Columns

Za'atar

By Barbara Beltrami

I’ve recently started using za’atar a lot. A Middle Eastern blend of equal amounts of dried culinary herbs, thyme, cumin, coriander, sesame seeds and sumac with a perhaps a little salt or crushed hot red pepper added, za’atar gives an interesting and savory dimension to both ordinary and exotic dishes. Like so many ethnic combinations, it varies from cook to cook and region to region with other additions or substitutions such as fennel or marjoram, for instance.

Moreover, I’ve found that recipes in which it is used often call for additional amounts of one of its elements. Make your own blend or buy it at specialty grocers, then add it to salad dressings, spreads, dips, veggies, meat, poultry or fish, and a whole lot more. Its flavor is subtle; it doesn’t sock it to you, make your eyes water, clear your sinuses or send you sputtering and sprinting for a glass of water. It’s just a nice flavor kick.

Basic Za’atar

YIELD: Makes generous 1/4 cup.

INGREDIENTS:

1 tablespoon crushed dried thyme leaves

1 tablespoon ground coriander

1 tablespoon ground cumin

1 tablespoon toasted sesame seeds

1 tablespoon sumac

Generous pinch coarse salt

Generous pinch crushed dried red pepper flakes

DIRECTIONS:

In a small bowl thoroughly combine ingredients. Store in air tight container or zip top bag.

Cucumber, Tomato and Feta Salad with Za’atar

YIELD: Makes 4 to 6 servings.

INGREDIENTS:

1/4 cup extra virgin olive oil

2 garlic cloves, bruised

1 tablespoon za’atar

Coarse salt and freshly ground black pepper to taste

2 tablespoons freshly squeezed lemon juice

1 small English hothouse cucumber, peeled and diced

1 cup grape or cherry tomatoes, halved

1 cup crumbled feta cheese

DIRECTIONS:

In a small skillet over medium high heat, warm oil; add garlic, reduce heat to low and cook until garlic releases its aroma and starts to turn golden, about 5 minutes. Add za’atar, stir and remove from heat. Discard garlic, let cool to lukewarm, add salt and pepper and lemon juice. In a salad bowl toss cucumber and tomatoes with warm dressing, then sprinkle feta on top. Serve with toasted pita bread and hummus.

Lemony Za’atar Chicken, Potatoes and Onions

YIELD: Makes 4 to 6 servings.

INGREDIENTS:

1/2 cup olive oil

1/4 cup freshly squeezed lemon juice

3 tablespoons za’atar

1 garlic bulb, cloves separated and peeled

1/2 cup dry white wine

Coarse salt and freshly ground black pepper to taste

1 broiler-fryer chicken, cut into 8 pieces

1 1/2 pounds baby potatoes, scrubbed and halved

1 large onion, peeled and cut into small wedges

DIRECTIONS:

In a small bowl, whisk together the oil, lemon juice, za’atar, garlic, wine, salt and pepper. Transfer to gallon zip top bag, add chicken, seal bag and turn it to be sure chicken is evenly coated. Refrigerate for two hours. Remove chicken from bag, but reserve bag of marinade; place chicken in bowl, cover with plastic wrap and refrigerate. In the bag of reserved liquid place the potatoes and onions; seal bag and tilt to coat them evenly; refrigerate for one hour. Preheat oven to 400 F, place chicken, garlic, potatoes and onions with the marinade in a shallow baking pan. Bake, basting occasionally, until chicken is cooked through and veggies are tender, about 40 to 50 minutes. Serve hot with a tossed salad.

Za’atar Red Snapper with Israeli Couscous

YIELD: Makes 4 servings.

INGREDIENTS:

1 cup Israeli couscous

Four 6-ounce red snapper fillets, skin on

1/4 cup olive oil

Coarse salt and freshly ground pepper to taste

3 tablespoons za’atar

DIRECTIONS:

Cook couscous according to package directions. Meanwhile coat the fish fillets on both sides with olive oil, season with salt and pepper and rub each side of the fillets evenly with the za’atar. Heat the remaining oil in a large nonstick skillet over medium-high heat; add the fish fillets, skin side down, and cook until skin is golden and crisp, about 5 minutes. Carefully turn fish over and cook until flesh is opaque and fish flakes easily. Divide couscous onto 4 plates and top with fish. Serve hot with sautéed greens.

