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Suppliers > Taiwan > Protech Systems
Protech Systems
It's the Right Device
Established in 1980, Protech Systems Co., Ltd. specializes in the design and manufacturing of industrial PCs, automation products and embedded computers for companies around the world. Product lines include single board computers, book-size PCs, POS, and Panel PCs. Protech Systems is an Associate Member of the Intel Communications Alliance, a community of communications and embedded developers and solution providers. Protech is certified by TUV Product Services for ISO 9001 and ISO 14001. Protech is dedicated to providing customers with top quality, high performance solutions along with the most reliable professional service.
Protech Systems is a provider of Industrial IoT processors and edge intelligence technologies, and also active in the healthcare and hospitals, and transportation industries.
Processors & Edge Intelligence
Embedded & Edge Computers
Microcontrollers & Printed Circuit Boards
Healthcare & Hospitals
Protech Systems's Technology Stack maps Protech Systems's participation in the processors and edge intelligence IoT Technology stack.
Devices Layer
Edge Layer
Functional Applications
Analytics & Modeling
Application Infrastructure & Middleware
Networks & Connectivity
Technological Capability:
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Eurotech is a global company focusing on embedded computers and Pervasive Computing, which combines three key factors: the miniaturisation of computers capable of processing information; their spread in the real world - in buildings and machinery, on board vehicles, on persons and in the environment; and their ability to network and communicate. Year founded: 1992 Revenue: $69 million (2014) BIT: ETH
Ennoconn
Ennoconn Corporation, founded in 1999, a leading Industrial mother board designer and a total hardware system solution provider to various vertical market applications (POS, Banking Automation, Kiosk, Lottery and Industrial Automation). With extensive professional knowledge, Ennoconn aims to deliver the state-of-the-art technology with high quality and speed for keeping our customer ahead among competitors. In 2007, Foxconn Technology Group, largest "Electronic Manufacturing Service" company in the world, became the majority share holder of Ennoconn, forming a strong strategic alliance in embedded system and electronic manufacturing business.
Litemax has enjoyed a strong reputation for expertise in sunlight readable, high brightness industrial displays, but there is so much more that we offer. Through resizing, customizations and industrial computing, we raise the standards of industrial-grade displays, digital signage applications and embedded computing to enable intelligent vertical market platforms around the world.
Neousys Technology
Neousys Technology, established in 2010, designs and manufactures rugged embedded platforms and modules.With the core expertise ranging from embedded computing to data acquisition and processing, our goal is to innovate and integrate feature sets into products for various vertical markets with simple yet elegant architecture.
Alinket Electronic Technology(Shanghai) Co.,Ltd
Alinket Technology is an IoT complete solution company that integrates IoT Controllers, IoT middleware, cloud access technologies and application technologies. The company's products and solutions serve the fields of medical electronics, industrial equipment, precision instrument, and music equipment.As the pioneer of IoT technology, Alinket has actively promoted the development of medical and Industrial Internet of Things. The company has passed the ISO9001:2015 quality system certification; the IoT products with many patents have passed the FCC and CE certification with ID. Alinket Technology provides cloud platforms together with world-renowned companies such as Microsoft, Qihoo 360 and Tencent.We are innovative, close to customer demends, to provide customers with comprehensive product support and services. Current partners include Japan Optoelectronics, General Electric, Mindray Medical, Smith Medical and other internationally renowned companies.
Intel designs, manufactures, and sells integrated digital technology platforms worldwide. The company's platforms are used in various computing applications comprising notebooks, desktops, servers, tablets, smartphones, wireless and wired connectivity products, Wearables, transportation systems, and retail devices. It offers microprocessors that processes system data and controls other devices in the system; chipsets, which send data between the microprocessor and input, display, and storage devices, such as keyboard, mouse, monitor, hard drive or solid-state drive, and optical disc drives; system-on-chip products that integrate its central processing units with other system components onto a single chip; and wired network connectivity products.Featured Subsidiaries/ Business Units:- Intel Inside- Intel Data Center Manager (DCM)- Saffron Technology- Wind River
Microsoft Azure (Microsoft)
Microsoft Azure is a Cloud Computing platform and infrastructure created by Microsoft for building, deploying, and managing applications and services through a global network of Microsoft-managed data centers. It provides both PaaS and IaaS services and supports many different programming languages, tools and frameworks, including both Microsoft-specific and third-party software and systems. Azure was announced in October 2008 and released on 1 February 2010 as Windows Azure, before being renamed to Microsoft Azure on 25 March 2014.


Home » Politics of the World » When Evil Rules. Innocent in Jail Released: Charged Room and Board!
When Evil Rules. Innocent in Jail Released: Charged Room and Board!
An apology, maybe? Counselling? Champagne? Compensation? Well, if you're David Blunkett, the Labour Home Secretary, the choice is simple: you give them a big, fat bill for the cost of board and lodgings for the time they spent ……. freeloading at Her Majesty's Pleasure in British prisons.
On Tuesday, Blunkett will fight in the Royal Courts of Justice in London for the right to charge victims of miscarriages of justice more than 3000 for every year they spent in jail while wrongly convicted. The logic is that the innocent man shouldn't have been in prison eating free porridge and sleeping for nothing under regulation grey blankets.
Paddy Hill was one of the Birmingham Six. He spent 16 years behind bars for the 1974 Birmingham pub bombings by the IRA. Hill now lives on a farm with his wife and children near Beith in Scotland. He has been charged 50,000 for living expenses by the Home Office.
It wasn't until two years ago that Hill was finally awarded 960,000 in compensation. However, during the years since his release, while waiting for the pay-out, the government had given him advances of around 300,000. When his compensation came through, the 300,000 was taken back along with interest on the interim payments charged at 23% – that cost him a further 70,000.
O'Brien spent 10 years in jail wrongly convicted of killing a Cardiff newsagent. His baby daughter died while he was in prison and he was charged 37,500 by the Home Office for his time behind bars.
'I was a hostage, now they are billing me' ROBERT Brown was just a 19-year-old from Glasgow when he was jailed for life for murdering a woman called Annie Walsh in Manchester in 1977. He served 25 years before he was finally freed in 2002, when the courts ruled him innocent of the crime.
He is now facing a bill of around 80,000 for the living expenses he cost the state. For Brown, it is the final straw. An interim payment he was given pending his full compensation offer is exhausted; his mother recently died; his relationship with his girlfriend has fallen apart and he is facing eviction from his home following a mix-up over benefits.


text:
Follow Tom's Progress
Build A Better Boat on Instagram
Build A Better Boat Kenny Chesney
We walked into the Crazy Horse Saloon and ordered a drink. The dance floor was full, mostly with couple two-stepping to the country music the DJ was playing however, some people were dancing freestyle in the middle of the floor.
I said, "let's dance," and Tom would not dance. He said he couldn't country dance. I laughed so hard. "We can just freestyle dance, you can do that right?" Yet he would not dance that night with me. He had never been to a country bar and wasn't about to venture on to the dance floor.
This was during the time we dated. Tom had grown up and worked in New York and moved to Florida after visiting his parents who lived here. It was November and he went to the beach. It was then he decided he was done with the cold and the snow and was moving to Florida. This was several years before we met.
We went on to spend many Friday and Saturday nights dancing the two-step, the waltz, the swing, and of course many slow songs for many years. Together we found we loved so many types of music. One singer's music has been profound in our life-Kenny Chesney.
I finally got Tom on the dance floor, learning a line dance. We were both focused, yes? 
His island, boating, laid-back country music style stuck with us. It was a standing tradition for us to go every year and hear him in concert with my sister and her now-husband when he would play in Jacksonville. A huge part of our lives.
Twelve years ago, we spent our last summer with my mom at the beach here and in the Keys with Kenny Chesney's new CD at the time, Summertime. It brings me back to that special summer every time I hear the songs. So glad to have had that summer but it was the last summer before we lost her to cancer.
We've had some tough times since then and last year when Tom got the cancer diagnosis, Kenny's CD Song for the Saints had been released. As we listened to the CD one evening sitting on the front porch, the song "Better Boat" began to play. I had fallen in love with the song for many reasons. Tom become misty-eyed and said, "this song really resonates with me, it's my anthem. Its how I feel. I'm building a better body, a better boat."
And that's what we've been doing for almost a year. With Kenny's music and in particular this song, we've spent the last year researching, studying, and implementing holistic, natural treatments to heal Tom's body of Bladder Cancer.
We listen to so many different types of music but the music we listen to the most, that seems to reflect our life, is from Kenny Chesney.
Love to juice? Learn these simple mistakes before making your next concoction.
(NaturalNews) More and more people are learning of the benefits of juicing as a way to manage weight and ensure getting enough of the right nutrients to keep the body running like a well-oiled machine.
But a lot of us have not been properly educated in the best ways to approach juicing. If you're doing it incorrectly, you may not only be missing out on the full health benefits, but may also end up suffering from stomach discomfort – or even causing harm to your body.
One of the popular juicing trends is known as "green juicing," which simply means using green vegetables and sometimes other ingredients to make healthy, super-nutritious juice concoctions.
If you know how to prepare and consume green juice correctly, the benefits can be amazing – but there are a few important factors to keep in mind.
Avoiding common juicing mistakes
Vani Hari, better known as "The Food Babe," has provided some great advice on her website – FoodBabe.com – concerning the common mistakes you should learn to avoid when making and consuming your own health-promoting green juice recipes.
Here are a few of the Food Babe's Top Common Juicing Mistakes:
Drinking green juice after eating other foods: Green juice should always be consumed on an empty stomach. Otherwise, you may end up with a case of heartburn and miss out on the full benefits due to the fact that an empty stomach allows the nutrients to be fully absorbed into the bloodstream through the stomach lining. Hari recommends waiting at least two hours after eating meals before consuming green juice. You should also wait at least 20 minutes after drinking green juice before eating anything else.
Waiting too long before drinking green juice: When you make your green juice concoction, you should drink it immediately. The beneficial live enzymes contained in green juice begin to degrade as soon as they are exposed to the air, and the nutritional content drops the longer it sits before consumption. If you have a "slow" or twin gear juicer, this is less of an issue and the juice can be stored; however, the juice should be stored in an airtight container filled to the top, and refrigerated to preserve the nutrients and to keep any bacteria from having a chance to grow. If you're using a standard juicer, be sure to drink the juice within 15 minutes of preparation.
Making green juice with too many fruits and sweet vegetables: There's nothing wrong with adding some fruit or sweet vegetables such as apples or carrots to your green juice, but too much natural sugar can boost your insulin to unhealthy levels and may also cause weight gain. Hari recommends only one sweet fruit or vegetable per serving. Lemons and limes are an exception.
Replacing meals with green juice: Unless you're on a juice fast, green juice should be treated as a supplement to your diet, not a replacement for meals. Green juicing is a great way to help you get the daily recommended portion of vegetables in your diet, but it's best to consume it along with other healthy solid foods.
Not chewing while consuming: Okay, it may sound funny to actually attempt "chewing" your green juice, but the idea is to swish the juice around in your mouth before swallowing so that the digestive enzymes contained in your saliva can help to release the nutrients into your body.
Not cleaning your juicer: If you leave your juicer dirty, it will be a lot harder to clean later. If you're in a hurry after making your green juice, soak the parts in water to make cleanup easier when you get around to it.
Using specific greens too often: Be sure to rotate your greens, such as kale, spinach, arugula and turnip greens, for example, to keep from building up unhealthy levels of oxalic acid which can affect your thyroid gland, as well as to keep a healthy balance of nutrients.
Switching to smoothies: There is a common belief that smoothies are better than juice because of fiber content, but Hari recommends consuming both. Fiber is good, but juicing makes for better absorption of nutrients.
Better Boat Update on Tom 05/19/19
Test Results- What do they mean?
Happy Birthday to my Dear Husband!
dianeleone on Hello 2019, Goodbye 2018
Judy Hicks on Hello 2019, Goodbye 2018
Updates on Tom

