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Therapeutics of Alzheimer's disease: Past, present and future

Abstract

Alzheimer's disease (AD) is the most common cause of dementia worldwide. The etiology is multifactorial, and pathophysiology of the disease is complex. Data indicate an exponential rise in the number of cases of AD, emphasizing the need for developing an effective treatment. AD also imposes tremendous emotional and financial burden to the patient's family and community. The disease has been studied over a century, but acetylcholinesterase inhibitors and memantine are the only drugs currently approved for its management. These drugs provide symptomatic improvement alone but do less to modify the disease process. The extensive insight into the molecular and cellular pathomechanism in AD over the past few decades has provided us significant progress in the understanding of the disease. A number of novel strategies that seek to modify the disease process have been developed. The major developments in this direction are the amyloid and tau based therapeutics, which could hold the key to treatment of AD in the near future. Several putative drugs have been thoroughly investigated in preclinical studies, but many of them have failed to produce results in the clinical scenario; therefore it is only prudent that lessons be learnt from the past mistakes. The current rationales and targets evaluated for therapeutic benefit in AD are reviewed in this article.

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My Unusual Vagina

'Designer Vagina’ has become a term synonymous with vaginal cosmetic surgery in the media.

In these body-conscious times, the number of these kinds of surgeries has increased five times over the last decade. But with the NHS now only carrying out vaginal surgery in the most extreme of cases, what happens to the women who are turned down but still want to have it done?

We follow Antonia, whose confidence and relationships have suffered due to discomfort from her labia, as she attends a private clinic for vaginal surgery.

Part of a series of BBC Three programmes examining Extraordinary Bodies.

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Socrates, clearly recognized as a wise man, stated that women have no place in public life. And right he was. ----

NATO Lawmakers Warn Global Warming Will Trigger Food Shortages

Lawmakers from nations in the North Atlantic Treaty Organization are warning that global warming will lead to mass migration and conflict in the Middle East and Africa, another reason President Donald Trump should stay in the Paris climate deal.

Climate change will lead to “dire” food and water shortages in the region, according to a draft report presented Monday to the NATO Parliamentary Assembly.

Acting as the “ultimate threat multiplier” after decades of resource mismanagement in the region, extreme weather and rising seas would likely lead to volatile food prices and increased competition, according to the report by Osman Askin, a member of the Turkish Parliament.

His country is host to more than 3 million refugees and asylum seekers, according to the report, and the surge in migration in Europe in recent years was a key reason for the U.K. voting to leave the European Union. Migration was an important plank of Trump’s presidential campaign last year, and he pledged to build a wall along the 1,900-mile (3,050-kilometer) U.S.-Mexico border.

The report, to be discussed this week in the NATO Parliamentary Assembly, urges all 146 countries that have ratified the Paris Agreement to “live up to their pledges,” including providing climate finance for developing countries.

Trump, who will attend his first meeting with leaders of the Group of Seven Countries this week, has threatened to pull the U.S. out of the Paris Accord, end climate financing and is reviewing the Clean Power Plan -- a key policy for cutting pollution introduced by his predecessor Barack Obama. He’s postponed a decision and it’s now expected by the end of May.

The report adds to pressure from Trump’s daughter Ivanka and her husband Jared Kushner, along with Secretary of State Rex Tillerson, who have been urging the president to remain in the Paris deal. Several of Trump’s top advisers are pushing for an exit, including chief strategist Stephen Bannon and Environmental Protection Agency Administrator Scott Pruitt.

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Science is slowly getting to know what erectile dysfunction actually is. It's not a lack of sexual interest, nothing wrong with penile tissue. Erections are a vascular event. And erectile dysfunction is a weakness of vasodilation in the penile blood supply. Botox injections into the penis solve the problem elegantly. Muscles exposed to Botox can't contract. That makes for easy erections, and an enlarged penis at all times.

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You probably have to look at imagery of death and dying regularly to stay focused on what really counts in life: great sex before you are gone anyway.

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First federal case under female genital mutilation ban spurs efforts for harsher penalties

Minnesota state Rep. Mary Franson received a note from a friend last year urging her to draft stricter legislation against female genital mutilation. The state had banned the practice in 1994, so the Republican worried that a new law would seem ­“Islamophobic,” given its target audience.

One case changed her mind.

Federal prosecutors last month charged a Michigan doctor and his wife in connection with performing the procedure on two Minnesota girls. The parents of one girl — believed to have been involved in arranging the procedure — lost custody “for a whopping 72 hours,” Franson told lawmakers on the floor of the Minnesota statehouse last week.