Arkarup Banerjee. Photo from CSHL

By Daniel Dunaief

Arkarup Banerjee is coming back home to Cold Spring Harbor Laboratory. This time, instead of working on the olfactory system, the way he did in Associate Professor Dinu Florin Albeanu’s lab from 2010 to 2016, he is studying vocalizations in the Alston’s singing mouse, a Central American rodent.

Banerjee rejoined Cold Spring Harbor Laboratory in November after almost four years of post-doctoral work at NYU Langone Medical Center. He hopes to use the study of the way these mice react to songs and the way they formulate them to understand how signals from the brain lead to vocalizations.

Singing Mouse

“The reason I decided to come back to Cold Spring Harbor Laboratory is not just because I did my PhD here,” said Banerjee, who is an assistant professor. “Neuroscience [at the lab] is amazing. I have fantastic colleagues. I expect to have lots of collaborations.” CSHL is one of his “top choices” in part because of the ability to interact with other researchers and to attend meetings and courses, he said.

To hear Albeanu tell it, CSHL’s colleagues appreciate the skill and determination Banerjee, whom Albeanu described as a “rare catch,” brings to the site.

“There was pretty much unanimous excitement about his vision for his research,” Albeanu said. “Pretty much everyone was in agreement that [hiring Banerjee] is a must.”

Fundamentally, Banerjee is interested in understanding how the brain computes information. In his new lab at CSHL, he wanted to study the natural behaviors that animals produce without having to teach them anything.

“That’s why my fascination arose in singing mice,” he said. “Nobody has to train them to vocalize.” He hopes to understand the neural circuits in the context of a natural behavior.

In the longer term, Banerjee is interested in contributing to the field of human communication. While numerous other creatures, such as birds, interact with each other vocally, singing from trees as they establish territorial dominance and soliciting mates through their songs, mice, which have cerebral cortexes, have brain architecture that is more similar to humans.

The Alston’s singing mice, which is found in the cloud forests of Costa Rica and Panama, is also different from numerous other species of mice. Many rodents produce vocalizations in the ultrasonic range. These animals can hear calls that are outside the range of human capacity to pick up such sounds.

The singing mice Banerjee is studying produces a stereotyped song that is audible to people. “These mice seem to specialize in this behavior,” he said. In neuroscience, scientists seek animals that are specialists with the hope that understanding that species will reveal how they work, he said.

Audible communications are important for male mice in attracting mates and in guarding their locations against other males. These lower-frequency sounds travel across greater distances.

Specifically, Banerjee would like to know the anatomical differences between the brains of typical rodents and the singing mice. He plans to probe “what kind of changes does it require for a new behavior to emerge during evolution.”

The songs have some value to the males who sing them. Females prefer males who sing more notes per unit time in a 10-second period.

In his experiments, Banerjee has demonstrated that the conventional view about one of the differences between humans and other vocalizing animals may not be accurate. Scientists had previously believed that other animals didn’t use their cortex to produce songs. Banerjee, however, showed that the motor cortex was important for vocal behaviors. Specifically, animals with temporarily inactivated cortexes could not participate in vocal interactions.

As a long term goal, Banerjee is also interested in the genetic sequence that makes the development of any anatomical or behavioral feature different in these singing mice. By using the gene editing tool CRISPR, which CSHL scientists employ regularly, Banerjee hopes to find specific genetic regions that lead to these unique behaviors.

Arkarup Banerjee with Honggoo Chae, a post-doctoral fellow at CSHL, from a Society of Neuroscience Meeting in 2018.

An extension of this research could apply to people with various communication challenges. Through studies of mice with different genetic sequences, Banerjee and other researchers can try to find genes that are necessary for more typical vocalizations. By figuring out the genetic differences, the CSHL scientist may one day discover what researchers could do to minimize these differences.

A resident of Mineola, Banerjee lives with his wife Sanchari Ghosh, who works at Cold Spring Harbor Laboratory press for the preprint service bioRxiv. The couple, who met in India, spend considerable time discussing their shared interest in neuroscience. Banerjee said his wife is a “much better writer” than he and has helped edit his manuscripts.

