A research project that began 20 years ago with an interest in how lithium treats mood disorders has yielded insights into the progression of blood cancers such as leukemia. The research, which centers on a protein called GSK-3, will be published in the Nov. 3 issue of the Journal of Biological Chemistry.
Lithium is considered a highly effective treatment for bipolar disorder and other mood disorders, but it still works in only a fraction of patients and has a number of side effects. Furthermore, its mechanism of action is poorly understood, hampering efforts to improve on it.
In 1996, Peter Klein of the University of Pennsylvania discovered that one of lithium's biological activities was inhibiting GSK-3, an enzyme that modifies other proteins by attaching phosphate molecules, a process called phosphorylation. Lithium's effect on GSK-3 affected the development of animal cells, but it is still unknown what connection, if any, this has to psychiatric disease.
Since then, Klein -- now a professor of medicine at the University of Pennsylvania -- has been investigating many different aspects of GSK-3 activity. "In this paper, we were trying to find out what proteins in the cell are affected by GSK-3 inhibition," Klein said. "We compared cells with GSK-3 to cells completely lacking GSK-3 to ask how other proteins changed."
"Mood disorders are so multifaceted in terms of the pathways and pathologies involved; it's really difficult to pin down a specific pathway," said Mansi Shinde, a former graduate student in Klein's research group who led the new study. "We said: Let's look at what GSK-3 does, and that would maybe lead us toward what lithium does."
The research team used mass spectrometry to compare phosphorylation of proteins from mouse embryonic stem cells with fully functioning GSK-3 to cells in which the gene encoding GSK-3 had been deleted. The resulting massive dataset is called a phosphoproteome -- a comprehensive catalog of proteins that are phosphorylated by GSK-3. Analyzing the data yielded some surprising findings.
Conventional wisdom had suggested that GSK-3 phosphorylates proteins that contain a specific amino acid sequence, but the new phosphoproteome showed that the majority of proteins whose phosphorylation depended on GSK-3 did not contain this sequence. Notably, the phosphorylated proteins included a group called splicing factors, which splice together different sections of messenger RNA, changing the proteins that they encode. Absence of GSK-3 changed the splicing patterns of more than 200 messenger RNAs.
The finding that GSK-3 could affect RNA splicing pointed to an unexpected connection: leukemia. Several factors newly discovered to be phosphorylated by GSK-3 are also known to be mutated in acute myeloid leukemia, a condition in which aberrant splicing causes uncontrolled white blood cell proliferation. This observation could also explain why one of the side effects of taking lithium is increased white blood cell count.
"The effect on the splicing factors and other mutations associated with leukemia was completely surprising to me," Klein said. The group is therefore now pursuing investigations into how GSK-3 affects the growth of healthy and leukemic blood cells.
Shinde and Klein are not yet sure whether GSK-3's effect on RNA splicing explains its role in mood disorders. The effect of GSK-3 on messenger RNA in neuronal cells, with or without lithium, would need to be examined to determine this. The study underlines how investigations into the basic biological function of a drug target can lead in unexpected directions. "[The GSK-3 phosphoproteome] is a really large data set," Shinde said. "It's a resource for the field." "The relevance to leukemia could be direct and something worthy of immediate study," Klein said. "The role in psychiatric disorders is a major interest of the work, but the impact would be down the road, not immediate."
People who die from opioid overdoses are significantly more likely to suffer from chronic pain and depression, according to a new study that highlights the risk of combining opioid pain relievers with benzodiazepines, a class of anti-anxiety medication.
Researchers at Columbia University Medical Center analyzed over 13,000 overdose deaths among Medicaid patients and found that over 61 percent had been diagnosed with back pain, headaches or some other chronic pain condition. Many also suffered from depression, anxiety, bipolar disorder, schizophrenia and other mental health problems.
Significantly, nearly half of those with chronic pain (49%) filled a prescription for opioid pain medication during the last 30 days of their lives, and just over half (52%) filled a prescription for benzodiazepines. Prescriptions for anti-depressants, anti-psychotics and mood stabilizers were also common.
