what happens around us is here

Alyson Hannigan and Jason Biggs Talk About ‘American Reunion’

Jason Biggs and Alyson Hannigan in 'American Reunion'

Jason Biggs and Alyson Hannigan in ‘American Reunion’

© Universal Pictures


The entire American Pie gang returns for American Reunion, the fourth film of the comedy franchise which is hitting theaters nine years after American Wedding (aka American Pie #3). Heading up the R-rated antics are Jason Biggs, who will forever be known as ‘The Pie Guy’, and Alyson Hannigan who uttered the memorable “One time, at band camp…” line in the first film. Biggs and Hannigan play Jim and Michelle, the now-married couple who’ve hit a rough patch in their marriage after discovering that being parents has put a damper on their love life. They hope to reignite the spark at their 13 year high school reunion, however they soon discover that getting back together with the old gang is much more time-consuming and energy-sapping than having a toddler around.

Together at the LA press conference for the Universal Pictures release, Biggs and Hannigan discussed what it was like to revisit these characters and how it felt to play a couple once again.

Jason Biggs and Alyson Hannigan American Reunion Press Conference

Jason, can you talk about how your character has grown up but he still has that teenage boy part of his personality?

Jason Biggs: “I love that Jim has grown up and Jim and Michelle are married now and he’s got a kid and he means well. But, in his mind, he has grown up. The problem is he finds himself, much like in the first film, and frankly all of the American Pie films, he finds himself in a situation where he’s once again sexually frustrated. When Jim is sexually frustrated, he ends up making some poor decisions. When he makes some poor decisions…”

Alyson Hannigan: “We make a movie. “

Jason Biggs: “We make a film. When we make a film, we get rich. When we get rich… No, I’m kidding. The thing that I love now that Jim is 31 – how old would he be? 30, 31? We’ve been trying to figure out the age of our characters. We’re not exactly sure.”

Alyson Hannigan: “We didn’t do much research.”

Jason Biggs: “And so, the truth is, after you’re 30 years old, men still masturbate. There are still sexual problems that happen, that arise for guys.”

Alyson Hannigan: “Jason, do you want to tell us something?”

Jason Biggs: “I’m masturbating right now as we speak, right under the table. Is that what you meant?”

Alyson Hannigan: “No.”

Jason Biggs: “I don’t even know what your question was.”

Jason, when you read the dominatrix scene, were you like, “Is that all you’ve got, guys? I’m Jason Biggs!”

Jason Biggs: “Yeah, I’m like, ‘C’mon guys, step up to the plate. Don’t be a pussy. Let’s do this, all right?’ Sorry about my language. It’s that time of day. I’m also that type of person always so… Actually, it’s funny because the dominatrix scene was in the earlier drafts and I was like, ‘This is great. This is funny. I think that’ll be really funny. But what’s the next step? There’s more to do here.’ And so, if there was any sort of concern I had with the very, very early drafts, and I mean a minor concern, because when I tell you that this script was in the shape it was, it blew my mind. Jon and Hayden came in and you read the script and I was like, ‘Did these guys write the first American Pie?’ They did such justice, I felt, to Adam Herz’s original screenplay and the characters that he had originally created, and I think it comes across on screen. I feel like this movie is more like the first one than any of the other ones.”

Alyson Hannigan: “They were like the perfect combination of the Weitz Brothers and Adam.”

Jason Biggs: “Actually, they were. The Weitz Brothers directed the first film and Adam wrote it. I’d say that’s pretty accurate. So, if there was anything, I was just, ‘Okay, let’s keep [going]. How much further can we go?’ That’s one of the biggest challenges because now that you have these characters who are in their 30s, it’s tougher to credibly find these situations where you can push these boundaries and put them in these ridiculous scenarios that are believable, aren’t gratuitous, that aren’t awkward/just illegal in some way. I mean, they’re older. Some of the things they did in the previous films would be not acceptable for a 30 year old. They had to update it, if you will, so that’s why the penis scene, I think, works organically – ‘organ’ being the appropriate root word there.”

Alyson, in that scene was it natural to you that Michelle would become the dominatrix?

Alyson Hannigan: “Yeah. I mean, she was in the first film, right?”

Jason Biggs: “She was. You made me your b*tch.”

Alyson Hannigan: “Absolutely. Still are.”

Jason Biggs: “I always will be.”

Alyson Hannigan: So yeah, I definitely am, and especially if she is feeling responsible for letting the sparks fade a little on their sexual life because she’s been so focused on being a mom. So she sees this weekend as a way to reinvigorate their lives and remind themselves of where they started. So yeah, definitely.”

