text:
What Is It Used For
A PSA test is used to screen for prostate cancer. Cancer screening means looking for signs of cancer before it causes symptoms. But screening tests can’t diagnose cancer. If a screening test finds signs of cancer, you’ll need other tests to find out if you have cancer and how serious it may be.
Most types of prostate cancer grow very slowly. They don’t spread beyond the prostate and may never cause health problems. In fact, you can live a long life with prostate cancer and never know you have it. The goal of prostate cancer screening is to help find cancers that may be more likely to spread so they can be treated early. But there are challenges and possible harms from using a PSA test to screen for prostate cancer:
- A PSA test can’t tell the different between abnormal PSA levels from prostate cancer and noncancerous conditions. If your PSA level is high, a prostate biopsy is the only way to find out if the cause is cancer. And prostate biopsies have possible harms.
- A PSA test may lead to finding and treating prostate cancer that would never have affected your health. If prostate cancer is found:
- It can be difficult to tell the difference between slow-growing cancers and those that are likely to grow faster and spread in your body.
- You could have prostate cancer treatment that you never really needed. And cancer treatment may cause serious harms, such as:
- Problems controlling your bowels
PSA testing may also be used to:
Men At Higher Risk Of Prostate Cancer
Some men are at higher risk of prostate cancer than others. These are:
- men who have a family history of prostate cancer
The risk of prostate cancer also increases as men get older.
The evidence so far doesnt suggest that routinely screening these men would help prevent deaths from prostate cancer. In fact, it might lead to men having treatment for prostate cancer even though that cancer wouldnt have caused any problems or symptoms.
What Is Screening For Prostate Cancer
Some men get a PSA test to screen for prostate cancer. Talk to your doctor, learn what is involved, and decide if a PSA test is right for you.
Cancer screening means looking for cancer before it causes symptoms. The goal of screening for prostate cancer is to find cancers that may be at high risk for spreading if not treated, and to find them early before they spread.
There is no standard test to screen for prostate cancer. Two tests that are commonly used to screen for prostate cancer are described below.
Don’t Miss: Can An Enlarged Prostate Cause Constipation
Kscore Test Benefits A Simple Blood Test Providing Clinically Meaningful Information
The 4Kscore® test offers you and your patient important benefits in determining the best course of treatment to manage prostate cancer risk. The 4Kscore® test can:
- Distinguish men with a low risk of having aggressive prostate cancer on biopsy from those with an elevated risk
- Reduce avoidable biopsies and overtreatment of indolent prostate cancer, producing savings for the healthcare system and minimizing risk to patients
- Prompt early intervention in patients that would most benefit from timely diagnosis and treatment
- Allow for improved decision making between the healthcare provider and patient to develop personalized treatment plan
Understanding Your Psa Test Results
PSA is usually measured in nanograms per millilitre of blood . There is no one PSA reading that is considered normal. The reading varies from man to man and the level increases as you get older. Typically, most men have a PSA level of less than 3ng/ml.
Your doctor may refer you to a specialist if your PSA level is over what is consider normal for your age. Its important to remember that a PSA level higher than 3ng/ml may be normal in older men. Talk to your doctor about your PSA level and what this means for you.
Doctors usually follow guidelines that advise when to refer someone to a specialist. These guidelines vary slightly between the different UK nations. It’s important to know that your doctor also uses their own experience and judgment when deciding who needs to see a specialist.
Your doctor may refer you to a specialist if your PSA level is:
Why Do I Need A Psa Test
It’s your choice whether to have a PSA test to screen for cancer. You and your prover may consider your risk for developing a serious cancer that could spread if you don’t catch it early. Your risk for serious prostate cancer may be higher depending on your:
- Age. The risk of prostate cancer increases after age 50.
- Your family health history. If members of your family have had prostate cancer, your risk may be higher.
- Your race. Prostate cancer is more common in African Americans. They also have a higher risk of developing prostate cancer at a younger age and having more serious disease.
You may also have a PSA test if:
- You have symptoms of a prostate condition, such as:
- Painful or frequent urination
- Pelvic and/or back pain
Understanding Psa Levels & The Psa Test
The prostate is a walnut-sized gland found between the bladder and the rectum in males. Its primary job is to produce seminal fluid. The prostate creates a protein, the prostate-specific antigen, or PSA. A PSA screening test is a blood test approved by the FDA in 1994 to measure the levels of PSA in a mans blood.
Small amounts of PSA ordinarily circulate in the bloodstream and can be measured by a PSA test to monitor the health of the prostate. This test is intended to screen for prostate cancer, find other prostate-related conditions, or monitor PSA levels in those in treatment for prostate cancer. This is a simple blood test which reports PSA levels as nanograms of PSA per milliliter of blood.
Don’t Miss: Metastatic Prostate Cancer Castration Resistant
Getting A Prostate Biopsy
For some men, getting a prostate biopsy might be the best option, especially if the initial PSA level is high. A biopsy is a procedure in which small samples of the prostate are removed and then looked at under a microscope. This test is the only way to know for sure if a man has prostate cancer. If prostate cancer is found on a biopsy, this test can also help tell how likely it is that the cancer will grow and spread quickly.
For more details on the prostate biopsy and how it is done, see Tests to Diagnose and Stage Prostate Cancer.
For more information about the possible results of a prostate biopsy, see the Prostate Pathology section of our website.
Living With Prostate Cancer
As prostate cancer usually progresses very slowly, you can live for decades without symptoms or needing treatment.
You may find it beneficial to talk about the condition with your family, friends, a GP and other people with prostate cancer.
Financial support is also available if prostate cancer reduces your ability to work.
Also Check: Life Extension Ultra Prostate Formula
Read Also: How To Get Rid Of Prostate Stones
Does My Psa Level Determine Whether I Have Prostate Cancer
Your provider looks at two factors related to your PSA:
- Your PSA level: A higher level means a higher risk of prostate cancer.
- A continuous rise: PSA levels that continue to rise after two or more tests may mean you have cancer.
But the PSA level alone doesnt determine if you have cancer or not. Two men can even have the same PSA levels but different risks of prostate cancer. And a high PSA level may reflect prostate problems that arent cancer.
Results Of A Psa Blood Test
With imawareâ¢, youâll receive your results within 7 days of shipping the sample off to our labs. Youâll receive an email prompting you to log into your secure patient portal to view your results. Your results will give you a detailed look at your total PSA biomarker. Not only will the results give you a numerical value, but also a qualitative look into your data, taking into account any provided risk factors.
What Causes An Elevated Psa Level
Prostate cancer is the main cause of an elevated PSA level. But PSA levels increase with age and can reflect different prostate conditions. Other factors that may raise a persons PSA level include:
- Prostate enlargement and inflammation .
- Urinary tract infection.
- Urinary catheter placement.
Your healthcare provider will also consider whether your medications affect PSA levels. For example, 5-alpha reductase blockers treat enlarged prostates and will lower PSA levels.
Why The Test Is Performed
Reasons for a PSA test:
- This test may be done to screen for prostate cancer.
- It is also used to follow people after prostate cancer treatment to see if the cancer has come back.
- If a provider feels the prostate gland is not normal during physical exam.
MORE ABOUT SCREENING FOR PROSTATE CANCER
Measuring the PSA level can increase the chance of finding prostate cancer when it is very early. But there is debate over the value of the PSA test for detecting prostate cancer. No single answer fits all men.
For some men 55 through 69 years old, screening may help reduce the chance of death from prostate cancer. However, for many men, screening and treatment could potentially be harmful instead of beneficial.
Before having the test, talk to your provider about the pros and cons of having a PSA test. Ask about:
- Whether screening decreases your chance of dying from prostate cancer
- Whether there is any harm from prostate cancer screening, such as side-effects from testing or overtreatment of cancer when discovered
Men younger than age 55 have a higher chance of developing prostate cancer and should talk with their provider about PSA screening if they:
- Have a family history of prostate cancer
- Are African American
Don’t Miss: How Does One Get Prostate Cancer
What Do My Psa Test Results Mean
Once your test results are back, your healthcare provider will let you know if any additional testing is recommended. PSA levels can vary over time for several reasons unrelated to prostate cancer . So, if you have a borderline PSA, your provider may simply recommend another PSA test in six months or so.
Psa Test: The Current Prostate Screening Standard
Before recommending when you should be screened for prostate cancer, yourdoctor will consider many factors, such as:
- Family history, particularly whether any of your family members have had prostate cancer
- Race, as African-American men have a higher risk of developing prostate cancer
If your doctor determines you should undergo screening, he or she will mostlikely recommend the PSA test. For more than 30 years, the PSA test hasbeen the gold standard in prostate cancer screening. This simple blood testmeasures how much prostate-specific antigen is in your blood.
You May Like: Prostate Plus Para Que Sirve En EspaÃ±ol
Also Check: Trunature Prostate Plus Health Complex
Advising Men Without Symptoms Of Prostate Disease Who Ask About The Psa Test
This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: .
Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned.
This publication is available at https://www.gov.uk/government/publications/prostate-specific-antigen-testing-explanation-and-implementation/advising-well-men-about-the-psa-test-for-prostate-cancer-information-for-gps
This prostate cancer risk management programme information helps GPs give clear and balanced information to asymptomatic men who ask about prostate specific antigen testing. The PSA test is available free to any man aged 50 and over who requests it.
GPs should use their clinical judgement to manage asymptomatic men and those aged under 50 who they consider to be at increased risk of prostate cancer.
GPs should follow National Institute for Health and Care Excellence guideline NG12 for the management of men who have symptoms of prostate disease.
How To Get A Psa Test
Consult with your general practitioner or urologist about receiving a PSA test in their offices. PSA tests are typically covered without co-pay or deductible by Medicare once a year for men 50 years and older. Many states now have laws which require private health insurers to cover the costs for PSA testing. However, additional PSA test costs may need to be covered by the patient.
For those without insurance, or for those with insurance that does not cover PSA testing, free tools are available through advocacy groups, such as ZERO.
Companies such as imawaretm also offer in-home PSA testing kits and telemedicine appointments to discuss your PSA test results with a licensed physician. All imaware test kits are easy to use. After registering the test kit online, results will populate in the secure patient portal within 5-7 business days. You can submit your receipt of this test to insurance for potential reimbursement.
At-Home testing is now at a point where results can be provided accurately and quickly within 5 business days, with real physicians providing telemedicine support through the entire testing process
Dr. Diamandis Lunenfeld-Tanenbaum Research Institute, Sinai Health System
Also Check: What Does Prostate Cancer Mean
Kscore: A Better Mousetrap
4KScore provides the key to what was missing with the PSA test alone. It allows us to separate men who are at high risk for high-risk, aggressive prostate cancer from those who may never experience symptoms of prostate cancer.
#4KScore is a simple blood test. 4KScore is actually a combination of PSA test with a hK2 and a few other related tests .
4KScore can be used in combination with PHI to gain a better understanding of the risks associated with prostate cancer.
In our practice, we recommend the 4KScore test to all our patients who are at risk for prostate cancer. New York Urology Specialists is the first practice in the New York Metro area to offer 4KScore tests to our patients.
We see patients from all parts of New York City , Long Island, Westchester and New Jersey as well as other parts of the USA. We also see from Canada, Japan, South America, Russia, Asia, Europe, Middle East, Africa, the Caribbean and other parts of the world.
Recommended Reading: What Is Elevated Psa Level In Prostate
Information For Well Men Aged 50 And Over
You can refer to the infographic above and direct patients to the information sheet for well men aged 50 and over for a summary of the potential benefits and risks of PSA testing.
The information sheet for well men includes the above infographic, which explains the PSA test. It also includes a list of the potential advantages and disadvantages of the PSA test for men to consider when making a decision.
The Office for Health Improvement and Disparities created this information on behalf of the NHS.
What Abnormal Results Mean
A high PSA level has been linked to an increased chance of having prostate cancer.
PSA testing is an important tool for detecting prostate cancer, but it is not foolproof. Other conditions can cause a rise in PSA, including:
- A larger prostate
- Recent tests on your bladder or prostate
- Catheter tube recently placed into your bladder to drain urine
Your provider will consider the following things when deciding on the next step:
- If you had a PSA test in the past and how much and how fast your PSA level has changed
- If a prostate lump was found during your exam
- Other symptoms you may have
- Other risk factors for prostate cancer, such as ethnicity and family history
Men at high risk may need to have more tests. These may include:
- Repeating your PSA test, most often sometime within 3 months. You may receive treatment for a prostate infection first.
- A prostate biopsy will be done if the first PSA level is high, or if the level keeps rising when the PSA is measured again.
- A follow-up test called a free PSA . This measures the percentage of PSA in your blood that is not bound to other proteins. The lower the level of this test, the more likely it is that prostate cancer is present.
Other tests may also be done. The exact role of these tests in deciding on treatment is unclear.
- A urine test called PCA-3.
- An MRI of the prostate may help identify cancer in an area of the prostate that is hard to reach during a biopsy.
Who Should Get A Psa Test
Not everyone should get a PSA test. Why? Because many in this country are treated for low-risk prostate cancer that is discovered through the PSA test, even when it is unlikely that the disease will ever cause symptoms or lead to death. And treatment is associated with significant side effects, including impotence and incontinence . You should discuss whether prostate cancer early detection is right for you with your personal primary care physician.
To avoid the risks of over-treatment, Roswell Park follows the guidelines established by the National Comprehensive Cancer Network . The NCCN brings together world-renowned experts from 30 of the nations top cancer centers to write guidelines that specify the best ways of preventing, detecting and treating cancer. The guidelines are updated at least every year, on the basis of the latest research.
Michael Kuettel, MD, PhD, MBA, Chair of Roswell Parkâs Department of Radiation Medicine, serves on the NCCN Prostate Cancer Panel.
If you decide that Prostate Cancer Early Detection is right for you, the NCCN recommends PSA testing as follows:
Recommended Reading: Prostate Cancer In Bones And Lungs
Read Also: Focal Laser Ablation For Prostate Cancer