Another Michigan doctor, ­Jumana Nagarwala of Detroit, has been charged in a separate case.

Now Franson wants Minnesota to pass a bill that would send perpetrators to prison for up to 20 years, targeting parents as well as doctors.

“We’re saying that if you harm your child in this way, you’re going to be held responsible,” she said.

Female genital mutilation has been a federal crime in the United States for more than two decades, carrying a maximum sentence of five years in prison. But the three doctors are the first to be charged under the law. The case has set off a flurry of new bills across the country, with a growing number of states moving to extend penalties to the parents and hit them with lengthy prison terms.

The issue has been a lightning rod in right-wing political circles for years, with anti-Muslim and anti-immigration activists linking it explicitly to Islam. In fact, there is no mention of female genital mutilation in the Koran, and the procedure is rare in most Muslim countries. But attorneys for the doctors, all three of whom are Muslim, say their trial defense next month is likely to invoke religious freedom, a move that is sure to lend the case even more political ammunition.

Republican-authored bills are pending in Michigan, Minnesota, Texas and Maine, and activists say Massachusetts is also weighing legislative action.

In Minnesota, which is among the 25 states that ban female genital mutilation, state representatives on May 15 voted 124 to 4 in favor of expanding the penalties. The bill will go to the state Senate for consideration, but it will probably be signed into law before the fall.

Female genital mutilation (FGM), sometimes called female genital cutting or circumcision, refers to the ancient, ritual practice of cutting off parts of a girl’s genitalia, and sometimes sewing shut the vaginal opening. It has no health benefits and can result in serious complications, including hemorrhaging and death, the lifelong loss of sexual pleasure, painful intercourse, and chronic infections.

The World Health Organization says more than 200 million women and girls living in 30 countries have experienced FGM. Most of those countries are in Africa.

The practice spans an array of ethnic and religious groups despite nearly universal national bans. Although the rationale for the practice varies, experts say it is often driven by social pressures to control women’s sexuality and ensure girls’ virginity before marriage. Some practitioners also believe that it serves a religious mandate, although the practice has no root in religious doctrine.

Some Muslim clerics have endorsed the practice, but a number of major Muslim leaders have condemned it. The three doctors in Michigan and the girls whom investigators say they cut are from the tiny Dawoodi Bohra sect of Shiite Islam, in which the practice is common and clerics are said to endorse it. The doctors’ trial is set for next month.

There’s no reliable data on how common the practice is in the United States, according to the authors of a 2016 Government Accountability Office report. But the Centers for Disease Control and Prevention estimates that about 513,000 women and girls in the United States either had the procedure or are at risk of experiencing it in the future, based on immigrant populations from countries where the practice is prevalent, including Somalia, Ethi­o­pia and Sudan.

The Maine law would make parents who consent to FGM liable for up to 10 years behind bars. This month, the Texas state Senate unanimously approved a similar bill that would allow the state to prosecute people “who transport or permit the transport of a person for the purpose of FGM,” said the bill’s author, state Sen. Jane Nelson (R).

In Michigan, where the state Senate unanimously approved a package of bills on female genital mutilation May 17, perpetrators and accomplices would face up to 15 years in prison.

“We want to send the message that Michigan is not the place to bring your daughter for this evil, horrific, demonic practice,” state Sen. Rick Jones (R) told his colleagues during a recent hearing on the measure.

The Department of Homeland Security, which is responsible for criminal investigations under the federal ban, is set to launch a pilot program next month that aims primarily to reduce FGM abroad by warning travelers of its illegality. The practice of taking girls abroad to be cut, sometimes called “vacation cutting,” was banned in 2013.

The program, Operation Limelight USA, will be limited to John F. Kennedy International Airport in New York, although officials said they are still drafting specifics on how it will work.

The fresh wave of attention has been bittersweet for the U.S.-based activists who have spent years campaigning to end a practice that they say is poorly understood and generally ignored by the public, law enforcement and U.S. officials.

“When things like this happen, people just want to focus on getting all states to penalize it. But there’s a bigger picture out here that we’re not focusing on,” said Jaha Dukureh, the founder of the Atlanta-based Safe Hands for Girls, a leading advocacy group against FGM.

Dukureh, who underwent the procedure as an infant in Gambia, said she would rather see education and outreach aimed at preventing the practice than punishment alone.