Banerjee is passionate about teaching and hopes he has a chance to educate more students once the pandemic recedes. Outside the lab, Banerjee shares an important quality with the mice he studies: he sings. He trained as a vocalist when he was growing up in India, and listens to a range of music.

Albeanu, who was teaching a course in Bangalore, India in 2009 when he met Banerjee, said it is a “pleasure to listen to [Banerjee] singing.”

Albeanu recalls how Banerjee stood out for many reasons when he first met him, including developing a way to modify a microscope.

As for his work, Banerjee hopes to understand behaviors like vocalizations from numerous perspectives. “We can seek explanations for all of these levels,” he said.

A neuroscientist by training, Banerjee would like to determine the connection between neural circuitry and the behavior it produces. “The understanding would be incomplete if I didn’t understand why this behavior is being generated.”

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A good pace and mindset may improve your outcomes

By David Dunaief, M.D.

Dr. David Dunaief

Medical professionals (including me!) often press you to exercise. This sage advice seems simple enough; however, the type, intensity level and frequency of exercise may not be well-defined. For instance, any type of walking is beneficial, right? Well, as one study that quantifies walking pace notes that some types of walking are better than others.

We know exercise is beneficial for prevention and treatment of chronic disease. But another very important aspect of exercise is the impact it has on specific diseases, such as diabetes and osteoarthritis. Also, certain supplements and drugs may decrease the beneficial effects of exercise. They are not necessarily the ones you think. They include resveratrol and nonsteroidal anti-inflammatory drugs (such as ibuprofen). Let’s look at the evidence.

Walk with a spring in your step

While pedometers give a sense of how many steps you take on a daily basis, this number isn’t all that’s important. Intensity, rather than quantity or distance, may be the primary indicator of walking’s benefit.

In the National Walkers’ Health Study, results showed that those who walk with more pace are more likely to decrease their mortality from all causes and to increase their longevity (1). This is one of the first studies to quantify specific speed and its impact. In the study, there were four groups. The fastest group was almost jogging, walking at a mean pace of less than 13.5 minutes per mile, while the slowest group was walking at a pace of 17 minutes or more per mile.

The slowest walkers had a higher probability of dying, especially from dementia and heart disease. Those in the slowest group stratified even further: those whose pace equaled 24-minute miles or greater had twice the risk of death, compared to those who walked with greater speed.

However, the most intriguing aspect of the study was that there were big differences in mortality reduction in the second slowest category compared to the slowest, which might only be separated by a minute-per-mile pace. So, don’t fret: you don’t have to be a speedwalker to realize significant benefit.

Align your mind and body

The mind also plays a significant role in exercise. The results of one study note that a positive mindset while exercising makes a big difference in the exercise’s impact (2). Researchers created two groups. The first was told to find four positive phrases, chosen by the participants, to motivate them while on a stationary bike and repeat these phrases consistently for the next two weeks while exercising.

Members of the group who repeated these motivating phrases consistently throughout each workout were able to increase their stamina for intensive exercise after only two weeks, while the same could not be said for the control group, which did not use reinforcing phrases.

‘Longevity’ supplement may negate exercise benefits

Resveratrol is a substance that is thought to provide increased longevity through proteins called Sirtuin 1. So how could it negate some benefit from exercise? Well it turns out that we need acute inflammation to achieve some exercise benefits, and resveratrol has anti-inflammatory effects. Acute inflammation is short-term inflammation and is different from chronic inflammation, the basis for many diseases.

In a small randomized controlled study, treatment group participants were given 250 mg supplements of resveratrol and saw significantly less benefit from aerobic exercise over an eight-week period, compared to those who were in the control group (3). Participants in the control group had improvements in both cholesterol and blood pressure that were not seen in the treatment group. This was a small study of short duration, although it was well-designed.

Impact on diabetes complications

The majority of Type 2 diabetes patients suffer from cardiovascular disease. The good news is that exercise may improve outcomes. In a prospective (forward-looking) observational study, results show that diabetes patients who exercise less frequently, once or twice a week for 30 minutes, are at a higher risk of developing cardiovascular disease and almost a 70 percent greater risk of dying from it than those who exercised at least three times a week for 30 minutes each session. In addition, those who exercised only twice a week had an almost 50 percent increased risk of all-cause mortality (4).