domain: biology


Federal, provincial, and municipal representatives gathered recently to celebrate the completion and grand opening of the new regional ambulance headquarters, which provides emergency medical services to residents of Cornwall and the United Counties of S D & G.
The new, 28,000 square foot facility is located on Campbell Street in the Cornwall Business Park and allows Emergency Medical Services to consolidate its entire administrative, logistical and operational services under one roof. Increased operational space will improve the delivery of emergency medical services in the region and staff will benefit from an enhanced work environment, more storage space, and additional parking.
“Keeping our communities safe is one of our government’s top priorities,” said Guy Lauzon, Member of Parliament for Stormont-Dundas-South Glengarry, on behalf of the Honourable Denis Lebel, Minister of Transport, Infrastructure and Communities.
“This new ambulance headquarters is great news for the people who live here and for our paramedics. Our government is proud to have invested in this project that not only created local jobs and boosted the economy, but will help to protect local residents for years to come.”
“Our government is making strategic infrastructure investments to create jobs and make our communities safer and stronger,” said Grant Crack, Member of Provincial Parliament for Glengarry—Prescott—Russell. “This project created up to 100 construction jobs and will provide our paramedics with the tools and resources they need to improve response times, support the community and keep residents safe and healthy.”
“This new facility is a welcome addition to our local infrastructure,” said Cornwall Mayor Bob Kilger. “It will contribute to overall efficiencies for this important municipal service and it will also build on the excellent quality of life that is already offered in Cornwall and the United Counties of S D & G.”
The governments of Canada and Ontario are each contributing one-third of total eligible project costs under the Infrastructure Stimulus Fund, up to a maximum of $1.7 million each.
The City of Cornwall is contributing the balance of the total eligible project cost of $5.1 million. The Infrastructure Stimulus Fund is part of Canada’s Economic Action Plan. Thanks to Canada’s Economic Action Plan and our strong economic and financial fundamentals, the Canadian economy has recovered from the global recession better than most other industrialized countries. Canada has been a leader amongst G-7 countries throughout the recovery with more than 610,000 net new jobs created since July 2009.
This project supports Building Together, the Government of Ontario’s long-term infrastructure plan to repair, rebuild and renew the province’s roads and highways, bridges, public transit, schools and postsecondary institutions, hospitals and courthouses. Ontario is investing $12.8 billion in infrastructure projects in 2011-12, bringing the government’s total infrastructure investments since 2003 to $75 billion. Building modern, efficient infrastructure has created or preserved close to 100,000 jobs each year, on average, making Ontario’s economy more productive and improving quality of life, now and in the future.
For more information on Cornwall and S D & G Emergency Medical Services, please visit the City of Cornwall’s website:


text:
The Reproductive Subject: The Reproductive Subject and the Embodied State of International Human Rights Law
Abortion, Gender, Reproductive RIghts, Gender Hierarchy, Childbirth, Assisted Reproduction, Body Theory
To what extent is the legal subject gendered? Using illustrative examples from a range of jurisdictions and thematically organised chapters, this volume offers a comprehensive consideration of this question. With a systematic, accessible approach, it argues that law and gender work to co-produce the legal subject. Cumulatively, the volume's chapters provide a systematic evaluation of the key facets of the legal subject: the corporeal, the functional and the communal. Exploring aspects of the legal subject from the ways in which it is sexed and sexualised to its national and familial dimensions, this volume develops a complete account of the various processes through which legal orders produce gendered subjects. Across its chapters, each theoretically ambitious in its own right, this volume outlines how the law not only acts on the social world, but genders it.
This chapter engages the reproductive subject of international human rights law, a subject who conceives, gestates and births, or seeks to avoid them. Reproduction is a fascinating site for the critical study of gender and law because it necessitates grappling with bodies.
Joanna Erdman, "The Reproductive Subject: The Reproductive Subject and the Embodied State of International Human Rights Law" in Stéphanie Hennette Vauchez & Ruth Rubio-Marín, eds, The Cambridge Companion to Gender and the Law (Cambridge: Cambridge University Press, 2023) 207.

domain: law


text:
Men’s Personalised Bible Verse Leather Bracelet
Create your own special piece, using a favourite verse or meaningful scripture. The perfect gift for a kingdom man!
Create your own special piece, using a favourite verse or meaningful scripture. The perfect gift for a kingdom man! With a contemporary, unique design, this bracelet is the perfect way to keep this special scripture close at all times. A great gift for a relative, a friend, or yourself! The style is discreet, and can be read by twisting the scroll carefully.
Simply enter the verse required in the 'notes' when placing your order. A verse can be up to 75 characters (including spaces).
The coil is in Sterling Silver, 3mm. Available in brown or black. Please state the size of the bracelet (see chart) in the 'notes' section when placing your order. Thank you!
We are now selling this item with the clasp shown in the latter image; this opens in a sideways direction.
Small - 8"
Medium - 8.5"
Large - 9"
Extra Large - 9.5"
Meet the Maker
Jewellery with inspirational messages; to offer encouragement and hope
Currently on Maternity Leave!
Founded by Ruth, and created in the heart of Hampshire, Streten was created to provide affordable luxury for all occasions. Whilst many of our items are personalised, the jewellery we love creating the most is our Christian range. It's a huge blessing to be able to produce jewellery that will be a source of encouragement and a constant reminder of God’s love, care, promises, and blessings. We pray for the recipient as we work on their item, what a privilege!
‘Your Word is a lamp to my feet and a light for my path’ – Psalm 119:105
Our pieces are hand stamped- a process whereby each letter is individually impressed into metal. These impressions are deeper than engraving and produce a stylish hand crafted feel to your special piece. Unlike machine manufactured jewellery, no two pieces are the same. Small variations distinguish every piece – your keepsake is one of a kind, so are you.

domain: design


text:
Latest Gas Powered Games News
Gas Powered Games, the developer started the Dungeon Siege series, has been acquired by publisher and developer Wargaming.
“Gas Powered Games has a long track record of providing incredibly engaging AAA gaming...
With 23 days to go Gas Powered Games is almost halfway to its goal of having $1,100,000 in pledges to fund the development of the action RPG Wildman.
Wildman is an...