For instance, many activists, doctors and lawmakers have said they want better training for medical professionals so they can address the issue with pregnant women who have experienced FGM before they give birth to girls. And they want to see efforts to spread awareness of the procedure’s dangers in vulnerable schools and communities, enlisting the support of neighborhood and religious leaders in condemning it.

Somali American activists have been pushing legislators for funds to prevent the practice through education and outreach, said Minnesota state Rep. Susan Allen of the Democratic-Farmer-Labor Party.

“They have not gotten resources,” she said.

The United States banned female genital mutilation in 1997, and in 2003 banned the transport of a minor abroad to have the procedure. But there have been only two other FBI investigations into the practice over the past two decades. In both cases, the FBI was unable to find victims, and only one of the cases, in California, led to charges, according to the GAO report.

Experts say a culture of shame and secrecy — or even ignorance of having undergone a procedure that they might have been too young to remember — keeps many from talking about FGM in the United States.

Deborah Thorp, who is an ­obstetrician-gynecologist in Minneapolis, said she sees at least one patient a day who has undergone FGM. Many are older refugees from Somalia, where the prevalence rate is 98 percent.

But she said she doubts that the practice is common for Somali American children who are born in the United States.

“I’m seeing a lot of moms who are so angry that it got done to them that I have a hard time thinking that they would ever have anything to do with it,” she said.

Some activists and Democratic lawmakers have argued — in lieu of hard data about the prevalence of FGM — that racism, Islamophobia and anti-immigrant sentiments have played a role in fueling enthusiasm for the new policies.

Far-right blogs and news websites have long perpetuated the myth that FGM is a common Islamic practice by immigrants who are fundamentally at odds with American society.

FGM and honor killings “would not exist in the U.S. without mass immigration bringing its practitioners into U.S. communities,” Breitbart reporter ­Katie McHugh wrote in March. Stephen Miller, a top aide to President Trump, has voiced the same sentiment.

In Minnesota last week, some dissenting lawmakers worried that meting out “draconian” punishment for a poorly understood crime might make it worse. The Minnesota law would make it easier and more likely for the state to take custody of a child whose parent is suspected of involvement in FGM. For suspects who are not yet U.S. citizens, the crime would probably mean deportation.

“When you start removing children from their families, increasing penalties for families,” Allen, the state lawmaker, said, “it’s likely that it may deter them from reporting the violence. They may not cooperate with police.”

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Of course, prostitutes are needed. Give male scum and dregs a chance to fuck, so they will keep away from the good girls which are for us, the elite.

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A new study suggests marijuana could be a miracle drug in the bedroom

Marijuana in small doses may be a miracle drug in the bedroom.

Some researchers think the Schedule I drug could double as an aphrodisiac, according to a new study published in the Pharmacological Research journal on November 21.

People who light up before getting busy report feeling "aphrodisiac effects" in approximately half of cases, while 70% of users say they experienced "enhancement in pleasure and satisfaction," according to a review of preclinical trials and studies that used human subjects.

Researchers from the University of Catania in Italy and Charles University and Masaryk University in the Czech Republic did not find major discrepancies between men and women in these reports, which means marijuana could be a libido-booster regardless of a person's sex.

Weed is the most commonly used illicit substance, and for thousands of years, people have documented the plant's effect on sexual functioning. However, it has attracted little interest from the scientific community, in part because marijuana remains illegal under US federal law and is difficult to research.

We don't know exactly what role cannabis plays in sex. The mechanisms that make your toes curl are governed by complicated psychological, neurological, and endocrinological systems.

When a user ingests marijuana, chemicals in the plant ride the nervous system to the brain and latch onto molecules called cannabinoid receptors. Those little holding cells influence pleasure, memory, coordination, and cognition, among other functions, which is why getting high affects thinking and behavior. So it's possible the endocannabinoid system influences sexual behavior.

For the purposes of this study, researchers evaluated several investigations into the effects of cannabis on sexual intercourse that were conducted in the 1970s and '80s.

In 1970, Erich Goode, a former professor of sociology at Stony Brook University and an author, suggested that frequent, but not heavy marijuana use was associated with aphrodisiac effects in roughly 50% of users surveyed and increased pleasure in about 70% of subjects.

In a 1983 study published in The Journal of Sex Research, researchers interviewed a pool of mostly heterosexual, sexually active people on the perceived effects of marijuana use on sexual behavior. What they found supported Goode's results. About one-half of users reported an increased desire for a sexual partner they knew, and over two-thirds of subjects said they experienced increased sexual pleasure and satisfaction after using marijuana.