redpajama_set_name: RedPajamaCommonCrawl


The attorneys at Adams, Hill & Hess have extensive experience in a number of serious injury and death cases.
Have you been injured in a traffic accident? If so, contact us today for immediate and qualified representation.
When the death of a loved one occurs due to the actions of another person or entity you may have a legal claim and be entitled to compensation.
Have you been injured as a result of the actions of another person or entity? If so, we can help you recover for your damages.
Negligence and abuse is all too common in nursing homes. This is a serious issue which requires an experienced attorney in order to protect your loved one's rights and wellbeing.
If you have been hurt or injured due to a medical error you may have a legal claim and may be entitled to compensation. We can help you sort through these complicated and trying situations.
Have you been injured on property belonging to another person or entity? If so, you may have a right to file a claim against the owner or possessor of the property.


Hemmed with beautiful palm trees, this exotic beach is a place worth visiting. It also houses a small hamlet of fishermen. You can go and experience the lifestyle of the fisherman.
It is one of the best natural beaches you'll ever visit. It is a paradise for swimmers and a perfect place to hang out with your friends and family. You'll also find plenty of food stalls to satiate your appetite.
This beach is a delight for both locals and tourists. Locals usually visit this place for enjoying their morning and evening walks. You can sit lazily around the long stretch of rocky shores feeling the waves crashing on your feet. Just before sunset, this beach turns alive as people flock the shores for enjoying the sunset.
Auroville beach is one of the major tourist attractions in Pondicherry. The shallow waters will allow you to enjoy swimming. You can indulge in a variety of recreational activities here or just sit in the shore watching the beach thrive with activities. In either way, we can bet that you'll have a great time.
The azure blue water crashing on the golden sand makes this beach incredibly beautiful. Visiting this place is a must. You can indulge in beach sports, go swimming or enjoy the beautiful scenery here.
True to its name, this beach offers you tranquility, away from the bustling city life. The only sound that'll disturb your quiet retreat is the crashing of waves on the shore.
This is one of the most recognized beaches in Pondicherry. You have to cross the Chunnambar backwaters to reach this beach. Regular boats are available.You'll only find a few shanties selling snacks and cold-drinks. Otherwise, this beach is still untouched by the commercialization.


Reasons today from Chief Justice Bauman, still of the Supreme Court at the time of the application, on a proposed class action against Visa, MasterCard, Royal Bank, BMO, and most of the major financial institutions in Canada. By my count, 31 lawyers, including several of the top litigators in the province, are listed as counsel on the matter (4 for the plaintiff, 27 for the various defendants).
 The defendants quite dramatically contrasted the fact that they literally represent the largest and most respected financial institutions in Canada with the serious allegations of corporate impropriety levelled at them by the plaintiff over the 29 pages of the Amended Notice of Civil Claim. This submission was as much to say: how could such large and revered institutions have ever stooped to the scandalous conduct alleged by this reckless plaintiff? While, in part, it is an effective bit of advocacy in setting a realistic stage for the plaintiff's difficult case, its relevance on the certification hearing bears serious critical consideration.


One of the best things about the Craft Savvy Market experience is truly the people!! Every👏🏾single👏🏾person👏🏾!! Thanks for your support!! Video Repost from @dreaday!
Have you seen the #hitlist 📰 Link in our bio for the free digital magazine or find all the locations for a hard copy on our website MarketMafia.com 💻 Shop makers directly from the digital, and read up on ways to #supportlocal inside!
✨VENDOR SPOTLIGHT✨ Attention all muggers: mug lovers. We have some awesome ceramic artists selling at our summer night market! Artists like @xisapottery from Jacksonville who will be bringing her gorgeous work! Tag a fellow mugger and mark your calendars for May 10th!
We have so many prizes that we're throwing in a mid week giveaway! One luck winner will receive: • •15% off from @rockoilnaturals •a free book from @cor2ney • a free bracelet or pair of earrings of your choice from @metricjewels • a free hooded towel from Me & My Quilts Etc. • and a $25 credit from @summerpaints • • To enter: 1) like and follow @thefarmgirlmarket 2) like this post 3) Follow the shops listed above 4) tag a friend in the comments (1 tag=1 entry) For bonus entries share this post on your feed or stories and be sure to tag us so we see it! Then head to Facebook for more chances to win! Giveaway ends Tuesday April 23rd at 11pm MST. Winner will be chosen from either Instagram or Facebook. Must be present at the market to claim your prize. Good luck! • • This giveaway is in no way sponsored or endorsed by Facebook or Instagram.
Is anyone else hoping to get a few @peggyjeanspies tarts in their Christmas stocking this year?! . Now is a good time to call your Mom and invite her to the @holidaymartjc this year! 🥧 Event details can be found with the link in our bio!


text:
using System;
using System.Collections.Generic;
using System.Text;

namespace Xceed.Wpf.DataGrid
{
  internal class SortDescriptionsSyncContext
  {
    //public bool IsInitializing
    //{
    //  get
    //  {
    //    return m_isInitializing;
    //  }
    //  set
    //  {
    //    m_isInitializing = value;
    //  }
    //}

    public bool ProcessingSortSynchronization
    {
      get
      {
        return m_processingSortSynchronization;
      }
      set
      {
        m_processingSortSynchronization = value;
      }
    }

    //public bool SynchronizeSortDelayed
    //{
    //  get
    //  {
    //    return m_synchronizeSortDelayed;
    //  }
    //  set
    //  {
    //    m_synchronizeSortDelayed = value;
    //  }
    //}

    private bool m_processingSortSynchronization;
    //private bool m_synchronizeSortDelayed;
    //private bool m_isInitializing;

  }
}

redpajama_set_name: RedPajamaGithub


We have a network of about 70 sites we're using Infinite SEO's Automatic Linking feature. I can see where we can control the links from the Network side on the settings page, but is there a way to override this on a per-site basis?
On the bottom of the settings screen it says "Allow Site Admin access - If enabled, this tab will be available to Site Admins once you switch to per-blog mode." --- Where can Site Admins see this tab? How do you switch to "per-blog" mode?
Also to add to this, is it possible to make automatic linking non-case sensitive?


text:
Яков Александрович Кутепов () — советский авиаконструктор, Герой Социалистического Труда (1975).

Биография
Яков Александрович Кутепов родился 10 ноября 1911 года в селе Дмитриевское (ныне — в составе Старооскольского городского округа Белгородской области). В 1931 году он окончил Воронежский авиационный техникум и начал работать на авиационном заводе в Воронеже.

С 1934 года работал конструктором на заводе № 39 Народного комиссариата тяжёлой (впоследствии — оборонной) промышленности СССР — ОКБ С. В. Ильюшина. В 1941 году окончил Московский авиационный институт, после чего был направлен на работу на завод № 240 Народного комиссариата (впоследствии — Министерства) оборонной промышленности СССР (ныне — ОАО «Авиационный комплекс имени С. В. Ильюшина»).

