice exhibit autotomy-like biting behaviors [30], augmentation of neuropathic pain is observed in NPY Y1 receptor-null mice [31], and i.t. injection of NPY inhibits neuropathic pain [32]. Similarly, neuropathic pain is decreased in transgenic mice overexpressing galanin, and augmented in galanin receptor 1-null mice [33, 34]. On the contrary, some molecules, such as substance P [28, 35], Nav1.8, and Nav1.9, are down-regulated [36, 37]. These modifications may be generalized functional switches of C-fibers to A-fibers, as evidenced by the down-regulation of C-fiber mechanisms and the up-regulation of A-fiber mechanisms [3].
Sensory fiber-specific plasticity in neuropathic allodynia
Allodynia is the best target to investigate molecular mechanisms underlying neuropathic pain. In the APF test, hypoalgesia could be characterized through peptidergic C-fibers and A(δ)-hyperalgesia, another feature of neuropathic pain. This test mimics the physiological event where, upon exposure to noxious stimuli, chemicals are secreted in the vicinity of nerve endings to stimulate these nociceptive fibers. However, because the peripheral nerve terminals of innocuous Aβ fibers, which are thought to mediate allodynia, are covered by nonneuronal supporting cells, and protected from chemicals, different nociception tests are needed to characterize Aβ-fibers.
Matsumoto et al. [38] also confirmed frequency-specificity with a pharmacological study; neonatal capsaicin treatments to cause a damage of C-fibers eliminated LF-stimuli-induced nociceptive behavior, but not MF- or HF-stimuli-induced behaviors. These results suggest that nociceptive behavior from LF-stimuli is a result of C-fiber stimulation, while MF- or HF-stimuli-induced behavior is due to A-fiber stimulation. Furthermore, MF-stimulus to the finger results in sharp pain (prickly feeling), while HF-stimulus causes an unpleasant vibrating perception (light tickle).
Further pharmacological characterizations strengthened the validity of behavioral studies using Neurometer® [38, 44]. Both NK1 and NMDA receptor antagonists inhibited LF-stimuli-induced nociceptive responses; NMDA receptor antagonists inhibited MF-responses, while AMPA/kainate (non-NMDA) receptor antagonists specifically inhibited HF-induced behaviors (Fig. 1c), which is consistent with previous reports [45]. The characteristics of pain behavior were consistent to those obtained with the measurement of neuron-specific phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK). Studies [46]have shown that LF-stimuli induced neuronal p-ERK signals at the spinal dorsal horn (lamina I and II) were inhibited by NK1 and NMDA receptor antagonists, while MF-induced signals (lamina I) were specifically inhibited by the NMDA receptor. Moreover, HF stimuli resulted in no signal in the spinal cord. Thus, it seems likely that LF-stimuli causes C-fiber stimulation, while MF- or HF-stimuli causes nociceptive A(δ) or innocuous A(β)-fiber stimulation, respectively, in naïve animals and humans. It is unlikely that cutaneous application of high frequency (250 or 2000 Hz) electrical stimuli is capable of completely stimulating sensory fibers at the same frequency. Koga et al. [41] reported ~3 Hz C-fiber, ~22 Hz Aδ-fiber, and ~140 Hz Aβ-fiber responses after 5, 250, and 2000 Hz stimulation, respectively; these responses are similar to physiological levels [47].
Functional mechanisms influencing neuropathic allodynia
According to the previous hypothesis for neuropathic allodynia, nerve damage results in a retraction of C-fibers and allows for intrusion of A-fibers to the newly created space and loss of C-fiber pain transmission. This hypothesis was originally proposed with anatomical studies that demonstrated that nerve transection produces central sprouting of large fibers from deep laminae to lamina II [48, 49]. Although nerve injury-induced intrusion of Aβ-fibers to the superficial dorsal horn layers has not been well documented, this hypothesis received functional support through electrophysiological studies [50].
Behavioral studies (APF test) have determined a loss of peptidergic C-fiber responses after nerve injury [25, 35]. The down-regulation of C-fiber specific molecules, such as Nav1.8 and 1.9 [36, 37] and bradykinin B2 receptor [15], could be responsible for this type of neuropathic pain. The down-regulation of pain transmitter SP in the dorsal horn of spinal cord could be another mechanism [3, 35, 51]. Because SP precursor preprotachykinin (PPT)-null mice continued to exhibit neuropathic pain, the loss of peptidergic C-fiber function may not be significant stimuli to cause nociceptive behaviors. Alternatively, up-regulation of NK1 receptor expression in the spinal cord [52] may counteract the threshold change.