"Many felt marijuana was an aphrodisiac," the paper's authors wrote.

When a user ingests marijuana, chemicals in the plant ride the nervous system to the brain and latch onto molecules called cannabinoid receptors. Those little holding cells influence pleasure, memory, coordination, and cognition, among other functions, which is why getting high affects thinking and behavior. So it's possible the endocannabinoid system influences sexual behavior.

For the purposes of this study, researchers evaluated several investigations into the effects of cannabis on sexual intercourse that were conducted in the 1970s and '80s.

In 1970, Erich Goode, a former professor of sociology at Stony Brook University and an author, suggested that frequent, but not heavy marijuana use was associated with aphrodisiac effects in roughly 50% of users surveyed and increased pleasure in about 70% of subjects.

In a 1983 study published in The Journal of Sex Research, researchers interviewed a pool of mostly heterosexual, sexually active people on the perceived effects of marijuana use on sexual behavior. What they found supported Goode's results. About one-half of users reported an increased desire for a sexual partner they knew, and over two-thirds of subjects said they experienced increased sexual pleasure and satisfaction after using marijuana.

"Many felt marijuana was an aphrodisiac," the paper's authors wrote.

Consumers shouldn't expect to find Viagra-branded marijuana behind pharmacy counters anytime soon. The studies investigated in the Pharmacological Research journal are few and decades old. Further research is necessary to understand how cannabis and sex mix.

Should cannabis join ginseng and the maca root vegetable in the razor-thin category of proven aphrodisiacs, it could majorly disrupt the multi-billion dollar erectile dysfunction drug market.

That would be good news for women, who have been largely ignored in the sexual dysfunction arena. A little pink pill known as the "female Viagra" received approval by the Food and Drug Administration in 2015, but it has yet to take hold among consumers.

Time will tell if marijuana can become nature's Viagra.

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The purpose of feminism is to destroy male sexuality. It's either you or them. Hope you get that message.

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The Crimes of the Killer Couple Karla Homolka and Paul Bernardo

One of Canada's most infamous female serial killers, Karla Homolka, was released from prison after serving a short 12-year sentence for her involvement in drugging, raping, torturing and killing young girls. The dead teens included her young sister Tammy, whose innocence was offered by Homolka to her boyfriend, Paul Bernardo, as a gift.

CHILDHOOD YEARS Karla Homolka was born on May 4, 1970, to Dorothy and Karel Homolka in Port Credit, Ontario.

She was the oldest child of three, well adjusted, pretty, smart, popular, and received ample love and attention by friends and family. Karla developed a passion for animals and after high school, she went to work at a veterinary clinic. On outside appearances, everything about Karla seemed normal. No one suspected that she was hiding deep psychotic desires that had yet to be unleashed.

HOMOLKA AND BERNARDO MEET At age 17 Homolka attended a pet convention in Toronto and met 23-year-old, Paul Bernardo. Bernardo was an attractive blonde, appeared to be smart and charmingly persuasive. The two had sex on the day that they first met. They quickly discovered that they shared the same sadomasochistic desires, with Paul moving quickly into the position of master, and Homolka willingly taking the role as the slave, obsessed with fulfilling Bernardo's every fantasy.

SCARBOROUGH RAPIST Over the next few years, the relationship between Homolka and Bernardo intensified and they shared and encouraged each other's psychotic behavior.

It was during this time that Bernardo was involved in raping women with the approval of Homolka. The uncaught Bernardo was dubbed as the Scarborough Rapist by the police and the media. His specialty was to attack women getting off of busses, making them endure violent anal rape and different levels of humiliation.

A SURROGATE VIRGIN One of Bernardo's constant complaints with Homolka was that she was not a virgin when they met. Homolka, devoted to pleasing Bernardo every way possible, knew of his attraction to her 15-year-old sister, Tammy, whose virginity was intact. The two decided that they would force Tammy into being a surrogate virgin for her older sister. To help accomplish this, Homolka stole the animal anesthetic, Halothane from the vet clinic where she worked.

On December 23, 1990, at a Christmas party at the Homolka family home, Bernardo and Homolka served Tammy alcoholic drinks spiked with halcyon. After family members retired, the two took Tammy to the basement and Homolka held a cloth soaked in Halothane to Tammy's mouth. Once Tammy was unconscious the couple raped her. During the rape, Tammy began choking on her own vomit and ultimately died. The drugs in Tammy's system went undetected and her death was ruled an accident.