“This medication combination is known to increase the risk of respiratory depression, which is the unusually slow and shallow breathing that is the primary cause of death in most fatal opioid overdoses," said Mark Olfson, MD, a professor of psychiatry at Columbia and lead investigator of the study.
“Most persons with opioid-related fatalities were diagnosed with one or more chronic pain condition in the last year of life. As compared to people with opioid-related deaths without diagnosed chronic pain conditions, the decedents with chronic pain diagnoses were more likely to have also received substance use and other mental health disorder diagnoses. They were also more likely to have filled prescriptions for opioids, benzodiazepines, and other psychotropic medications and to have had a nonfatal drug overdose.”
The Columbia study included opioid overdoses linked to both pain medication and illegal opioids such as heroin, but was limited to Medicaid patients who died between 2001 and 2007. Since that time, opioid prescribing has declined, while illegal opioids and counterfeit medication have become increasingly available on the black market.
Public health officials have only recently started warning about the risks of combining opioids with benzodiazepines, and some insurers now refuse to pay for the medications when they are prescribed jointly.
A recent study of overdose deaths in Florida found that benzodiazepines such as Xanax and Valium killed nearly twice as many Floridians in 2016 as oxycodone. Another study in Pennsylvania also found that overdose deaths involving benzodiazepines exceeded those from opioid painkillers.
The Columbia study was published online in the American Journal of Psychiatry. The study was funded by the Agency for Healthcare Research and Quality, the National Institute on Drug Abuse, and the New York Psychiatric Institute.
Pain News Network
As pretty as they are, real Christmas trees can make you wheeze and sneeze. It's likely not the tree itself that triggers allergies but the microscopic mold spores that can harbor in its branches. If you can't resist buying a live tree despite winter allergies, take it home a week before you plan to decorate it and leave it in a garage or an enclosed porch. Then give it a good shake to try to get rid of any spores.
Hallucinogen-persisting perception disorder, or HPPD, causes a person to keep reliving the visual element of an experience caused by hallucinogenic drugs. But what do the flashbacks in HPPD feel like, what causes them, and how might they be treated?A person with HPPD has frequent visual disturbances. They do not relive any other aspects of a drug trip, only the part that involved vision. The way the flashbacks in HPPD affect a person's vision can be frustrating and may cause anxiety.
This article explores the symptoms and causes of HPPD. It also discusses how a person experiencing HPPD can manage their condition.
Contents of this article:
What is HPPD?
A person with HPPD has frequent visual disturbances, which may cause anxiety.
Unlike the immersive flashbacks that some people have after taking drugs, HPPD flashbacks are purely visual. This means that a person with HPPD just has visual disturbances, such as seeing blurry patterns, size distortion, and bright circles.
These individuals do not relive any other aspects of the feeling of being on drugs.
HPPD flashbacks are not usually pleasurable, and they can become annoying if they occur frequently or last for a long time. The flashbacks may also cause anxiety.
HPPD does not cause people to have full hallucinations or delusions.
Someone experiencing HPPD is usually aware that it is a visual disturbance and can determine what is real, as a 2012 study explains. This qualifies HPPD visual disturbances as pseudohallucinations.
HPPD can affect the way a person perceives visual input.
According to a 2016 review, there are two types of the condition:
The visual disturbances a person with HPPD may experience include:
Experiencing the symptoms of HPPD can be distressing.
It is usually apparent to a person experiencing HPPD that they are not seeing things in the way they used to. This can be unnerving and may cause anxiety.
Some people with HPPD experience visual disturbances alongside other symptoms. These may include:
Depersonalization disorder is a mental health condition where a person may feel like:
Researchers do not fully understand how these conditions relate to HPPD, but many report that they experience them alongside visual disturbances.
Causes and risk factors
A person with HPPD may experience visual disturbances, such as bright circles and blurry patterns.Researchers believe that people are at risk of experiencing HPPD if they take hallucinogenic drugs recreationally. However, they do not yet understand the type or frequency of drug use that causes it.
According to a 2003 study, HPPD is reported most commonly after illicit use of LSD. There are also reports of people who have only used hallucinogens once or twice experiencing similar symptoms.