Являлся активным участником разработки многих боевых и пассажирских самолётов, выпускавшихся в его ОКБ, в том числе: «ЦКБ-26», «Ил-2», «Ил-4», «Ил-8», «Ил-10», «Ил-14», «Ил-18». Став ведущим конструктором, возглавлял работы по конструированию самолётов «Ил-12», «Ил-22», «Ил-28», «Ил-46», «Ил-54», «Ил-18», аэробуса «Ил-86». Кроме того, под руководством Кутепова разрабатывались и внедрялись в разрабатываемую технику системы управления, охлаждения, обогрева.

Яков Александрович Кутепов жил в Москве. Он скончался 4 июня 1985 года, похоронен на  Москвы.

Награды и звания
 Закрытым Указом Президиума Верховного Совета СССР в 1975 году удостоен звания Герой Социалистического Труда с вручением ордена Ленина и медали «Серп и Молот»
 Награждён тремя орденами Ленина, орденом Отечественной войны 2-й степени, тремя орденами Трудового Красного Знамени, орденами Красной Звезды и «Знак Почёта», медалями
 Лауреат Ленинской (1970) и Государственной (1971) премий СССР
 Почётный авиастроитель СССР

Примечания

Ссылки

Выпускники Московского авиационного института
Авиаконструкторы СССР

redpajama_set_name: RedPajamaWikipedia


This year at I/O Google announced its video chatting app called Duo, along with a messaging app Allo. The release of both the app is by the end of this summer, and here it is. Currently we only seen the video calling app Duo, and that too not available yet.
Currently Duo app is listed on Google play store, but showing pre-registration. Means users can't download the app right now, but can register for the app when it will available.
Duo is designed to be a simple 1-on-1 video chat client without all the complications and baggage of Hangouts. It's based on your phone number, so you can chat with anyone in your contact list that has Duo—it's compatible with both Android and iOS out of the gate. It's just one tap to start a call. When someone hits you up on Duo, you'll also see a live video of them before you answer; like a digital peephole.
As users can't download the app right now from play store, but we have latest Duo app apk for Android users. Just download Duo app from here.


text:
Q: How to increase space between one icon and another icon in material-bottom-tabs in react-native I am using @react-navigation/material-bottom-tabs in my react-native application. How can I increase space between icons and align them equally based on the width of the device.
react-native: 0.62.1
@react-navigation/native: ^5.1.5
@react-navigation/material-bottom-tabs: ^5.1.8
Current Behavior
More space is left on Right and Left of the bottom tab bar, I am not able to align space equally between icons.
sample
Expected Behavior
I am using material-bottom-tabs and I want to increase space between one icon and another icon in material-bottom-tabs ( or ) align icons space equally.

A:
<Tab.Navigator
  initialRouteName="Home"
  activeColor="#f0edf6"
  inactiveColor="#3e2465"
  barStyle={{ backgroundColor: '#694fad' }}
>
  {/* ... */}
</Tab.Navigator>

There is a prop like barStyle, you can add your custom styles for your tab navigator.
Hope this will fix your issue.