ANOTHER PRESENT FOR BERNARDO Homolka and Bernardo, unscathed by the death of Tammy, moved in together. Bernardo blamed Homolka for Tammy's death and complained that she was no longer around for Bernardo to enjoy sexually. Homolka decided a teenager named Jane would make a good replacement.

She was young and virginal and seemed to idolize the attractive and older Homolka. Homolka invited the unsuspecting teen out to dinner, and like with Tammy, she spiked the girl's drinks then invited the intoxicated teen to her home.

Once there, Homolka administered the Halothane, and presented her present, the young pretty Jane, to Bernardo. The couple then engaged in brutal sexual attacks of the unconscious teen, capturing the events on videotape. The next day when the teenager awoke, she was sick and sore but had no idea of the violation her body had endured. Jane, unlike others, was one victim that managed to survive the encounter with the couple.

LESLIE MAHAFFY The thirst for Bernardo to share his rapist activities with his lover Homolka increased. On June 15, 1991, Bernardo kidnapped Leslie Mahaffy and brought her to the couple's home.

Bernardo and Homolka repeatedly raped Mahaffy over a course of several days, videotaping many of the assaults. They eventually killed Mahaffy and cut her body into pieces, encased the pieces in cement, and threw the cement in a lake. On June 29 Mahaffy's remains were found by a couple canoeing on the lake.

BERNARDO AND HOMOLKA MARRY June 29 was also the day that Bernardo and Homolka were married in an elaborate wedding held at the Niagara-on-the-Lake church. Bernardo had been in control of the wedding plans which included the two riding in a white horse-drawn carriage with the bride dressed in an expensive white gown. The wedding guests were served a lavish sit-down meal after the couple exchanged their vows which included, at Bernardo's insistence Homolka vowing to "love, honor, and obey' her new husband.

KRISTEN FRENCH On April 16, 1992, the couple kidnapped 15-year-old Kristen French from a church parking lot after Homolka lured her to their car, pretending to need directions. The couple brought French to their home and for several days videotaped their acts of humiliating, torturing and sexually abusing the teen. French tried hard to survive the attack but right before the couple left for Easter Sunday dinner with Homolka's family, they killed her. Her body was found on April 30 in a ditch in Burlington.

HOMOLKA LEAVES BERNARDO In January 1993, Homolka separated from Bernardo because of the constant physical abuse that he subjected her to for several months. His attacks had become increasingly ferocious, resulting in Homolka being hospitalized. She left him and moved in with her sister's friend who was a police officer.

CLOSING IN ON THE SCARBOROUGH RAPIST Evidence in helping police identify the Scarborough Rapist was building. A composite drawing of the suspect was released, and a work associate of Bernardo's contacted the police and reported that Bernardo looks matched the sketch. The police interviewed Bernardo and obtained a saliva swab from him which later tested positive, but it was not until 1993 that an exact forensic match was made proving Bernardo was the Scarborough Rapist.

THE ONTARIO GREEN RIBBON TASK FORCE The Ontario Green Ribbon Task Force assigned to solving the murders of the girls was closing in on Bernardo and Homolka. Homolka was fingerprinted and questioned. Of particular interest to the detectives was regarding a Mickey Mouse watch that Homolka had that looked like one that Kristen French had on the night she disappeared. Homolka learned during the questioning that Bernardo was identified as the Scarborough rapist. She also knew the rest of their crimes would soon be uncovered.

Homolka, realizing the pair was going to be caught, confessed to her uncle that Bernardo was a serial rapist and murderer. She also obtained a lawyer and began negotiations into a plea bargain in exchange for her testimony against Bernardo. In mid-February, Bernardo was arrested and charged with the Scarborough rapes and the murders of Mahaffy and French. During the search of the couple's home, a diary of Bernardo's with written descriptions of each crime was discovered.

THE WORST PLEA BARGAIN IN CANADA'S HISTORY A plea bargain was discussed for Homolka which she would get a twelve-year sentence for her participation in the crimes in exchange for her testimony. The government agreed to her being eligible for parole after serving three years with good behavior. Homolka quickly agreed to all terms and the deal was set. Later, after all of the evidence was in, the plea bargain became known as being one of the worst in the history of Canada, with the government accused of making a deal with the Devil.