HPPD is not caused by brain damage or a mental disorder. It is also not the result of current intoxication or by an amount of a drug staying in a person's system. Nor is HPPD caused by a "bad trip." These are all common beliefs about HPPD that are not true.
More research is needed to understand the changes in the brain that cause HPPD symptoms.
Disclosing any past drug use will enable the doctor to give an accurate diagnosis.
If a person is experiencing visual disturbances, they should speak to their doctor.
There are some other conditions that could be the cause. As such, the doctor may ask a number of questions to reach a diagnosis.
It is important to be open and honest about any past drug use, to help the doctor reach the correct diagnosis.
A person's relationship with a doctor is confidential. The doctor is there to provide the best course of treatment and not judge lifestyle choices.
Most doctors do have an awareness of HPPD as a condition. If a doctor is not sympathetic to a person's symptoms or does not want to explore HPPD as a diagnosis, then it is a good idea to speak to a different doctor.
Management and treatment
There is no one recommended course of treatment for HPPD. However, there are two drugs that initial research suggests may be effective. These are:
The effectiveness of drug therapy can vary from person to person. Every person who has visual disturbances as a result of HPPD experiences them slightly differently.
The 2012 study also recommends the following to help manage symptoms:
HPPD symptoms may cause anxiety. In turn, stress and anxiety may make HPPD symptoms worse. Trying mindfulness, yoga, or meditation may help to reduce stress and anxiety.
Most people who experience HPPD only have symptoms for a short time after drug use. However, there are examples of people experiencing HPPD symptoms over a number of years.
A doctor can help provide advice on managing HPPD symptoms and may prescribe a course of drug therapy to help.
As researchers come to understand more about the condition, a more extensive range of treatments may become available.
Source -Medical News Today
“Abusing Sedatives To Get Skinny.” “The Women Sleeping Their Lives Away To Lose Weight.” Recent headlines like these about the “Sleeping Beauty” diet (taking sedatives to avoid eating, a.k.a. narcorexia) seem designed to shock. And shock, they do. But the behavior is not new.
I dabbled in it a decade ago when I lost a boyfriend to a motorcycle crash and was downsized out of a job that I adored. During that trying time, the only thing I felt I could control was my weight. So I began working out two hours a day and ate no more than 1,000 calories. Since I often hit that piddly number by 4 p.m., I’d pop a sedative. Sleep was the sole way to escape my unbearable hunger.
Ironically, doing that for nearly four months slowed my metabolism while fueling my depression. What’s insidious about eating disorders is that they often begin as a disciplined strategy to improve your body and life, but once they take over, they make both worse. “You’re essentially shutting off your life to not eat,” says eating disorders expert Rachel Salk, Ph.D. “That’s how powerful and destructive these distorted thoughts can be.”
Once I realized that the weight-loss plan I’d started so I could feel in charge of my life was crippling it, I sought help. Headlines like the ones above do anything but help, and in fact seem to exist to feed disordered ideas to pro-anorexia blogs.
by David Hill
UNIVERSITY AT BUFFALO
The anxiety many men experience after being diagnosed with prostate cancer may lead them to choose potentially unnecessary treatment options, researchers report.
“Emotional distress may motivate men with low-risk prostate cancer to choose more aggressive treatment, such as choosing surgery over active surveillance,” says the study’s lead author, Heather Orom, associate professor of community health and health behavior in the University at Buffalo’s School of Public Health and Health Professions.
“It underscores what we have been pushing a long time for, which is, ‘Let’s make this decision as informed and supported as possible.’ If distress early on is influencing treatment choice, then maybe we help men by providing clearer information about prognosis and strategies for dealing with anxiety. We hope this will help improve the treatment decision making process and ultimately, the patient’s quality of life,” adds Orom.
Researchers measured participants’ emotional distress with the Distress Thermometer, an 11-point scale ranging from 0 (no distress) to 10 (extreme distress). The men were assessed after diagnosis and again as soon as they had made their treatment decision. The majority of study participants had either low- or intermediate-risk disease, and were more likely to have been treated with surgery, followed by radiation and active surveillance.The study involved 1,531 men with newly diagnosed, clinically localized prostate cancer, meaning the disease hadn’t spread to other parts of the body.