On the other hand, hypersensitization or allodynia upon innocuous stimulation has been studied. These studies demonstrated, in particular, the up-regulation of large-fiber-specific molecules [15, 24, 25, 27]. Although these changes may be responsible for neuropathic hyperalgesia, they cannot explain the mechanism of allodynia. The novel method using the Neurometer® clearly demonstrates Aβ-fiber stimulation-induced nociceptive flexor responses [38]. Following partial sciatic nerve injury, LF-stimuli-induced behavioral responses were significantly inhibited in the EPF test, while MF-stimuli-induced responses were enhanced [38]. These results are in accordance with studies using the APF test to determine that peptidergic C-fiber responses were lost, while Aδ-fiber responses were hypersensitized [25]. It should be noted that similar injury-specific hypersensitization was also observed with HF-stimuli [38, 44], which should stimulate innocuous fibers in naïve mice. Consistent results were also observed when neuronal p-ERK signals were measured at the spinal dorsal horn [46]. Most interestingly, HF-stimuli generated significant p-ERK signals at the spinal cord lamina I and II after nerve injury. Pharmacological characterization after the injury also verified the plasticity that HF-stimuli (Aβ)-induced spinal transmission is mediated by NMDA receptor, but not by non-NMDA receptor [44, 46].
Thus, functional changes following nerve injury suggest that two molecular events are taking place: communication between different sensory fibers and C-fiber retraction. Demyelination, and subsequent physical cross-talk, might be the mechanism responsible for neuropathic pain, because many demyelinating diseases accompany chronic pain, as with Guillain-Barre syndrome [53], Charcot-Marie-Tooth type I disease [54], and multiple sclerosis [55]. Indeed, it has been reported that neuropathic pain develops as a result of aberrant myelination (splitting, detachment, and loss of myelin) in mice deficient in the myelin protein periaxin [56]. However, little is known of the molecular events causing demyelination in the diseases that accompany neuropathic pain.
Lysophosphatidic acid (LPA) mimics nerve injury-induced neuropathic pain
A number of pharmacological studies suggest that lysophosphatidic acid (LPA) might cause neuropathic pain and demyelination following partial sciatic nerve injury. LPA is one of several lipid metabolites released after tissue injury, as well as from various cancer cells [57–59]. LPA receptors activate multiple signaling pathways and multiple G-proteins [60–64]. Direct stimulation of peripheral nociceptor endings by LPA, through LPA1 receptors, also suggests a role in nociceptive processes [65, 66]. Of particular note, receptor-mediated LPA signaling via Gα12/13 activates the small GTPase RhoA [63, 64, 67]. In the active state, Rho is translocated to the plasma membrane and thereby relays extracellular signals to multiple downstream effectors, including Rho-kinase or ROCK, which can be inhibited by the pyridine derivative compound, Y-27632. Inhibition of the Rho pathway can also be accomplished by selective ADP-ribosylation of RhoA, using Clostridium botulinum C3 exoenzyme (BoTN/C3). The involvement of Rho-ROCK system in neuropathic pain mechanisms was initially demonstrated by i.t. injections of BoTN/C3 prior to peripheral nerve injury in mice, which blocked the development of hyperalgesia [68]. LPA receptors and LPA receptor gene expression activates Rho in peripheral nerves [69–71], which suggests that LPA receptors might pathophysiologically activate Rho in neuropathic pain states of peripheral nerve injury. An interesting study illustrated that LPA inhibits the filopodia of growth cones [72]. LPA could be involved in C-fiber retraction, which is a hypothesis supporting functional changes induced by neuropathic pain. Together, these findings present LPA as an attractive signaling molecule in the development of neuropathic pain.
Indeed, a single i.t. injection of LPA produced marked mechanical allodynia and thermal hyperalgesia that persisted for at least 7–8 days before returning to baseline levels at day 13 [73]. Sphingosine 1-phosphate (S1P), which signals through S1P receptors and shares similar signaling pathways with LPA receptors [63], did not produce mechanical allodynia after i.t. injections in mice. These findings, therefore, highlight the specificity of LPA. Further studies have shown that LPA-induced thermal hyperalgesia and mechanical allodynia could be blocked by BoTN/C3 (i.t.) and Y-27632 [73]. In addition, LPA decreased the peptidergic [35], but not non-peptidergic C-fiber responses, but markedly increased A(δ)-fiber responses in the APF test, which strongly suggests that LPA mimics partial sciatic nerve injury by causing neuropathic pain [25].