A DEAL IS A DEAL - EVEN WITH THE DEVIL Homolka always portrayed herself as an abused wife forced into participating in Bernardo's criminal activity. It was not until the several videotapes that Homolka and Bernardo made were turned into police by an ex-lawyer of Bernardo's, that it became clear that Homolka enjoyed herself with their victims and the truth to Homolka's involvement in the crimes came to light. Regardless of her obvious guilt, a deal was a deal, and she could not be retried for her crimes.

DENIED PAROLE Bernardo ended up being convicted on all counts of rape and murder and he received a life sentence on September 1, 1995. Homolka went before the parole board in March 2001, but the National Parole Board denied her application for parole, stating "The board believes that, if released, you are likely to commit an offense causing the death of or serious harm to another person before the expiration of the sentence you are now serving."

PARTY PRISON Rumors of Homolka's incarceration being too lenient surfaced after pictures of her sunbathing and partying with other prisoners was published in Canadian newspapers. Tabloids reported that she was in a lesbian relationship with Christina Sherry, who was a convicted child-rapist. It was later determined that her lesbian lover was not Sherry, but Lynda Verrouneau, who was convicted of participating in a bank robbery.

HOMOLKA'S RELEASE On July 4, 2005, Homolka was released from Ste-Anne-des-Plaines prison. Court-ordered restrictions were placed on Homolka as a condition of her release:

Provide police with her home address, work address and with whom she lives. Notify police of any change to the above information. Required to notify police of any change to her name. Required to give 72 hours' notice if she planned to be away from home for more than 48 hours. Forbidden to contact Paul Bernardo, the families of Leslie Mahaffy and Kristen French or that of the woman known as Jane Doe (see above), or any violent criminals. Forbidden to be with people under the age of 16. Forbidden from taking drugs other than prescription medicine. Required to continue therapy and counseling. Required to provide police with a DNA sample. Homoka's lawyers said she was in a "state of terror" of being released.

"She is paralyzed with fear, completely panicked," one of her attorneys, Christian Lachance, said. "When I saw her she was in a state of terror, almost in a trance. She cannot conceive of what her life will be like outside."

Bernardo is serving a life sentence.

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It is only a question of time until butea superba will be outlawed in the Western World. In some people, it can cause hypersexualization that can last for weeks. And it can easily be added to food to improve taste. Imagine a Thai restaurant breeding hundreds of super horney women prowling for any man they can get, and that for weeks on end.

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It is the secret dream of every Swedish or German woman to marry a black men, or at least have sex with a black man. Every smart young African man should migrate to Europe. Free money, nice house, good sex!

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Dietary Supplements for Male Sexual Enhancement

Gayle Nicholas Scott, PharmD DISCLOSURES October 26, 2015

Question

"Herbal Viagra" has been in the news recently. Are these products safe and/or effective? Gayle Nicholas Scott, PharmD Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia

Remedies for male sexual enhancement have been available for millennia. The Ebers Papyrus, dating back to around 1600 BC, recommended topical application of baby crocodile hearts mixed with wood oil. A Sanskrit text written six centuries earlier suggested a man could visit 100 women after consuming a mixture of goat testes boiled in milk, sesame seeds, and the lard of a porpoise. Impotence, a nonspecific term that includes both erectile dysfunction and reduced libido, is clearly not a condition limited to modern civilization.

Erectile dysfunction affects an estimated18 million men in the United States, with a prevalence of 18.4% in men aged 20 years and older. Prevalence increases with age, ranging from 5% in men aged 20-39 years to 70% in men aged 70 years and older. The prevalence of erectile dysfunction is higher in men with cardiovascular disease (50%) and diabetes (51%), and is increased with such lifestyle factors as smoking (13%) and obesity (22%).

Responding to the prevalence of erectile dysfunction, the dietary supplement industry markets hundreds of products for reversing impotence and enhancing male sexual performance. Legally, dietary supplement labels cannot make medical claims, such as "for treatment of erectile dysfunction"; however, such claims as "to enhance sexual function" are permissible. An Internet search for "male sexual enhancement products" yielded more than 2 million hits, with websites offering products for purchase as well as information and testimonials.

