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Posts Tagged 'psychiatry'
Broccoli sprout compound may restore brain chemistry imbalance linked to schizophrenia
Posted: May 9, 2019 in Uncategorized
Tags: broccoli, mental health, psychiatry, schizophrenia
In a series of recently published studies using animals and people, Johns Hopkins Medicine researchers say they have further characterized a set of chemical imbalances in the brains of people with schizophrenia related to the chemical glutamate. And they figured out how to tweak the level using a compound derived from broccoli sprouts.
They say the results advance the hope that supplementing with broccoli sprout extract, which contains high levels of the chemical sulforaphane, may someday provide a way to lower the doses of traditional antipsychotic medicines needed to manage schizophrenia symptoms, thus reducing unwanted side effects of the medicines.
"It's possible that future studies could show sulforaphane to be a safe supplement to give people at risk of developing schizophrenia as a way to prevent, delay or blunt the onset of symptoms," adds Akira Sawa, M.D., Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Schizophrenia Center.
Schizophrenia is marked by hallucinations, delusions and disordered thinking, feeling, behavior, perception and speaking. Drugs used to treat schizophrenia don't work completely for everyone, and they can cause a variety of undesirable side effects, including metabolic problems increasing cardiovascular risk, involuntary movements, restlessness, stiffness and "the shakes."
In a study described in the Jan. 9 edition of the journal JAMA Psychiatry, the researchers looked for differences in brain metabolism between people with schizophrenia and healthy controls. They recruited 81 people from the Johns Hopkins Schizophrenia Center within 24 months of their first psychosis episode, which can be a characteristic symptom of schizophrenia, as well as 91 healthy controls from the community. The participants were an average of 22 years old, and 58% were men.
The researchers used a powerful magnet to measure and compare five regions in the brain between the people with and without psychosis. A computer analysis of 7-Tesla magnetic resonance spectroscopy (MRS) data identified individual chemical metabolites and their quantities.
The researchers found on average 4% significantly lower levels of the brain chemical glutamate in the anterior cingulate cortex region of the brain in people with psychosis compared to healthy people.
Glutamate is known for its role in sending messages between brain cells, and has been linked to depression and schizophrenia, so these findings added to evidence that glutamate levels have a role in schizophrenia.
Additionally, the researchers found a significant reduction of 3% of the chemical glutathione in the brain's anterior cingulate cortex and 8% in the thalamus. Glutathione is made of three smaller molecules, and one of them is glutamate.
Next, the researchers asked how glutamate might be managed in the brain and whether that management is faulty in disease. They first looked at how it's stored. Because glutamate is a building block of glutathione, the researchers wondered if the brain might use glutathione as a way to store extra glutamate. And if so, the researchers questioned if they could use known drugs to shift this balance to either release glutamate from storage when there isn't enough, or send it into storage if there is too much.
In another study, described in the Feb. 12 issue of the journal PNAS, the team used the drug L-Buthionine sulfoximine in rat brain cells to block an enzyme that turns glutamate into glutathione, allowing it to be used up. The researchers found that theses nerves were more excited and fired faster, which means they were sending more messages to other brain cells. The researchers say shifting the balance this way is akin to shifting the brain cells to a pattern similar to one found in the brains of people with schizophrenia. Next, the researchers wanted to see if they could do the opposite and shift the balance to get more glutamate stored in the form of glutathione. They used the chemical sulforaphane found in broccoli sprouts, which is known to turn on a gene that makes more of the enzyme that sticks glutamate with another molecule to make glutathione. When they treated rat brain cells with glutathione, it slowed the speed at which the nerve cells fired, meaning they were sending fewer messages. The researchers say this pushed the brain cells to behave less like the pattern found in brains with schizophrenia.
"We are thinking of glutathione as glutamate stored in a gas tank," says Thomas Sedlak, M.D., Ph.D., assistant professor of psychiatry and behavioral sciences. "If you have a bigger gas tank, you have more leeway on how far you can drive, but as soon as you take the gas out of the tank it's burned up quickly. We can think of those with schizophrenia as having a smaller gas tank."
Because sulforaphane changed the glutamate imbalance in the rat brains and affected how messages were transmitted between the rat brain cells, the researchers wanted to test whether sulforaphane could change glutathione levels in healthy people's brains and see if this could eventually be a strategy for people with mental disorders. For their study, published in April 2018 in Molecular Neuropsychiatry, the researchers recruited nine healthy volunteers (four women, five men) to take two capsules with 100 micromoles daily of sulforaphane in the form of broccoli sprout extract for seven days.
The volunteers reported that a few of them were gassy and some had stomach upset when eating the capsules on an empty stomach, but overall the sulforaphane was relatively well tolerated.
The researchers used MRS again to monitor three brain regions for glutathione levels in the healthy volunteers before and after taking sulforaphane. They found that after seven days, there was about a 30% increase in average glutathione levels in the subjects' brains. For example, in the hippocampus, glutathione levels rose an average of 0.27 millimolar from a baseline of 1.1 millimolar after seven days of taking sulforaphane.
The scientists say further research is needed to learn whether sulforaphane can safely reduce symptoms of psychosis or hallucinations in people with schizophrenia. They would need to determine an optimal dose and see how long people must take it to observe an effect. The researchers caution that their studies don't justify or demonstrate the value of using commercially available sulforaphane supplements to treat or prevent schizophrenia, and patients should consult their physicians before trying any kind of over-the-counter supplement. Versions of sulforaphane supplementsare sold in health food stores and at vitamin counters, and aren't regulated by the U.S. Food and Drug Administration.
"For people predisposed to heart disease, we know that changes in diet and exercise can help stave off the disease, but there isn't anything like that for severe mental disorders yet," says Sedlak. "We are hoping that we will one day make some mental illness preventable to a certain extent."
Sulforaphane is found in a variety of cruciferous vegetables, and was first identified as a "chemoprotective" substance decades ago by Paul Talalay and Jed Fahey at Johns Hopkins.
According to the World Health Organization, schizophrenia affects about 21 million people worldwide.
https://www.eurekalert.org/pub_releases/2019-05/jhm-bsc050619.php
A Growing Push To Loosen Laws Around Psilocybin, Treat Mushrooms As Medicine
Tags: hallucinogenic mushrooms, magic mushroom, mushroom, psilocybin, psychiatry
A growing body of research suggests psychedelic mushrooms may have therapeutic benefits for certain conditions. Now a movement seeks to decriminalize them.
Douglas rattles around a collection of glass jars in the storage closet of his Denver apartment. They're filled with sterilized rye grains, covered in a soft white fungus — a mushroom spawn. Soon, he'll transplant it in large plastic bins filled with nutrients such as dried manure and coconut fiber.
Over the course of two weeks, a crop of mushrooms that naturally contain psilocybin, a psychoactive ingredient, will sprout. The species he grows include psilocybe cubensis.
"I mean, it's a relatively quiet thing to do. There's just lots of waiting," says Douglas, which is his middle name. He didn't want to be identified because this is an illegal grow-and-sell operation; psychedelic mushrooms were federally banned in 1970, along with several other hallucinogens.
"Mushrooms are really easygoing, especially psilocybin," he says. "They kind of just grow themselves."
Denver is at the forefront of a national movement that seeks to access these mushrooms, largely for medicinal use. On Tuesday, voters are weighing in on a ballot measure to decriminalize them. And while that may sound ambitious, a campaign in Oregon is gathering signatures for a ballot measure in the 2020 election and seeks to legalize mushrooms with a medical prescription for use in approved clinics.
In Iowa, Republican lawmaker Jeff Shipley recently proposed two bills: one removing psilocybin from the state's list of controlled substances, and the other legalizing it for medical use. And last year, a campaign in California did not get enough signatures to qualify for the ballot. The group that led the campaign hopes to try again in 2020, according to their Facebook page.
For Douglas, it's a sign that change is on the horizon, one that could have implications for his business, which he says he runs for the supplemental income, but also because he believes mushrooms are beneficial.
"Cultivating psilocybin and offering medicine to people to change their lives, that will be my mission, or my way of serving others," he says.
With his DIY setup of glass jars, large plastic bins and a pressure cooker for sterilization, Douglas can produce up to $1,000 of mushrooms a month. He learned how to do this thanks to Internet videos. He purchased his first mushroom spores online and received them in the mail; companies legally are allowed to sell spores since they don't contain psilocybin.
If the Denver ballot measure passes, adults 21 and older who are caught with psilocybin mushrooms, or even growing them for personal use, would become the "lowest law enforcement priority" for local police. Plus, the city and county of Denver would be barred from spending any money to prosecute psilocybin cases.
The notion that state laws around mushrooms could be loosened up, much like they have been for cannabis, is not without controversy. Matthew Johnson, who has spent the past 15 years researching psychedelics at Johns Hopkins University in Baltimore, says decriminalization of illegal drugs is generally a good thing, but he wouldn't support policy that encourages people to use psilocybin without professional supervision.