There are a lot of themes in the movie that are very relatable, that are real life problems. What did you gravitate towards the most?

Alyson Hannigan: “Definitely balancing the married relationship now with parenthood I could relate to. My situation wasn’t as extreme as Jim and Michelle’s, of course, but when my daughter was first born, we were definitely all-consumed with just her. It was probably like quite a few months where we realized, ‘Okay, wait, we do need to actually set aside a date night instead of trying to fit it in between diaper changes or whatever?’ But you just get so wrapped up and it was brilliant and there was no problem there, but it was like, ‘Okay, we can’t do this for 18 years. We need to still have our couple times.’ So we try to have a date night every week, even if it’s just going to dinner and having a dinner that’s not interrupted by a 3-year-old. That’s just nice.”

What about you, Jason? Was there anything that you related to, such as the dad/son relationship or somebody still trying to find themselves as an adult?

Jason Biggs: “That’s certainly a good one. For me, the biggest change in my life personally since the last film has been getting married. Getting married for me has kind of shifted my focus in such a profound way. You just realize you can’t be so selfish anymore. There’s someone else. And it’s not just about the other person, but it’s about the relationship as well. Your priorities are realigned. Now the next step will be kids and I can’t imagine what that’s going to do, but that’ll be a game changer. It’s just interesting to see Jim wrestle with those same sort of big ideas where it’s not just about him anymore.”

“You think about the first movie, the whole movie rests upon how all these guys just want to get laid. It’s very me, me, me. Get me laid. You mentioned Jim and his dad, too. That’s really interesting. That’s a great part of the film for me. I’ve actually found this, as I’ve gotten older too, that my dynamic with my parents has changed quite a bit. There’s a beautiful moment in the film. It’s funny because a lot of my favorite moments in this movie are not really the funny ones but the more poignant, sweeter moments. Actually, that’s always been the case with the whole franchise. I love when Jim offers his dad advice in this movie and it’s kind of flipped. I think that’s really, really cool. That’s another genius thing, I think, from our writer-director guys that they came up with. I found that my relationship with my old man has changed considerably. As an adult, it’s a different thing. It’s like he’s a new person to me and it’s great. We have a totally different relationship than when I was growing up as you’re supposed to. But that resonates with me quite a bit. That’s cool.”

Are there any characters that you wanted closure for?

Alyson Hannigan: “I love the MILF guys’ storyline. I love that we really don’t know why they broke up but they’re back together.”

Jason Biggs: “And when we say ‘broke up,’ listen, Johnny Cho plays the role in a way that maybe is a little…I don’t know what you guys thought…but we’re not saying they were gay. We’re not saying that they broke up.”

Alyson Hannigan: “No, just their friendship.”

Jason Biggs: “We never intended that. I mean, they’re buddies.”

Alyson Hannigan: “We weren’t saying that they were in a relationship.”

Jason Biggs: “Right. But people have been questioning. I’ve heard that people have been like, ‘Is he gay or…?’ And then when you just said broken up, I was like I wonder if people are going to think that’s what we’re trying to imply.”

Alyson Hannigan: “No.”

Jason, what was the conversation like when you were discussing how to show your junk and the variations on how the lid would smash it? And Alyson, now that two of your onscreen husbands, Jason Segal and Jason Biggs, have both shown their goods, do we have you to blame for that?

Alyson Hannigan: “I guess.”

Jason Biggs: “She brings it out in guys. I don’t know what it is.”

Alyson Hannigan:” Obviously, I think with this, Jason Biggs, it was about time – because we’ve spent three movies listening to and talking about it and the pie got to see it – it was about time we all got to see it.”

Jason Biggs: “The penis has been a major player in the American Piefranchise.”

Its own character?

Jason Biggs: “It has been its own character.”

Alyson Hannigan: “It’s like the Rosebud.”

Jason Biggs: “Yeah. Nailed it. So it was about time.”

Alyson Hannigan: “We needed the reveal.”

Jason Biggs: “Yeah, it was about time. The conversation went something like I kept pushing the guys, Jon and Hayden, our writer/directors for that pie scene. ‘What’s going to be the pie scene this time, guys?’ Some earlier drafts felt like it was missing. I gave them carte blanche, just a blank canvas. I was like, ‘Guys, I will literally do anything as long as it makes sense in the context of the film and for the character and as long as it’s funny. As long as I think it’s funny.’ Jon wrote me one day and said. ‘Would you be willing to show your…?’ I was like, ‘Yes! Absolutely! If it’s funny.’ I laughed out loud and they pitched me the idea and I was like, ‘That sounds great.'”