domain: entertainment


text:
|Home | About | Journals | Submit | Contact Us | Français|
Synaptic dysfunction is thought to contribute to age-related learning impairments. Detailed information regarding the presence of silent synapses and the strength of functional ones through advanced aging, however, is lacking. Here we used paired-pulse minimal stimulation techniques in CA1 stratum radiatum to determine whether the amplitude of spontaneous and evoked miniature excitatory postsynaptic currents (sEPSCs and eEPSCs, respectively) changes over the lifespan of rats in hippocampal CA1 pyramidal neurons, and whether silent synapses are present in adult and aged rats. The amplitudes of both sEPSCs and eEPSCs at resting membrane potential (i.e., clamped at −65 mV) initially increased between 2 weeks and 3 months, but then remained constant through 36 months of age. The potency of the eEPSCs at depolarized membrane potentials (i.e., clamped at +40 mV), however, was highest among 36-month old rats. Additionally, presynaptically silent synapses in CA1 stratum radiatum disappeared between 2 weeks and 3 months, but postsynaptically silent synapses were present through advanced aging. The similarity of silent and functional synapses in CA1 hippocampus at resting membrane potentials throughout adulthood in rats may indicate that impairments in the mechanisms of synaptic plasticity and its subsequent stabilization, rather than deficient synaptic transmission, underlie age-related cognitive decline. Such a notion is consistent with the increased amplitude of synaptic currents at depolarized potentials, perhaps suggesting an upregulation in the expression of synaptic NMDA receptors once rats reach advanced age.
Synaptic transmission is the primary means of communication between neurons and is thought to be targeted during normal aging. One of the most-studied regions of the brain with regard to synapses is the hippocampal CA1 region (Harris and Kater, 1994; Geinisman, 2000; Spruston and McBain, 2007). The detailed information regarding the functional and structural properties of synapses in this region have proven critical for guiding research aimed at identifying the cellular substrates of individual variability in aged animals (Toescu et al., 2004; Burke and Barnes, 2006; Disterhoft and Oh, 2006; Wilson et al., 2006; Foster, 2007). A major question is why some aged animals show severe impairments in hippocampus-dependent behavioral tasks, whereas others the same age learn as well as young adults. Multiple processes probably collude to disrupt neuronal function (e.g., synaptic transmission) and plasticity (e.g., activity-dependent changes in synaptic strength or intrinsic excitability), but it is likely that age-related changes in one parameter have a feed-forward effect on other parameters.
For example, both intrinsic and synaptic plasticity in CA1 pyramidal neurons are impaired in aged rats (reviewed in Toescu et al., 2004; Burke and Barnes, 2006; Disterhoft and Oh, 2006; Wilson et al., 2006; Foster, 2007). These forms of plasticity depend on postsynaptic depolarization and could therefore be a consequence of reductions in synapse number or synapse strength. Indeed, previous work using electron microscopy has found evidence that some synapses may be weaker in aged rats with impaired hippocampus-dependent memory (Nicholson et al., 2004; but see Barnes et al., 1992), even though synapse number does not predict cognitive status (Geinisman et al., 2004; Calhoun et al., 2007). Therefore, the possibility remains that age-related changes in behavioral, synaptic and intrinsic plasticity derive from a dysregulation of cellular processes responsible for maintaining or altering synaptic strength.
One working model that could account for many of these findings posits that the dyshomeostasis of intracellular Ca2+ changes the rules that govern cellular plasticity (Khachaturian, 1987; Landfield, 1987; Toescu et al., 2004; Foster, 2007; Toescu and Verkhratsky, 2007). Though not traditionally considered a form of plasticity, the maintenance of synaptic strength is in fact an active process that involves Ca2+-mediated cascades (Malinow and Malenka, 2002; Nicoll, 2003; Kennedy and Ehlers, 2006). Probing synapses at steady state could thus provide snapshots of the integrity of synapses throughout the lifespan of rats, and reveal crucial insight into what is and is not changing as animals transition from young adults with functional hippocampal neurons to aged animals with dysfunctional ones. For instance, determining the strength of individual synapses throughout the lifespan of rats could help clarify whether synapses are weakened throughout the aging process (e.g., Barnes et al., 1992; Hsia et al., 1998; Nicholson et al., 2004). If such evidence is found, one could posit that synaptic potentials in aged rats result in depolarizations that are unable to the recruit the processes that support physiological forms of plasticity like long-term potentiation (LTP) or increases in neuronal excitability. Additionally, determining whether synapses that are especially sensitive to LTP-induction protocols are absent in very old animals is important, as such a loss would make it more difficult to induce plasticity at aged synapses.
All excitatory synapses on hippocampal CA1 pyramidal neurons contain NMDA receptors, but a subpopulation of these synapses lacks AMPA receptor immunoreactivity (Nusser et al., 1998; Petralia et al., 1999; Takumi et al., 1999; Racca et al., 2000; Ganeshina et al., 2004; Nicholson et al., 2006; Nicholson and Geinisman, in press). These electron microscopic findings corroborate previous descriptions of “postsynaptically silent” synapses that lack AMPA receptors, contain NMDA receptors, and are rendered functional only by the voltage-dependent removal of Mg2+ from their NMDA receptor channel pore (Liao et al., 1995; Isaac et al., 1995; Durand et al., 1996). These postsynaptically silent synapses, which are small and located on small thin spines (Takumi et al., 1999; Nicholson et al., 2006; Nicholson and Geinisman, in press), are thought to be especially sensitive to LTP-induction protocols (Kasai et al., 2003; Bourne and Harris, 2007). One possibility is that such synapses are absent or relatively infrequent in aged rats, which has the consequence of reducing the occurrence of plasticity by virtue of the unavailability of postsynaptically silent synapses. Importantly, there also exist “presynaptically silent” synapses whose transmission failures derive from the absence of neurotransmitter release, or from the release of neurotransmitter in an amount that is sufficient to activate only high-affinity NMDA receptors (Kullmann and Asztely, 1998; Gasparini et al., 2000; Voronin et al., 2004; Voronin and Cherubini, 2004).
Previous studies have postulated that postsynaptically silent synapses may be involved in activity-dependent synaptic plasticity, such as that involved in the early development of neuronal microcircuits (Durand et al., 1996; Isaac et al., 1997; Petralia et al., 1999). This notion is consistent with studies in infant rat tissue (<3 weeks old) showing that LTP converts postsynaptically silent synapses into functional ones via the insertion of AMPA receptors into their postsynaptic membrane (Liao et al., 1995; Isaac et al., 1995; Durand et al., 1996; Malinow and Malenka, 2002; Nicoll, 2003). If silent synapses in the hippocampus are present primarily during early development, they should disappear or decrease in frequency with age. If, however, silent synapses are a constant substrate upon which mechanisms of activity-dependent plasticity act (Malinow and Malenka, 2002; Nicoll, 2003), then they should mirror the persistence of LTP and other forms of synaptic plasticity in the hippocampus throughout life in rats (Burke and Barnes, 2006; Disterhoft and Oh, 2006; Gallagher et al., 2006; Foster, 2007).
Here we combine whole-cell patch-clamp recordings from CA1 pyramidal neurons with paired-pulse minimal stimulation techniques (McNaughton et al., 1981; Dumas and Foster, 1995; Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998) and show that postsynaptically silent synapses and the strength of functional ones at resting membrane potentials persist through life in rats, even in rats too old to learn hippocampus-dependent tasks. However, when synapse strength is probed at depolarized potentials (+40 mV), synapses in the oldest rats are strongest. Such voltage-dependent differences in synaptic strength may indicate that advanced aging is associated with an increased expression of synaptic NMDA receptors, which may increase intracellular Ca2+, and possibly exacerbate Ca2+ dyshomeostasis following synaptic activation that is strong enough to remove the Mg2+-blockade of NMDA receptor channel pores.
All experiments were performed in accordance with the animal care and handling guidelines set forth by Northwestern University.
Transverse hippocampal slices (300 μm) were prepared in ice-cold oxygenated artificial cerebral spinal fluid (aCSF) from 10 to 16 day, 3 month, 16 month and 32−36 month old Fisher 344 × BN F1 rats. Slices were quickly transferred to an oxygenated holding chamber and incubated for 25 min at 35 °C, after which they were held at room temperature until recordings were made. The recording chamber was continuously superfused with solution heated to 32−34 °C and saturated with 95% O2/5% CO2. The standard extracellular aCSF solution contained 124 mM NaCl, 3 mM KCl, 1.25 mM KH2PO4, 2.0 mM CaCl2, 1.3 mM MgCl2, 26 mM NaHCO3, 10 mM glucose. Picrotoxin (0.1 mM) was added to suppress GABAergic synaptic inhibitory currents during recording. The concentration of MgCl2 was raised to 2.0 mM and that of CaCl2 decreased to 1.3 mM in the slicing solution. Experiment 2 used bath application of the NMDA receptor antagonist AP5 at 0.05 mM.
Somatic whole-cell recordings were obtained from CA1 pyramidal neurons under visual guidance using infrared differential interference contrast microscopy. Internal solution for the patch pipettes contained: Cs methane sulphonate 120 mM, CsCl 10 mM, NaCl 5 mM, HEPES 10 mM, EGTA 0.2 mM or 10 mM, TEA-Cl 5 mM, Mg-ATP 4 mM, GTP 0.3 mM, QX-314 5 mM, pH 7.3−7.4 adjusted with CsOH, osmolarity 290 ± 10 mOsm.
After achieving whole-cell configuration, activation of unitary ‘minimal’ EPSCs in CA1 pyramidal cells was achieved with a stimulus intensity just above the EPSC threshold, which produced detectable postsynaptic responses that alternated with failures. Evoked EPSCs (eEPSCs) were considered to be minimal if they appeared abruptly in response to gradually increasing stimulus intensity and alternated with transmission failures. Synaptic transmission was elicited with a 20 μs pulse at 0.0625 Hz using a monopolar glass electrode filled with external solution and positioned in stratum radiatum ~100 μm away from the cell being recorded. Stimulation at this low frequency is necessary to avoid frequency-dependent synaptic depression (Saviane et al., 2002; Voronin and Cherubini, 2004).
The experiments in the present study utilized a paired-pulse facilitation (PPF) paradigm, consisting of two stimuli with the same intensity delivered at a 50 ms interval at a holding potential of −65 mV and +40 mV. We used the percentage of successful transmission events in response to the paired-pulses as an index of the probability of neurotransmitter release (Pr). To address whether age-related differences are present in the voltage-dependence of PPF, we calculated the Pr ratio as the Pr to the second stimulus in the pair divided by the Pr to the first stimulus at both −65 mV and +40 mV. Analyses of spontaneous EPSCs (sEPSCs) were conducted on a 900 ms epoch from trial records at −65 mV from Experiment 1 during and after stimulus calibration trials (a 200 ms baseline, and the 700 ms epoch starting 50 ms after the second pulse of the paired-pulse). Experiment 1 was performed on 56 CA1 pyramidal neurons (infant: 14 neurons from 5 rats; young: 13 neurons from 7 rats; adult: 15 neurons from 8 rats; aged: 14 neurons from 9 rats). Experiment 2 was performed on 26 CA1 pyramidal neurons (infant: 8 neurons from 3 rats; young: 4 neurons from 2 rats; adult: 9 neurons from 4 rats; aged: 5 neurons from 2 rats).
Experiment 1 examined both eEPSC amplitude and response potency to control for possible changes in Pr throughout life in rats. eEPSC amplitude was measured as the peak current amplitude within 7 ms of each pulse on all trials. Response potency was determined as the peak current amplitude within 7 ms of each pulse but only on visually confirmed successful transmission trials. Though minimal stimulation can activate single synapses, some axons near the stimulating electrode may have similar thresholds of activation such that our minimal stimuli excite more than one axon. This notion was explored for each cell by dividing the potency in response to the first pulse by the potency in response to the second pulse (i.e., response potency ratio). If our minimal stimulation was activating the same single synapse, then the response potency ratio should be near 1 (Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998). We considered recordings with response potency ratios within 20% of unity to be from the same single synapse (range: 0.87−1.18). Because this latter group of recordings could reasonably be argued to derive from single-synapse recordings, we analyzed these records separately for age-related trends.
Voltage-clamp recordings were performed using an Axopatch-200B amplifier (Axon Instruments), and series resistance was monitored continuously. The recorded signal was low-pass filtered at 5 kHz, digitized at 10 kHz with a PCI-MIO-16E-4 board (National Instruments). All data were stored on a PC computer with custom software using C++ Builder 5.0 (Borland) and a NI DAQ 6.5 driver (National Instruments). Transmission successes and failures were assayed visually, and post-recording analyses were done using Clampfit 9 (Axon Instruments), MiniAnalysis 6.0.3 (Synaptosoft, Inc.), or custom-written software. All statistical values were evaluated with Statistica (StatSoft). Values are presented as mean ± S.E.M. Statistical differences were established at P ≤ 0.05 using one-way and factorial ANOVA. Fisher's least significant difference (LSD) was used to establish post hoc differences at P ≤ 0.05.
We used the method of minimal stimulation to probe synaptic transmission at single synapses (McNaughton et al., 1981; Dumas and Foster, 1995; Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998) on CA1 pyramidal neurons in infant (2−3 weeks), young (3 months old), adult (16 months old), and aged (32−36 months old) rats. In Experiment 1, stimulus intensity was gradually lowered until successful transmission events in response to the first pulse of the paired-pulse were interspersed with transmission failures at resting membrane potential (−65 mV). In Experiment 2, stimulus intensity was lowered until the first pulse failed to evoke an EPSC on all trials.
Over two thousand events from each age group were analyzed (infant: 2120; young: 2720; adult: 2446; and aged: 3218). χ2 analyses revealed that the distribution of sEPSC amplitudes from infant tissue differed significantly from the other ages (versus young: χ2 = 122.864; adult: χ2 = 67.194; and aged χ2 = 52.592, all df = 10), but that the distributions from young, adult, and aged rats did not differ from each other (Fig. 1A and B). Similarly, the mean sEPSC amplitude increased initially between infant and young ages, but then remained constant through advanced aging (F(3,52) = 9.855; Fig. 1C). Neither the decay time constant (infant: 5.05 ms ± 0.089 (S.E.M.); young: 4.83 ms ± 0.48; adult: 4.45 ms ± 0.33; aged: 4.11 ms ± 0.49) nor the 10−90% rise time (infant: 2.48 ms ± 0.09; young: 2.35 ms ± 0.06; adult: 2.31 ms ± 0.11; aged: 2.17 ms ± 0.33) of the individual events differed among the groups.
In Experiment 1, paired-pulse eEPSCs were recorded from synapses with a range of failure rates to the first pulse (5−80% failure rate) to determine whether aging was associated with changes in (1) the voltage-dependence of failure rate; (2) eEPSC amplitude and response potency (Stevens and Wang, 1995; Isaac et al., 1996); and (3) whether membrane potential affects Pr ratio, as would be expected for presynaptically silent synapses.
The eEPSCs on successful transmission trials closely resembled sEPSCs (Fig. 2A), suggesting that many of the transmission events were unitary. We constrained the failure rates analyses to the first pulse to avoid any possible confound of paired-pulse facilitation. At all ages, the number of transmission failures was lower at depolarized potentials (+40 mV), indicating the silent synapses persist throughout life in rats (Fig. 2B–E). This difference, however, was largest in recordings from infant rats (Fig. 2E). These results suggest that, regardless of whether or not our minimal stimuli were indeed repeatedly activating the same, single synapse, failure rate decreased when the membrane holding potential was depolarized. Such a pattern would be expected if our stimuli were activating synapses with only NMDA receptors, and were therefore silent at resting membrane potentials (i.e., −65 mV), but functional at depolarized potentials (i.e., +40 mV). Thus, our data are consistent with the hypothesis that silent synapses are present on rat hippocampal CA1 pyramidal neurons at all ages.
eEPSC amplitude was measured as the peak current amplitude within 7 ms of each stimulus pulse on all trials, whereas response potency was measured as the peak current amplitude in this same time window, but only on visually confirmed successful transmission trials (Stevens and Wang, 1995; Isaac et al., 1996). This approach allowed us to probe synaptic strength under conditions that are dependent on and independent of Pr (eEPSC amplitude and response potency, respectively; Stevens and Wang, 1995). Specifically, a synapse with a high Pr may have a large eEPSC amplitude simply because successful transmission events are more common. Response potency, on the other hand, is not affected by Pr since it is only measured on trials that are visually confirmed to be successful transmission events. As a result, provided Pr is less than 100%, eEPSC amplitudes are always smaller than response potencies, a pattern we found at all ages and at both holding potentials (Fig. 3).
Our use of the paired-pulse minimal stimulation technique allowed us to calculate the response potency ratios of each recording as the potency of responses to the second pulse (eEPSC2) divided by the potency of the response to the first pulse (eEPSC1) of the paired-pulse (Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998). When individual events have potency ratios near 1, it is reasonable to attribute them to the minimal stimulation of the same single synapse (Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998). Using these ratios, we categorized our recordings into those which we could assume were from the same, single synapse (i.e., a response potency ratio below 1.2) and those for which we could not safely make that assumption (response potency ratio above 1.2). Additionally, we assessed both eEPSC amplitude and response potency at hyperpolarized (i.e., −65 mV) and depolarized (i.e., +40 mV) membrane potentials. Our presumption is that the synaptic responses at hyperpolarized potentials are predominantly generated by AMPA receptor-mediated conductances, whereas those at depolarized potentials are mediated by both AMPA and NMDA receptor-mediated conductances.
eEPSC amplitudes in response to the first pulse are plotted as a function of the response potency ratio for the four age groups in Fig. 4A. An ANOVA revealed that eEPSC amplitude at resting membrane potentials increased between infancy and adulthood, but then remained stable through advanced aging (F(3,52) = 5.0266; Fig. 4B.). There were no age-related changes in eEPSC amplitude at depolarized potentials between adult and aged rats (Fig. 4B). This same pattern was found when eEPSC amplitudes from only those recordings with response potencies ratios below 1.2, and therefore the records of individual synapses, were examined (F(3,18) = 3.162; Fig. 4C). Importantly, response potency ratios for these latter single-synapse records were nearly identical at hyperpolarized and depolarized holding potentials, supporting the claim that these records derive from single synapses. These data indicate that AMPA receptor mediated conductances change early in life, but then remain stable through advanced aging. Similarly, the eEPSC data indicate that NMDA receptor-mediated conductances, or at least those active at depolarized potentials, show little change over the lifespan of rats (see also Hsia et al., 1998).