"(This therapy) needs to be done by appropriately trained and credentialed medical and psychological professionals," he says.
Research suggests that psilocybin is not addictive, causes few ER visits compared to other illegal drugs and could be used to treat a number of ailments. Johnson believes the most promising research is on treating anxiety and depression in cancer patients. In a study he conducted with other researchers at Johns Hopkins, he says they found even a single dose can positively affect an individual for several months.
"It's really unprecedented in medical history to see effects for depression that are caused by a single medication," he says.
Preliminary research has been conducted for other potential uses, including curbing nicotine addiction and for treatment-resistant depression. And while Johnson believes psilocybin could one day become a groundbreaking treatment, he's emphatic about the potential risks involved.
"The most common side effect is the so-called 'bad trip,' " he says. "(It) can be well-managed in a medical research setting, but that sometimes leads to dangerous behavior when out in the wild."
Under the influence of psilocybin, people can panic and put themselves in unsafe situations; there have been fatalities, he says.
Johnson says he thinks that, in as little as five years, research on psilocybin will lead to the first medication approved by the Federal Drug Administration. Once that happens, he thinks the government will have to remove it as a Schedule 1 drug — a substance like heroin that the DEA considers to have "no accepted medical use and a high potential for abuse."
Until then, Deanne Reuter, the assistant special agent in charge at the DEA's Denver office, says the agency will continue prosecuting cases of psilocybin possession and trafficking.
"Any controlled substance is a concern," she says. "It's obviously on a Schedule 1 for a reason."
Reuter admits they don't see many cases of psilocybin trafficking. Typically, they'll bust a drug dealer carrying several types of narcotics, including mushrooms.
"The trafficking of psilocybin seems to be like a small, niche kind of community," she says.
Douglas would agree. He has little competition and knows most of the people he sells his product to. Still, he knows the work he does it risky.
"With decriminalization and stuff I can operate a little bit more freely, have to worry less," he says.
If the Denver ballot measure passes, it wouldn't protect someone like him, who's selling mushrooms for profit. Still, he says it'd be a step closer to a future where he can freely provide people with something he believes in.
https://www.npr.org/sections/health-shots/2019/05/07/720828367/a-growing-push-to-loosen-laws-around-psilocybin-treat-mushrooms-as-medicine
FDA gives green light to first medical device to treat ADHD in children: Monarch external Trigeminal Nerve Stimulation System (eTNS)
Tags: ADHD, FDA, psychiatry
The Food and Drug Administration (FDA) approved Friday the first medical device to treat childhood attention deficit hyperactivity disorder, or ADHD.
The device, approved for children ages 7 to 12 who do not currently take ADHD medicine, delivers a low-level electrical pulse to a patch placed on the forehead that interacts with the parts of the brain responsible for ADHD symptoms.
"This new device offers a safe, non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind," Carlos Peña, director of the Division of Neurological and Physical Medicine Devices in the FDA's Center for Devices and Radiological Health, said in a statement.
"Today's action reflects our deep commitment to working with device manufacturers to advance the development of pediatric medical devices so that children have access to innovative, safe and effective medical devices that meet their unique needs."
The device, called the Monarch external Trigeminal Nerve Stimulation System (eTNS), is marketed by NeuroSigma and is only available by prescription and must be monitored by a caregiver.
eTNS, which is designed to fit inside one's pocket, is connected by wire to a patch that is placed on the forehead while sleeping and delivers a "tingling" electrical impulse to branches of the trigeminal nerve.
"While the exact mechanism of eTNS is not yet known, neuroimaging studies have shown that eTNS increases activity in the brain regions that are known to be important in regulating attention, emotion and behavior," the FDA said.
The FDA also conducted a trial with 62 children with ADHD in which a group that used eTNS had "significant improvement" in their symptoms as opposed to another group that used a placebo.
Side effects of the treatment include drowsiness, an increase in appetite, trouble sleeping, teeth clenching, headache and fatigue. The device should not be placed near a phone or used by children on an insulin pump, pacemaker or implanted neurostimulator, the FDA said.
The FDA found no serious adverse events associated with eTNS.
The device is not currently covered by insurance and has a price tag of just over $1,000 for a starter kit, according to the NeuroSigma website.
https://thehill.com/policy/healthcare/439836-fda-gives-green-light-to-first-medical-device-to-treat-adhd-in-children
How Ketamine Changes the Depressed Patient's Brain
Tags: depression, ketamine, psychiatry, Simon Makin
By Simon Makin
The Food and Drug Administration's approval last month of a depression treatment based on ketamine generated headlines, in part, because the drug represents a completely new approach for dealing with a condition the World Health Organisation has labelled the leading cause of disability worldwide. The FDA's approval marks the first genuinely new type of psychiatric drug—for any condition—to be brought to market in more than 30 years.
Although better known as a party drug, the anesthetic ketamine has spurred excitement in psychiatry for almost 20 years, since researchers first showed that it alleviated depression in a matter of hours. The rapid reversal of symptoms contrasted sharply with the existing set of antidepressants, which take weeks to begin working. Subsequent studies have shown ketamine works for patients who have failed to respond to multiple other treatments, and so are deemed "treatment-resistant."
Despite this excitement, researchers still don't know exactly how ketamine exerts its effects. A leading theory proposes that it stimulates regrowth of synapses (connections between neurons), effectively rewiring the brain. Researchers have seen these effects in animals' brains, but the exact details and timing are elusive.
A new study, from a team led by neuroscientist and psychiatrist Conor Liston at Weill Cornell Medicine, has confirmed that synapse growth is involved, but not in the way many researchers were expecting. Using cutting-edge technology to visualize and manipulate the brains of stressed mice, the study reveals how ketamine first induces changes in brain circuit function, improving "depressed" mice's behavior within three hours, and only later stimulating regrowth of synapses.
As well as shedding new light on the biology underlying depression, the work suggests new avenues for exploring how to sustain antidepressant effects over the long term. "It's a remarkable engineering feat, where they were able to visualize changes in neural circuits over time, corresponding with behavioral effects of ketamine," says Carlos Zarate, chief of the Experimental Therapeutics and Pathophysiology Branch at the National Institute of Mental Health, who was not involved in the study. "This work will likely set a path for what treatments should be doing before we move them into the clinic."
Another reason ketamine has researchers excited is that it works differently than existing antidepressants. Rather than affecting one of the "monoamine" neurotransmitters (serotonin, norepinephrine, and dopamine), as standard antidepressants do, it acts on glutamate, the most common chemical messenger in the brain. Glutamate plays an important role in the changes synapses undergo in response to experiences that underlie learning and memory. That is why researchers suspected such "neuroplasticity" would lie at the heart of ketamine's antidepressant effects.
Ketamine's main drawback is its side effects, which include out-of-body experiences, addiction and bladder problems. It is also not a "cure." The majority of recipients who have severe, difficult-to-treat depression will ultimately relapse. A course of multiple doses typically wears off within a few weeks to months. Little is known about the biology underlying depressive states, remission and relapse. "A big question in the field concerns the mechanisms that mediate transitions between depression states over time," Liston says. "We were trying to get a better handle on that in the hopes we might be able to figure out better ways of preventing depression and sustaining recovery."
Chronic stress depletes synapses in certain brain regions, notably the medial prefrontal cortex (mPFC), an area implicated in multiple aspects of depression. Mice subjected to stress display depressionlike behaviors, and with antidepressant treatment, they often improve. In the new study, the researchers used light microscopes to observe tiny structures called spines located on dendrites (a neuron's "input" wires) in the mPFC of stressed mice. Spines play a key role because they form synapses if they survive for more than a few days.
For the experiment, some mice became stressed when repeatedly restrained, others became so after they were administered the stress hormone corticosterone. "That's a strength of this study," says neuroscientist Anna Beyeler, of the University of Bordeaux, France, who was not involved in the work, but wrote an accompanying commentary article in Science. "If you're able to observe the same effects in two different models, this really strengthens the findings." The team first observed the effects of subjecting mice to stress for 21 days, confirming that this resulted in lost spines. The losses were not random, but clustered on certain dendrite branches, suggesting the damage targets specific brain circuits.
The researchers then looked a day after administering ketamine and found that the number of spines increased. Just over half appeared in the same location as spines that were previously lost, suggesting a partial reversal of stress-induced damage. Depressionlike behaviors caused by the stress also improved. The team measured brain circuit function in the mPFC, also impaired by stress, by calculating the degree to which activity in cells was coordinated, a measure researchers term "functional connectivity." This too improved with ketamine.
When the team looked closely at the timing of all this, they found that improvements in behavior and circuit function both occurred within three hours, but new spines were not seen until 12 to 24 hours after treatment. This suggests that the formation of new synapses is a consequence, rather than cause, of improved circuit function. Yet they also saw that mice who regrew more spines after treatment performed better two to seven days later. "These findings suggest that increased ensemble activity contributes to the rapid effects of ketamine, while increased spine formation contributes to the sustained antidepressant actions of ketamine," says neuroscientist Ronald Duman, of the Yale School of Medicine, who was not involved in the study. Although the molecular details of what happens in the first hours are not yet fully understood, it seems a restoration of coordinated circuit activity occurs first; this is then entrenched by neuroplasticity effects in synapses, which then maintain behavioral benefits over time.