Alyson Hannigan: “And as far as the technicalities of doing the scene, which was my first day of shooting by the way…”

Jason Biggs: “Yeah! Welcome back to the franchise, Alyson! Here’s my penis.”

Alyson Hannigan: “Yay! It was quite technically difficult because I had to sort of become his eyes because he couldn’t lean down and see, because then he wasn’t squishing it enough.”

Jason Biggs: “It was not easy.”

Alyson Hannigan: “And there are so many positions and we had to decide which one was the funniest.”

Jason Biggs: “Yeah. Two o’clock, or the Eiffel Tour, or the Sydney Harbor Bridge, or the straight-up hot dog bun.”

Alyson Hannigan: “The dead insect on the windshield.”

Jason Biggs: “Exactly. Yes. The drugged astronaut. The purple nurple. The options were endless. I should also tell you that I used to star in Puppetry of the Penis in Sydney, Australia when it first came out, so that’s why we had so many options. I was very skilled.”

Alyson Hannigan: “It was good you took out all the piercings for the scene.”

Jason Biggs: “Yeah, two of the holes closed. Bummer!”

Alyson Hannigan: “Not the hole he wanted to close either.”

Jason Biggs: “Yeah, that’s right. I pee through my mouth now. It’s very strange.”

Alyson Hannigan: “We’re a little punchy. Sorry!”

April 6, 2012 Posted by | Uncategorized | 1 Comment

Brain Wired in an ‘Astonishingly’ Simple Grid Structure

A new brain imaging study shows that the human brain is wired in a simple and orderly 3-dimensional grid, akin to a checkerboard, with no diagonal paths.

“Far from being just a tangle of wires, the brain’s connections turn out to be more like ribbon cables — folding 2D sheets of parallel neuronal fibers that cross paths at right angles, like the warp and weft of a fabric,” Van J. Wedeen, MD, from Massachusetts General Hospital (MGH), the Martinos Center for Biomedical Imaging, and Harvard Medical School in Boston, explained in a statement. “This grid structure is continuous and consistent at all scales and across humans and other primate species,” he added.

The highly detailed images were obtained with the Connectom diffusion magnetic resonance imaging (MRI) scanner installed at MGH’s Martinos Center for Biomedical Imaging last fall. The scanner can visualize the networks of crisscrossing fibers in 10-fold higher detail than can conventional scanners.

Detail from DSI scan shows fabric-like 3-dimensional grid structure of connections in monkey brain. Van Wedeen, MD, Martinos Center and Department of Radiology, Massachusetts General Hospital and Harvard University Medical School

“This one-of-a-kind instrument is bringing into sharper focus an astonishingly simple architecture that makes sense in light of how the brain grows,” Dr. Wedeen said.

Their report is published online March 30 in Science.

A Landmark in Human Neuroanatomy

In a statement, Thomas R. Insel, MD, director of the National Institutes of Mental Health said, “Getting a high resolution wiring diagram of our brains is a landmark in human neuroanatomy. This new technology may reveal individual differences in brain connections that could aid diagnosis and treatment of brain disorders.”

As reported in the Science paper, Dr. Wedeen’s team scanned the brains of living humans and the postmortem brains of 4 types of monkeys: rhesus, owl, marmoset, and galago. They found that the wiring of the mature brain appears to mirror 3 primal pathways established in embryonic development.

During early development, the researchers explain, the brain’s connections form along perpendicular pathways, running horizontally, vertically, and transversely. This grid structure appears to guide connectivity as do lane markers on a highway. This structure may help enforce a more efficient, orderly way for the fibers to find their proper connections, and for the structure to adapt through evolution, the researchers say.

Obtaining highly detailed images of these pathways in the human brain has long eluded scientists, in part because the many folds, nooks, and crannies in the human cortex obscure the structure of its connections.

Dr. Wedeen’s team is part of the Human Connectome Project Harvard/MGH-University of California, Los Angeles, consortium that aims to optimize MRI technology to more accurately and precisely image the human brain.

Converging Lines of Evidence

This paper is “very interesting,” Olivier Coulon, PhD, CNRS research fellow in the Laboratory for Information Science and Systems in Marseilles, France, told Medscape Medical News. “To my knowledge, it’s the first that reports such organization at the whole brain level,” he pointed out.

The findings are consistent with observations made in a previous paper, he said, “although in that paper only the medial frontal cortex was studied and the orthogonal organization of fibers was described at a gross scale without any notion of the fine grid described by Wedeen et al.”