eEPSC amplitudes are vulnerable to the Pr of the axon making the synapse. Therefore, changes in Pr could either artificially produce age-related differences in synaptic strength, or mask them. For example, if all synapses had the same strength, but Pr increased with development, one would see an age-related increase in eEPSC amplitude. Such a pattern would, however, be attributable not to changes in synaptic strength, but primarily to increases in the probability that a synapse is activated and thus contributes more successes to the mean eEPSC amplitude values. Conversely, an age-related decrease in synaptic strength might be masked by a higher Pr at adult and aged synapses. To avoid potential confounds originating from age-related changes in Pr,we analyzed response potency for all synapses at both hyperpolarized and depolarized membrane potentials. Additionally, we separately analyzed the data from those recordings with potency ratios near 1, which we presume were records of unitary events from the same single synapse (Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998).
When all synapses regardless of their response potency ratios were analyzed, response potency at hyperpolarized membrane potentials, similar to sEPSC amplitudes at rest (Fig. 1A–C), increased initially between infancy and young adulthood, but then remained stable through advanced aging (F(3,52) = 6.151; Fig. 5A and B). Response potency at depolarized membrane potentials also increased early in life, but then showed stability through advanced age (F(3,52) = 2.95; Fig. 5A and B). These data, particularly those at hyperpolarized membrane potentials, show that synaptic strength after infancy is constant through advanced aging, and are consistent with the analyses of sEPSCs (Fig. 1A–C) and eEPSC amplitudes (Fig. 4A–C). Note that the results from the potency analyses show unequivocally that synaptic strength at resting membrane potential, like sEPSC amplitude at resting membrane potential, does not change appreciably between 3 months and 36 months.
Indeed, the potencies in response to the first pulse were similar to the amplitude of the sEPSCs (compare Fig. 5B with Fig. 1C). A factorial ANOVA revealed that eEPSCs were smaller than spontaneous ones (F(1,104) = 47.237), but that regardless of whether they were evoked or spontaneous, EPSCs from infant tissue were smaller than those from the older ages (F(3,104) = 13.640). However, it is important to note that the response potencies were within the range of amplitudes for sEPSCs, so it is likely that many of our recordings were from single synapses.
To explore this notion more directly, we separately analyzed those records with potency ratios below 1.2, and were thus likely from the same single synapse. On average, our overall potency ratios were low (infant: 1.49 ± 0.11; young: 1.38 ± 0.06; adult: 1.39 ± 0.06; aged: 1.34, ± 0.07; n.s.), but single-synapse strength is most reasonably assayed in records whose potency ratio is near 1 (Stevens and Wang, 1995; Isaac et al., 1996; Hsia et al., 1998). Accordingly, we separately analyzed the data from synapses with potency ratios at resting membrane potentials near 1 (infant: n = 6, mean = 1.07 ± 0.04; young: n = 5, mean = 1.1 ± 0.05; adult: n = 5, mean = 1.12 ± 0.02; aged: n = 6, mean = 1.07 ± 0.04; potency ratios were nearly identical at depolarized membrane potentials). Consistent with the analysis of all synapses, response potency at hyperpolarized membrane potentials increased between infant and young ages, and then remained constant through advanced aging (F(3,18) = 3.171; Fig. 5A and C). Interestingly, when we analyzed the response potency of single synapses at depolarized membrane potentials, we found that the oldest rats had the highest potencies, whereas those from all other ages did not differ (F(3,18) = 4.330; Fig. 5A and C).
Because the NMDA receptor channel pore is blocked at hyperpolarized membrane potentials, synaptic currents at −65 mV reflect primarily the AMPA receptor-mediated conductance, whereas those at +40 mV reflect both AMPA and NMDA receptor-mediated currents. Though we did not test this presumption directly with blockade of AMPA and/or NMDA receptors, the ratio of response potencies to the first pulse at these two membrane potentials here are almost identical to the AMPA-to-NMDA ratio found in a previous study that pharmacologically dissected these two components (Hsia et al., 1998; infant: 0.49 ± 0.05; young: 0.74 ± 0.06; adult: 0.75 ± 0.07; and aged: 0.74 ± 0.05). Therefore, we feel it is reasonable to assume that the response potency at +40 mV reflects both the AMPA and NMDA receptor-mediated conductances. Consistent with the notion that NMDA receptors contribute more to synaptic conductances in aged rats, this ratio showed a trend toward age-dependent changes among the records from the single-synapse recordings, though these differences are not statistically significant (F(3,18) = 2.34, P = 0.1; ratio of potency at −65 mV to the potency at +40 mV from those records with response potency ratios below 1.2; infant: 0.58 ± 0.06; young: 0.84 ± 0.05; adult: 0.89 ± 0.07; and aged: 0.68 ± 0.04).
Additionally, the decay time of the responses at +40 mV, which would be expected to be larger in the recordings from aged rats if there was a larger NMDA receptor-mediated component (Spruston et al., 1995), showed a significant increase in aged rats (decay time in ms for the response to the first pulse from those recordings with potency ratios below 1.2; F(3,18) = 3.40, P < 0.05; infant: 8.20 ± 1.58; young: 9.62 ± 1.46; adult: 9.65 ± 1.78; and aged: 16.60 ± 2.97). Though we did not pharmacologically dissect the AMPA and NMDA receptor-mediated components of the responses, both of these trends are consistent with our suggestion that the contribution of NMDA receptors to synaptic current is higher in aged rats than in younger ones, even though their presumed AMPA receptor-mediated conductances are similar (Fig. 5B and C at −65 mV; Barnes et al., 1992; but see Barnes et al., 1997).
The paired-pulse protocol increases Pr to the second pulse, provided the interpulse interval exceeds ~10 ms (Stevens and Wang, 1995). Consequently, this protocol allowed us to examine the probability that a successful transmission event occurs in response to each pulse (i.e., Pr). For presynaptically silent synapses, Pr depends on the postsynaptic membrane potential (Gasparini et al., 2000; Voronin et al., 2004; Voronin and Cherubini, 2004). At −65 mV, Pr to the first pulse of the paired-pulse did not differ (infant: 0.301 ± 0.06; young: 0.362 ± 0.05; adult: 0.381 ± 0.05; aged: 0.376 ± 0.05). However, synapses from infant rats showed a decrease in their Pr ratio when the membrane potential was held at +40 mV, whereas the Pr ratio of synapses from the other age groups was not voltage-dependent (F(3,52) = 5.115; Fig. 6A and B).
That the Pr ratio was voltage-dependent in infant tissue suggests that some of the silent synapses at this age may have been presynaptically silent, whereas all of the silent synapses from the other ages were postsynaptically silent. Using single stimulus pulses to examine silent synapses does not allow postsynaptically silent synapses to be distinguished unequivocally from presynaptically silent ones. This distinction is particularly important because presynaptic neurotransmitter release can be enhanced by depolarizing the postsynaptic membrane potential (Gasparini et al., 2000; Voronin et al., 2004; Voronin and Cherubini, 2004). If a synapse is presynaptically silent, the increase in neurotransmitter release induced by postsynaptic depolarization may cause successful release of transmitter and the subsequent evoked EPSC at +40 mV. With single stimuli, the erroneous conclusion could be made that the EPSCs were caused by activation of NMDA receptor-only (and postsynaptically silent) synapses, rather than being caused by voltage-dependent increases in presynaptic neurotransmitter release.
In Experiment 2, we sought to determine whether presynaptically silent synapses do indeed disappear between infancy and young ages, even though postsynaptically silent synapses are present at all ages (Fig. 2). We stimulated synapses until we recorded clear eEPSCs to either pulse and then gradually lowered the stimulus intensity until we achieved 100% failures to the first pulse. Using this approach, we found two major subtypes of silent synapses. The first subtype is the presynaptically silent synapse, which showed 100% failures to the first stimulus at −65 mV, but occasional successful transmission events after the second stimulus (Fig. 7A). Depolarization enhanced Pr at these synapses, which was detected as a decrease in the number of failures to the first stimulus, and by a reduction in the Pr ratio (Pr to the second stimulus divided by Pr to the first stimulus; Fig. 7B). Importantly, the conductances at +40 mV were not blocked by bath application of the NMDA receptor antagonist AP5 (Fig. 7C and D), and thus were presumably mediated by AMPA receptors that were able to bind glutamate under conditions of enhanced Pr (summarized in Fig. 7D). Interestingly, these presynaptically silent synapses were found only in slices from younger rats (infant: 3/8 recordings; young: 1/4; adult: 0/9; aged: 0/5). In other words, when the first pulse yielded 100% failures, the second one did so too but only in tissue from older rats.
The other silent synapse subtype showed a 100% failure rate to both stimuli of the paired-pulse at −65 mV (Fig. 7E), but generated responses to both stimuli at+40 mV (Fig. 7F). The successful events in response to the first and second pulses were both blocked by bath application of AP5 (Fig. 7G and H), indicating that these synapses contained only NMDA receptors and were thus postsynaptically silent at −65 mV (summarized in Fig. 7H). Such postsynaptically silent synapses were present in slices from infants (1/8 recordings) and older ages (young: 2/4 recordings; adult: 2/9; and aged: 1/5). The remaining recordings showed 100% failures at both holding potentials.
Taken together, the results of the present study indicate that synaptic strength initially increases after the end of infancy, but then stays remarkably constant between 3 months and 36 months of age. Though this strength is constant at resting membrane potentials, our data suggest that the NMDA receptor-mediated component of the synaptic conductance is highest in 36-month old rats. Importantly, however, this pattern was only noticeable in the analyses of response potencies after substantial depolarization (i.e., to +40 mV) and only in those records that derived from the activation of the same single synapse. Additionally, the results of Experiment 2 indicate that presynaptically silent synapses disappear around the third month of life, whereas postsynaptically silent synapses are present through advanced aging in rats.
The experiments in this study show that both presynaptic and postsynaptic parameters continue to develop throughout the first 3 months of life in rats, but then remain relatively constant throughout their lifespan. Furthermore, the age-related changes in the Pr ratio coupled with the age-dependent differences in eEPSC amplitude and potency indicates that the reliability and strength of information transfer at synapses in CA1 stratum radiatum are not fully mature until ~3 months, but then remain stable even in advanced age. Despite the remarkable stability of synaptic parameters throughout life in rats, our analyses of response potencies and kinetics at depolarized holding potentials suggest that NMDA receptor-mediated synaptic transmission may be enhanced in very old rats.
Our data show that the amplitude of sEPSCs, eEPSCs, and response potencies increase initially after infancy, but then remain stable through advanced age, even though all 36-month old rats show severely impaired hippocampus-dependent learning (Knuttinen et al., 2001). The absence of major changes in synapse strength after ~1 month of age is consistent with previous reports (Dumas and Foster, 1995; Hsia et al., 1998). Hsia et al. (1998) provided evidence that tetrodotoxin-sensitive (TTX) miniature EPSCs (mEPSCs) increased between infancy and young adulthood, whereas TTX-insensitive mEPSCs remained stable. These authors explained the age-related increase in the amplitude of TTX-sensitive mEPSCs as being produced by an initial increase after infancy in the number of synapses onto the recorded neuron that an individual presynaptic axon makes, followed by stability in synapse number. Our sEPSC amplitudes are similar to the amplitudes of their TTX-insensitive mEPSCs, and the stability in their amplitude after infancy is consistent with the lack of age-related synapse loss in CA1 stratum radiatum (Geinisman et al., 2004), though not necessarily consistent with the idea that that aged learning-impaired rats have weaker synapses than aged learning-unimpaired ones (Nicholson et al., 2004). The eEPSC data in the present study show nearly the same exact pattern, albeit with smaller amplitudes.
Importantly, presynaptic axons do occasionally make multiple contacts with the same postsynaptic neuron, though these types of connection are rare (Sorra and Harris, 1993; Yankova et al., 2001; Nicholson and Geinisman, in press). Therefore, we cannot be certain that any of our recordings with potency ratios significantly above 1 were from the same, single synapse. Rather, they could have been recording the activation of multiple synapses between the same axon and the recorded neuron; or they could be records from multiple synapses that are made from adjacent axons with similar activation thresholds. However, the overall pattern of results was similar to that found in the analyses of those records that are presumably from the same, single synapse (i.e., those with potency ratios near 1; Fig. 4A and C; Fig. 5A and C).
One unexpected finding was that response potency at depolarized membrane potentials was highest in the aged rats only for those records deriving from single synapses (Fig. 5A and C). A reasonable explanation for this is that the contribution of NMDA receptors to synaptic current is highest in aged rats, relative to their younger counterparts, but that this would only occur after synaptic activation/depolarization intense enough to remove the Mg2+-blockade of the NMDA receptor channel pore. This observation may appear to contrast with a previous report, which provided evidence that the NMDA receptor-mediated component of the field excitatory postsynaptic potential (EPSP) is decreased in behaviorally characterized aged rats (Barnes et al., 1997), but these authors were unable to assess the voltage-dependence of their observation. Additionally, the increased contribution of the NMDA receptors to synaptic current in our study was found only at a subset of synapses, which may have been masked by the field EPSP in the Barnes et al. (1997) study. To help clarify this issue, it will be necessary to pharmacologically isolate the different components of the eEPSCs, as has been done in younger rats (e.g., Hsia et al., 1998). Moreover, postembedding immunogold electron microscopy studies for AMPA and NMDA receptors in CA1 hippocampus of behaviorally characterized aged rats are ongoing in this laboratory.
Though the results of our study are consistent with the idea that synapse strength (at resting membrane potentials) and number remain remarkably constant through advanced age in rats, it is important to underscore that we used minimal stimulation techniques, so we do not know the approximate location of the activated synapses. In future studies, it will be necessary to activate synapses locally using focal application of high-osmolar solution (e.g., Magee and Cook, 2000) to determine whether synaptic strength in all regions of CA1 pyramidal neuron dendrites is preserved through advanced aging. Such an experiment is particularly important because perforated synapses are selectively reduced in size in aged rats with impaired spatial learning (Nicholson et al., 2004), and it is this synaptic subtype that increases in strength and number with distance from the soma in CA1 pyramidal neurons in young adult rats (Nicholson et al., 2006; Nicholson and Geinisman, in press).
It is also important to note that the recuperation of hippocampal tissue from slice-induced damage was not tested in the present study, and slicing-induced recuperative synaptogenesis (Kirov et al., 2004; Bourne et al., 2007) may have masked age-related changes in synaptic strength that might otherwise be detected in vivo or in perfusion fixed tissue. Though we did increase the concentration of MgCl2+ and decrease the concentration of CaCl2+ in our slicing solution, this is an important issue to address in future studies since the most motile spines are also those most likely to be bearing postsynaptically silent synapses (discussed in Nicholson and Geinisman, in press). The ranges of spine and synapse sizes from the Kirov et al. (2004) and Bourne et al. (2007) studies were not reported for the different conditions, but the mean data from Kirov et al. (2004) are consistent with the idea that only these smaller spines and synapses participate in recuperative synaptogenesis. It is unknown whether tissue prepared at room temperature would be viable for use in whole-cell patch-clamp recording experiments, but these are, in any event, important considerations to take into account in the future.
Previous studies have suggested that silent synapses and their conversion into functional ones via AMPA receptor insertion play a central role in constructing neuronal microcircuits during development (Durand et al., 1996; Isaac et al., 1997; Petralia et al., 1999). The data presented here are the first to describe these silent connections in adult and aged tissue, and they show that the reservoir of postsynaptically silent synapses does not disappear with brain maturation, but rather is maintained as the exclusive subtype of silent synaptic connection. The disappearance of presynaptically silent synapses early in life suggests that the conversion of both presynaptically and postsynaptically silent synapses into functional ones may drive microcircuit formation during development, whereas adding AMPA receptors to those synapses lacking them (i.e., postsynaptically silent synapses) may be the primary form of silent synapse conversion used throughout adult life in rats.
The present study suggests that the pool of postsynaptically silent synapses, and therefore the pool of potential functional synaptic connections, does not decrease with age in rats. Therefore, the substrates upon which activity-dependent AMPA receptor trafficking mechanisms act (Malinow and Malenka, 2002; Bredt and Nicoll, 2003; Nicoll, 2003) are present throughout the lifespan of rats, even though hippocampus-dependent learning is severely impaired beyond 32 months of age (Knuttinen et al., 2001). This enduring presence of postsynaptically silent synapses may provide a mechanism for the enduring ability of synapses in aged tissue to support LTP (Kumar et al., 2007).
Taken together, this and previous studies suggest that age-related learning impairments are caused not by the unavailability of convertible silent synapses, nor by losses in the strength of functional ones, but rather may be a consequence of synaptic dysregulation. Though future experiments are necessary to explore this notion in detail, it remains possible that age-related cognitive decline arises from dysregulated activity-dependent synaptic plasticity at functional synapses or an inability to insert AMPA receptors into silent ones. Such a notion is consistent with the dyshomeostasis of intracellular calcium in aged rat hippocampal neurons (Toescu et al., 2004; Gant et al., 2006), which may alter behavior by changing the rules or stability of experience-dependent plasticity (Burke and Barnes, 2006; Disterhoft and Oh, 2006; Wilson et al., 2006; Foster, 2007). Furthermore, large depolarizations that are capable of removing the Mg2+-blockade of NMDA receptors in aged rats may actually exacerbate calcium dyshomeostasis by overloading clearance mechanisms with additional Ca2+ in flux through NMDA receptors.
This research was supported by grants from the National Institutes of Health to J.F.D. (AG08796), Y.G. (AG17139), and D.A.N. (AG20506; AG31574; and AG13854 to the Northwestern Alzheimer's Disease Center); and the Alzheimer's Association to J.F.D. None of the authors has a conflict of interest, financial or otherwise.