The study followed more than 15,000 men and women with a mean age of 60 for five years. The authors stressed the importance of exercise and its role in reducing diabetes complications.

Calculate your fitness age

You can calculate your fitness age without the use of a treadmill, according to the HUNT study (5). An online calculator utilizes basic parameters – age, gender, height, weight, waist circumference and frequency and intensity of exercise – to help you judge where you stand with exercise health. This calculator can be found at www.ntnu.edu/cerg/vo2max. Your results may surprise you.

Even in winter, you can walk and talk yourself to improved health by increasing your intensity while repeating positive phrases that help you overcome premature exhaustion. Exercise can also have a significant impact on complications of chronic diseases, such as cardiovascular disease and resulting death with diabetes. As a bonus, getting outside during the day may also help you avoid the effects of the “winter blues.”

References:

(1) PLoS One. 2013;8:e81098. (2) Med Sci Sports Exerc. 2013 Oct. 10. (3) J Physiol Online. 2013 July 22. (4) Eur J Prev Cardiol Online. 2013 Nov. 13. (5) Med Sci Sports Exerc. 2011;43:2024-2030.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

Lily Bergh stands behind the counter at Little Switzerland Toys & Dolls. Photo by Lina Weingarten

Amazon is not going to go the extra mile and wrap your Christmas presents with professional flair. Amazon is not going to sponsor your local baseball or soccer team. Amazon does not know the names of customers’ family members or shops in the same supermarket that we do.

At the same time, Amazon is still raking in profits. The retail giant moved its annual Prime Day to October this year, essentially setting up an earlier holiday rush than usual. Amazon and other online retailers are anticipated to make $189 billion in revenue this season, up 33% from 2019. Meanwhile many of our local mom-and-pop brick and mortar remain without a hint of additional federal stimulus, praying they do well enough in the next few weeks to stay open in 2021. While Cyber Monday sales are expected to grow this year, American Express, which promotes Small Business Saturday, has reported that in a survey of owners 62% said they need to see spending return to pre-COVID levels to survive 2020.

Though that’s not to say the community isn’t getting involved. Many shop owners we spoke to praised their customers, the ones who have sought out their stores to see how they were doing, buy items or even gift cards.

Some owners managed to take some of their business online during the height of the pandemic in spring, but many did not have the resources  to go further. Over the year, we’ve talked to other small business owners who said the additional stresses caused by the pandemic were simply too much to bear and have already closed up shop.

Yet the beast only grows bigger and hungrier. Amazon is planning for a total of three last-mile warehouses on Long Island, with the latest one announced to be in Shirley.

In the Nov. 26 issue of TBR newspapers, we shared the very real and very legitimate concerns of local pharmacists over Amazon’s new pill delivery service, which is rolling out at the end of this year. Amazon won’t know patients’ family history. Amazon won’t be able to look at a person at their counter and tell if there may be something else wrong healthwise.

All the emphasis on staying at home has led to the ballooning of mail-in delivery services for everything from packages, to food and even alcohol. Some of these delivery businesses, like Door Dash have been a minor boon to brick and mortar who were not allowed to open their doors. Others, such as Amazon Pharmacy, have been taking away larger and larger slices of the economic pie. Will there be a time when your local pharmacy or corner store can no longer compete with a national brand? Maybe, but we’re not there quite yet.

All our local shops were impacted by the ongoing pandemic, and though some industries have managed to compete better than others, the tell-tale signs of anxiety are there in each one. As New York City and Long Island witness increases in COVID-19 infection rates, all eyes are on Albany to see if there will be more restrictions. Experts have already said trends are worrying and have suggested stricter measures.

In that way, we ask people to be considerate not only of business owners but also to your neighbors as well. It may be smart to call ahead before visiting a local shop for a Christmas gift, so as not to spend as much time indoors, potentially with strangers. It’s better to get shopping done early, especially to avoid any kind of gathering crowds on the horizon.