To prove that new synapses were a cause of antidepressant effects, rather than just coinciding with the improved behaviors, the team used a newly developed optogenetic technique, which allowed them to eliminate newly formed spines using light. Optogenetics works by introducing viruses that genetically target cells, causing them to produce light-sensitive proteins. In this case, the protein is expressed in newly formed synapses, and exposure to blue light causes the synapse to collapse. The researchers found that eliminating newly formed synapses in ketamine-treated mice abolished some of the drug's positive effects, two days after treatment, confirming that new synapses are needed to maintain benefits. "Many mechanisms are surely involved in determining why some people relapse and some don't," Liston says, " but we think our work shows that one of those involves the durability of these new synapses that form."
And Liston adds: "Our findings open up new avenues for research, suggesting that interventions aimed at enhancing the survival of these new synapses might be useful for extending ketamine's antidepressant effects." The implication is that targeting newly formed spines might be useful for maintaining remission after ketamine treatment. "This is a great question and one the field has been considering," Duman says. "This could include other drugs that target stabilization of spines, or behavioral therapies designed to engage the new synapses and circuits, thereby strengthening them."
The study used three behavioral tests: one involving exploration, a second a struggle to escape, and a third an assessment of how keen the mice are on a sugar solution. This last test is designed to measure anhedonia—a symptom of depression in which the ability to experience pleasure is lost. This test was unaffected by deleting newly formed spines, suggesting that the formation of new synapses in the mPFC is important for some symptoms, such as apathy, but not others (anhedonia)—and that different aspects of depression involve a variety of brain circuits.
These results could relate to a study published last year that found activity in another brain region, the lateral habenula, is crucially involved in anhedonia, and injecting ketamine directly into this region improves anhedonia-related behavior in mice. "We're slowly identifying specific regions associated with specific behaviors," Beyeler says. "The factors leading to depression might be different depending on the individual, so these different models might provide information regarding the causes of depression."
One caveat is that the study looked at only a single dose, rather than the multiple doses involved in a course of human treatment, Zarate says. After weeks of repeated treatments, might the spines remain, despite a relapse, or might they dwindle, despite the mice still doing well? "Ongoing effects with repeated administration, we don't know," Zarate says. "Some of that work will start taking off now, and we'll learn a lot more." Of course, the main caution is that stressed mice are quite far from humans with depression. "There's no real way to measure synaptic plasticity in people, so it's going to be hard to confirm these findings in humans," Beyeler says.
https://www.scientificamerican.com/article/behind-the-buzz-how-ketamine-changes-the-depressed-patients-brain/
FDA approves first drug for postpartum depression
Tags: brain, depression, Elizabeth Chuck, Lauren Dunn, psychiatry
By Elizabeth Chuck and Lauren Dunn
The intrusive thoughts started weeks after Stephanie Hathaway gave birth: an overwhelming feeling that her daughter deserved a better mother; that her husband deserved a better wife; that her future was hopeless.
"They just played on repeat in my head," Hathaway, 33, of South Glastonbury, Connecticut, said. "I was holding my baby one night, and my husband was at a meeting, and I just thought, 'Oh, my goodness. If I put the baby down, I might hurt myself.'"
Hathaway was diagnosed with postpartum depression — the intense sadness, anxiety or despair that occurs within the first year after giving birth, according to the Centers for Disease Control and Prevention. It affects about one in nine women, although the rate may be as high as one in every five women, the CDC finds.
Hathaway's doctor put her on antidepressants, which helped some, but it took two weeks for the medication to kick in, and even longer until her doctor found the appropriate dosage for her. As she waited for relief, Hathaway found herself struggling to bond with her newborn, Hadley, who is now 4.
"It's heartbreaking," Hathaway, who had never suffered from depression before and is now a mother to two girls, said. "That's not what I expected to feel."
Up until this point, new mothers experiencing postpartum depression have been prescribed the same antidepressants used for treating depression in the general population, such as selective serotonin reuptake inhibitors. The drugs can take weeks to take effect, and do not address the hormonal changes that women go through during and after pregnancy.
But on Tuesday, the Food and Drug Administration approved the first drug specifically developed for postpartum depression, called brexanolone, or Zulresso.
Brexanolone is novel because it has a synthetic form of the hormone allopregnanolone, a progesterone derivative, in it. The hormone increases throughout a woman's pregnancy and then plummets after she gives birth, a possible contributor to postpartum depression.
"This can potentially transform women's lives and that of their families," said Dr. Steve Kanes, chief medical officer of Sage Therapeutics, the Cambridge, Mass., biopharmaceutical company that developed brexanolone. "It's not just the mother who suffers when there's postpartum depression. It's the newborn. It's the other people in their family."
Brexanolone is not a pill. The drug is delivered intravenously over the course of a 60-hour infusion, meaning it must be administered in a medically supervised setting, such as a skilled facility or a hospital, rather than at patients' homes.
IMPROVEMENT IN JUST 24 HOURS
Clinical trials for the drug were promising — not just in the number of women it helped, but in the near-instantaneous relief that is provided.
In double-blind, placebo-controlled trials, many women with moderate to severe postpartum depression saw a marked improvement of their symptoms within just 24 hours of receiving the drug. That improvement was still present 30 days after the infusion, the length of the trial.
"This is for postpartum depression, but it is a step in understanding how we treat depression more broadly," said Dr. Samantha Meltzer-Brody, director of the perinatal psychiatry program at the University of North Carolina at Chapel Hill and the academic principal investigator in the brexanolone trials. "We have had the same treatments for depression for 30 years. There's an enormous need for new, novel ways to treat depression, and to treat it quickly."
The drug's approval comes just weeks after the FDA signed off on esketamine, a fast-acting nasal spray that uses the active ingredients in the club drug ketamine, as a treatment for severe depression.
For patients who are depressed, rapid relief is a priority. Hathaway, the Connecticut mother, was again diagnosed with postpartum depression after she gave birth to her second, a girl named Brenley who is now 2. This time, the antidepressants did not help at all, and Hathaway felt herself slipping deeper and deeper into a state of hopelessness.
She participated in a brexanolone trial, and her response was striking. Between hours 12 and 18 of the 60-hour infusion, she noticed her despair had waned.
"I woke up from a nap, and the thoughts were gone. And they never came back," Hathaway said. "And then hour after hour, I got my energy back. I got my appetite back. I was eating because I was actually hungry, not because people were making me eat."
A COMMON CONDITION
Postpartum depression afflicts as many as 400,000 women in the United States each year. It can include disturbances in sleep or eating patterns in addition to feelings of sadness or apathy. Affected women are often confused and guilt-ridden about why they are feeling down during what is supposed to be a happy time, said Dr. Christine C. Greves, an obstetrician-gynecologist at Orlando Health Winnie Palmer Hospital for Women and Babies.
"As women, we feel like we were born to have a child, and there's a white picket fence, and life will be great," said Greves, who does not have ties to Sage Therapeutics. "Then regular life comes into play. You have a child and then you top that with extensive fatigue, hormones, expectations that just can't be met. It's all fantasy until we actually have the baby. And then you do feel guilty, because we all want to be Super Mom."
In the past decade, experts say, there has been more awareness about postpartum depression and more efforts among obstetricians and pediatricians to screen mothers for it.
But having a drug specifically aimed at treating postpartum depression will be one of the most significant steps toward removing any stigma still associated with the condition, said Dr. Kimberly Yonkers, professor of psychiatry, epidemiology and obstetrics, gynecology and reproductive sciences at the Yale School of Medicine.
"It does women a service because it really brings attention to a major medical problem and provides legitimacy, and hopefully will encourage people, whether they use this medication or not, to seek and obtain treatment," said Yonkers, who does not have ties to the drug company. "We're all thrilled about that."
SOME SIDE EFFECTS, AND A HEFTY PRICE TAG
The most common side effects during the brexanolone trial were drowsiness and dizziness. The drug is not believed to have any long-term safety concerns. Kanes, Sage Therapeutics' chief medical officer, said he expects it will be deemed safe for all mothers, including breastfeeding mothers, but the company is waiting for an FDA ruling on breastfeeding.
The drug comes with a hefty price tag: Sage says it is expected to cost somewhere between $20,000 to $35,000 for the infusion. That does not include the price of a stay in whatever facility it is administered in. It is not clear yet how much insurance would cover.
Kanes pointed out that while high, the cost is a one-time price.
"That's such an important piece as to why this is so novel. We're talking about a single treatment that has durable effects," he said. "This really is a one-time intervention that gets people on their way. It's transformative."
For Hathaway, the brexanolone infusion enabled her to return home and be the mother to her daughters that she had wanted to be before postpartum depression took over.