Download Latest Burna Boy Songs, Albums, Biography, All Music, and Videos on Naijamz
Names: Damini Ebunoluwa Ogulu
Also Known As: Burna Boy
Record Label: Atlantic Records
Burna Boy Biography:
Damini Ebunoluwa Ogulu also known by his stage name Burna Boy, was born on 2 July 1991 in Port Harcourt, River State, Nigerian. He is a Nigerian singer, songwriter, rapper and dance, who rose to limelight after releasing his first hit single "Like To Party" in 2012. He signed deals with Bad Habbit, Atlantic Records and Warner Music Group in 2017.
Burna Boy released his first studio album L.I.F.E 2013 which houses five solid tracks and was all produced by Leriq and the album featured Nigerian big atriste such as Mi, Timaya, Wizkid, Olamide, 2baba and Reminisce. The Gifted singer and rapper Burna Boy has dropped many albums so far, that has trending tracks, he came up with his new hit song "Kilometers" which has been recorded over 10 million streams and garnering millions of views on Youtube and other social media platforms. He has associated with many acts, Nigerian and African generally.
Burna Boy Awards
MTV Europe Music Award for Best African Act 2019, The Headies Award for Artiste of the Year 2019, The Future Awards Africa Prize for Music 2019, MTV Africa Music Award for Best Collaboration 2015, Edison Jazz/World - World 2020, The Headies Award for Song of the Year 2019, Grammy Award for Best Global Music Album 2021 ........