Ex vivo studies of LPA-mediated demyelination
Involvement of LPA1-signaling in nerve injury-induced neuropathic pain
LPA acts through G-protein-coupled LPA receptors, designated LPA1, LPA2, LPA3, and LPA4, each exhibiting different G protein interactions [63, 64]. However, only the lpa1 receptor gene is expressed in both DRG neurons and dorsal root [73]. LPA1-null mice reversed LPA-induced demyelination, as well as mechanical allodynia [73]. Furthermore, LPA1 receptor-mediated demyelination was evidenced by down-regulation of myelin-associated proteins, such as MBP and peripheral myelin protein 22 kDa (PMP22), in the dorsal root after LPA injection or peripheral nerve injury. These changes were identical to nerve injury changes resulting in neuropathic pain. Indeed, LPA1-null, reversed nerve injury-induced neuropathic pain and demyelination, as well down-regulation of myelin proteins and up-regulation of A-fiber Cavα2δ-1 and spinal PKCγ [73].
Nerve injury-induced de novo LPA biosynthesis
LPA as an initiator of nerve-injury-induced neuropathic pain
Neuropathic pain behavior at day 14 was absent after pretreatment with AS-ODN for LPA1, but not with later treatments that started at day 7 post-injury [73]. Neuropathic pain was also blocked when BoTN/C3 was administered within 1 h post-injury. A time-course study using Ki-16425, a short-lived LPA1 antagonist [86] revealed that LPA1 receptor signaling was found to terminate within 3 h following injury (Lin and Ueda et al., unpublished data). These findings suggest that de novo-produced LPA after nerve injury might initiate various mechanisms of neuropathic pain through the LPA1 receptor [73].
Working hypothesis for LPA1 signaling initiating neuropathic pain
Future direction
Neuropathic pain is thought to become worse with time, if not appropriately treated. This present review proposes initial mechanisms at the level of peripheral nerves following nerve injury. The development of agents to block enhanced pain transmission is an important therapeutic direction for research. It would be important to target the crosstalk between noxious and innocuous fibers after demyelination to cure or prevent neuropathic pain. Sustained mechanisms could occur at the spinal and supraspinal levels. Plasticity or reorganization of neural networks in pain and pain-inhibitory pathways could make treatment more problematic. Pain induces pain in a vicious circle. Complete blockade of the plasticity responsible for neuropathic pain at the initial stage and at the peripheral level might be an appropriate strategy.
I thank Makoto Inoue, Ryousuke Fujita, and Misaki Matsumoto for kind help in preparing this manuscript. This study was supported by Special Coordination Funds of the Science and Technology Agency of the Japanese Government and Grant-in-Aid from the Ministry of Education, Science, Culture and Sports of Japan and Human Frontier Science Program.
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'World's fastest man' Usain Bolt to compete at USA vs. The World at the Penn Relays
Vicky Oddi
Communications Coordinator
USA Track & Field
INDIANAPOLIS - One of the world's most celebrated and recognizable athletes, Jamaican sprinter Usain Bolt, will compete April 24 at the 2010 USA vs. The World at the Penn Relays at historic Franklin Field in Philadelphia. Widely recognized for its unrivaled history and tradition, the Penn Relays Carnival is one of the oldest and longest-running trackand field events in the world.
The first event of USA Track & Field's 2010 Outdoor Visa Championship Series, USA vs. The World at the 116th Penn Relays will be televised on ESPN2 on Saturday, April 24, from 8-10 p.m. Eastern Time.
Bolt, who will compete for Jamaica in the 4x100m relay at Penn, was named the IAAF 2009 World Athlete of the Year for the second year in a row after winning the 100m and 200m finals in world record times at the World Outdoor Championships in Berlin, which matched his sprint double at the 2008 Beijing Olympics. Bolt's finals performances in Berlin, 9.58 in the 100 meters and 19.19 in the 200m, bettered the world records he set in the Olympic finals in Beijing of 9.69 and 19.30.
Also known for his prowess in relay competition, Bolt teamed up with his Jamaican compatriots Steve Mullings, Michael Frater and Asafa Powell in winning the men's 4x100m relay gold medal at the 2009 World Outdoor Championships in the meet record time of 37.31 seconds. He was part of the Jamaican world-record setting 4x100m relay at the 2008 Olympics as well (37.10).