"It's given them their mom back," she said. "This is what it was supposed to be like."
https://www.nbcnews.com/health/womens-health/fda-approves-first-drug-postpartum-depression-n984521
The Robot Will See You Now: The Increasing Role of Robotics in Psychiatric Care
Posted: January 23, 2019 in Uncategorized
Tags: AI, Nicola Davies, psychiatry, The Future, therapy
by Nicola Davies, PhD
Robots are infiltrating the field of psychiatry, with experts like Dr Joanne Pransky of the San Francisco Bay area in California advocating for robots to be embraced in the medical field. In this article, Dr Pransky shares some examples of robots that have shown impressive psychiatric applications, as well as her thoughts on giving robots the critical role of delivering healthcare to human beings.
Meet the world's first robotic psychiatrist
Dr Pransky, who was named the world's first "robotic psychiatrist" because her patients are robots, said, "In 1986, I said that one day, when robots are as intelligent as humans, they would need assistance in dealing with humans on a day-to-day basis." She imagines that in the near future it will be normal for families to come to a clinic with their robot to help the robot deal with the emotions it develops as a result of interacting with human beings. She also believes that having a robot as part of the family will reshape human family dynamics.
While Dr Pransky's expertise may sound like science fiction to some, it illustrates just how interlaced robotics and psychiatry are becoming. With 32 years of experience in robotics, she said technology has come a long way, "to the point where robots are used as therapeutic tools."
Robots in psychiatry
Dr Pransky cites some cases of robots that have been developed to help people with psychiatric health needs. One example is Paro, a robotic baby harp seal developed by the National Institute of Advanced Industrial Science and Technology (AIST), one of the largest public research organizations in Japan. Paro is used in the care of elderly people with dementia, Alzheimer disease, and other mental conditions.1 It has an appealing physical appearance that helps create a calming effect and encourages emotional responses from people. "The designers found that Paro enhances social interaction and communication. Patients can hold and pet the fur-covered seal, which is equipped with different tactile sensors. The seal can also respond to sounds and learn names, including its own," said Dr Pransky. In 2009, Paro was certified as a type of neurologic therapeutic device by the US Food and Drug Administration (FDA).
Mabu, which is being developed by the patient care management firm Catalia Health in San Francisco, California, is another example. Mabu is a voice-activated robot designed to provide cognitive behavioral therapy by coaching patients on their daily health needs and sending health data to medical professionals.2 Dr Pransky points out that the team developing Mabu is composed of experts in psychiatry and robotics.
Then there is ElliQ, which was developed by Intuition Robotics in San Francisco to provide a social companion for the elderly. ElliQ is powered by artificial intelligence (AI) to provide personalized advice to senior patients regarding activities that can help them stay engaged, active, and mentally sharp.3 It also provides a communication channel between elderly patients and their loved ones.
Beside small robot assistants, however, robotics technology is also integrated into current medical devices, such as Axilum Robotics (Strasbourg, France) TMS-Robot, which assists with transcranial magnetic stimulation (TMS). TMS is a painless, non-invasive brain stimulation technique performed in patients with major depression and other neurologic diseases.4 TMS is usually performed manually, but the TMS-robot automates the procedure, providing more accuracy for patients while saving the operator from performing a repetitive and painful task.
Chatbots are another way in which robotics technology is providing care to psychiatric patients. Using AI and a conversational user interface, chatbots interact with individuals in a human-like manner. For example, Woebot (Woebot Labs, Inc, San Francisco), which runs in Facebook Messenger, converses with users to monitor their mood, make assessments, and recommend psychological treatments.5
Will robots replace psychiatrists?
Robotics has started to become an integral part of mental health treatment and management. Yet critics say there are potential negative side-effects and safety issues in incorporating robotics technology too far into human lives. For instance, over-reliance on robots may have social and legal implications, as well as encroaching on human dignity.6 These issues can be distinctly problematic in the field of psychiatry, in which patients share highly emotional and sensitive personal information. Dr Pransky herself has worked on films such as Ender's Game and Eagle Eye, which have presented the risks to humans of robots with excessive control and intelligence.
However, Dr Pransky points out that robots are meant to supplement, not supplant, and to facilitate physicians' work, not replace them. "I think there will be therapeutic success for robotics, but there's nothing like the understanding of the human experience by a qualified human being. Robotics should extend and augment what a psychiatrist can do, she said. "It's not the technology I would worry about but the people developing and using it. Robotics needs to be safe, so we have to design safe," she adds, explaining that emotional and psychological safety should be key components in the design.
Who stands to benefit from robotics in psychiatry?
Dr Pransky explains that robots can help address psychiatric issues that a psychiatrist may be unable to with traditional techniques and tools: "The greatest benefit of robotics use will be in filling gaps. For example, for people who are not comfortable or available to talk about their problems with another human being, a robotic tool can be a therapeutic asset or a diagnostic tool."
An interesting example of a robot that could be used to fill gaps in psychiatric care is the robot used in BlabDroid, a 2012 documentary created by Alex Reben at the MIT Media Lab for his Master's thesis. It was the first documentary ever filmed and directed by robots. The robot interviewed strangers on the streets of New York City7 and people surprisingly opened up to the robot. "Some humans are better off with something they feel is non-threatening," said Dr Pransky.
https://www.psychiatryadvisor.com/practice-management/the-robot-will-see-you-now-the-increasing-role-of-robotics-in-psychiatric-care/article/828253/2/
Lewis Judd, psychiatrist who probed the science of the brain, dies at 88
Tags: brain, death, Emily Langer, Lewis Judd, mental health, neuroscience, NIMH, psychiatry
Dr. Lewis L. Judd led the National Institute of Mental Health from 1988 to 1990. (National Library of Medicine)
By Emily Langer
Lewis L. Judd, a nationally known psychiatrist who helped turn the focus of his profession from psychoanalysis to neuroscience, an approach that sought to destigmatize mental illness by treating it as cancer, heart disease or any other medical problem, died Dec. 16 in La Jolla, Calif. He was 88.
The cause was cardiac arrest, said his wife, Pat Judd.
For decades, psychiatrists were schooled in the theories of Sigmund Freud, the founder of psychoanalysis, who posited that mental disturbances could be treated through dialogue with a therapist. Practitioners sought to interpret their patients' dreams, giving little attention to the physical functioning of the brain or the chemicals that regulate it.
Dr. Judd agreed, he once told the Associated Press, that a physician must look at patients as a "whole individual," with all their "worries, concerns, aspirations and needs," and not resort to simply "popping a pill in their mouth." But he found the long-prevailing psychoanalytic approach too limiting to explain or treat afflictions such as depression, bipolar disorder, severe anxiety and schizophrenia — "these serious mental disorders that have defied our understanding for centuries," he once told the Chicago Tribune.
Instead, he advocated a biological approach, starting at the molecular level of the brain. As director of the National Institute of Mental Health in Bethesda, Md. — a post he held from 1988 to 1990, during a hiatus from his decades-long chairmanship of the psychiatry department at the University of California at San Diego — he helped launch a federal research initiative known as the "Decade of the Brain."
"He was obsessed with educating the public and the profession . . . that mental illnesses were biological illnesses, that schizophrenia and depression were diseases of the brain," Alan I. Leshner, Dr. Judd's deputy at NIMH and later chief executive of the American Association for the Advancement of Science, said in an interview. "At the time, that was a heretical thought."
Today, the biological component of many mental illnesses is widely accepted. When Dr. Judd led NIMH, it was not; he once cited a survey in which 71 percent of respondents said mental illness was a result of personal weakness and a third attributed it to sinful behavior. Poor parenting was another common alleged culprit.
Dr. Judd argued that the biological approach to psychiatry held the promise not only of deepening understanding of the body's most complex organ but of improving lives: If mental disorders could be shown to be a result of brain chemistry or of physical dysfunction, patients might feel less stigmatized and therefore more willing to seek treatment.
"We look at the homeless and feel that if they only got their act together, they could lift themselves up," Dr. Judd told the Los Angeles Times in 1988, discussing the prevalence of mental illness among homeless people. "We would never believe that about someone who has cancer or some other physical disease."
As head of NIMH, which is an arm of the National Institutes of Health and the chief federal agency for research on mental illness, Dr. Judd oversaw more than $500 million in research money. He described the Decade of the Brain — a designation conferred by Congress and President George H.W. Bush — as a "research plan designed to bring a precise and detailed understanding of all the elements of brain function within our own lifetimes."
During his tenure at NIMH, scientists for the first time successfully grew brain tissue in a laboratory. Dr. Judd was among those scientists who touted the potential of medical imaging, such as MRIs and PET scans, to reveal the inner workings of the brain and the potential causes of diseases such as schizophrenia.
Almost 30 years after the Decade of the Brain began, much about the organ remains elusive. Leshner credited the initiative with helping bring attention to the importance of brain research as well as inspiring the Brain Initiative, a public-private research effort advanced by the Obama administration.
"The brain is really the last frontier for scientists," Dr. Judd said.