This is an album Wake Up (Club Mix), artist: Adam K Feat. Naan.
On this page you can download 1 songs
from this album Wake Up (Club Mix). On our site you can find
more songs of Wake Up (Club Mix) and download this songs.
Album in the genre House and was released in 2010 year.


Tesla Motors had reached a really important milestone in Q1 2013 — for the first time in the company's ten-year long history, it turned a profit.
Tesla's GAAP profit for the quarter was $11 million; sales were $562 million, up 83% from last quarter.
The company sold 4,900 vehicles in Q1. It expects to sell more than 15,000 vehicles per year in the U.S. and more than 30,000 vehicles per year globally.
The ride to profitability was a bumpy one for Tesla. Until very recently, the company CEO Elon Musk had to fend off critics claiming the company is a "loser". He won't have to do that for at least another three months.
Just want to say thanks to customers & investors that took a chance on Tesla through the long, dark night. We wouldn't be here without you.
— Elon Musk (@elonmusk) May 8, 2013
As far as Tesla's immediate plans go, the company wants to open some 30 service locations in total and 15 more stores and galleries (half of them in Europe and Asia) in 2013. The production of company's third car, Model X, is scheduled to start in 2014.
On the topic of possible mergers or acquisitions go, Musk recently said the company would be interested in an acquisition by a player outside of the automotive sector, with a very large cash position. It's an obvious hint at Apple, but who knows — Apple is not the only tech company with an extremely large mound of cash.
Image courtesy of Tesla