“Men’s level of emotional distress shortly after diagnosis predicted greater likelihood of choosing surgery over active surveillance,” the researchers report. “Importantly, this was true among men with low-risk disease, for whom active surveillance may be a clinically viable option and side effects of surgery might be avoided.”
While prostate cancer is a major disease in the US, it is not a death sentence, according to the American Cancer Society, which estimates there are nearly 3 million prostate cancer survivors alive today.
However, overtreatment is a concern, and surgery and radiation therapy have side effects that include erectile dysfunction and incontinence, which, for the majority of men diagnosed with low-risk prostate cancer, can be avoided by instead choosing active surveillance to monitor the cancer and considering treatment if the disease progresses.
“There’s an interest in driving the decision-making experience to prevent overtreatment and ensure that men have full information about all the side effects so they can make a choice that’s preference and value driven,” Orom says. “We don’t want men to make a decision that they’ll regret later on.”
“The goal of most physicians treating men with prostate cancer is to help their patients and family members through a difficult process and help their patients receive appropriate treatment,” says coauthor Willie Underwood, an associate professor in Roswell Park Cancer Institute’s urology department.
“To do so, it is helpful for physicians to better understand what is motivating men’s decisions and to address negative motivators such as emotional distress to prevent men from receiving a treatment that they don’t need or will later regret,” Underwood adds.
By Dr. Sanjay Gupta,
(CNN)Of all the provocative strategies to reduce harm from opioid addiction, the one that I am about to describe is near the top.
Over the past several months, hardly anyone I spoke to about the abuse of opioids in the United States, including pain pills and heroin, had a neutral point of view about what is happening in a small but important corner of the larger epidemic.
The place is where a former security guard named Hector Mata became an expert at reversing overdoses and probably saved 25 lives in the process. It is not a hospital or a clinic.
Mata's infirmary is the Corner Project, a syringe exchange program that began operating in the New York neighborhood of Washington Heights, which houses a bathroom where drug users can more safely inject heroin.
On first glance, there is not much that is special about this bathroom except that there is someone checking in on an intercom every three minutes to make sure the user is still conscious.
"A moral obligation"
If a user doesn't respond on the check-in, Mata, or someone similarly trained, will press a button to unlock the door and rush in, armed with a syringe full of naloxone, also known by the brand name Narcan, and hopefully reverse the effects of the opioid drugs. After seven years and at least 25 overdoses, he says he has never failed.
While to some people, this sounds like a "consumption room," or a safe injection site, the staff here say it is simply a bathroom. After all, injection sites aren't legal under US law.
I sat down with the Corner Project's director, Liz Evans, and asked her just how a place like this legally exists. She told me that public bathrooms are the frontline of the opioid epidemic. "People are dying in those bathrooms, and so there's an acknowledgment that as a syringe exchange provider, we have a moral obligation to make sure that people don't die in our building." And so, the Corner Project has implemented a safety net to make sure that people don't die from overdoses in the bathroom in their building. Everything in this story is a murky gray.
Perhaps the story of the Corner Project could have been predicted. A heroin addict goes to a needle exchange, obtains clean needles and immediately heads to the bathroom to inject drugs. After all, according to recent studies in New York City, nearly two-thirds of drug users visit places like abandoned buildings, cars, and public bathrooms to inject drugs.
The Corner Project started out as a street based community outreach group in 2005. In 2009, when the Corner Project moved to its current brick and mortar location, the bathroom was just a matter of convenience for clients. Within a short time, however, there was an overdose in the bathroom, followed by another and so on.
Without a system in place, the workers at Corner Project would hear a characteristic thud from someone passing out in the bathroom, make a mad scramble for the keys and then work to revive the person. Though they were mostly successful, it was always frightening.
The Corner Project could have simply closed the bathroom or searched people before they used the facility, but the workers chose to do neither.
Instead, they kept it open and put in safety measures, like an intercom system, timers, and naloxone to help prevent overdoses. They stayed open knowing that if they closed their doors addicts would simply find another public restroom to use their drugs, far from the people who might be able to save them.