Lewis Lund Judd was born in Los Angeles on Feb. 10, 1930. His father was an obstetrician-gynecologist, and his mother was a homemaker. Dr. Judd's brother, Howard Judd, also became an OB/GYN and a noted researcher in women's health at the University of California at Los Angeles.
Dr. Judd received a bachelor's degree in psychology from the University of Utah in 1954 and a medical degree from UCLA in 1958. In the early years of his career, he served in the Air Force as a base psychiatrist.
He joined UC-San Diego in 1970 and became department chairman in 1977, helping grow his faculty into one of the most respected the country. He stepped down as chairman in 2013 and retired in 2015.
Dr. Judd's first marriage, to Anne Nealy, ended in divorce. Survivors include his wife of 45 years, the former Patricia Hoffman, who is also a psychiatry professor at UC-San Diego, of La Jolla; three daughters from his first marriage, Allison Fee of Whidbey Island, Wash., Catherine Judd of Miami and Stephanie Judd of Chevy Chase, Md.; and four grandchildren.
Ever exploring the outer reaches of his field, Dr. Judd participated in a dialogue with the Dalai Lama in 1989 about life and the mind.
"Our model of mental health is mostly defined in terms of the absence of mental illness," Dr. Judd told the New York Times, reflecting on the Tibetan Buddhist leader's discussion of wisdom and compassion. "They may have more positive ones that might be worth our study."
https://www.washingtonpost.com/local/obituaries/lewis-judd-psychiatrist-who-probed-the-science-of-the-brain-dies-at-88/2019/01/11/271e1f48-1549-11e9-b6ad-9cfd62dbb0a8_story.html?noredirect=on&utm_term=.18ed788ae8b3


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The latest on sexual transmission of hep C
By Andrew ReynoldsMay 5, 2020 @AndrewKnowsHepC
In 2014, I wrote an article titled "Can Hepatitis C be Sexually Transmitted?" with a subhead that answered, "Yes. No. Maybe. It's complicated. All of the above." Fast forward more than five years later and while we have more clarification on sexual transmission of HCV thanks to excellent research on the topic, it can still be pretty complicated. We have consensus that MSM living with HIV are at increased risk of sexual transmission of HCV. We have a clearer picture of risk factors and sexual practices that may enhance the chance of infection, including re-infection of HCV. We are also starting to see warning signs for a potentially newly emerging population at risk of sexual transmission of HCV: More and more examples of HIV-negative MSM on PrEP with no history of injecting drugs. Finally, and most importantly: In 2014, we were at the start of the direct acting antiviral era, in which HCV can be treated and cured without interferon injections, with far fewer side effects and at much higher cure rates. Today, we have come even further, with HCV cure and treatment that is short (8–12 weeks), effective (a cure rate of over 95%) and easy (very few side effects).
This article will provide an update on our current state of knowledge about sexual transmission of HCV in HIV-infected MSM and in HIV-uninfected MSM on PrEP, and close with a list of ways to reduce the chances of getting HCV.
For more information on hepatitis C, what it is, how it's transmitted, tested for and treated, check out the Positively Aware Viral Hepatitis Drug Guide: positivelyaware.com/issues/july-august-2019.
HIV and sexual transmission of HCV?
There is consensus that people living with HIV (PLWH) are at risk of sexual transmission of HCV, but it's still not entirely clear why. We know some of the activities and behaviors associated with HCV transmission, and that there are some likely biological reasons, too (see Harm reduction tips to reduce your risk for hepatitis C). A recent scientific review of sexual transmission of HCV in MSM living with HIV found a prevalence (that is, the percentage of people who acquired HCV) of 8.3%. By comparison, that same study found a prevalence of 1.5% in HIV-negative MSM.
Research has shown that condomless anal sex, group sex, fisting, use of non-injectable drugs (often with sex), are commonly associated with sexual transmission of HCV. Biologically, a review shows that there is a relationship between lower CD4 counts and increased risk of HCV acquisition. Additionally, rates of HCV were higher in HIV-positive gay men with lower CD4 counts even when they had fewer risk factors for HCV. Small studies have also found HCV in the semen and non-bloody rectal fluids of HIV/HCV co-infected MSM, so even in the absence of blood, there could be risk of transmission from sexual fluids.
Regardless of the how it happens, we know that it happens more frequently in people living with HIV; regular testing for HCV, followed by treatment is a great way to stay healthy. Hepatitis C treatment is safe and effective for people living with HIV.
What about HIV-negative MSM who are on PrEP?
We are learning a lot about this, with more and more scientific papers and conference presentations addressing sexual transmission of HCV in MSM taking PrEP, and there is emerging evidence of increased risk for it in this group.
We don't have as much data and information with MSM on PrEP as we do for MSM living with HIV, but there is enough to inform our health education and prevention work. A report looking at 14 case studies of HIV-negative MSM on PrEP who acquired HCV through sex found that, similar to people living with HIV, risk factors such as multiple partners, non-injection drug use, condomless receptive anal sex, and co-occurring STIs were associated with sexual transmission of HCV. Another recent study out of France found new infection rates for HIV-negative MSM on PrEP exactly mirrored the new infection rates of MSM living with HIV, and another recent study out of Amsterdam found higher rates of sexually transmitted HCV in MSM on PrEP.
A final thought on HCV risk and PrEP: PrEP is an effective and excellent way to prevent HIV. Overall, the studies referenced here and the number of HCV cases is pretty small compared to the over 90,000 people taking PrEP in the U.S, not to mention all those in Europe who are taking it. It's worth noting that none of the men in the studies referenced above tested positive for HIV, and ultimately, that is what PrEP is: an HIV prevention intervention. In this respect, it is a remarkable success. Routine prevention counseling, screening, and treatment of HCV and STIs are important components of PrEP service delivery.
Screening recommendations for hepatitis C in MSM
Routine HCV screening, followed by treatment for all people is the ideal way to improve both the individual health of the person living with HCV as well to reduce transmission and improve public health. We're not there yet, but in the meantime, testing for HCV—at least annually, and maybe even every six months—is a great way to keep up with your HCV status.
There has been so much progress in both HIV prevention and treatment, and we can eliminate HCV among MSM, too. We're learning more and more about the sexual transmission of HCV: We know it's a significant risk for MSM living with HIV and it may be an emerging concern for HIV-negative MSM on PrEP. As we learn more, we can engage in prevention education and awareness, test for HCV routinely, and get people treated and cured. It's my hope that the next time I write an update about sexual transmission of HCV, it's to tell you that it's gone.
What activities increase the risk of sexually transmitted HCV?
Fisting: Fisting can cause trauma to the surfaces of the anus and rectum that could lead to bleeding, including microscopic bleeding. Fisting someone else might also increase your risk if you have breaks in your skin fingers and hands.
Sharing sex toys: As with fisting, sex toys can lead to anal/rectal bleeding. If a sex toy has HCV-infected blood on it, it may facilitate transmission of the virus. Note: There have not yet been any studies examining HCV on sex toys, but we know that HCV can live on surfaces for as long as 16 days, so it's a safe assumption that it can live at least that long on sex toys, and the same caution should be exercised.
Group sex: Engaging in group sex appears to increase the risk of sexual transmission of HCV. This may be due to longer sex sessions that might lead to more trauma and bleeding, but it could also increase the likelihood of coming into contact with someone with HCV.
Multiple sex partners: As with group sex, having multiple partners is associated with sexual transmission of HCV: More partners increases the possibility of having sex with someone with HCV, but it has also been shown to coincide with other risk behaviors.
STDs (STIs): Sexually transmitted diseases that cause sores are associated with HCV because of the presence of blood, especially syphilis and herpes. Anal warts, specifically sex following anal wart removal and before sufficient healing, have also been found to increase the risk of HCV.
Using non-injectable drugs with sex: HCV transmission can occur due to the sharing of intranasal straws or pipes, but using substances during sex might also decrease one's inhibitions and lead to more risk taking than usual.
See Harm reduction tips to reduce your risk for hepatitis C
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Choice Options
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Harm Reduction Tips to Reduce your Risk for Hepatitis C

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Slava Yaryshkin interviews Nick Vatterott and asks him, "Do you have a favorite topic to talk about on stage?"
My favorite topic to talk about on stage is whatever stream of conscious is happening. But sometimes, something hits you while you're on stage. Every day we have a thousand thoughts, and some of those thoughts we feel would be worth exploring on stage. And every once in awhile, we have one of those thoughts, WHILE we're on stage. And exploring those ideas in that moment, whatever the topic is, are my favorite to talk about.
I was at an outdoor show recently at a food festival. The type of show you roll your eyes at as a comic. Two in the afternoon, on the hottest day of the year. The whole point of the festival was for people to try foods they never had before, and I was supposed to perform in this comedy tent, for people to take a break from food. I asked everyone if they enjoyed all the unique foods, they all said 'YEAH!!!' What's been your favorite so far? And this very sweet old man in the front row, in complete honestly yelled, "Corn!"