redpajama_set_name: RedPajamaStackExchange


Inosine, a naturally occurring purine, was long considered to be an inactive metabolite of adenosine. However, recently inosine has been shown to be an immunomodulator and anti-inflammatory agent. The aim of this study was to determine whether inosine influences anti-inflammatory effects and affects the development of type 1 diabetes in murine models. Type 1 diabetes was induced either chemically by streptozotocin or genetically using the nonobese diabetic mouse (NOD) model. Mice were treated with inosine (100 or 200 mg kg−1d−1) and diabetes incidence was monitored. The effect of inosine on pancreas immune cell infiltration, oxidative stress, and cytokine profile also was determined. For the transplantation model islets were placed under the renal capsule of NOD mice and inosine (200 mg kg−1d−1) treatment started the day of islet transplantation. Graft rejection was diagnosed by return of hyperglycemia accompanied by glucosuria and ketonuria. Inosine reduced the incidence of diabetes in both streptozotocin-induced diabetes and spontaneous diabetes in NOD mice. Inosine decreased pancreatic leukocyte infiltration and oxidative stress in addition to switching the cytokine profile from a Th1 to a Th2 profile. Inosine prolonged pancreatic islet graft survival, increased the number of surviving β cells, and reduced the number of infiltrating leukocytes. Inosine protects against both the development of diabetes and against the rejection of transplanted islets. The purine exerts anti-inflammatory effects in the pancreas, which is its likely mode of action. The use of inosine should be considered as a potential preventative therapy in humans susceptible to developing Type 1 diabetes and as a possible antirejection therapy for islet transplant recipients.
It is well recognized that certain naturally occurring purines can exert powerful modulatory effects on the immune system. The nucleoside adenosine is the best characterized of these purines and has been shown to affect almost all aspects of an immune response (1, 2, 3). Adenosine and its analogs can affect the development of a variety of inflammatory diseases including endotoxic shock (4), rheumatoid arthritis (5), pleural inflammation (6), nephritis (7), uveitis (8), and colitis (9). Adenosine's effects are partly mediated by the inhibition of deleterious immune-mediated processes, including the release of proinflammatory cytokines and free radicals (10). Inosine is a naturally occurring purine, formed from the breakdown of adenosine by adenosine deaminase (11). Although inosine was widely believed to be inert, we have demonstrated that inosine inhibits the release of proinflammatory cytokines and chemokines by activated murine macrophages (12), and that this compound exerts powerful in vivo anti-inflammatory effects in murine endotoxic shock (12,13), colitis (9), septic shock (14), and severe lung inflammation (15). Inosine also has anti-inflammatory effects on human cells in vitro, reducing tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β production by monocytes and epithelial cells in response to lipopolysaccharide treatment, as well as inhibiting superoxide radical production by activated human neutrophils (16).
Type 1 diabetes is a disease characterized by the specific destruction of insulin-producing β cells in the pancreatic islets of Langerhans by the immune system (17). The islet is invaded by immune cells, particularly macrophages and T cells, and these cells are cytotoxic to islet β cells, in part by generating cytokines and free radicals (18). It has been proposed that the insulitis lesion is β-cell destructive when Th1 cytokines (IL-12, interferon (IFN)-γ, IL-1, and TNF-α) produced by islet infiltrating macrophages and T cells dominate over Th2 cytokines (IL-4, IL-10) (19).
There are 2 murine models of autoimmune diabetes: the multiple-low-dose streptozotocin (MLDS) model and the spontaneous nonobese diabetic (NOD) mouse model. The MLDS model of diabetes is characterized by a progressive hyperglycemia and insulitis similar to that observed in human subjects with recent-onset type 1 diabetes (20,21). The NOD mouse model also shares clinical, serological, and histoimmunological features with human type 1 diabetes (22). Both models have been used extensively to study preventative therapies for type 1 diabetes (22,23). A variety of procedures and therapies that delete, suppress, or modulate functions of the immune system cells can block the autoimmune response against islet β cells and prevent β-cell destruction and may even reverse established diabetes in the NOD mouse (24,25). In view of the finding that inosine is a potent immunomodulating agent (9,12, 13, 14, 15, 16), the present study was designed to test the potential effects of inosine in murine models of type 1 diabetes.
Reagents were obtained from the following sources. Streptozotocin and sodium citrate were obtained from Sigma (St. Louis, MO, USA). BALB/c mice and NOD mice were purchased from Taconic (Germantown, NY, USA). Insulin ELISA kits were obtained from Alpco (Windham, NH, USA) and insulin radioimmunoassay kits were from Linco Research (St Charles, MO, USA). Urine glucose Tes-Tape was from Eli Lilly (Toronto, ON, Canada), and a One-Touch II hospital blood glucose meter was from Lifescan (Johnson & Johnson company, Milpitas, CA, USA). Cytokine ELISA kits were from R&D Systems (Minneapolis, MN, USA).
All animal experiments were carried out in accordance with the guidelines published by the NIH in Principles of Laboratory Animal Care (NIH publication no. 85–23, revised 1985) and the guidelines of the Canadian Council on Animal Care. Male BALB/c mice were treated with streptozotocin (40 mg/kg dissolved in citrate buffer, pH 4.5) or vehicle (citrate buffer) intraperitoneally for 5 consecutive days. Mice were treated everyday starting on day 1 with either inosine (30, 100, or 200 mg kg−1d−1) or vehicle (water) orally by gavage. Blood glucose was measured on days 1, 7, 14, and 21 from blood obtained from the tail vein. Hyperglycemia was defined as a nonfasting blood glucose level ≥ 11 mmol/L. Cumulative incidence of diabetes was calculated as a percentage of hyperglycemic mice at each time point. Biopsies of pancreas were removed on day 21 for biochemical and cytokine assays.
Female NOD mice were purchased at 4 wk of age and allowed to acclimatize to our animal facility for 1 wk prior to daily treatment with inosine (200 mg kg−1d−1, orally) commencing at 5 wk of age. In the 1st study, spontaneous diabetes incidence was monitored until 30 wk of age. Urine glucose levels were checked daily and a mouse was defined as diabetic following 3 d of glucosuria and a blood glucose level of ≥ 11mmol/L. In the 2nd study, female NOD mice were treated in the same way, and when the mice reached 18 wk of age, pancreas biopsies were taken from normoglycemic NOD mice for biochemical, cytokine, and histological analysis.
Insulin contents in pancreata of BALB/c mice were determined from a pancreas biopsy, which was homogenized in acidified ethanol (75% ethanol, 1.5% 12 mol/L HCl, and 23.5% H2O), and then incubated for 72 h at 4 °C and centrifuged. Care was taken to remove biopsies from the same location of the pancreas (body) to avoid differences between the regions of the pancreas in regards to insulin content. The insulin content of the supernatant was determined using an ELISA kit (Alpco). Pancreatic insulin content was expressed as ng insulin/mg protein, which was determined by the Bradford assay (26). For the pancreatic insulin content of NOD mice, a 90% portion of the pancreas (the other 10% going toward histological study) was removed, weighed, homogenized in acidified ethanol, and insulin was measured using a radioimmunoassay kit (Linco Research) and expressed as ng/mg pancreas.
For assay of myeloperoxidase (MPO) activity in pancreas, the pancreas biopsy was homogenized in 0.5% hexade-cyltrimethylammonium bromide dissolved in 10 mmol/L 3-(N-morpholino)propanesulfonic acid and centrifuged at 15000 × g for 40 min. The suspension was then sonicated 3 times for 30 s. An aliquot of supernatant was mixed with a solution of 1.6 mmol/L tetra-methyl-benzidine and 1 mmol/L hydrogen peroxide. MPO activity was measured spectrophotometrically as the change in absorbance at 650 nm, using a Spectramax microplate reader (Molecular Devices, Sunnyvale, CA, USA) (14). Results are expressed as milliunits of MPO activity per mg protein.
Malondialdehyde (MDA) content in the pancreas was determined from a pancreatic biopsy homogenized in 1.15% KCl buffer. Homogenate (200 µL) was added to a reaction mixture consisting of 1.5 mL 0.8% thiobarbituric acid, 200 µL 8.1% sodium dodecyl sulfate, 1.5 mL 20% acetic acid (pH 3.5), and 600 µL distilled H2O. The mixture was incubated at 90 °C for 45 min. After cooling to room temperature, the sample was cleared by centrifugation (10000 × g, 10 min) and absorbance measured at 532 nm, using 1,1,3,3-tetramethoxypropane as an external standard (14). Results are expressed as pmol MDA/mg protein.
Cytokines expressed in pancreas were determined from a pancreas biopsy snap frozen in liquid nitrogen. The biopsies were homogenized in 700 µL of a Tris HCl buffer containing protease inhibitors (27), centrifuged for 30 min, and then the supernatant was removed and frozen at −80 °C until assay. Cytokine contents in pancreas were determined using specific ELISA kits (R&D Systems) and expressed as pg cytokine protein/mg protein.
A portion (10%) of pancreas from NOD mice was fixed in 10% buffered formalin, embedded in paraffin, sectioned at 4.5 µm, and then stained with an anti-insulin antibody (Dako, Carpinteria, CA, USA) using an immunoperoxidase technique and counter-stained with hematoxylin. Coded slides were examined by light microscopy. Islet infiltration (insulitis) was graded 0 to 3, according to the extent of intra-islet infiltration by leucocytes: 0, none; 1, <10%; 2, 10% to 50%; and 3, >50% infiltration. A mean insulitis score was calculated for each pancreas by dividing the sum of the insulitis scores for individual islets by the number of islets examined. Islet grafts transplanted into NOD mice were fixed, embedded, and sectioned, as above, then stained with hematoxylin and eosin and examined by light microscopy.
Islets were isolated from 4-wk-old female NOD mice by collagenase digestion of the pancreas and Ficoll density gradient centrifugation and then hand picked (28). A total of 500 freshly isolated islets were transplanted under the left renal capsule in each diabetic NOD mouse, according to a previously described procedure (29). The islet recipient mice were given either vehicle (water) or inosine (200 mg kg−1d−1) by gavage beginning the day of islet transplantation. Transplantation was considered successful if the non-fasting blood glucose returned to normal (< 7mmol/L) and remained normal for the 1st 4 d after transplantation. Urine was monitored daily after transplantation and if glucosuria and ketonuria appeared, then tail vein blood glucose was measured. Graft rejection was diagnosed by return of hyperglycemia (blood glucose ≥ 11mmol/L) accompanied by glucosuria and ketonuria on 2 consecutive days.
The islet grafts were removed and cut into small pieces with fine scissors, disrupted by syringe injection through progressively narrower gauge needles, and dissociated into single cells by incubation in Ca2+/Mg2+-free phosphate-buffered saline with 0.2 mg/mL EDTA. Leukocytes and islet β cells isolated from the grafts were identified by using immunohistochemical methods, as previously described (30). Briefly, cells were fixed in 4% para-formaldehyde and placed on glass slides coated with 3-amino-propyltriethoxysilane. Primary antibodies for cell staining were a guinea pig anti-insulin (Dako) or control antibody diluted 1:20 in phosphate-buffered saline, a rat monoclonal antibody (Ly-5/T200; Cedarlane, Hornby, ON, Canada) to mouse total leukocytes (CD45+) or rat IgG control antibody. Secondary antibodies were biotinylated goat anti-guinea pig Ig and biotinylated goat anti-rat mouse-absorbed IgG. Next, cells were incubated with steptavidin-alkaline phosphatase conjugate and then with alkaline phosphatase Fast-blue chromogen, and the slides were sealed for microscopic examination.
Data are presented as means ± SE. Statistical analysis was performed using the ANOVA with Bonferroni's correction, Fisher's exact test, or Student's t-test as appropriate; P < 0.05 was considered significant.
MLDS treatment induced a progressive hyperglycemia over a 21-d period, with a corresponding increase in diabetes incidence (blood glucose ≥ 11 mmol/L) in BALB/c mice (Figure 1A and 1B). Inosine at both 100 and 200 mg kg−1d−1 significantly reduced the rise in mean blood glucose level at 21 d (see Figure 1A). Furthermore, the incidence of diabetes on day 21 decreased from 80% to 30% and 13% in response to 100 and 200 mg kg−1d−1 inosine, respectively (see Figure 1B). A lower dose of inosine 30 mg kg−1d−1 had no effect on the MLDS-mediated rise in blood glucose levels (251 ± 17 compared with 231 ± 16 mg/dL for vehicle and inosine treatment respectively on day 21), increased incidence of diabetes (82% compared with 73% on day 21), and decreased pancreas insulin content (16 ± 3 compared with 18 ± 3 ng insulin/mg protein). Inosine alone had no effect on blood glucose (see Figure 1A) or diabetes incidence (see Figure 1B).
Daily treatment with inosine (100 or 200 mg kg−1d−1) for 21 d decreases hyperglycemia (A) and incidence of diabetes (B) following MLDS treatment of BALB/c mice on days 1 to 5. Diabetes incidence is expressed as a cumulative percentage of mice with a blood glucose ≥ 11mmol/L. Mice were either untreated (◯), given inosine 200 mg kg−1d−1 alone ( Open image in new window ), or treated with streptozotocin in combination with vehicle (●), inosine 100 mg kg−1d−1 (▲), or 200 mg kg−1d−1 (▪) starting on day 1. Results are means ± SE for n = 20 mice in 2 separate experiments with 10 mice per experimental group. **P < 0.01 compared with vehicle-treated mice; †P < 0.05; ††P < 0.01 compared with MLDS-treated mice.
MLDS treatment significantly decreased the pancreatic insulin content in BALB/c mice on day 21, and this was significantly reversed by inosine treatment (Figure 2A). MPO activity was found to be 3-fold higher in the pancreas following MLDS treatment (see Figure 2B), indicative of an invasion of the pancreatic tissue by polymorphonuclear leukocytes and monocytes. Inosine treatment dose-dependently reduced pancreatic MPO activity (see Figure 2B). MDA formation was used to quantify lipid peroxidation in the pancreas, a measure of oxidative stress. MDA was found to be elevated 3-fold by MLDS treatment and inosine attenuated this effect (see Figure 2C).
Inosine treatment attenuates the effects of MLDS treatment on pancreatic insulin content (A), MPO activity (B), and MDA content (C) in BALB/c mice. Mice were either untreated (■), given inosine 200 mg kg−1d−1 alone (▤), or treated with streptozotocin in combination with vehicle (□), inosine 100 mg kg−1d−1 (■), or 200 mg kg−1d−1 (▨) starting on day 1. Results are means ± SE for n = 10 to 20 mice in 2 separate experiments with 10 mice per experimental group. *P < 0.05 compared with vehicle-treated mice; †P < 0.05 compared with MLDS-treated mice.