But we have to see the end of 2020, we all crave the end to 2020, but we do not want to see the end to small business on the North Shore and all of Long Island. This holiday season, let’s keep our local mom-and-pops in mind.

Photo courtesy of Pixabay

By Daniel Dunaief

Daniel Dunaief

My five-year-old neighbor Jack keeps me and his parents on our toes, and for that, I am grateful.

In this strange and challenging year, Jack offers a refreshing, clear-eyed and honest assessment of everything he sees. He speaks directly, asks questions and expects people to treat him the way his kind, caring and supportive parents do.

During the spring, at the start of longer walks around the neighborhood with my dog, I started the pattern of wearing sweatpants and sweatshirts during cooler weather. After all, with nowhere else to go, I didn’t feel compelled to put on a collared shirt, to change my outerwear or to put on my dress shoes. Speaking of which, I don’t think I’ve even looked for my shoes in months. The search for those shoes, and the black socks at the bottom of a drawer somewhere, will be a welcome return to a more normal routine some day.

Anyway, back in the first stages of an endless homebound existence, Jack saw me one morning, greeted my dog , who is 30 pounds heavier than he, and asked me one of the many five-year-old questions that he shares.

“Why are you wearing the same clothes as yesterday?” he asked, as if I were somehow on a walk of shame after an evening that stretched into morning in a college dorm.

“Oh, honey, he’s just wearing the same sweatshirt as yesterday. You do that, too,” his mother gently offered.

Then again, Jack was right. I was wearing the same sweatshirt and sweatpants.

Later, when a nephew who tested negative for the virus came to visit and took a walk with me, Jack listened to his mother chat with us. As we were walking away, Jack watched my nephew and me head to my house.

“Dan,” he shouted, “Don’t forget about six feet.”

Again, Jack was right. Comfortable as I was, even outside with my nephew, Jack learned the rules and was encouraging me to follow them.

Recently, Jack delved into the minefield of politics. Without any hesitation, he asked my wife and daughter about their votes for the presidential election.

His mother, once again, tried to provide a filter, suggesting that such a conversation might not be necessary or comfortable.

Our daughter, who has had extensive experience babysitting children of all ages, had no trouble answering the question in a way that wouldn’t upset Jack, regardless of his or, more likely, his parents’ thoughts on the subject.

Cliche as it seems, it occurred to me, listening to my wife recount this conversation, that Jack, and the need to meet his earnestness and honesty, offered a reminder about public discourse.

Five-year-olds may not know everything, but they know when an adult is being condescending or is belittling them. They need the same kind of honesty they give.

At the same time, they need answers that don’t insult them. Even if they, or their parents, have different views, they need to know that others respect them.

Therein, it occurred to me, lies the lesson. We don’t need to avoid conversations with each other about topics on which we disagree. We are guaranteed the freedom to disagree with everyone, from our siblings, to our parents, to the president.

We also might do well to think of others who are speaking to us as Jack. We don’t need to picture others as five-year-olds. We can, and will, engage in more satisfying discourse if we follow some of the same principles when speaking with anyone. With so many challenges ahead, we will accomplish more together, and respectfully, than if we take each other down.

Photo courtesy of Pixabay

By Leah S. Dunaief

Leah Dunaief

Thanksgiving Day would have been my sister’s 78th birthday. But my parents were told at her birth that she would not live long because she had Down syndrome, a genetic disorder. In fact, one of the physicians at the hospital commented, “Best to just throw her in the garbage.” My mother, who was deeply religious, advised the doctor that he was not God, told him in no uncertain terms where he could go, and together with my father, brought my sister Maxine to our loving and supportive home.

That was 1942, when no one ever saw a Down syndrome child, with the characteristic physical markings of a round face, almond-shaped and up-slanting eyes and short stature, on the streets of New York. As a result, she was the object of stares when we were in public. Fortunately, she was a happy and social child, and when she saw people staring, she would wave at them, smile and say, “Hello.” If they stopped, she would continue with, “How are you?” and even, “How old are you?” She would then advise them that they looked much older and thus make them laugh.

Even as late as 1960, the life expectancy of people with Down syndrome was considered to be 10. But by 2007, on average and according to the Centers for Disease Control and Prevention, persons born with Down would live to be about 47 years old. My sister made it to 65.