And that killed me, that this guy had never had corn before. Every tent had funnel cakes, and pate, and sushimi, and this guy was blown away by the corn. And there is, for the next ten minutes I just get to riff about a guy who is blown away by corn, amazed by water, and was scared of the future technology of forks...those moments feel like you're just joking around with your buddies, as opposed to being on stage telling a joke that 'you're working on', or a joke that doesn't work because you can't recreate the moment when its circumstances occurred. And those spontaneous topics are my favorite.
A well crafted joke gets told over and over in front of lots of audiences. But a spontaneous one can only be shared by the people in that room at that time. I think that's a big part of why audiences respond so strongly to in-the-moment riffs.


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There were two battles of Kashgar, The battles were fought at the old city of Kashgar (as opposed to the "new city") in Xinjiang.

 Battle of Kashgar (1933)
 Battle of Kashgar (1934)

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Admail West is a proud sponsor of Non-Profit organizations and our team has years of experience helping charitable organizations grow in both donations and awareness. At Admail West, we understand that it takes more than just donation acquisition to make your organization successful. This is why, when we work with non-profit organizations, we begin with an all inclusive plan on creating a sustainable business around their mission and values. From there, we implement services that nurture and fulfill each goal. Similarly, Admail West's team understands that when it comes to spending donation dollars, costs must be kept to a minimum. Therefore, we only create marketing plans that ensure your marketing dollars are well spent and successful. From direct mail to online marketing, we tailor plans to your organization's needs and will never try to sell you a product that will not pay for itself with time. Working in the Non-Profit space requires integrity and quality; two of the main features of the Admail West system.
We have been assisting Non-Profits target the right prospects, deliver relevant and persuasive communications and effectively solicit donations for more than two decades. Finding just the right mix and tone of messaging to build a donor base requires experience and talent; two abundant resources at Admail West. With this amazing history, we are confident that our past and present success in the Non-Profit space speaks for itself. When you work with Admail West, you will get the best care, strategy, and most importantly, the best results.
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Since its beginning in 2001, BRJ & Associates, LLC has provided owner-agency services in the areas of Planning, Program Management, Project Management, and Construction Management. Our work includes multi-project programs and individual projects. In addition to our company's exceptional breadth and depth of experience, we have a staff of highly trained professionals whose own breadth of expertise further expands the firm's capabilities. We have provided thorough and effective management services to maintain project budgets, schedules, and scopes for our clients.
BRJ manages planning, design, construction, and post-construction on time-tested, effective methods while remaining alert to innovative approaches which will provide additional value to our clients' project goals. Each BRJ team member is empowered to fully employ their own professional expertise while being held strictly accountable for deep collaboration among all project participants; we know this balance is necessary for ultimate project success. Our secret to effectively controlling the outcomes of projects is our thorough anticipation of project needs that enables our proactive guidance of all phases of project development.
BRJ has, in just a decade, amassed an enviable background of managing projects and programs to successful conclusions. Our company and each of our highly qualified staff have participated in the management of every aspect of project planning, design, procurement, construction, and post construction. Our professional qualifications in managing programs and projects makes us exceptionally well suited to provide these services with the highest possible value.
As a company, BRJ has had the honor of representing several institutional clients in their pursuit of effective facilities in the face of challenging budgets and schedules. We are thoroughly familiar with public agency work and its operational, procedural, and statutory demands. Among our most valuable experiences is the successful melding of client and BRJ personnel into effective, collaborative teams of professionals creating comprehensive facilities systems and solutions.


Our mission is to assure you of a confident smile. When you visit our office, your smile is our top priority.Our entire team is dedicated to providing you with personalized, gentle care that you deserve. We do our best to be knowledgeable about State-of-the -Art procedures and to offer them at affordable prices. We provide our patients with information that helps them make informed decisions about their oral health needs. This website is a resource we hope you will find useful.
When you decide to straighten your teeth, you do not want to compromise your daily routine. DentoCorrect is the most attractive choice for orthodontic because aligners are Krystal Klear.
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The future relationship between the UK and Europe remains frustratingly unclear. In time for the European Parliamentary elections next month, Pax Christi International have today launched a European Manifesto, subtitled 'The Europe We Want'. The document encourages citizens of Europe to choose members of the European parliament based on values of solidarity, fraternity and peace.
In contrast to the recent rhetoric suggesting that the British Trident nuclear deterrent is responsible for maintaining peace in Europe for the last 50 years, this document highlights the achievements of Europe as a 'project for peace' since 1945. A central 'pillar' of that achievement has been 'the promotion and protection of human rights'.
Read the document for yourself here.


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Hundreds of cash-strapped contestants accept an invitation to compete in children's games for a tempting prize, but the stakes are deadly. The contestants are locked inside a maze-like warehouse, with one chance to escape: They must play their way to the end by figuring out puzzles and outwitting each other for all the cash. As they race for the prize, they learn that this game is less about solving games than it is about solving life. In a few hours, everyone's lives will change forever. And each player becomes a suspect in a crime no one understands—yet whose victim is clear.
What is the plot of the story ?
The plot of the story is about a bunch of people . Who want to win the "Squid Game", but the Squid game is rigged and no one knows who did it. They all start to suspect each other . And try to redeem themselves. But the only way to win the game is to get out alive and avoid the murder. The resolution of the story is that the killer is revealed as a solider. The solider was not who he seemed to be, he was actually a good guy . Who took his problems out on other people to justify his own sins. The story explores how desperation can cause people, who have no chance of winning the game, to commit murder. In this way the author shows how desperate people can become when they are not given a chance to win, but are expected to win by playing against other contestants.
Who is in the cast ? What role did each character portray ?
The cast include HoYeon Jung , Lee Jung Jae , Kim Min Ki , Park Yong Ha , Namgoong Min , Lee Sung Jae and Kim Seul Gi . HoYeon Jung portrays the role of a sister . Who wants to win something for her family . But as the game progresses she begins to suspect everyone, including her own brother. Lee Jung Jae's role is that of a popular actor who starts to doubt his popularity . Because of his appearance on this television show called the "Squid Game".
What are the challenges they face ?
The challenges they face are not to get out alive, but a lot of them seem to be forgetting the possibility of winning. The challenges they face are first to figure out the puzzles, then second to figure out which contestant is the killer before they have lost all their money. The themes in this story are basically the trials . And tribulations of people who want to win the game, and after they have taken part in the game they face with the murder of a contestant which makes them all suspect each other of being the murderer. In this way, the story explores how desperate people can become . When they are not given a chance to win . But are expected to win by playing against other contestants.
What are the epic scenes ?
The epic scenes are the murder that took place in the "Squid Game". It was a horrible scene to watch, because there were many different people suspects who could have done it. In this way, there was plenty of tension and suspense to keep you watching until the end. HoYeon Jung who is the sister portrays a very strong and intelligent character, who is always willing to help her family, even though she did not win anything. In addition she seems to be a good actress who can play any role.
Would you recommend watching this ?
Yes, because it has many different layers of meaning, it is one of those dramas that everyone can relate to. The story seems to be based on some sort of reality show. In addition, the drama keeps you focused on the events that happen and makes you want to watch the next episode. Also this drama will make you think about what is more important in life (money or life) and how greedy people can become when they are not given a chance to win everything but are instead forced/expected to win by playing against other contestants. Thanks for reading !
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For 2015, the Chevy Spark mini-car gets standard OnStar 4G LTE Wi-Fi service. It's free for the first three months or 3GB of data use, whichever comes first. After that, prepare to receive a regular bill.
There are five flavors of Chevy Spark from which to choose: LS, 1LT, 2LT, EV 1LT, and EV 2LT. Each is remarkably well equipped, even the base Spark LS.
Nevertheless, if you select the Spark 1LT you'll benefit from a Chevrolet MyLink touchscreen infotainment system with a USB port, satellite radio, and extra stereo speakers. This model also comes with floor mats, cruise control, power exterior mirrors, power door locks, remote keyless entry, and more. Upgrade to the 2LT for leatherette seat upholstery, a leather-wrapped steering wheel, heated outside mirrors, sportier trim, fog lights, and special aluminum wheels.
The Spark EV 1LT is an electric version of the car, and includes everything except leatherette seats and a leather-wrapped steering wheel as standard equipment. Guess that the EV 2LT model adds? Yep, you guessed it.
The Spark's standard 1.2-liter 4-cylinder gasoline engine generates 84 horsepower and 83 lb.-ft. of torque. Remember, this is a very small, 4-passenger car, so with just the driver aboard it actually feels rather lively. A 5-speed manual gearbox is standard, with a continuously variable transmission (CVT) optional.
The Spark EV has an electric motor making 140 horsepower and 327 lb.-ft. of torque from the moment you step on the accelerator pedal. Though heavier than a standard Spark, the Spark EV is nevertheless the performance car of the family, getting to 60 mph in 7.2 seconds, according to Chevrolet.