“What is interesting,” he added, “is the fact that it is consistent with how we think cortical sulci or folds are organized. There have been a few papers describing the cortical folds as organized according to an orthogonal grid.

“We recently published a short conference paper in which such organization becomes clearer thanks to a flat angle-preserving projection of the cortex on a rectangular domain,” he added. “A longer paper should follow this year.”

“All these papers,” Dr. Coulon said, “are converging to propose evidence that there is a genetically-driven organization, which could help to find an invariant structure beyond the apparent great variability of the brain (cortex and fibers). Developmental studies and the improvement of fetal MRI acquisitions should help to clarify all these ideas in the future,” he concluded.

Dr. Coulon is principal investigator in the BrainMorph Project, which is funded by the French Agence Nationale de la Recherche and dedicated to the development and validation of surface-based brain morphometrics methods.

Dr. Wedeen’s research was funded by grants from the National Science Foundation, the National Institutes of Health, and the Human Connectome Project. The authors have disclosed no relevant financial relationships.

Science. Published online March 30, 2012. Abstract

April 6, 2012 Posted by | Uncategorized | Leave a comment

Immunotherapy Promising for Intractable Epilepsy

March 29, 2012 — Immunotherapy may be effective in treating medically intractable epilepsy in patients with specific clinical and serologic markers, new research suggests.

The seizure freedom we saw in our study is better than any antiepileptic drug ever studied.

According to investigators a “striking” 67% of patients with daily seizures who were resistant to treatment with 2 or more antiepileptic drugs (AEDs) were free of seizures after receiving immunotherapy.

“The seizure freedom we saw in our study is better than any antiepileptic drug ever studied,” senior investigator Sean Pittock, MD, from the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News.

“This is very exciting and there is growing literature to support autoimmunity, not just in epilepsy, but in other areas of neurology as well — dementia, movement disorders, and neurodegenerative diseases.”

The results, published online March 26 in the Archives of Neurology, suggest an autoimmune basis for intractable epilepsy.

History of Autoimmune Disease

Dr. Pittock noted many of the patients he sees have a personal history of autoimmune thyroid problems, lupus, or type 1 diabetes or a family history of rheumatoid arthritis.

“There is something different about these patients,” he said, pointing out that his team found neural autoantibodies in most patients.

Table 1. Neural Autoantibodies

Antibody Percentage
Voltage-gated potassium channel complex 56
Glutamic acid decarboxylase 65 22
Collapsin response-mediator protein 5 6

The researchers led by Amy Quek, MBBS, also at the Mayo Clinic, found Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each.

The observational retrospective case series included 32 patients with partial seizures. Most (81%) had failed treatment with 2 or more AEDs and 38% had seizure semiologies that were multifocal or changed with time.

Head magnetic resonance imaging was normal in 47% of patients at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20 patients, electrographic seizures in 15, and focal slowing in 13.

Patients received immunotherapy with intravenous methylprednisolone, intravenous immune globulin, and combinations of these drugs with plasmapheresis or cyclophosphamide.

New Subspecialty

After a median of 17 months, 81% of patients reported postimmunotherapy improvement. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P<.05).

Table 2. Epilepsy Outcomes (n=27)

Outcome Percentage
Seizure freedom 67
Seizure improvement 15
No change 18

All voltage-gated potassium channel complex antibody–positive patients reported initial or lasting benefit (P<.05). One voltage-gated potassium channel complex antibody–positive patient was seizure free after thyroid cancer resection and another responded to antiepileptic drug change alone.

When autoimmune epilepsy is suspected on clinical grounds, the authors suggest cerebrospinal fluid evaluation and comprehensive screening for neural autoantibodies are indicated.

Selective autoantibody testing is not advised because no single neural antibody is definitively associated with seizures.

In the absence of other treatment options, a trial of 6 to 12 weeks of immunotherapy is justified, the authors suggest. Long-term immunosuppressive treatment, overlapping with gradual taper, should be considered for patients whose seizures respond favorably to the initial trial of immunotherapy.

Clinical experience suggests that immunotherapy should not be used alone to control seizures, but should be used in combination with antiepileptic drugs to optimize seizure control.

Many questions remain, Dr. Pittock told Medscape Medical News. These include the natural history of autoimmune epilepsy, the selection criteria for patients with epilepsy most likely to benefit from an autoimmune evaluation, the timing for immunotherapy trial, and optimal duration of long-term immunotherapy maintenance.

“There’s a whole new subspecialty emerging in neurology,” Dr. Pittock said. “It’s known as autoimmune neurology and we are working with the American Academy of Neurology (AAN) to launch courses exploring this area.”