Why the dramatic difference within one lifetime? The easiest answer is the change in attitudes about children with Down syndrome. When Maxine was born, such children were routinely institutionalized, where they received notoriously poor treatment and lived in horrible conditions. Journalist and lawyer Geraldo Rivera, in 1972, exposed the neglect and abuse in Staten Island’s Willowbrook State School. It broke people’s hearts and was a change agent, and such facilities began to disappear.

Since the 1970s, a Down syndrome child is to be given a free and appropriate education like any other child in the United States by law. When my sister was six, my mother brought her to the neighborhood elementary school to register her for first grade. That was the first of many times she and Maxine were turned away. With great patience, my mother taught Maxine how to read “Dick, Jane and Baby,” to write her name and address between the lines, and to do arithmetic on a second-grade level. Ultimately Maxine attended a Catholic school in Brooklyn for children with special needs. My sister also had a natural gift for music, often spending many minutes playing familiar melodies by ear on the household piano.

I was reminded of all this by December’s Atlantic monthly magazine’s cover story, “The Last Children of Down Syndrome.” The article, by Sarah Zhang, focuses on prenatal genetic testing, the impact it’s having on the number of children born with special needs, and its effects on world-wide population as it becomes easier and more widespread. Her report is centered in Denmark, which in 2004 became one of the first countries to offer free genetic Down syndrome screening to every pregnant woman. She writes that since universal screening was offered, the number of parents who chose to continue a pregnancy after a Down diagnosis, in 2019 for example, was seven. What does the universal introduction of choice indicate about the future of humanity as genetic testing gets more sophisticated? she asks.

What is the value of a human life? The article poses the question, as well as dealing with the terrible pressures of choice. My mother was 36 when she gave birth to my sister. Age 35 and older is considered higher risk for the birthing of a Down syndrome child. There wasn’t the choice of amniocentesis then, certainly not other genetic testing, but had there been, I know how my parents would have reacted. They would have carried on in the same way.

Tobias Janowitz. Photo from CSHL

By Daniel Dunaief

The body’s savior in its battle against disease, immune cells respond to a collection of signals which tell them to dial up or down their patrolling efforts.

Scientists and doctors are constantly trying to determine what combination of beneficial or detrimental signals can lead to different outcomes.

Recently, Assistant Professor Tobias Janowitz and Professor Douglas Fearon of Cold Spring Harbor Laboratory, working with Duncan Jodrell at the University of Cambridge Cancer Research Institute, used an inhibitor developed and tested for the treatment of the human immunodeficiency virus (HIV), the virus that causes AIDS, in patients with colorectal and pancreatic cancer for a week.

Douglas Fearon. Photo from CSHL

The study was done on 24 patients and is a phase 0 effort, in which scientists and doctors test the pharmacokinetics and pharmacodynamics of the treatment.

In the study, which was published in the prestigious journal Proceedings of the National Academy of Sciences of the United States of America, the researchers showed that the treatment got into the blood, that the patients tolerated it, and that it enabled immune treatments to reach the tumors.

While this is an encouraging step, Janowitz cautioned that any such studies are far from a potentially viable treatment for either type of cancer. Indeed, the Food and Drug Administration requires a lengthy and rigorous scientific process for any possible therapy, in part because numerous promising efforts haven’t led to viable therapies for a host of reasons.

Still, this study offers a promising beginning for a potential approach to treating various forms of cancer.

Janowitz said patients “tolerated the treatment by and large very well,” and that “no new toxicities were observed compared to the ones that were known.” Some people developed slight disturbances in their sleep, which were immediately resolved after they discontinued using the treatment.

The history of the possible treatment for HIV showed similar side effects years ago. “We anticipated it would have a favorable toxicity profile,” said Janowitz.

The link between this early candidate for HIV treatment and cancer came from an analysis of the receptor that is expressed on immune cells, called CXCR4.

This receptor is targeted by the drug plerixafor. Most of the work linking the inhibited receptor to potential cancer treatment came from Fearon’s lab, Janowitz explained.