MLDS treatment increased the pancreatic contents of IL-12 (p40), TNF-α and IFN-γ (Th1 cytokines), and IL-1 in BALB/c mice on day 21 (Figure 3A). Inosine treatment prevented the increase in both IL-12 (p40) and IFN-γ levels following MLDS treatment and partially attenuated the rise in TNF-α levels (see Figure 3A). However, inosine had no effect on the MLDS-induced increase in pancreatic IL-1 (see Figure 3A). MLDS treatment had no effect on the pancreatic levels of the Th2 cytokines, IL-4 and IL-10 (see Figure 3B). However, mice treated with MLDS plus inosine had a significantly increased pancreatic IL-4 content (see Figure 3B) and a trend toward an increased IL-10 content. However, this latter effect was not statistically significant (P = 0.07).
Inosine (200 mg kg−1d−1) prevents the MLDS-induced increases in IL-12 (p40) and IFN-γ in pancreata of BALB/c mice, while increasing the level of IL-4. Mice were untreated (■) or treated with streptozotocin in combination with either vehicle (□) or inosine 200 mg kg−1d−1 ( Open image in new window ) starting on day 1. Results are means ± SE (n = 10 mice per group). *P < 0.05 compared with vehicle-treated mice; †P < 0.05 compared with MLDS-treated mice.
Female NOD mice were treated daily from the age of 5 wk with either inosine or vehicle (water). Inosine treatment decreased diabetes incidence, with only 22% of mice that were diabetic at 20 wk of age compared with 66% in the vehicle-treated group (P = 0.018), and this protection continued until 30 wk when 83% of the vehicle-treated mice were diabetic compared with 33% of the inosine-treated mice (P = 0.006) (Figure 4A). In addition, inosine treatment reduced islet leukocyte infiltration (Figure 5A to 5C), and this effect was reflected in the insulitis score, which was 3-fold lower in the inosine-treated mice compared with vehicle-treated mice (see Figure 5D). The number of viable β cells as reflected by pancreatic insulin content, also was significantly higher in inosine-treated NOD mice than in vehicle-treated NOD mice (see Figure 5D).
Daily inosine (200 mg kg−1d−1 orally) (■) treatment starting at 5 wk of age decreases the incidence of diabetes as compared with vehicle-treated (◯) female NOD mice. *P = 0.018; **P = 0.006 compared with vehicle-treated mice at 20 and 30 wk of age, respectively (n = 18 mice in each group).
Histological analyses of pancreata from female NOD mice that were treated with vehicle and became diabetic (A), vehicle-treated and normoglycemic at 30 wk of age (B), and inosine-treated and normoglycemic at 30 wk of age (C). Leukocytic infiltration of islets is the most and insulin-containing β-cells (stained brown) are the least in pancreata of vehicle-treated diabetic mice (A), whereas leukocytic infiltration of islets is the least and β-cell mass is the most in islets of inosine-treated mice (C). Inosine (■) significantly decreased the degree of insulitis (insulitis score) and prevented the loss of pancreatic insulin content in NOD mice normoglycemic at age 30 wk compared with vehicle-treated mice (□) (D). Results are means ± SE (n = 5 to 7) *P < 0.05; **P < 0.01 compared with vehicle-treated mice.
Pancreatic contents of the Th1 cytokines, IL-12 (p40) and TNF-α were significantly lower in NOD mice treated with inosine than in vehicle-treated NOD mice (Figure 6A). In addition, the diabetes-associated increase in the pancreatic content of the chemokine, MIP-1α, was significantly attenuated by inosine (Figure 6A). There was no difference in the pancreatic content of the Th2 cytokine, IL-4 (Figure 6B), and there was a trend (P = 0.06, not significant) toward an increased IL-10 content in the pancreata of diabetic NOD mice treated with inosine (Figure 6B).
Cytokine and chemokine levels in the pancreata of 18-wk-old normoglycemic female NOD mice treated with either vehicle (□) or inosine 200 mg kg−1d−1(▨) from 5 wk of age. Inosine significantly reduced levels of IL-12 (p40), TNF-α, and MIP-1α (A); however, no significant effects were observed on levels of IL-4 and IL-10 (B). Results are means ± SE (n = 10 mice per group). *P < 0.05 compared with vehicle-treated mice.
Transplantation of syngeneic islets into diabetic NOD mice was used to assess the potential of inosine to block a strong established autoimmune response. In the vehicle-treated mice, diabetes recurred in 100% of the islet-grafted mice by day 14 whereas inosine treatment (200 mg kg−1d−1) prolonged the survival of the grafts and 50% of the mice remained normoglycemic at day 70 (Figure 7A). Insulin content of the islet graft was significantly higher in the inosine-treated mice as compared with both diabetic and normoglycemic vehicle-treated mice (see Figure 7B). Histological analysis of the grafts showed abundant leukocyte infiltration of these islets in vehicle-treated mice (Figure 8A) compared with inosine-treated mice (see Figure 8B). Immunohistochemical analyses of the grafts revealed that inosine treatment significantly decreased leukocyte infiltration into the grafts and reduced the loss of β cells in the islet grafts (see Figure 8C).
Inosine prolongs survival (A) and insulin content (B) of syngeneic islet grafts transplanted into female diabetic NOD mice. Diabetes recurred in all vehicle-treated (□) mice (7 of 7) by day 14 after islet transplantation, whereas 50% (5 of 10) mice treated with inosine 200 mg kg−1d−1 (■) were normoglycemic at 70 d after islet transplantation. Grafts from inosine-treated mice which were normoglycemic (■) had significantly more insulin as compared with vehicle-treated grafts removed from both diabetic (□) and normoglycemic mice ( Open image in new window ).
Photomicrographs of islet grafts transplanted under the left renal capsule in diabetic NOD mice treated with vehicle (A) and inosine 200 mg kg−1d−1 (B). Grafts were examined 10 to 14 d after transplantation. Islet graft infiltration by leukocytes is greater in the grafts from vehicle-treated diabetic mice (A) than in inosine-treated normoglycemic mice (B). Inosine-treated mice (■) had significantly lower blood glucose levels, fewer CD45+ graft-infiltrating leukocytes, and more β-cells in the grafts than vehicle-treated (□) mice (C). Results are means ± SE (n = 6). *P < 0.05; **P < 0.01 compared with vehicle-treated mice.
Our study demonstrates that inosine, a naturally occurring purine, protects against diabetes development in 2 animal models of type 1 diabetes, MLDS-induced diabetes in BALB/c mice and spontaneous diabetes in NOD mice. In addition, inosine was effective in preventing recurrence of autoimmune disease after islet transplantation in NOD mice. Previous reports revealed that inosine had marked anti-inflammatory effects, both in vitro and in vivo in acute inflammatory conditions (9,12, 13, 14, 15, 16). Here we report on the effectiveness of inosine in protecting against the development of an autoimmune disease.
Our study in the MLDS-induced model of type 1 diabetes demonstrated that inosine dose-dependently protects against hyperglycemia and significantly reduces the incidence of diabetes. Doses of inosine under 100 mg−1kg−1d−1 appear to be ineffective in protecting against MLDS-induced diabetes; similar to our previous published studies on colitis (9), endotoxic or septic shock (12,14), and lung inflammation (15), inosine was effective only at dosages greater than 100 mg−1kg−1d−1. Inosine reduced pancreatic infiltration by polymorphonuclear leukocytes and monocytes resulting in decreased pancreatic damage (lipid peroxidation) and a greater survival of β cells. The effects of inosine appeared to be via a reduction of the pancreatic levels of the Th1 cytokines (IL-12, IFN-γ, TNF-α). However, inosine failed to reduce pancreatic levels of IL-1. The cytokines IFN-γ, TNF-α, and IL-1 all have been implicated in β-cell functional inhibition, destruction, and autoimmune diabetes (18,31). Also, IL-12 expression has been correlated with development of diabetes in the NOD mouse (32) and treatment of NOD mice with an IL-12 antagonist-suppressed diabetes development and decreased pancreatic expression of mRNA for IFN-γ (33). In addition to decreasing pancreatic levels of Th1 cytokines (IL-12, IFN-γ, TNF-α), inosine increased pancreatic levels of the Th2 cytokine, IL-4 in mice with MLDS-induced diabetes. Previous in vitro experiments have demonstrated inhibition of Th1 cytokines by inosine, without any increase in Th2 cytokine production from macrophages stimulated with lipopolysaccharide (12). In contrast, in endotoxemic mice inosine not only significantly reduced Th1 cytokine levels but also increased the levels of Th2 cytokines (12), suggesting that inosine's overall effect is a shift from a Th1- to a Th2-type cytokine profile.
A chemical form of inosine, inosine pranobex, has been reported previously to be partially protective against hyperglycemia in the MLDS-induced model of diabetes (34). Inosine pranobex was not as effective as inosine in protecting against MLDS-induced hyperglycemia and diabetes. However, inosine pranobex was administered at lower doses than inosine and given intraperitoneally rather than orally. Based on the current results, we believe that the protective effects of inosine pranobex (34) are related to the inosine component. Higher doses of inosine pranobex in the previous study may have produced more of a protection against MLDS-induced diabetes. It is noteworthy that in some countries inosine pranobex has been approved for the treatment of humans with various inflammatory conditions including hepatitis and arthritis, and in humans, the doses of the compound range from 3 g/d to 200 mg kg−1d−1 (35,36).
We also examined the effects of inosine in the NOD mouse, a genetic model of type 1 diabetes with more in common with the human condition than the chemically induced MLDS model of diabetes (22). Inosine significantly decreased the incidence of diabetes in NOD mice, and this was accompanied by reduced pancreatic islet leukocyte infiltration. The mechanism of action of inosine was similar to that observed in the MLDS model, namely a reduction in pancreatic Th1 cytokine levels with a trend to increased pancreatic levels of Th2 cytokines. Also, inosine reduced NOD mouse pancreatic levels of MIP-1α, a chemokine responsible for innate and adaptive immune responses because of its ability to recruit, activate, and co-stimulate T cells and monocytes (37). Similar to data presented here, another study reported increased levels of MIP-1α in the NOD mouse pancreas and this was correlated with insulitis, whereas removing MIP-1α either by gene disruption or neutralization using specific antibodies reduced diabetes incidence (38). Interestingly, the reduction of MIP-1α by inosine appears to be a common observation seen not only in diabetes but also in lipopolysaccharide-induced shock (13), septic shock (14), lung inflammation (15), arthritis, and colitis (9). Increased MIP-1α levels are pivotal in the pathogenesis of various inflammatory diseases, and inhibiting its production/expression may, in part, explain why inosine is protective in a wide variety of inflammatory conditions.
The effects of inosine on inflammatory cytokine and chemokine production were proposed to be mediated, at least in part, by adenosine-receptor related mechanisms (12). Activation of the adenosine A2a receptor has been shown to downregulate inflammation and protect against tissue damage (39). The use of specific inhibitors for this receptor subtype has demonstrated that inosine's inhibitory effect on inflammatory cytokine production is mediated in part by activation of this adenosine receptor (12). It also is possible that inosine produces its inhibitory effects on cytokine production via binding to adenosine A3 receptors shown to be present on monocytes and macrophages (40). However, no specific rodent A3 receptor antagonist has been tested so far to investigate this possibility (12). It also is possible that part of the anti-inflammatory effects of inosine are not mediated by adenosine receptor activation but, rather, by other mechanisms (12). The effect of inosine on cytokine release by inflammatory cells is post-transcriptional and does not involve interference with the activation of p38, p42/44 and JNK, degradation of IκB, or elevation of intracellular cAMP levels (12). Recently, it has been established that production of proinflammatory cytokines can be regulated at the translational level. For example, tetracycline (41), metalloproteinase inhibitors (42), and polyamines (43) all suppress the production of inflammatory mediators without affecting transcriptional events. The post-transcriptional nature of inosine's mechanism of action would be preferable to transcriptional inhibitors, because it would be expected to increase the window of therapeutic opportunity, and may remain effective even in a post-treatment paradigm.
Recent data has also indicated that inosine at millimolar concentrations in vitro can inhibit the enzyme, poly (ADP-ribose) polymerase (44), an enzyme implicated in the pathogenesis of various forms of inflammation including autoimmune diabetes (23,45). We do not know whether the concentrations of inosine achieved in this study in vivo reached levels at which a significant inhibition of poly (ADP-ribose) polymerase could have accounted for the protective effects of inosine against diabetes.
Transplantation of islets into humans with type 1 diabetes has proved an effective therapy to produce insulin-independence (46), however immunosuppression may be required for life. Therefore, the search for immunosuppressive drugs with minimal side effects is an important endeavor. By using syngeneic islet transplantation in diabetic NOD mice as a model of recurrent autoimmune disease, we found inosine to be an effective therapy. Inosine reduced leukocyte infiltration into the islet graft and maintained the graft insulin content by preventing autoimmune β-cell destruction resulting in a protection against diabetes recurrence.
Inosine has recently been shown to be more than just an "inactive" metabolite of adenosine, acting not only as an antiinflammatory agent (9,12, 13, 14, 15, 16) but also preventing glial cell death during glucose deprivation (47), decreasing the release of intracellular enzymes from hypoxic lymphocytes (48), improving renal function during ischemia (49), removing the harmful effects of total hepatic ischemia (50), and protecting against allergic encephalomyelitis (51).
As described above, the mechanism through which inosine exerts its anti-inflammatory effect is still unclear, and likely to employ multiple mechanisms. An additional mechanism, recently highlighted by studies in murine encephalomyelitis models, may be related to direct antioxidant effects: Inosine is broken down in vivo to produce uric acid, and uric acid has potent antioxidant properties against peroxynitrite and other reactive oxidant species (51). Therefore, at least some of the therapeutic effects, particularly on the inflammatory processes and possibly islet cell damage could be mediated by the antioxidant action of uric acid. In fact, the protective effects of uric acid in a variety of models of inflammation are now well established (52). Future testing of the effect of uric acid in the NOD model of diabetes may directly address this question.
Inosine is a safe, naturally occurring purine, which appears to be nontoxic to humans, even when ingested at high doses (53). Inosine has recently been used in small patient populations for the therapy of multiple sclerosis (54). With an increasing body of preclinical evidence showing that inosine is effective in a wide variety of inflammatory diseases, it may be worthwhile re-evaluating its therapeutic potential in humans suffering from a variety of inflammatory and autoimmune diseases.
This study was supported by grants from the National Institutes of Health (1R43 DK59676 to GS) and the Canadian Institutes of Health Research (1-199-908 to AR).