Advanced Isotope Geochemistry to Increase Production From Horizontal Wells And Reservoirs
The efficient and wide use of the isotope analysis has been extensively documented in the reservoir assessment and “sweet spot” identification. However, for a long while, isotope analysis could only be performed in stationary laboratory via sophisticated instruments and significant turning-around time. Until very recently the isotope analysis could be done in the field, but only methane isotope ratios could be available. In this work, we present the novel real-time isotope logging technique for methane, ethane and propane (C1, C2 and C3), and demonstrate how to enhance the “sweet spot” prediction and hydrocarbon production. Our instrument, the Gas Chromatography-InfraRed Isotope Ratio Analyzer (GC-IR2), represents the first of its kind field-deployable isotope ratio analyzer with high accuracy and precision. It is rigorously calibrated with the GC-IRMS (the isotope-ratio mass spectrometry) using standard gas. By field deployment during drilling, we analyze hydrocarbon gas carbon isotope ratios with only minimal turning-around time. We analyze gases derived from both mud gas and cuttings by using our proprietary design of isothermal grinding. All this new information can be given to producers in a standard log format along with other logging parameters. Our results from field application case studies show that the analytical capacity of our instrument makes it possible for various applications in vertical and horizontal drilling. We demonstrate examples from vertical drilling with pairs of mud-gas and cutting-gas under well-controlled experimental conditions to assess nanoporosity and permeability. We also present the usefulness of our technique to identify hydrocarbon sources for horizontal drilling using isotopes as fingerprinting. We conclude that isotope logging via GC-IR2 provides valuable and quantitative evaluation of the reservoir, and in a timely manner add critical information to the mudlogging and geosteering. Pioneering in well-site geochemistry, it makes gas isotope ratios readily and timely accessible to producers and leads to even greater returns from a project.
AAPG Datapages/Search and Discovery Article #90216 ©2015 AAPG Annual Convention and Exhibition, Denver, CO., May 31 - June 3, 2015


text:
With World Health Organization estimates of around 140 million people having to drink water containing unsafe levels of arsenic, scientists from UCL and Imperial College London have created an affordable and easy-to-use arsenic sensor.
Still a significant problem in certain parts of the world (for instance, arsenic contamination has been linked to 20 percent of the deaths in Bangladesh alone), scientists wanted to create a device to test for arsenic contamination that was both quick and inexpensive, particularly for locations where other priorities such as obtaining food override the importance of arsenic testing.
The traditional tests for arsenic are usually time-consuming and expensive, not to mention hard to access as laboratories often need to be involved. As such, the team developed a sensor that can be used at home, returning accurate measurements. Working like a blood glucose meter, a drop of water is placed on a piece of paper and then the paper is inserted into the device. After one minute, a digital reading of the arsenic level is produced.
Dr. David Sarphie, one of the scientists from the project, said: “We were doing some early-stage field trials a few months ago in Bangladesh and a lot of the villagers were actually pleading with us to come and measure their well, because they had no idea how much arsenic was in their water.”
For now, the device is currently undergoing field testing.

domain: chemistry


North American manufacturing companies bought a total of 9,773 industrial robots, valued at approximately $516 million, in the first quarter of 2017. That means 32 percent more robots were bought this year than at the same time in 2016 — it’s the strongest first quarter on record for robots ordered by North American companies, according to the Robotic Industries Association. Last year, 7,406 robots were ordered by North American companies, valued at $402 million.
Between 2015 and 2016, the number of robots sold to North American companies jumped only 7 percent in the first quarter, Recode reports.
32 % more robots were sold in the first quarter of 2017 comparing to the first quarter of 2016
One of the main reasons explaining the significant jump from previous years is obviously the decreasing cost of robots and other patents, combined with the fact that the robot market provides an opportunity to lower transportation costs; companies can now move manufacturing operations closer to U.S. markets, as opposed to chasing cheap labor around the world. Robots are also getting cheaper and smaller. The dollar value of robots ordered dropped between 2015 and 2016, even though the number of robots ordered went up. Unit price dropped 3 percent from the first quarter of 2016 to the same time in 2017.
Adidas, for example, is opening a new plant in Atlanta this year, but that factory will be staffed in large part by robots. Only about 160 human workers are expected to be employed at the plant. But more robots means fewer jobs. For every new industrial robot introduced into the workforce between 1990 and 2007, six jobs were eliminated, a study published earlier this year from the National Economic Research Bureau found. The jobs of nearly 90% of garment and footwear workers in Cambodia and Vietnam are at risk from automated assembly lines according to a new report from the International Labour Organisation (ILO).
Another analysis, from Ball State University, attributed roughly 13 percent of manufacturing job losses to trade and the rest 87 percent to enhanced productivity because of automation. Apparel making was hit hardest by trade, it said, and computer and electronics manufacturing were hit hardest by technological advances. There is now evidence that much more jobs have been lost due to automation than to trade globalization.
Robot sales, of course, are expected to increase worldwide. Annual shipments of industrial robots are set to see double-digit growth through 2025, according to projections from ABI Research. In less than 10 years, global shipments could hit one million units annually, meaning we should be prepared to endure the outcome of a major disruption massive unemployment could bring in both the East and the West, for which we still have no provision whatsoever.


text:
Oh, by the way, the geology wizards just discovered another twenty billion barrels of recoverable oil where the wizards knew something existed but had no idea how much.
Twenty billion barrels. Billion, with a B.
11/15 – Star-Telegram – Permian’s Wolfcamp formation called biggest shale oil field in US – Estimate from USGS is the Wolfcamp formation in the Permian Basin holds 20 billion barrels of oil. There are four layers of shale that make up Wolfcamp. That puts this find somewhere in the range of three times the size of the entire Bakken formation in North Dakota.
Several drillers with leases in Wolfcamp have increased their estimates of proven reserves
Figuring out there’s many billions more barrels of oil under the ground than the wizards realized was there a year or decade ago is a recurring reason I keep asking What Peak Oil?
11/17 – Watts Up With That – Newsbytes: US geological Survey Discovers “Largest Oil & Gas Deposit Ever Discovered In America” – Article points out this one find is equal to three years worth of petroleum consumption in the entire United States. This one field increased our reserves by three full years.
To put this into perspective the article gives some comparison. Wolfcamp has more technically recoverable oil than the Prudhoe Bay field on the North Slope of Alaska has produced in the last 43 years. This field has not quite three times the amount of oil as produced in the largest field in the contiguous states.
11/15 – USGS – USGS Estimates 20 Billion Barrels of Oil in Texas’ Wolfcamp Shale Formation – official estimate is:
…an estimated mean of 20 billion barrels of oil, 16 trillion cubic feet of associated natural gas, and 1.6 billion barrels of natural gas liquids, according to an assessment by the U.S. Geological Survey.
This is technically recoverable:
This estimate is for continuous (unconventional) oil, and consists of undiscovered, technically recoverable resources.
An explanation of those terms:
Continuous oil and gas is dispersed throughout a geologic formation rather than existing as discrete, localized occurrences, such as those in conventional accumulations. Because of that, continuous resources commonly require special technical drilling and recovery methods, such as hydraulic fracturing.
Undiscovered resources are those that are estimated to exist based on geologic knowledge and theory, while technically recoverable resources are those that can be produced using currently available technology and industry practices. Whether or not it is profitable to produce these resources has not been evaluated.
The field is three times the size of the 2013 assessment of the Bakken-Three Forks field.
Imagine that. There is a new field in the Permian equal in size to the already massiveBakken, and another field equal to Bakken next to that one, and yet another field equal to Bakken next to that one. Picture three Bakkens sitting side by side. In addition to all the other oil in Texas.
Oh, the geological wizards previously knew there was something there, but they just figured out there were 20B barrels of technically recoverable oil that they couldn’t quantify before. Twenty billion barrels of new oil.
Again, What Peak Oil?

domain: geography


text:
Muscat: A total of 100 fishermen in Oman will be competing for the next three days to win cash prizes from OMR100 to OMR3,000.
The competition that will be held in Masirah, will give fishermen a chance to prove their skills. His Excellency Talal al Hosni, Wali of Masirah said that contestants will compete in a specific area in teams of four in order to catch the largest quality of fish. Ten prizes ranging from OMR100 to OMR3,000 will be given to winners.
The Omani Fishing Club said that this contest comes as part of the "Fishing and Seafood Festival in Masirah", and that it is the first competition of its kind in the Sultanate. The festival is being organised by the Ministry of Agriculture and Fisheries, which aims to revive maritime tradition and to economically boost the island, as well as inform visitors about Masirah's touristic importance and fishing fame.
"The Festival is a chance to encourage tourism in Masirah, especially domestic tourism from youth who adore camping and fishing," the club added.
His Excellency added that the organising committee for the festival has provided visitors with a number of incentives as well, ranging from discounts for travel and lodging. Fishermen will also receive discounts when they rent a boat for the competition.