In its remarkable 10-year run, where Team USA has won 50 of the 60 races contested throughout the series, USA vs. The World has provided countless thrills and unforgettable moments in front of many of the largest crowds in the glorious history of The Penn Relays. The event has featured such all-time greats as Michael Johnson, Allyson Felix, Maurice Greene, Sanya Richards, Bernard Lagat, Lauryn Williams, Tyson Gay, Torri Edwards, Angelo Taylor and Carmelita Jeter. USA vs. The World since 2000 has brought the best relay teams from around the globe to Philadelphia to compete at one of the world's premier track and field events. Participating countries have included Jamaica, Trinidad and Tobago, Great Britain, Russia, Australia, Canada, France, Saudi Arabia, Zimbabwe, Netherlands Antilles, Kenya, Germany, Bahamas, South Africa and Nigeria among others.
To purchase tickets for the 2010 USA vs. The World at the Penn Relays, dial the Penn Relays' 24-hour hotline (1-888-PENN-TIX...USATF welcomes you to pay with your Visa) - or visit: http://www.thepennrelays.com.
For more information on the 2010 USA vs. The World at the Penn Relays and the 2010 Visa Championship Series, visit: www.visachampionshipseries.com


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Mets' Yoenis Cespedes day-to-day with right wrist soreness— March 13, 2018
PORT ST. LUCIE — Mets left fielder Yoenis Cespedes was scratched from the first game of Tuesday's split-city doubleheader due to right wrist soreness. He is day-to-day, according to a team release.
"In last Tuesday's game (against Houston at First Data Field), I made a swing and I felt something on my wrist. I didn't care much about that," Cespedes said through a translator while seated at his locker Tuesday. "I felt with the day off (Monday), it will be good for today but it isn't." Cespedes said he felt wrist pain again Tuesday morning.
Cespedes, 32, said he had X-rays taken of his wrist Tuesday morning, but he had not learned the results as of 12:10 p.m. Tuesday, when the clubhouse access ended. He was originally listed in the early lineup card for the afternoon game against the Astros that was posted in the clubhouse Tuesday morning. Phillip Evans replaced Cespedes in left field for the day game, and is batting sixth. Jay Bruce took over the No. 2 spot in the batting order, which is Cespedes' customary spot.
The Mets will travel to West Palm Beach to play the Nationals Tuesday night following the day game.
Zack Wheeler still making Mets debate makeup of pitching staff
Mets general manager Sandy Alderson said of Cespedes that it's "nothing serious" prior to the team release.
Earlier this spring training, Cespedes said he was giving up playing golf on the side since he wanted to devote himself to trying to remain healthy through the grind of a 162-game campaign. Cespedes has come under criticism for his golf hobby ever since he revealed his love for the links after joining the Mets in 2015. He also said during spring training this year that he is battling right shoulder soreness, although Mets manager Mickey Callaway said Sunday that he did not see any concerns with Cespedes' throwing ability.
In other injury news, team captain David Wright's battle to make a comeback from back and shoulder injuries continues to stall. The team announced Tuesday that Wright, 35, was re-examined Monday in Los Angeles by Dr. Robert Watkins and his "shoulder and lower back issues persist." Wright will not perform any baseball activity for eight weeks.
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CLOSED: WIN! Day 3: New Hutchinsons Cheese flavours for the perfect Christmas fare
It's no secret that I believe Kiwi-made produce is among the best in the world, and Hutchinsons cheese is no exception.
Hutchinsons has been discovering the world of cheese since its humble beginnings in 1914, sourcing and supplying the best cheese varieties from around the globe.
I have three vouchers for Hutchinsons newest three flavours – Original Club Cheddar, Sweet Chilli Club Cheddar and Smoked Salmon Flavoured Cream Cheese, worth $30 each, to give away. To be in to win, just click on the link below:
Need some Cheese-piration? Check out my recipes below using Hutchinsons cheeses.


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by Claire Freedman
Illustrations Ben Cort
2015 (published in UK in 2014)
32 pages
Monstrously wonderful illustrations by Ben Cort bring each of the wacky monsters alive. Each seems to have his own individual personality. Sure, monsters are hairy and scary, but what few of us know is that monsters love to wear wacky boxers and briefs. They cavort happily through the woods and have a disco ball showing off their best undergarments. They love being ugly and scary, but they love underpants more than anything!
Much of the fun of this particular children's book is in the language. British writer Clair Freedman will teach American youngsters words like: twanging, dingy, armour (notice the spelling), pinched (meaning stolen), bloomers, wobbly, jive, and snazzy.
This witty, whimsical read is sure to be a new favorite. The children's pet cat appears at the beginning and ending, but he adds greatly to the story. He is visibly on edge and ready to spit and scratch and probably run away.