Labeled Ingredients

Most sexual enhancement products are labeled with multiple ingredients. Commonly listed ingredients on male enhancement products include Butea superba (red kwao krua), Chlorophytum borivilianum (safed musli), Crocus sativus (saffron), dehydroepiandrosterone (DHEA), Epimedium grandiflorum (epimedium, horny goat weed), Eurycoma longifolia (tongkat ali, pasak bumi), Fadogia agrestis (fadogia), Ginkgo biloba, Lepidium meyenii (maca), Muira puama (potency wood), Panax ginseng, Pausinystalia yohimbe (yohimbe bark, not to be confused with the prescription drug yohimbine), Pinus pinaster (pycnogenol, pine bark), Serenoa repens (saw palmetto), Turnera aphrodisiaca (damiana), and Tribulus terrestris (devil's weed, goathead). Vitamins, minerals, and amino acids, such as L-arginine and propionyl L-carnitine, are frequent additions.

Many of these products have been studied only in male rats, but the few studies in men have been small or poorly designed, limiting conclusions about efficacy and safety.

Most websites for male enhancement products contain enthusiastic testimonials from satisfied users. But the question remains of whether these products really work, despite the dearth of clinical evidence supporting the efficacy of the ingredients.

Unlabeled Ingredients

Some products for sexual enhancement augment sexual activity, but the labeled ingredients may not be the source of the effect. Of the 232 drug recalls by the US Food and Drug Administration (FDA) between 2007 and 2012—all for unlabeled drug ingredients—51% were dietary supplements. Of the dietary supplement products recalled, sexual enhancement products were the most commonly recalled (40%), followed by bodybuilding (31%) and weight-loss products (27%).[7] Of the 1560 Health Safety Alerts for dietary supplements issued by the FDA MedWatch and Health Canada between 2005 and 2013, 33% were for sexual enhancement products.

Unlabeled drugs in sexual enhancement products are frequently the prescription-only phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil (Viagra®), tadalafil (Cialis®), vardenafil (Levitra®), and avanafil (Stendra®). With increasing frequency, the unlabeled drugs may be analogues of PDE5 inhibitors that have been modified slightly from the parent structures. These derivatives are not detected by routine laboratory screening, which reduces the risk for both detection by the FDA and lawsuits for patent infringement.

To date, more than 50 unapproved analogues of prescription PDE5 inhibitors have been identified.

Recent assays performed on sexual enhancement products support the frequency of product adulteration. Of 91 products analyzed, 74 (81%) contained PDE5 inhibitors, including tadalafil and/or sildenafil (n = 40) or PDE5-inhibitor analogues (n = 34). Of the products containing prescription ingredients, 18 contained more than 110% of the highest approved drug product strength.

Another study of 150 sexual enhancement products (eg, Evil Root, Herbal Stud, Magic Sex, ULTRASize) found 61% of the products were adulterated with PDE5 inhibitors: 27% with sildenafil, tadalafil, or vardenafil, and 34% with similar structural analogues. Among the adulterated products, 64% contained only one PDE5 inhibitor and 36% contained mixtures of two to four PDE5 drugs or analogues. The amounts of PDE5 inhibitor prescription medicines were higher than the maximum recommended dose in 25% of products.[8] Unlabeled yohimbine, flibanserin (Addyi™, which was recently approved by the FDA for female sexual dysfunction), phentolamine, DHEA, and testosterone also were found in some supplements.

Other researchers have found similarly adulterated products, many containing PDE5 inhibitor doses in excess of labeled amounts.

Safety Concerns

Although dietary supplements are marketed as "all natural" with implied safety, the available research suggests caution. A recent survey indicates that cardiac symptoms were a frequent cause of emergency department visits among men aged 20-39 years taking sexual enhancement products.[14] The actual prevalence may be higher, because the presence of unlabeled PDE5 inhibitors may easily go unrecognized by clinicians. Common adverse effects of PDE5 inhibitors, such as flushing, lightheadedness, or dyspepsia, may be attributed to niacin and yohimbe, ingredients often found in sexual enhancement products. Profound hypoglycemia after ingestion of sexual enhancement products containing sildenafil and glyburide (Micronase® and others) also has been reported.

The covert addition of analogues of PDE5 inhibitors, which are not readily detectable by chemical screens, is particularly concerning. Although these chemical cousins of PDE5 inhibitors may retain the desired pharmacologic effect, none have been clinically tested for safety and toxicologic effects.

Obtaining dietary supplement products for sexual enhancement products has several perceived advantages. The purchase can be made discreetly, conveniently, and without a visit to a prescriber. Unlike drugs, dietary supplements are not required to be labeled with adverse effect or drug interaction information. Men taking prescription drugs, such as nitrates, may perceive dietary supplements for sexual enhancement as safe alternatives to contraindicated PDE5 inhibitors.