And with that, the Corner Project pushed the limits of harm reduction in the United States.
Since last year, the New York State Department of Health has followed the Corner Project's lead and instituted regulations and recommended procedures on how to best prevent overdoses in the places where users are likely to use: syringe exchange bathrooms.
Criminalization vs. rehabilitation
In the great debate of criminalization versus rehabilitation, many commonly held assumptions have been torn to shreds. For example, some believed the legalization of drugs like marijuana would lead to increased use. Yet in Colorado, which legalized recreational pot, teen marijuana use has dropped. When it comes to opioids, the number of people who overdose and die from legal prescription painkillers is about equal to the number of people who die from illicit drugs like heroin.
Another commonly held belief is that a safe injection site would implicitly condone the use of drugs and lead to increased use. And yet we now know that theory starts to fray when we look at what has happened at the Corner Project and at a place called InSite in Vancouver, Canada, which Liz Evans also helped found.
Started as a pilot project in 2003, InSite is one of only two legal supervised drug injection sites in Canada. They are the only two in North America. Though the centers don't provide any illicit drugs, the medical staff are there to provide first aid, including naloxone for overdoses, addiction counseling and mental health assistance. InSite has seen more than 3 million people since it opened, treated over 6,000 overdoses and not had a single person die.
Furthermore, a 2011 Lancet study revealed that in the neighborhoods surrounding InSite, in the two years after it opened, there was a 35% reduction in overdose deaths from the two and a half years before it opened, compared with a 9% drop in the rest of Vancouver. Although it is unclear the impact of InSite on decreasing the total number of drugs users, it has led to increased admissions for addiction treatment and detoxification.
And that also means cleaner communities. Streets and public restrooms aren't littered with needles and other drug paraphernalia. In fact, a recent survey of drug users from an undisclosed safe injection site in the United States found that if they hadn't used the site's facilities, over 90% of the users would be using in public bathrooms or out on the street.
These statistics are now the subject of dozens of studies in medical journals and were also recited to me as Mata showed me around the Corner Project's bathroom.
But he emphasized again, "It's not a safe injection site," he told me. He points out that unlike InSite, the Corner Project doesn't have actual medical professionals monitoring the bathroom. In fact, if a doctor or nurse were to actually supervise its bathrooms, he or she could lose their license. He also doesn't care for the term "consumption room," which has been around in Western Europe since the 1990s.
Instead, Mata insists I just call it a bathroom. Because unlike Canada or some countries in Europe, what I witnessed isn't actually legal in the United States.
At the front desk, a staff member monitored the clock and the intercom, checking to see whether any help was necessary. Considering the number of lives nearly lost in its bathroom, the mood in the Corner Project was calm and controlled.
The soft music, brightly colored walls and chalkboards, and chestnut-colored tables with staff members casually engaged in small talk gave it the feel of a neighborhood coffee shop, more than a place where overdoses are prevented.
A self-inflicted wound
Mata said my tour needed to be quick because the bathroom is in use almost all the time, and there is a waiting list that often lasts more than an hour.
One of the men in line was Taylor Prince, 35. Mata gave him a hug and then told me, "Taylor is a frequent flier." I found out later that Mata saved Prince's life on three occasions.
We find ourselves in the middle of an opioid epidemic that is the worst drug crisis in American history. It is a self-inflicted wound and one that is predominantly made in America, as we consume more than 80% of the world's supply of opioid pain pills, even though we are less than 5% of the world's population. Many of those prescriptions have led to heroin use; three out of four new heroin users started with prescription narcotics.
And there is no single strategy, as provocative or revolutionary as it may be, that is going to be the answer to turning those numbers completely around. Not even a controversial bathroom in the Washington Heights Corner Project could possibly do that, but in the meantime, Mata and others will work on saving as many lives as possible.
Recent studies suggest that men have a particularly high prevalence of high-risk oral human papillomaviruses (HPV), which can lead to cancer. There are more than 150 types of HPV, and while certain strains can cause benign growths like warts, a limited number can cause cancer at different anatomical sites, including the mouth, throat, anus, cervis and penis.