Dr. Pittock will be teaching a course on this topic next month at the AAN’s 64th Annual Meeting in New Orleans, Louisiana. He will be presenting with Drs. Josep Dalmau, Andrew McKeon, and Mark Keegan.


Perhaps the failure of new antiepileptic drugs is because some of these patients have autoimmune-mediated epilepsy.

In an accompanying editorial, Gregory Bergey, MD, from Johns Hopkins University in Baltimore, Maryland, noted that although the study was not a placebo-controlled trial and all patients were treated, two-thirds achieved seizure freedom for a median of 10 months and 44% became seizure free within 12 months of treatment.

“The typical investigational antiepileptic drug trial produces seizure freedom in fewer than 10% of patients even if seizure freedom is defined as only a 12-week period,” Dr. Bergey writes.

Screening for autoantibodies is not required for entry into investigational antiepileptic drug trials, he pointed out.

“Perhaps the failure of new antiepileptic drugs is because some of these patients have autoimmune-mediated epilepsy,” he writes.

Dr. Bergey added that the study is another reminder that “we need to broaden our concept of symptomatic chronic epilepsy from the structural realm into more dynamic processes not limited to acute inflammatory or infectious pathologies.”

Although not part of a controlled series, the subjects in the current study represent an extensive group of patients with diverse autoantibodies treated with immunotherapy.

“What is the true scope of autoimmune epilepsy in our populations of drug-resistant epilepsy? This is not known, but certainly at present it is probably being underdiagnosed,” he writes.

If a clear symptomatic cause for a patient’s epilepsy is identified such as mesial temporal sclerosis, cortical dysplasia, or cavernous malformation, then autoantibody testing is probably unnecessary, he noted.

“However, if imaging is unrevealing or suggests inflammation or focal swelling, then such screening may be warranted.”

EUROIMMUN provided assay kits for identifying autoantibodies in this study. Dr. Pittock is a named inventor on patents that relate to functional assays. He receives research support from Alexion Pharmaceuticals, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. Editorialist Dr. Bergey has disclosed no relevant financial relationships.

Arch Neurol. Published online March 26, 2012.

April 1, 2012 Posted by | Uncategorized | Leave a comment

Cerebellar dysfunction in MS

Samuel Pleasure

Samuel Pleasure, MD, PhD, is Professor of Neurology at UCSF. He got his MD and PhD (Neuroscience) degrees at the University of Pennsylvania and then trained in neurology and neuroscience at UCSF. He has authored numerous scientific papers on the basic mechanisms of brain development and how they relate to human neurodevelopmental disorders. He has clinical interests in epilepsy and multiple sclerosis.

Cerebellar dysfunction is a common feature in MS and is frequently among the more difficult to manage problems since it causes ataxia, dysarthria and incoordination. My assumption has always been that these symptoms are largely due to demyelination in the cerebellum or its afferent or efferent connections. A recent study in Annals of Neurology (Shields et al., February 2012) has introduced me to a new way to think about this problem in MS. The authors previously showed that Nav1.8, a voltage gated sodium channel, is ectopically expressed in Purkinje cells in the cerebellum in several models of MS and also in tissue taken from MS patients. This channel is normally not expressed in the central nervous system but rather is typically limited to the peripheral nervous system. In this study the authors examined mice that are genetically engineered to express Nav1.8 in Purkinje cells in order to test whether there are functional consequences to this misexpression. Indeed, these mice do develop motor coordination defects consistent with cerebellar dysfunction and isolated Purkinje cells from these mice have electrophysiologic defects. The authors then went on to induce EAE in mice that are genetically lacking the Nav1.8 gene and found that these mice fail to develop the typical cerebellar phenotypes seen in the EAE model used by the authors. Lastly, mice with EAE and with ectopic Nav1.8 expression in Purkinje cells responded positively to Nav1.8 antagonists with decrease in their cerebellar deficits.

What does this all mean? When taken along with other recent studies showing changes in metabotropic glutamate receptor subunit expression in the cerebellum, it implies that we are approaching a new understanding of a variety of the phenotypes seen in demyelinating disease. It seems that neurons in these diseases may be subject to a variety of changes in gene expression leading to the ectopic mixexpression of deleterious genes (when in the wrong context) such as Nav1.8 or perhaps the loss of other genes required for normal physiologic function. This may explain some of the more evanescent symptoms seen in MS that don’t seem to necessarily correlate with inflammatory activity. In addition, in some of these cases, as perhaps with Nav1.8, treatment with antagonists may be useful to treat clinical manisfestations of MS.


April 1, 2012 Posted by | Uncategorized | Leave a comment