Whether you choose the standard manual transmission or the optional CVT, the Spark is rated to get 34 mpg in combined driving. Go with the Spark EV, and Chevrolet says you can get up to 82 miles of range on a fully charged battery.
In crash tests, the 2015 Spark earns a 4-star overall rating from the NHTSA. According to the Insurance Institute for Highway Safety (IIHS), the Spark is the only car in its class to earn a "Top Safety Pick" rating. However, keep in mind that this accolade is relative; the Spark is, by far, much smaller and lighter than most of the vehicles with which it might collide.
Equipped with standard OnStar service, including Automatic Crash Response for the first six months of ownership, the Spark now offers 4G LTE high-speed Internet access, transforming the car into a mobile Wi-Fi hotspot.
The Spark's available Chevrolet MyLink infotainment system provides a 7-inch color touchscreen infotainment display, and features smartphone connectivity for access to a world of music via Pandora, Stitcher, and TuneIn apps. Apple iPhone users will enjoy Siri Eyes Free compatibility, and the system can be upgraded with an affordable BringGo navigation app.
The Spark EV is equipped with a charger compatible with a standard household outlet. Faster charging is available with the optional 240-volt setup, reducing the charging time to a claimed seven hours.


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West Yorkshire Combined Authority supports key worker bus timetable
The Combined Authority is combining its own financial resources with Government funding to commission the key worker bus timetable through the West Yorkshire Bus Alliance.
The West Yorkshire Combined Authority has set out its commitment to supporting a resilient bus service for key workers during the coronavirus (COVID-19) pandemic.
The Combined Authority is combining its own financial resources with Government funding to commission the key worker bus timetable through the West Yorkshire Bus Alliance. The Department for Transport is providing emergency funding to be managed in West Yorkshire by the Combined Authority which will oversee the bus service during the emergency and the recovery period afterwards.
In addition, the Combined Authority usually pays operators more than £6m per month to fund socially necessary bus services and the free and cheaper concessionary fare schemes. It will continue to do so during the pandemic despite huge falls in passenger numbers as people heed the instruction to stay at home.
Through the West Yorkshire Bus Alliance, operators will agree to hold bus fares at current levels, make changes to timetables in partnership with the Combined Authority, observe social distancing and hygiene standards and provide regularly updated information on how the network is operating. The Government has set out a package of direct support for the bus industry based on minimum continued service levels which will be reflected in the key worker timetable.
Cllr Kim Groves, Chair of the West Yorkshire Combined Authority Transport Committee, said:
"The number of people using buses in West Yorkshire is only 10% of usual levels which shows they are listening to instructions to stay at home but poses a massive challenge to the finances underpinning the network.
"We will continue to fund bus operators and work through the West Yorkshire Bus Alliance to commission the key worker bus timetable to ensure those who have to travel can do so and in a safe way that allows them to follow social-distancing guidelines.
"It is also increasingly clear that the long-term impact of the pandemic on public transport will be significant and sustained. I am committed to safeguarding the interests of West Yorkshire customers and businesses during this period and the recovery. We will need continued Government support to restore and strengthen the network when normality returns."


Recanto Azul Hostel is conveniently located close to the Historical Centre of Paraty, great restaurants, markets, drugstores, bakeries and the main plaza where the great festivals of Paraty, as the International Literature Fest, Cachaça Festival, Bourbon Jazz Festival, among many others. To enjoy the tours and beautiful scenery of the city the routes are also very close to the Hostel. Here you will find all the hospitality of paraty people in a simple place, cozy, comfortable and enjoy all this with economy.
Our approachable reception staff are on-call 24 hours a day. Our aim is for you to enjoy your stay in Paraty with the comfort and tranquility you deserve.
If you have to cancel your booking you must do it at least 48hrs before arrival.
In order to guarantee your reservation, beside the 10% deposit made on Hostelworld.com you will need to pay 50% in advance in order to secure your booking for those periods. We will contact you to send you the money transfer details.
We are one Block from the Historical Center and are 5 minutes from the Bus Station!


Inspired by your dreams of world-class media, we launched 3D Digital Design Studio to materialise your visions. Based in UK, we are offering ridiculously impeccable skills and hard-earned experience in Cinema 4d R16 Studio, Final Cut pro, Adobe After effects CC, High Definition Video, Advertisement, 3D modelling and Mobile application development. Only your visions are our limits!
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AZTECH FILMS make Media because we love to! Not because it's our job, its more than that, it's an obsession, to get perfection and beauty radiated throughout all we do for ourselves and our clients, every single day we do it!
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Through awe-inspiring abilities of animation to capture and hold the attention, we help to take your business's message to new levels. Our experts are employing their best techniques and utilising their splendid skills to make your brand message informational and entertaining. The concepts are innovative and our technologies and software are cutting-edge including Cinema 4D, 3d Studio MAX and After effects. We are at your service to help your business grow and reach its summit.
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The giants of business arena know the value of mobile applications for generating breathtaking results. Therefore, they rely on applications to provide superior services to their customers and attain world-class performance. Developing new applications and maintaining the existing ones involves risks. Every business wants to know about when it will be ready, how stable it would be and how much it would cost them. We realise the apprehensions of our clients thus deliver our best and most economical services that improve the return on their investments. Our application development team provides you with full scope of services and delivers the value that you adore.
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Home Around-the-World KIA Opens Mexico Manufacturing Plant, Creates 14,000 Jobs
KIA Opens Mexico Manufacturing Plant, Creates 14,000 Jobs
Kia Motors Mexico plant grand opening ceremony
[dropcap]K[/dropcap]IA Motors officially opened its new production facility in Mexico yesterday at a grand opening ceremony attended by over 500 people.
Construction of KIA's new manufacturing plant, located in Pesquería in the northern Mexican state of Nuevo Léon, began in October 2014. The facility – KIA's sixth overseas production base – represents an investment by KIA and suppliers of US$3 billion.
The ceremony, which took place in the plant's new assembly shop, was attended by Mexico's Secretary of Economy, Ildefonso Guajardo Villareal; the Nuevo Léon State Governor, Jaime Rodríguez Calderón; and the Mayor of Pesqueria, Miguel Ángel Lozano Munguía. The delegation of around 100 visitors from Korea included Hyundai Motor Group Chairman Mong-Koo Chung and KIA Motors Corporation Vice Chairman and CEO Hyoung-Keun Lee.
"The new plant here in Mexico represents the next step in KIA Motors' ambition to become one of the world's leading automakers," said Mong-Koo Chung, Chairman of Hyundai Motor Group, during his speech at the ceremony. "The innovative design and world-class quality possessed by the cars produced at the KIA Motors Mexico plant will be embraced by our valued customers not only here in Mexico but also in export-bound countries of Latin America and North America."
All-new Rio to be manufactured from Mexico plant before the end of 2017
KIA's new manufacturing plant will have an annual production capacity of 400 000 units, boosting the Korean brand's global manufacturing capacity to 3,56 million vehicles. Production began in May 2016, with the Mexico plant providing the company with a new production base for the C-segment KIA Cerato. Beginning of 2017, the plant will produce the all-new, fourth generation B-segment Rio, which will have its world premiere on 29 September in Paris at the 2016 Mondial de l'Automobile.
In addition to supplying the local Mexican market, where KIA is targeting a 5% market share by 2020, 80% of the facility's production is destined for numerous other countries in the region, including the USA and other Latin American markets – where demand for KIA cars is expected to increase. The facility is currently operating on one shift, producing around 100 000 cars per year, and is able to manufacture one car every 53 seconds (68 units per hour). A second and third shift will be added in 2017 to bring annual plant capacity to 300 000 units, and KIA expects the plant to be operating at full capacity of 400 000 units utilising three shifts by the end of 2018.
The new plant is a high-tech integrated automotive production facility, with 420 robots automating the press, body and paint shops, as well as the assembly line. Meanwhile, a new quality control centre was established to ensure that all vehicles are manufactured to the highest standards. As the final stage in the production process involves advanced component quality assessment and evaluation, quality control is carried out in tandem with KIA's suppliers, enabling all parties to benefit from any quality-related findings. The quality control centre will ensure continuous improvements to vehicle quality as well as the brand's reputation for producing cars that exceed buyers' expectations.
A significant number of new jobs are being created at the plant. By the end of 2017, approximately 14 000 workers will be employed by the KIA Motors Mexico plant and supplier firms.
The site also includes a training centre for assembly line workers. KIA's systematic approach to vocational training and human resource development will see every employee undergo a 15-day training period before they are assigned to positions on the assembly line, with further opportunities for more advanced training in future.
The KIA Motors Mexico production facility will also invest approximately US$1 million annually in CSR (corporate social responsibility) initiatives for the local citizens of Pesquería. These activities will include the donation of vehicles to public security organisations, support for low-income households and the creation of educational facilities and scholarships.
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Don Imus
Don Imus Song list
Just Like Frank Zappa (2005)
Watching The DetectivesElvis Costello
Lyrically, Elvis Costello's "Watching The Detectives" was inspired by American detective shows; musically, it was inspired by The Clash.