yeah but this is supposed to be fun! Next time I win the lottery I'll get a sako carbon wolf instead. 2.8kgs. I've never had the luxury of a ghillie, and I hunt in rough hill terrain. Every Kg counts!
The look of this rifle really suits my eye, but it weighs 4.9kg. Since I was looking at the 6.5 creedmoor for stalking, i,m a bit concerned that at that weight it is pretty much exclusively a target rifle. What do think?
Looks like a useul article but what's the craic with phtotbucket? Do I need my own photobucket account to see the embedded images or what am doing wrong?
Thanks for the advice folks, I don't think I've seen any pinkfooted around, but I'll maybe go noise-up some canada geese and have a taste of that! S.
Hi there, Does anybody have a list of the edible and inedible species of wild geese? Graylags, Canadas and brent are regularly grazing around here at the moment but I tend not to shoot anything I can't eat. Thanks. silverstoat.


Disulfiram (sold under the trade names Antabuse and Antabus) is a drug discovered in the 1920s that is used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, which means many of the effects of a "hangover" are felt immediately after alcohol is consumed.
In the body, alcohol is converted to acetaldehyde, which is then broken down by acetaldehyde dehydrogenase. If the dehydrogenase enzyme is inhibited, acetaldehyde builds up and causes unpleasant effects. Disulfiram should be used in conjunction with counseling and support.
Under normal metabolism, alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to the harmless acetic acid. Disulfiram blocks this reaction at the intermediate stage by blocking acetaldehyde dehydrogenase. After alcohol intake under the influence of disulfiram, the concentration of acetaldehyde in the blood may be five to 10 times higher than that found during metabolism of the same amount of alcohol alone. As acetaldehyde is one of the major causes of the symptoms of a "hangover", this produces immediate and severe negative reaction to alcohol intake. Some five to 10 minutes after alcohol intake, the patient may experience the effects of a severe hangover for a period of 30 minutes up to several hours. Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural syncope, and circulatory collapse.
The drug's action was discovered by accident in 1948 by researchers Erik Jacobsen, Jens Hald, and Keneth Ferguson at the Danish drug company Medicinalco. The substance was intended to provide a remedy for parasitic infestations; however, workers testing the substance on themselves reported severe symptoms after alcohol consumption.
However, other sources cite it as originally being used to vulcanize (make heat-resistant) rubber tires.
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^ Doyon, Geneviève; Zerbato, Jennifer; Mellors, John W.; Sluis-Cremer, Nicolas (2013). "Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog". AIDS 27 (2): F7–F11.
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^ Cvek, Boris; Dvorak, Zdenek (2008). "The value of proteasome inhibition in cancer". Drug Discovery Today 13 (15–16): 716–22.
^ Wickström, Malin; Danielsson, Katarina; Rickardson, Linda; Gullbo, Joachim; Nygren, Peter; Isaksson, Anders; Larsson, Rolf; Lövborg, Henrik (2007). "Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients".
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^ Loi, Cho-Ming; Day, John D; Jue, Sandra G; Bush, Ernie D; Costello, Patrick; Dewey, Larry V; Vestal, Robert E (1989). "Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics". Clinical Pharmacology and Therapeutics 45 (5): 476–86.
^ Beach, Cynthia A; Mays, Dennis C; Guiler, Robert C; Jacober, Cynthia H; Gerber, Nicholas (1986). "Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics". Clinical Pharmacology and Therapeutics 39 (3): 265–70.
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text:
Travels with Tai
So far this year, Tai has had his hackles raised by a wolf in northeastern Minnesota, been terrorized by a Chihuahua and yesterday in Alabama, he came snout to snout with a horse. But when we arrived at Pogo's pre Mardi Gras "Smokin' on the Bayou" Roadtrek gathering in Gautier, MS, he seemed rather indifferent to all the excitement of a dozen plus Roadtrekers coming together. Instead, he opted to just hang out on the rug outside his Roadtrek. Alone, if you don't mind.
His breed is known for its independence, the breeeders we have met over the years have told us. Tai is our Third Norwegian Elkhound and I think they use independent as a euphemism for stubborn. Tai definitely saunters to the beat of his own drum. In fact, that's just what he did yesterday when a large group of us, along with four dogs had congregated on Laura Robinson's campsite around the corner from our spot here at Shepard State Park: Tai snubbed them all and sauntered home, choosing to park his double-coated, curly-tailed butt outside our eTrek.
He did stop along the way to visit Ellie and Phil and Kathy and Les, where he was the only dog and got some serious pets. Maybe he just needed a rest.
Tai and his new horse pal outside the Montgomery South RV Park in Alabama
Later, after we all caravanned over to a local restaurant and came back to start a bonfire at Laura's, I tried to take Tai down there. He refused to go, stopping in the middle of the road at the end of his leash. I could have forced him of corse. But why bother. He wanted to go back to his own Roadtrek, where he promptly went inside and to sleep.
Tai at our Shepard State Park site in Gautier, MS
I'd say he was exhausted from the 1,050 mile trip down here from Michigan. But he slept the entire way, so that can't be it. And I know he's healthy. He had his annual checkup at the Vet just this past Monday.
We often wonder how much he enjoys our Roadtreking adventures and debate whether it would be best to leave him with relatives. That is, in fact, what we will do after this weekend. We'll leave him at my son's home in Georgia as Jen and I head down to Florida for a couple of stories. The temperature down towards Naples where we are headed will be in the 80's and Tai is still in full winter coat. That, we think, is too warm for him.
Dog experts I've talked to tell me dogs like routine and familiarity and assure me he'd rather be with us, his own people. Tai seems to have bonded well with the Roadtrek and indeed, perks up his ears when I ask him, "wanna go in the Roadtrek?"
So I guess we should count our blessings that Tai is a low maintenance dog.
10 Responses to "Travels with Tai"
February 25, 2014at9:22 am, Michele Cantor said:
Three years ago my dog and I were chased by huge wild boars while hiking on a trail in a Georgia State Park. I thought we were goners.
Two years ago she had a painful encounter with hundreds of yellow jackets at a gorge in Pennsylvania.
Last year involved a visit to a Stone Mountain vet after she tore off her dewclaw jumping into a lake at our campsite.
Despite it all, she still loves the adventure of travel. We recently returned from a 9 week cross-country trip. She checked out the house and the yard, then climbed back into her bed in the Roadtrek and refused to come out.
Next stop, please!
February 24, 2014at9:08 pm, Sheryl winningham said:
The best dog we ever has was a Norwegian Elkhound growing up. My dad worked worked on roads traveling often state to state and we all followed every 6 months with new schools. Our dog, Nicky, for short, rode on back of truck for miles and loved it. Never wanted to get off and very over protective, like your Roadtrek, we own as well, and take our Chi, everywhere we go, never have it any other way! Love hearing about Tai, thanks!
February 24, 2014at11:08 am, Dean Upson said:
We have always traveled with our dogs (cats, too at one time). We have usually had two Golden Retrievers and there have never been any problems. We lost one of our Goldens a year ago and will be getting a pup to join our 7 year old Golden that has always had another to play with. I cannot imagine leaving my dogs at home. If they could not go, I would not go.
February 24, 2014at10:47 am, Bev Baccelli said:
We bought our RT partially because we didn't want to leave our dog home when we traveled. Buddy, a cockapoo, is 14 pounds and has been on month long trips with us. No adverse reactions, as long as he gets to leave the RT for rest stops. He gets long daily walks and off-leash time if we can manage that as well. He kayaks with us and has a trailer that attaches to my bike so he never gets left behind!
He enjoys the attention he gets everywhere we go, and we've even had offers to "dog-sit" him when we've stayed at campgrounds and wanted to visit museums, etc.
I think the dog "experts" are correct: our dogs want to be with us, even if its not home!
February 24, 2014at10:35 am, Dody Dunning said:
Tai is a dog and has his own preferences. He may prefer to simply avoid one or more of the other dogs. I generally encourage dogs to make such decisions for themselves, as long as they are quiet about it. He should be watched around other dogs, especially when they come close to his RT, for he may well protect it. Barking can be a problem or a protective advantage. Teach him to shut up on command if he needs it. Groom out that heavy winter undercoat, for the temps down South will be too hot for him. Keep him in the a/c inside as much as practical while he sheds it out. Meanwhile he'll need lots of water, for he'll pant like crazy. The coat will come out in handfuls.
February 24, 2014at7:33 am, Don said:
Mammie (English Bull) loves camping and travel, she does not get left behind often. She loves humans but could do without other dogs. For some reason she does find cats interesting.
February 23, 2014at11:39 pm, Cheryl said:
Tai is so cool and just wants some alone time … just like the rest of us.
February 22, 2014at1:57 pm, Maureen said:
Ahhh…he's just lovin the RT so much he is staying home to protect his territory. Good on ya RT-Tai.
February 22, 2014at1:52 pm, Bob said:
We are on our second Elkhound. Ours is named Joker and talk about stubborn, (independent). We can't leave him out when we go away from the RV cause he'll bark & bark till one of us come within sight. Also he's not at all friendly to other dogs. He'll give them one sniff, from there, better stay away or they'll be a fight.
He got terrorized one time by a Shih tzu, which made him even more intolerant.
But the friendliest guy to other people.
And talk about hair!! Flies everywhere……
February 22, 2014at9:45 am, Dean Upson said:
We have traveled with our dogs for over 40 years and they have all loved it. As soon as I pick up the keys to any of our vehicles, they are ready to go. If they can't go, I don't.
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Welcome Executive Action on Highly Skilled Immigrants
This week, the Department of Homeland Security announced the publication of two rules: one to extend employment authorization to spouses of certain H-1B workers, and another to enhance opportunities for highly-skilled workers by removing obstacles to their remaining in the United States. DHS characterized these rules as "part of the Administration's continuing commitment to attract and retain highly skilled immigrants."
CCIA commends this commitment and welcomes these actions, particularly the employment authorization for spouses of H-1B workers. Enabling spouses to work and help support the households of H-1B workers who are waiting for their green cards would dramatically improve their quality of life during what can be a years-long wait.
Under current law, spouses of H-1B workers cannot work in the U.S. while H-1B workers wait for a green card. This places an enormous burden on their households, as the wait for a green card places them in a procedural limbo in which the worker cannot be promoted or significantly change their job description. This limbo could last for years depending on the size of the green card backlog. Despite this uncertainty, H-1B workers have had to be the sole supporters of their families.
As a former single H-1B worker (I could barely support myself back then, let alone a family), I can understand what a severe burden this places on them. It makes no sense to make life harder than necessary for foreign born talent the U.S. needs and should be welcoming. Work authorization for H-1B spouses is a common-sense proposal, and the administration should be commended for acting on it.
While this particular executive action is a welcome measure, enactment of comprehensive immigration reform by Congress is needed to address the larger problems of immigration. House Republicans have consistently opposed executive action on immigration, with Speaker John Boehner saying such action would "spoil the well to the point where no one will trust him by giving him a new law."
On the other hand, at the Urban Institute's "Discussion on Immigration Reform" event this week, Chicago Mayor Rahm Emanuel called the threat of executive action "not a prohibitor but an inspiration" for Congressional action. We shall see which view is correct. However, if the administration does decide to take executive action in the absence of Congressional action, Republicans would loudly denounce it, thereby giving the immigration issue the very prominence that some Republicans would rather avoid. If that were to happen, Republicans would be faced with having to fight something with nothing, which means it would seem to behoove them to have a Republican version of reform ready in their arsenal when that time comes.
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Q: error while updating a database in ASP.NET I am having trouble updating an SQL database, the problem is not that it doesn't update at all, but that particular parameters are being updated while the others are not.
here is the code for updating the parameters:
string EditRequest = "UPDATE Requests SET Description = @Desc, BJustif = @Justif, Priority = @Priority, Requested_System = @Requested, Request_Status = @Stat WHERE";
    EditRequest += " Req_ID=@ID";