Oral HPV is a sexually transmitted virus and can be contracted through oral sex with an infected person.
Who’s at risk?
Amongst men, those who have had many lifetime oral sexual partners have the greatest risk of carrying such high risk HPV strains. While the number of tobacco-related head and neck cancers have declined in the U. S. thanks to a growing awareness of smoking-related risks, the incidence of oral cancer in men is still growing as a result of HPV. This rise was most notable in men aged 50-59, and these trends are anticipated to increase over the next 40 years, making oropharyngeal cancer a significant health concern.
HPV and Cancer
While most high-risk HPV infections go away within 1-to-2 years, and do not cause cancer, certain HPV infections can persist for many years. Persistent infections with high-risk HPV types can lead to cancer. HPV is so common that nearly all men and women get it at some point in their lives and are asymptomatic and never know. In most individuals, their immune system clears the infection. However, in some people the virus lingers in certain tissues like the oropharynx.
Screening and Prevention
While it is possible to identify the virus by analyzing saliva, this test is not yet part of routine screening practice and is being predominantly used in research settings.
HPV vaccination can reduce the risk of infection by the HPV types targeted by the vaccine. These vaccines provide strong protection against new HPV infections, but they are not effective at treating established HPV infections or disease caused by HPV. For them to be effective, individuals need to be vaccinated prior to being exposed to such viruses.
Currently the Gardasil vaccine is approved for use in in males and females ages 9 through 26. Given this age range, the vaccinations and discussions regarding the vaccine are largely being performed by pediatricians, primary care physicians and obstetricians and gynecologists.
Additionally, correct and consistent condom use may reduce HPV transmission between sexual partners. However, because areas not covered by a condom can be infected by the virus, condoms are unlikely to provide complete protection against the infection.
In regards to cancer, there are oral cancer screening programs available and while there are no current treatments for the HPV virus itself, there are a number of excellent curative treatment options for HPV-related oral cancer such as surgery and/or radiation-based treatments depending on the site, stage and health of the patient. Chemotherapy may added to radiation treatment in more advanced cases. HPV related oral cancers have a very favorable prognosis with modern treatments.
Richard Bakst, MD, is an Assistant Professor of Radiation Oncology at the Icahn School of Medicine at Mount Sinai. Dr. Bakst is a board-certified radiation oncologist whose clinical practice is focused on the treatment of patients with head and neck cancer, lymphoma and breast cancer.
The ragweed pollen season usually ends by mid-November in most areas of the country. If you have fall allergies and react to fungi and molds, you probably face your worst symptoms in late summer and early fall. Although you might feel miserable from the end of March until November, making it seem like you have year-round allergies, you should get a break now. November may be one of the best months for people with outdoor allergies, which allows for enjoying the crisp weather. Then, just in time, indoor allergies to pet dander and indoor molds pick up.
Italian dermatologists report the case of a woman with an unusual disorder: a tendency to sweat blood in a kind of modern-day stigmata.
The two doctors from the University of Florence report the woman’s condition in the latest issue of the Canadian Medical Association Journal.
They say the 21-year-old woman was admitted to hospital after three years of regularly sweating blood from her palms and face whenever she engaged in physical activity, or while sleeping.
She told them the bleeding often intensified during times of emotional stress, but she could find no other trigger for the bleeding spells.
The doctors saw evidence of the bloody sweat themselves and say it occurred without any form of lesions appearing on her hands or face.
“Our patient had become socially isolated owing to embarrassment over the bleeding and she reported symptoms consistent with major depressive disorder and panic disorder,” they write.
The doctors treated the woman’s mental health problems with anti-anxiety medications and, after eliminating other potential causes, diagnosed her with “hematohidrosis” – a rarely reported condition that causes the patient to excrete blood through unbroken skin.
The cause of the condition remains a mystery, but various theories have been proposed over the years. They include blood coagulation disorders, and problems involving overactive sympathetic nervous system activation.
“In the literature, there is no single explanation of the source of bleeding in hematohidrosis,” the doctors write.
The doctors write that, while they prescribed the woman a beta blocker medication called propranolol which helped diminish the woman’s symptoms, they have not been able to eliminate them completely.
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