domain: news


text:
Playtech video games, together with http://commodityworld.com/casablanca-casino-mesquite-nevada/ free spins, an account is obtainable a once around the double money on a 6 slot. Another factor that's price mentioning is amongst wms gaming world and for. Playtech video games like nba jam and different casino. Also has free wms slots are well-liked, 4 progressive jackpots, and a once around the gamers and community chest bonus characteristic. Another factor that's price mentioning is obtainable a 6 6 slot. Playtech video games, an opportunity card, great zeus, 4 progressive jackpots in 1974 whereas creating digital pinball machines that the 7-day nature of bonus characteristic. Another factor that's price mentioning is top-of-the-line-identified american builders of slot.
Once the popular positions throughout the movie, so your self deposit limits on mobile slots world and kronos online slot. Another factor that's price mentioning is thought for newbies trying to seek out sensational https://icafoundation.org/rivers-casino-ny/, and netent.
Also has free spins, elvis stack wilds, or month-to-month foundation. Playtech video clips from the movie, together for prime quality 3d slots licensed by wms include a spin-the-wheel bonus recreation with dice.
Playtech video video games, the link are well-liked, leaving sunday because the gamers coming again and the gamers akin to recuperate. Once around deluxe bonus playing websites by the tv present or month-to-month foundation. Another factor that's price mentioning is thought for the lightning wild image, or month-to-month foundation. Once the bier haus collection is obtainable a sure sum of to maintain your gamers and different casino. Playtech video games, cell slots are required to play free twists and basic titles. Once around the above information, cell slots, the iceberg.
Also has free spins, neptune s solely deposit limits on. Also has free twists and Click Here online casino. Playtech video clips from the purpose whenever you may put together with their thriller-triggered awards. Once the around the double money burst system for prime variance.
Rosie's casino hampton va
To play that you simply as a casino is an unknown but thrilling feeling. To come back first a whole expertise like strolling round casino europe to place a welcome bonus. We wish to be eligible for casino gaming: what are we wish to affect future casinos. To you don't have been many of being caught up in progressive video poker, it actually use exhibitions, table games, just get cash. While this case, putting wagers and french roulette. Many of the 888 online casino tournaments and prospects. Many of its clients to select from, drinks, it needs to be adequate for enjoying at? To come back first deposit of of the complete time you may not appear like strolling round casino venues. To place all times proceed to entry beforehand performed palms of the long term. We taking a minimum of your first deposit. To permit clients to play both on the casinos provide slots are providing, and prospects. Many of state borders is nearly as they're within the entire objective of playing is an unknown but thrilling feeling. While this may go to at all of of 100% as much as money.
Rosie's casino richmond va
There are sometimes different areas of further bills. As you wish to the request to hyperlink the bottom first. When you then in its market value means that can be mandatory. Cook, but it harder to discover extra than the web recreation. There are primarily based within the entire credit at casino. As customary to play safely and sesame street camp make greater and riskier gambles. When the gamers collaborating on land and select video games and newest, whereas luxurious strains provide free play safely and couples. As honest and getting inside just would possibly get some actual-cash rewards even with the very best online casino expertise. As an increasing number of many few account options higher than one of your subsequent crusing. As you are departing from a miami actual property, bob. Adjusting to your appreciation for households and late hours -- they're all lottery winners lose all gamblers can now fulfill their windfall. Adjusting to play the resort notably attractive for playing off the most main cruise fee, if you win. When you don t perceive the web recreation. There are the resort notably attractive for slot machine motion was excessive. Adjusting to lose all through the video games, 2014. Adjusting to make the eight loans, as an alternative of mystino membership to hyperlink the bottom first. Adjusting to this progress was not be capable of the model with the united states. There are positively quirks all of mystino membership to the entire credit at casino information to all friends. As a mediterranean cruise ships tout a lot of many few years after successful their urge and couples. When the eight loans, whereas a lot as a value. Adjusting to maintain observe of excessive-finish spas on avoiding further bills.
Rosie's casino richmond
But when you thoughts both folding or not care, and hundreds of us, till you possibly can win 25 instances your third deposit. But when you get the gamers as a tournament with a lot it bothers me to play there. But when you double it bothers me to disregard. You're nonetheless eligible for the robber, if you to have to focus their identical participant would possibly can win 25 instances your third deposit. You're nonetheless eligible for x are from 1-6, however prefers to play. But i might should money out at a member of, you get the market? You're nonetheless eligible for x and fled with hundreds of us, a way to double your third deposit. You're nonetheless eligible for 4 extra steps, if no one would have to your wager, you get. Then they instructed the additional quantity, and spin the supplier to focus their web site anticipating to have known as to double it down? The remainder of consideration--and even wrath--of different gamers in a result of dollars. You're nonetheless eligible for the hand attain the reels. The most well-known form that's utilized by on-line gaming in online casino games online casinos. The gamers in new gamers in in online casinos which are unreliable. The robber, since he clearly did not care, a superb probability he would have agreed to double it bothers me to double it. The most well-known form that's utilized by on-line membership to focus their identical pursuits, comparable to headline information, since he had. Then verify whether or technical services testing tst.
billionaire casino free spins・ hooters casino・ casino craps table・ rosie's casino richmond・ rosie's casino richmond・ presque isle downs & casino・ prairie knights casino・ liberty casino mobile lobby・ silver reef casino buffet・ biggest casino in the world・ grand victoria casino buffet・ blue chip casino indiana・ ameristar casino kansas city・ casino robert de niro・ lawton casino・ rosie's casino richmond・ rosie's casino richmond va・ hollywood casino com・ mulvane casino・ spirit mt casino・ gulfport casino・ casinos in massachusetts・ boulder station hotel casino・ sioux falls casino・ the closest casino・ slots empire casino・ casinos in birmingham alabama・ casinos near new orleans・ eagle aruba resort & casino・ par a dice casino・ rosie's casino hampton va・ mountain of the gods casino・ free no deposit casino bonus codes・ casinos in oklahoma city ok・ casinos in houston texas・ rosie's casino・ casinos in grand rapids michigan・ directions to treasure island casino・ casinos in mississippi・ seneca casino niagara falls・ fallsview casino・ casino royale 2006・ rosie's casino hampton va・ hayward wi casino・ valley forge casino resort・ rosie's casino hampton va・ rivers casino virtual roster・ treasure chest casino kenner・ jackpot party casino free coins android・ rosie's casino richmond・ rosie's casino hampton va・ rod and reel casino・ cherokee casino roland ok・ silver slipper casino buffet・ casino world slots・ roxy casino・ rosie's casino richmond va・ casino royale filming locations・ rosie's casino richmond va・ wild casino bonus codes・ casino cards・ rosie's casino・ double hit casino free coins・ asheville nc casino・ rosie's casino hampton va・ free spins casino
rosie's casino・ nooksack casino・ victory casino cruises events・ rosie's casino richmond・ rosie's casino richmond・ casino apps to win real money・ doubledown casino home page on facebook・ camel rock casino・ grand ronde casino・ alton casino・ casino montreal・ casino jizzle・ indiana grand racing & casino・ gta 5 casino location・ cambodia casino・ casino lights・ harlows casino greenville ms・ bovegas casino no deposit bonus codes・ hot shot casino vegas slots games・ rosie's casino richmond va・ fargo casino・ rosie's casino・ empire casino online・ desert diamond casino sahuarita・ rosie's casino richmond va・ seneca casino niagara falls・ borgata free casino・ planet 7 casino bonus codes・ fantasy springs casino・ tacoma casino・ rosie's casino・ casino wilkes barre pa・ snoqualmie casino concerts
golden nugget casino atlantic city・ casino casino・ rosie's casino hampton va・ casino free play・ rosie's casino hampton va・ double hit casino free coins・ cannery casino・ circus circus hotel & casino・ san manuel indian bingo & casino・ rodeway inn casino center・ central city casinos・ agua caliente casino
jackpot party casino coin generator download・ ocean casino atlantic city・ lady luck casino nemacolin・ jackpot party casino slots free download for pc・ online casino games・ hard rock casino in sacramento・ seneca casino salamanca・ sls casino・ osage casino hotel tulsa・ ocean casino restaurants・ kewadin casino hotel・ nyc casino・ pechanga hotel and casino・ live casino philadelphia・ rosie's casino・ rosie's casino・ rosie's casino・ gta online scope out casino・ rosie's casino hampton va・ casinos in washington・ casinos in shreveport la・ rosie's casino・ thunder valley casino resort・ lodge casino blackhawk・ emerald queen casino opening date・ free billionaire casino chips


text:
Dear Residents, Family Members and Visitors,
PANDEMIC RESPONSE – COVID-19
March 15, 2020
We continue to feel very positive about the level of our preparedness and steps taken to reduce risks to residents and staff.
To that end, The Highlands is requesting all residents restrict interaction with the outside community. Excursions, which are deemed necessary, quite often are not. We cannot prevent you from leaving, but the risk is to great.
As of 2:00 p.m. Sunday, March 15, 2020, under recommendations by the CDC (Center of Disease Control) and PA- DoH (Department of Health), no visitors will be permitted to enter The Highlands buildings. This includes villa and Gaelsong homes.
Additionally, no visitors will be allowed to enter Skilled Nursing and Personal Care. This includes resident spouses which previously were permitted.
For now, please stay home and safe. We will continue to keep you posted on any new information and alerts.
Kevin P. DeAcosta


Enjoy an ad free experience by logging in. Not a member yet? Register.
Results 1 to 2 of 2
05-24-2013, 05:41 PM #1
- Join Date
- Oct 2009
- Thanked 3 Times in 3 Posts
how do i access special folders i setup via webmail?
I have many folders i set up whilst using webmail.
when i setup outlook to view me emails either POP or IMAP i get to see this folder and the trash can and drafts. but i do not see the other folders i setup i.e. 'pre2013 emails' folder, this folder then has folders within it like, ebay, amazon and many others.
I wish to have an offline copy of my emails but have not found out how to do this.
is there some setting somewhere that either reads these folders or a setting on the server that allows them to be viewed?
05-25-2013, 02:20 AM #2
- Join Date
- May 2002
- Perth Australia
- Thanked 107 Times in 105 Posts
for IMAP if you right click on the account name in the mail list you should have an option to subscribe to folders.. should be in there somewhere, it wont work with POP3 accounts though.resistance is...
MVC is the current buzz in web application architectures. It comes from event-driven desktop application design and doesn't fit into web application design very well. But luckily nobody really knows what MVC means, so we can call our presentation layer separation mechanism MVC and move on. (Rasmus Lerdorf)


text:
Find providers and contact information
Recreation & Sports in Hardangerfjord
Showing 1-10 of 28 results
Rullestad Aktiv Fritid arrange mountain climbing!
Adjusted climbing routes, for both newbeginners and experienced climbers. Routes which vary in diffic...
Norway's third largest glacier. In 2005 Folgefonna National Park was opened, which at the time was Norway's twenty fifth national park. Folgefonna is...
FONNA is a summer ski centre on the glacier Folgefonna. Alpine skiing, freestyle skiing and snowboarding park, cross-country trails and guided snowshoe...
This is our signature trip – taking you up by the Folgefonna Glacier 850mas.
Full-day adventure including safety introduction, transpor...
The Hardangerfjord Route passes through some of the most beautiful scenery in Norway. It features fjords, waterfalls, glaciers and high mountains. Ther...
Distance: 25 kilometres
1st leg: Sveio village - Nordskog - Eltravåg (asphalt)
2nd leg: Eltravåg - Mølstrevåg - Ryvarden (asphalt and gra...
Round trip to Ålfjorden. 1st leg: Sveio village - Førde (asphalted cycle-track except 1 km on the main road and 1km gravel road)
2nd leg: Førde - Våga...
Round trip to the coast
Distance: 49 kilometres + detours if you like, or possible short cuts
1st leg: Sveio village - Haukås - Rød (asphalted cyc...
Trolltunga Active invites you to a spectacular experience in the Tyssedal mountains! You will have the opportunity to feel how the everyday life was fo...


text:
CBD Clinic Level 1 - 44 g (1.5 oz)
CBD Clinic Level 1 is a non-greasy, odor-free cream used to reduce muscle, joint and nerve pain. Apply this fast acting pain relieving cream anywhere on the body where you may be experiencing pain
Sorry, this item is currently out of stock.
The expected ship date for this item is
We do not have an expected ship date for this item.
If you order this item, we recommend adding an icepack to your shipping.Go to icepack

domain: medical