    SqlConnection Submit_conn = new SqlConnection(WebConfigurationManager.ConnectionStrings["DBConn"].ConnectionString);
    SqlCommand Submit_comm = new SqlCommand(EditRequest, Submit_conn);

    Submit_comm.Parameters.AddWithValue("@ID", Request.QueryString["reqid"]);
    Submit_comm.Parameters.AddWithValue("@Desc", DescBox.Text);
    Submit_comm.Parameters.AddWithValue("@Justif", JustifBox.Text);
    Submit_comm.Parameters.AddWithValue("@Priority", PriorityList.SelectedValue);
    Submit_comm.Parameters.AddWithValue("@Requested", RelatedBox.Text);
    Submit_comm.Parameters.AddWithValue("@Stat", 1);

    Submit_conn.Open();

    Submit_comm.ExecuteNonQuery();

    Submit_comm.Dispose();

    Submit_comm = null;

    Submit_conn.Close();

    get_Description();

    Page.ClientScript.RegisterStartupScript(this.GetType(), "Refresh", "ReloadPage();", true);

this function is called by a button on a pop-up form which shows the parameters content that is being changed in a text box which is also used to submit the changes back to the database, but when I press submit, the parameters which are displayed on the form don't change, I can't find any problem wit the code, even though I've compared it to similar code which is working fine.
In case you need to, here is one of the text boxes I'm using to display and edit the content:
<asp:TextBox ID="JustifBox" TextMode="MultiLine" runat="server" Width="250" Height="50"></asp:TextBox>

What exactly is wrong with the code?
EDIT: I forgot to mention that when I traced the function, it appeared that the controls' content did not change when I submitted them, but were resubmitted as if they were unchanged in their original form.

A: You mentioned two problems here:
1) Fields in the database are not updated when the UPDATE is performed
2) The UI is not updated with the latest data
First tackle the SQL UPDATE query. What fields are not being updated? Copy paste the T-SQL query in the query analyzer and then check which field is being updated and which is NOT. Also, your code is OPEN to SQL injections so read about that and then adjust the code.
For the UI not being updated you need to see whether you are even populating the UI fields with the correct object.


Finding the right electrical service provider who can professionally install, maintain, and upgrade critical electrical systems in residential and commercial settings is of absolute importance. Safety should be the priority of every home or business owner, and that's why getting expert services when it comes to electrical wiring systems is the right way to go during new construction projects, when remodelling, or when being faced by emergency situations.
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CONSTRUCTION of the US$286.9 million Mongu-Kalabo Road is 75 percent complete and the road Development Agency (RDA) is optimistic that the project will be completed in April next year.
And the RDA has issued a pre-qualification for the construction of the 85-kilometre Kalabo-Sikongo road and has shortlisted five contractors to participate in the bidding process.
The 34 km stretch runs from Mongu town to a place called Tapo in Kalabo and will have a total of 26 bridges with the main one measuring 1,022 metres long across the Zambezi River.
Works on the road, which is one of the major projects under the Link Zambia 8,000 started in 2011.
Government has engaged Avic International to undertake the project under the supervision of Rankin Engineering Consultants.
RDA senior manager public relations Loyce Saili said when, she inspected the project on Tuesday that the contactor has made considerable progress of about 75 percent to completion.
Mrs Saili said the contractor has so far tarred about eight kilometers and is expected to complete the entire 34km of the highway by the end of this year.
"The contractor so far has paved eight kms of the road to back top. The projection is that by the end of this year, the contractor would have paved the entire 34 km surface and will remain with other works into next year," she said.
She said safety features such as guard rails and hand rails have been provided on the road and bridges, respectively.
Mrs Saili said RDA and the contractor are, however, concerned with overspeeding by motorists on the temporary diversion.
She said residents should be cognisance of the fact that the diversion is still a construction site and should adhere to the given speed limits to avoid fatalities.
Mrs Saili said the Mongu- Kalabo road will ease movement of people between the two towns.
On the Kalabo-Sikongo road, Mrs Saili said one contractor will be selected out of the five shortlisted to upgrade from gravel to bituminous standard at an estimated cost of US$60 million.
She said the project has four financiers namely the Arab Bank of Economic Development in Africa (BADEA), Opec Fund for International Development (OFID), Kuwait Fund and Saudi Fund.
"We hope that by the end of the year, this process would have been dealt with and the contractor identified. This is a very challenging terrain and very sandy but it is our desire to provide bituminous road for the people of this area," Mrs Saili said.
She said the Kalabo-Sikongo road project is of economic significance because ultimately, it will feed into the Mongu- Kalabo road and connect Zambia to Angola.
Mrs Saili said the full economic benefit of the Mongu-Kalabo road will be realised once the Kalabo-Sikongo road is tarred and connected with Angola.
"There is a lot of potential of trade between Angola and Zambia via Sikongo and the rest of our country. We are hopeful that with the delivery of this project, trade and other business opportunities will be enhanced between the two countries," she said.
Mrs Saili said Angola is an oil producing country and the two roads can provide an alternative source of oil and other commodities between the two countries.
And Rankin Engineering resident engineer Salah Gad said the Avic International has done extremely well on the Mongu- Kalabo road.