I'm A BelieverThe Monkees
Neil Diamond originally wrote "I'm A Believer" for the Country artist Eddy Arnold. He was surprised when record executive Don Kirshner passed it instead to The Monkees.
PillowtalkZayn
Zayn's "Pillowtalk" reached #1 on the Hot 100, something his former One Direction bandmates never achieved.
LolaThe Kinks
When The Kinks released "Lola," most people didn't realize it was about a transvestite.
It's the End of the World As We Know It (And I Feel Fine)R.E.M.
"It's the End of the World As We Know It (And I Feel Fine)" was inspired by a dream where Michael Stipe conjured up images of people with the initials L.B.: Lester Bangs, Leonid Breshnev, Lenny Bruce and Leonard Bernstein.
Dance Hall DaysWang Chung
Wang Chung's '80s classic "Dance Hall Days" is about how things can start simple but end up complex. First you "take your baby by the hand," but by the end she has an amethyst in her mouth.
Butch VigSongwriter Interviews
The Garbage drummer/songwriter produced the Nirvana album Nevermind, and Smashing Pumpkins' Gish and Siamese Dream.
Roger McGuinn of The ByrdsSongwriter Interviews
Roger reveals the songwriting formula Clive Davis told him, and if "Eight Miles High" is really about drugs.
TV Theme SongsFact or Fiction
Was a Beatles song a TV theme? And who came up with those Fresh Prince and Sopranos songs?
Is That Song Public Domain?Fact or Fiction
Are classic songs like "Over The Rainbow" and "Take Me Out to the Ballgame" in the public domain?
Mick Jones of ForeignerSongwriter Interviews
Foreigner's songwriter/guitarist tells the stories behind the songs "Juke Box Hero," "I Want To Know What Love Is," and many more.
Charlie Benante of AnthraxSongwriter Interviews
The drummer for Anthrax is also a key songwriter. He explains how the group puts their songs together and tells the stories behind some of their classics.


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Hiking the Divide to Unite Presents a Conversation with "Allegiance" Cast Members – to Benefit the Actors Fund
September 26, 2020 By MovieDebuts
e2e Treks – Hiking the Divide to Unite, a group bringing access and awareness of climate and culture through documentaries, podcasts and showcases of artists and Native communities, is proud to announce a special streaming event benefitting The Actors Fund, "How History, Location and Adversity Inform, Inspire and Influence Theatre" with various cast and creative team members of Broadway's Allegiance, on Monday, September 28 at 8:00pm ET / 5:00pm PT.
"How History, Location and Adversity Inform, Inspire and Influence Theatre," will be hosted by Mark Montague and Gary Adamsen of e2e Treks and will feature an Allegiance reunion with performers Telly Leung, George Takei, and Ellie Wang, music and lyrics co-author Jay Kuo, co-author and producer Lorenzo Thione, and producer Joey Monda.
Allegiance was based upon George Takei's personal experience as a child when his family was forced to live in the stables of Santa Anita Park before being sent to the Rohwer Relocation Center (internment camp) in Rohwer, Arkansas. Takei has written a New York Times best-selling graphic novel, They Called Us Enemy, a stunning memoir recounting his childhood imprisoned within an American concentration camp during World War II.
Hiking The Divide To Unite will be a 10-part series documentary capturing e2e Treks' almost 1,000-mile extreme hike down the Continental Divide Trail which began in August 2020 and will complete in October 2020. On the trail, the group will document the natural beauty while focusing on the Native people, communities, and rich history represented by the areas through which they will travel. By relaying these stories, e2e Treks hopes to provide a platform of positive inspiration for all creatives in the arts during this "pandemic shutdown". The team will be hiking near Heart Mountain Internment Camp, part of the historical inspiration for Allegiance, when the event is live on September 28.
The link to this event will be posted on the e2e Treks website, www.e2etreks.com, and The Actors Fund Facebook Page.
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Filed Under: Shows/Events Tagged With: Actors, Actors Fund of America, Artists, Awareness, Beauty, Broadway theatre, Child, Culture, documentary, Family, George Takei, Heart, History, Music, Music and Lyrics, Pandemic, Podcast, Telly Leung, Theatre


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Sequel Bits: 'Mission: Impossible 5', 'Dawn of the Planet of the Apes', 'Creed', 'Transformers 4'
Posted on Wednesday, April 30th, 2014 by Angie Han
Star Wars Episode VII has dominated the news over the past day or so, but it's certainly not the only sequel in town. After the jump:
Matt Reeves talks Planet of the Apes sequels
Ryan Coogler offers details on the Rocky spinoff Creed
John McTiernan wrote Thomas Crown 2 while in prison
Christopher McQuarrie shares a pic from M:I5 prep
Get an eyeful of Optimus Prime in a new Transformers still
This summer's Dawn of the Planet of the Apes gets us just a little bit closer to the events depicted in the original Planet of the Apes. But director Matt Reeves says the next film likely won't be the one to bridge the gap, as he thinks there's still more story to be told.
I think there may be more story even before that to be honest with you. Its kind of an epic story, it has a big sweep. […] How do you get from Caesar and what his world is about to that world? That's a long distance[…] He becomes kind of a mythic character, I think, in the canon of the story and even by the end of this film. […] When I first got involved they proposed an outline that had them talking much more like they do in the later film and all this stuff was far more advanced and closer to the way things are in Planet of the Apes. And I was like, "Wait a minute, we just came from Rise and the delicious thing about Rise was watching the beginning, and I think that there's more to that beginning. We should take a jump, but we should take the next step. We should watch as this evolution takes place." So for that evolution to get to that place there's a lot of story.
Dawn of the Planet of the Apes opens July 11. [Collider]
That Rocky spinoff Creed is coming along nicely, according to director Ryan Coogler. The Fruitvale Station filmmaker has just turned in the latest draft of the movie, which picks up years after Apollo Creed's bouts with Rocky in the ring. It's a story about family which Coogler says was inspired by his own family.
My dad and I are real close, and we were going through something pretty intense in our relationship around the time I was getting ready to make Fruitvale, and that's how I came up with the idea for Creed. He was a big Rocky fan, and I watched the movies with him.
Coogler added that although he wrote the script with Aaron Covington, Sylvester Stallone contributed as well.
He wrote every Rocky movie there ever was, so although I'm writing the script, I'll definitely talk to him about it. Not only because he invented these characters, but because he'll have to be an actor in the film, so it's talking to him in both ways. Rocky isn't the main character in the story, but he's a major supporting player.
As previously reported, Creed centers on Apollo Creed's privileged grandson (Michael B. Jordan), who asks Rocky Balboa to help him learn how to fight. [THR, Digital Spy]
John McTiernan was recently released from prison, where he'd been serving time for lying under oath during the Anthony Pellicano wiretapping case. And now that he's back out, he's preparing to get back to work — perhaps on a Thomas Crown Affair sequel he wrote while he was incarcerated.
Here's how he describes the plot of his new script Thomas Crown and the Missing Lioness:
Nebuchadnezzar had two lion statues commissioned in 1100BC: a male and a female. Alexander the Great took them when he conquered Persia. Mark Antony had them taken to Rome. Constantine moved them to Constantinople. And at some point the lioness went missing. The movie is about what happens when it turns up at an auction. By the way, it's all bullshit; none of that ever happened.
A sequel to McTiernan's The Thomas Crown Affair has been stuck in development for years with little to show for it. Could McTiernan's idea be the one that finally gets the ball rolling again? [Empire]
Christopher McQuarrie would like to have you know that he is ready for whatever Mission: Impossible 5 throws at him.
Keep the faith. #MI5Diary pic.twitter.com/fK9buehNws
— ChristopherMcQuarrie (@chrismcquarrie) April 27, 2014
The next installment of the long-running action franchise opens December 25, 2015. [Twitter]
Paramount has revealed a new look at Optimus Prime in Transformers: Age of Extinction.
The new Transformers isn't a small film by any standard, but compared to the last two films it's a relative bargain. The production budget for Age of Extinction has been revealed to be around $165 million, compared to $195 million for Dark of the Moon and $200 for Revenge of the Fallen. (The first Transformers cost $150 million.)
So find out what $165 million gets you when Transformers: Age of Extinction opens June 27. [LAT, USA Today via TLAMB]
Matt Reeves Unites with 'Searching' Team for HBO Max Series 'The Future'; 'Searching 2' Finds Directors
HBO Max's 'Batman' Spin-Off Series Recruits Joe Barton as New Showrunner
'Creed 3' Will Be Directed by Star Michael B. Jordan, Confirms Tessa Thompson
Here's How 'Black Panther' Director Ryan Coogler Contributed to Pixar's 'Soul'
Images, Sequels, Christopher McQuarrie, Creed, Dawn of the Planet of the Apes, John-McTiernan, Matt-Reeves, Mission: Impossible 5, Ryan Coogler, The Thomas Crown Affair, The Thomas Crown Affair 2, Transformers: Age of Extinction