Fearon found that blocking the receptor enabled immune cells to migrate to cancer in a mouse study. Along with Janowitz and CSHL Cancer Director David Tuveson, he published a paper on the preclinical study in a mouse model in PNAS in 2013.

This inhibitor also has been used to release stem cells from bone marrow that can be used in a hematological context for treatment and transplantation. During their cancer study, the scientists found these stem cells circulating in the blood. It’s unclear from this first study how the combination of cancer therapy and releasing stem cells from bone marrow affects patients.

“We are not able to say that that has a relevancy to the cancer patient,” Janowitz said.

While some drug treatments work for a period of time until a cancer returns, immunotherapy may have a longer term benefit than chemotherapeutics, as some studies suggest.

“By giving this drug, our hope is that we enable an influx of immune cells into the tumor and have an across the board integrated immune response,” Janowitz said.

Down the road, Janowitz said the group hopes that this treatment will be a part of a combination of treatments that treat cancer.

By enabling immune cells to access cancer where the mutation rate is lower, these treatments could provide a sustained treatment.

The researchers chose pancreatic and colorectal cancer because those cancers don’t respond to current immunotherapy. “It’s really important to uncover why that is,” said Janowitz. The scientists had evidence from pre-clinical models that the pathway and the biochemistry that this drug activates can be effective.

In his lab, Janowitz performed some of the mechanistic work to understand why this drug might function. A medical doctor who is awaiting his license to practice in New York, Janowitz was also involved in the trial management group and in analyzing the multiplicity of data that came together.

The researchers in this study came from fields including bioinformatics, clinical medicine, pharmacology, and immunology. Fearon explained in an email that Jodrell wrote the grant to Stand Up to Cancer, or SU2C, in 2014 to obtain funding for the trial. Jodrell oversaw the clinical trial and Fearon directed the evaluation of the immunology findings.

Janowitz had a “major role in putting together the clinical data for the write-up,” and Daniele Biasci, a computational biologist at Cambridge, developed the analysis of the transcriptional data of the tumor biopsies, said Fearon.

As for the next stages in this work, physicians at Johns Hopkins Medicine International and Dana Farber Cancer Institute will soon start a phase 2 trial that is already registered and that combines this inhibitor with anti-PD-1.

Fearon said his continued pre-clinical research has shown that this immune suppressive pathway may be relevant to multiple human carcinomas, and has identified new potential targets for more effective immunotherapy.

Janowitz, meanwhile, will explore the systemic immune competence of the body as he continues to take a top down, broad-based approach to cancer.

He would like to know the degree to which the body can mount an effective immune response, while also exploring the factors that diminish that ability.

Separately, with three young children at home, Janowitz and his wife Clary, who is a radiation oncologist, have been balancing between their busy careers and the demands of parenting during the pandemic. Their extended families are both in Europe.

“We can’t visit them and they can’t visit us,” he said adding that he appreciated the way CSHL has offered day care to young children on campus.

As for this study, Janowitz said he’s encouraged by the early results.

METRO photo

By David Dunaief, M.D.

Dr. David Dunaief

There are some compelling studies that show exercise’s powerful effects in altering our genes. Recent studies show its impact on specific diseases. Exercise has effects on diabetes and a host of other chronic diseases, including kidney stones, osteoarthritis, cardiovascular disease and breast, colorectal and endometrial cancers (1).

There are also studies on simple ways to motivate yourself during exercise. One showed that those who repeat positive mantras like “feels good” while exercising were able to persist in their exercise routines for longer periods (2).

Why is this so important and why am I harping on exercise during the holidays? Because we are too sedentary, and this is the time of the year when we are inclined to overeat. According to data from the 2015-2016 National Health & Nutrition Examination Survey, we spend 6.4 hours a day sedentary (3). And this percentage is trending up.

Exercise and your genes

While you may be waiting for gene therapy to cure our chronic illnesses, it turns out that exercise may have a significant impact on our genes.

No waiting required; this is here and now.

Photo from Pixabay

In a study, results showed that thousands upon thousands of genes in fat cells were affected when participants exercised (4). The study involved sedentary men and asked them to exercise twice a week at a one-hour spin class. According to the researchers, the genes impacted were those involved most likely in storing fat and in risk for subsequent diabetes and obesity development. Participants’ gene expression was altered by DNA methylation, the addition of a methyl group made up of a carbon and hydrogens. These participants also improved their biometrics, reducing fat and subsequently shrinking their waist circumferences, and improved their cholesterol and blood-pressure indices.