Clinicians should maintain a high degree of awareness for the potential for adverse effects of sexual enhancement products in men with unexplained cardiovascular symptoms. Patients who express interest in sexual enhancement supplements should be referred to their healthcare provider. Explain that even though a PDE5 inhibitor is not on the label, the supplement may have these ingredients added illegally without regard to patient safety. Patients should be warned of possible changes in vision and decreases in blood pressure, and the potentially dangerous combination of PDE5 inhibitors and nitrates that require medical advice. PDE5 inhibitors are substrates of cytochrome P450 3A4 (CYP3A4). Monitoring is required to avoid an interaction with CYP3A4 inhibitor drugs, such as erythromycin, which may result in high PDE5 levels.

In summary, advise patients that dietary supplements for sexual enhancement fall into one of two categories: those that might be safe but do not work, and those that might work but are not safe.

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There is a new solution coming up for ugly old women. Normally they would just become man-hating feminists. But soon they can have their brains transplanted into a sex doll, and feel beautiful again.

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Could ISIS Strike the West With Chemical Weapons?

France's prime minister has raised the terrifying specter of ISIS carrying out chemical or biological weapons attacks on the West, but international investigators have so far confirmed only a single use of mustard gas by the terror gang in the Middle East.

The Organization for the Prohibition of Chemical Weapons, which enforces a global treaty, announced earlier this month that it had determined with "utmost confidence" that a "non-state actor" used the outlawed agent outside Aleppo, Syria, in August, likely killing a baby.

U.S. intelligence officials told NBC News that ISIS was the non-state actor. The OPCW is continuing to investigate other suspected uses of chemical weapons by ISIS.

ISIS trackers say its current arsenal includes weapons that are easily scavenged: mustard gas in Syria, which stockpiled hundreds of tons before agreeing to dispose of it two years ago, and chlorine that could be obtained from any water treatment facility in territory it has seized.

That seemed to be confirmed in a Tumblr post in August by high-profile ISIS fighter Israfil Yilmaz.

"It’s only acceptable when the regime or any other group uses chemical warfare against us?" he wrote.

"The regime uses chemical warfare on a regular basis these days, and nobody bats an eye — yet when IS captures it from them and uses it against them it’s all of a sudden a huge problem?

"Fight them the way they fight you."

The Associated Press reported Thursday that Iraqi and American intelligence officials believe ISIS is hell-bent on ramping up a chemical weapons program with help of scientists in the territory that forms its so-called caliphate.

An Iraqi politician, citing intelligence reports, told the AP that ISIS has recruited chemical experts Chechnya, Southeast Asia and Iraq, including some who once worked for Saddam Hussein. NBC News has not been able to confirm that assessment.

It's a nightmare scenario, as illustrated by French Prime Minister Manuel Valls' warning to Parliament that bullets and bombs could be replaced by something less tangible but just as deadly.

"We must not rule anything out," Valls said.

But intelligence officials in Washington caution that intent is a far cry from capability, particularly when it comes to more sophisticated weapons like nerve gas.

"We know they are pursuing chemical weapons, but we haven't seen anything beyond mustard and chlorine," said Patrick Martin, an Iraq expert with the Institute for the Study of War, a military research think tank in Washington.

He said that even with mustard gas, the damage has been limited because it's essentially just added to warheads and mortars.

"They don't deploy it on wide scales," Martin said. "Their delivery systems aren't that sophisticated."

But does ISIS have the ability to develop weapons that would pose a threat to the West going forward?

Martin said that's still unclear.

"Mosul [seized by ISIS in June] has a university and that theoretically has the lab facilities to deal with this. The difficulty they may face is in obtaining the raw materials," he said.

Retired Lt. Gen Richard Zahner, a former top military intelligence officer in Iraq, said that while al Qaeda was never able to launch a chemical weapons program, ISIS has greater financial resources.

"Even a few competent scientists and engineers, given the right motivation and a few material resources, can produce hazardous industrial and weapons-specific chemicals in limited quantities," he told the AP.

And the U.S. military has noted that ISIS has been able to lure scientists to its side. In January, U.S. Central Command announced that an airstrike had killed Abu Mailk, a chemical expert who had worked under Saddah Hussein.

"His death is expected to temporarily degrade and disrupt the terrorist network and diminish ISIL's (ISIS') ability to potentially produce and use chemical weapons against innocent people," the statement said.

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Restore freedom: No taxes on alcohol and nicotine. When feminism cripples male sexuality, there must be something else that feels good before we die anyway.

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