Recommended for early readers and anyone who loves crazy underpants.
FTC Required Disclosure: I received this book form the publisher. I did not receive monetary compensation for this review.
This review has been posted in compliance with the FTC requirements set forth in the Guides Concerning the Use of Endorsements and Testimonials in Advertising (available at ftc.gov/os/2009/10/091005revisedendorsementguides.pdf)


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SAN BERNARDINO >> A Covina man was formally charged and arraigned Thursday for the murder of a Studio City man in the backyard of a home in San Bernardino.
Marvin Ivan Ramirez, 29, pleaded not guilty in San Bernardino Superior Court to charges of felony murder in the death of his friend, Thurston Watkins, 39, of Studio City.
According to police, Ramirez and Watkins were drinking at a home in the 1600 block of West 26th Street late Tuesday night when a fight between the two men broke out.
Police were called shortly before 10:30 p.m. about a possible murder in progress at the home.
When they arrived, officers allegedly found a naked Ramirez, covered in blood, standing near Watkins' body in the backyard of the home.
That's when Ramirez was taken into custody. Watkins had suffered significant trauma and was pronounced dead at the scene.
Police said evidence of significant alcohol use was present at the crime scene.
One officer said this was the most gruesome crime scene he'd been to in his career.
Ramirez is being held in lieu of $1 million bail at West Valley Detention Center in Rancho Cucamonga.


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12-year-old Charlie Bothuell went missing 12 days ago and police had told the father of this child to prepare for the worst after the boy had been missing almost two weeks. Charles Bothuell went on the Nancy Grace TV show Wednesday night and pleaded for help in finding his missing son. While on live TV, Nancy Grace received word that the boy had been found alive in the father's basement and she told Bothuell while he was still on the air, as Click on Detroit reports today.
Charlie was found barricaded in the father's basement, which was shocking for the father to hear after the police had searched the Bothuell home a number of times, even bringing in dogs, and they found no trace of his son. If his father had known his son was in the basement, he is an excellent actor because this man appeared genuinely shocked. Nancy Grace said that she believed the father was telling the truth and that he had no idea where his son was, according to "Fox and Friends" on Thursday morning.
CBS News reports today that a PVC pipe with blood was discovered in the house and the police are running tests to see who the blood belongs to. This case is bizarre and it is baffling the police. They are trying to piece together why Charlie was hiding or being contained in the basement and who was helping him. They also want to know how long he was actually in the basement because he wasn't seen there during the previous numerous searches of the house.
After comparing what they have so far, the police believe that it is possible that the father or the step-mother could have hid Charlie in the basement, but the father seems very sincere when it comes to his son's disappearance. While Charlie did not cry out for help when police came down into the basement, Detroit Police Chief James Craig said that Charlie was happy to see them. He said he seemed a bit nervous and hungry, although there was evidence that he had food in his hiding place. There was also bedding found with the boy, which seems to indicate he was sleeping in that small barricaded area.
The child's father, step-mother and mother are under investigation in this bizarre incident. The boy's biological mother is said to now be with her son at the hospital with the father and step-mother still being kept separated from Charlie today. I
Overjoyed that his son is alive the father is now faced with a barrage of questions and accusations about his missing son in the basement. The bizarre mystery of how this happened is unfolding. The father took a lie detector test a few days after Charlie was reported missing and the results were "inconclusive." Charlie's step-mother refused to take the test. Police decided to get one more warrant and they returned to the Bothuell house on Wednesday to look for any clues they may have missed and that is when they found Charlie.
When they found Charlie he was barricaded behind boxes in the basement and the police say that they don't believe he could have done this without help. There was a 5-gallon drum among the boxes in this make-shift barricade. Since police had been through that area of the basement a number of times, they don't think that Charlie was down in that basement the entire time he went missing.
Bothuell snapped at the media today when they asked if his wife, Charlie's step-mother, could have hidden the boy in the basement. "My wife wouldn't do that" said the father. He called those accusations "absurd." He started to cry during a impromptu interview with the media saying "I thought my boy was dead, I had no idea where he was." Police are not letting Charlie have contact with his Bothuell or his wife as of yet. They removed the boy from the house.
According to Click on Detroit, Bothuell "told a different story about the last day he saw Charlie. He also said that Charlie ran away from home a few year ago, but he was back home in a couple of hours after police found him. Bothuell told police originally that he was "working out" with his 12-year-old son at home when he left the room to go use the bathroom. Charlie never returned and that is the last time Charlie was seen. The investigation is on-going today.