text:
Definition of "habeas corpus" []
One of a variety of writs that may be issued to bring a party before a court or judge, having as its function the release of the party from unlawful restraint. (noun)
The right of a citizen to obtain such a writ. (noun)
American Heritage(R) Dictionary of the English Language, Fifth Edition. Copyright (c) 2011 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved.
Use "habeas corpus" in a sentence
"Some state judges so captiously disputed the constitutionality of various military laws that the writ of habeas corpus had to be suspended.31"
"His most noted legal argument was the appeal in habeas corpus proceedings on behalf of Vallandigham in"
"First the omission of a bill of rights providing clearly & without the aid of sophisms for freedom of religion, freedom of the press, protection against standing armies, restriction against monopolies, the eternal & unremitting force of the habeas corpus laws, and trials by jury in all matters of fact triable by the laws of the land & not by the law of nations."
Words like "habeas corpus"
judicial writ
civil right


Object and purpose of research.This paper discusses stability verification of conical shells belonging to the class of pressure hull structures for underwater technology.
Main results.This paper gives an assessment of boundary conditions for conical shells, determined by a special parameter, G. Four variants of boundary conditions are discussed: both ends simply supported; both ends fixed; greater diameter fixed, smaller simply supported; greater diameter simply supported, smaller fixed. Comparison of numerical and theoretical solution demonstrates quite a good correlation of G parameter for above-mentioned variants of boundary conditions in a wide range of r1/r2 ratios, where r1 and r2 are greatest and smallest radii of conical shells respectively. For shells without stiffeners, the paper suggests a calculation formula yielding the value of constant thickness for an equally stable shell, corresponding to given theoretical critical pressure for a conical shell with constant t/r ratio. To calculate the least theoretical pressure at constant t/r, this paper suggests a simplified formula that works well for "mediumlength" shells. Stability analysis of stiffened conical shells has demonstrated that the basic formula yields satisfactory results for critical theoretical pressures of medium-length shells with internal stiffeners, whereas for those with external ones these results are somewhat too high.


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Q: arguments on checkbox on NativeScript Vue <Checkbox v-model="chkbox" @tap="onTap($event)"></Checkbox>

I got this on my HTML, while my method looks like this:
onTap(args){
  console.log(args)
}

But I got error that goes like this
System.err: Calling js method onSingleTapUp failed
System.err: Error: java.lang.NoSuchFieldError: no "I" field "AXIS_RELATIVE_X"
in class "Landroid/view/MotionEvent;" or its superclasses

Can someone help me to solve this? Thanks

A: First, change the code:
@tap="onTap($event)"

to
@tap="onTap"

Secondly, if you try logging the event, you'll get an explosion :)
So, go on with your code, do whatever you want, but don't log the event.


text:
Home Entertainment Chris Hemsworth Displays Comedic Chops in "Vacation"
Chris Hemsworth Displays Comedic Chops in "Vacation"
Australian actor and "Thor" himself, Chris Hemsworth dips his toes in the comedy pool with New Line Cinema's adult ribtickler, "Vacation."
Hemsworth plays Stone Crandall, a popular on-air forecaster who has done very well and is on the cusp of even more success, with the ranch and cattle and man toys to prove it. And as the Griswold's trip spirals out of control, Rusty (Ed Helms) and his family find themselves on his doorstep.
To find the perfect man that is Stone Crandall, the filmmakers looked to the gods, or at least one of them. Hemsworth, who has notably saved the world as the popular mythical figure Thor, was excited to come on board. "I grew up on the 'Vacation' films like most people my age, so I was all in," says Hemsworth. "But this was also an opportunity to do something different. I loved the script and the character and the cast involved. It was a no-brainer. I knew it would be a blast."
Hemsworth describes his character as "a cheesy weatherman, a bit of a douche bag who has some old-fashioned views of the world. He gets away with a lot of the outrageous things he's saying and doing because he's charming and you kind of forgive him for it."
Although Hemsworth is known as a dramatic actor, he was thrown into the comedy deep end with the rest of the veteran cast.
"He was astounding. Just so funny and likeable," remarks director John Francis Daley. "You know, you wanna hate a guy who's that handsome but we all developed man crushes and just wanted to hang around him."
Hemsworth describes Stone's relationship with his wife, Audrey (Leslie Mann), as "hugely sexual, I believe. It's probably the only thing that they have in common or agree upon."
That isn't all that is huge. Even bigger than his ego are his family jewels. Stone Crandall is distractingly, epicly endowed. Unfortunately, having his brother-in-law's natural perfection literally in his face only makes things worse for Rusty, who holds his own relationship up to Stone's as a measuring stick….which leads to one of the film's most outrageous scenes.
"I don't have a background in comedy, but everyone on this film couldn't be more welcoming or more supportive," shares Hemsworth. "I was nervous coming into it but they've all made it a wonderful experience."
Following in his father's footsteps and hoping for some much-needed family bonding, a grown-up Rusty Griswold (Ed Helms) surprises his wife, Debbie (Christina Applegate), and their two sons with a cross-country trip back to America's "favorite family fun park," Walley World.
Opening across the Philippines August 19, "Vacation" is a New Line Cinema presentation and will be distributed by Warner Bros. Pictures, a Warner Bros. Entertainment company.
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One thing to know about me with style is I don't like to follow any rules, if I like it, it fits good, price is descent, then more than likely it's in my closet. Take my collection of fanny packs that if given the opportunity and the weather is nice, it's a great addition to any outfit if you don't want to carry anything. Not sure why I wanted everyone to know about my collection of fanny packs but I can be random like that. I know a few friends that are cringing at that but once again I like what I like. I wish I could say I follow trends but I've always found great joy in putting the simplest pieces together. I guess I say all this to mean, truly do what works best for you when it comes to fashion, if you want to wear white after Labor Day, do it,if you want to mix and match prints, do that as well. All I'm saying is, if you're trying too hard and what you're wearing doesn't fit who you are people can tell, so take all the magazines and other outlets that provide this style advice with a grain of salt because at the end of the day, it's really putting your own spin on all the things that influence you to buy the things you do, follow your own style and be your own trendsetter. If you can rock the mess out of a paper bag and people still want to know where you got it from at the end of the day, that shows how comfortable you are in your own skin and that fashion doesn't make you, you make the fashion, reference to a movie, if anyone can guess but the word fashion isn't used. :). I was fidgeting to throw some psych thoughts of mine in that, but I'll save that for Wellness Wednesday's, see you then.
P.S. Took these awesome pictures at Future of Sports.
My goal this week: Focus on me and everything I have going on, what someone else does has nothing to do with me. I will measure this by keeping a log, just to see how often I entertain this and allow it to take me away from specific things I need to focus on.
Happy Monday it will be. Talk to you soon.
Don't forget to follow the blog for updates or follow me on Instagram.
Oh hey there, *extends hand to shake yours* this is my first post of many and just wanted to say hi and introduce myself. I enjoy long walks on the beach ;), few glasses of rosé every now and then, fave color is bubblegum pink (yes, I had to specify), anything psych related is my passion and if I could travel more often than my bank account is set up for, I would. I have a tendency to overthink things, but when it comes to fashion, I do what works for me. Its the beginning of the week and can't quite get over the hump, maybe due to stress, feeling like I don't have enough time in the day to complete things, but I guess its all in how I perceive it. I can choose to think differently on how I would like my week to go to maybe have a different outcome and this is really what my blog is about, a space for me to express my current feelings, sharing what I know about wellness and taking care of self, while also adding a tinge of fashion flare to spice things up. I feel like what you wear can set the stage for how you want your day to go. I had someone say to me yesterday that even though she didn't feel too happy and wanted to stay in bed, she took the time to pick out her outfit, do her makeup and it really did help to boost her energy, which improved her mood as the day went on. So in starting this 1-day anniversary right in getting this blog up and running for anyone looking for a mixture of wellness, style and all things that create balance, do something for yourself today, starting with an article of clothing, maybe something bright, something shiny, a pop of color never hurt anyone and wear it like its no tomorrow. I know I will with these shoes.
If you have found yourself here for any reason, thanks and welcome.