The effect is referred to as epigenetics, where lifestyle modifications can ultimately lead to changes in gene expression, turning them on and off. This has been shown with dietary changes, but this is one of the first studies to show that exercise also has significant impacts on our genes. It took only six months to see these numerous gene changes with modest amounts of cardiovascular exercise.

If this was not enough, another study showed substantial gene changes in muscle cells after one workout on a stationary bike (5).

Exercise versus drug therapy

We don’t think of exercise as being a drug, but what if it had similar benefits to certain drugs in cardiovascular diseases and mortality risk? A meta-analysis — a group of 57 studies that involved drugs and exercise — showed that exercise potentially has equivalent effects to statins in terms of mortality with secondary prevention of coronary heart disease (6).

This means that, in patients who already have heart disease, both statins and exercise reduce the risk of mortality by similar amounts. The same was true with prediabetes and the use of metformin vs. exercise. It didn’t matter which one was used, the drug or the lifestyle change.

Don’t change your medication without consulting your physician.

Kidney stones and exercise

Anyone who has tried to pass a kidney stone knows it can be an excruciating experience. Most of the treatment revolves around pain medication, fluids and waiting for the stone to pass. However, the best way to treat kidney stones is to prevent them. In the Women’s Health Initiative Observational Study, exercise reduced the risk of kidney stones by as much as 31 percent (7).

Even better, the intensity of the exercise was irrelevant to its beneficial effect. What mattered more was exercise quantity. One hour of jogging or three hours of walking got the top results. But lesser amounts of exercise also saw substantial reductions. This study involved 84,000 postmenopausal women, the population most likely to suffer from kidney stones.

Sex as exercise

We have heard that sex may be thought of as exercise, but is this myth or is there actual evidence? Try to keep a straight face. Well, it turns out this may be true. In a study published in the PLoS One journal, researchers found that young healthy couples exert 6 METs — metabolic energy, or the amount of oxygen consumed per kilogram per minute — during sexual activity (8).

How does this compare to other activities? Well, we exert about 1 MET while sitting and 8.5 METs while jogging. Sexual activity falls between walking and jogging, in terms of the energy utilized, and thus may be qualified as moderate activity. Men and women burned slightly less than half as many calories with sex as with jogging, burning a mean of 85 calories over about 25 minutes. Who says exercise can’t be fun?

I can’t stress the importance of exercise enough. It not only influences the way you feel, but also may influence gene expression and, ultimately, affects the development and prevention of disease. In certain circumstances, it may be as powerful as drugs and, in combination, may pack a powerful punch. Therefore, make exercise a priority — part of the fabric of your life. It may already be impacting the fabric of your body: your genes.

References:

(1) JAMA. 2009;301(19):2024. (2) Med Sci Sports Exerc. 2013 Oct 10. (3) JAMA Netw Open. 2019;2(7):e197597. (4) PLoS Genet. 2013 Jun;9(6):e1003572. (5) Cell Metab. 2012 Mar 7;15(3):405-11. (6) BMJ 2013; 347. (7) JASN online 2013, Dec. 12. (8) PLoS One 8(10): e79342.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

Grey Squirrel. Photo from Pixabay

By John L. Turner

While it was more than 50 years ago I remember the details sharply, as if the event had happened a few days ago. The oak I carefully but rapidly climbed was a young tree about 30 feet tall with a full canopy of branches, growing in a small patch of woods between the elementary school I had attended and a residential street (It was in these woods I first saw Pink Lady’s Slipper, a wonderful native orchid). And there in a nook where two branches emerged from the main trunk was the object of my scamper — the nest of a grey squirrel that I wanted to inspect.

My interest in squirrels and their nests came about from a book I had looked at in the junior high school library; I think it was entitled “Animal Homes”— although this factoid I don’t remember quite so clearly! But what I do remember in the book was the account which explained that grey squirrels make two types of nests — those in tree cavities, often used in winter, and the one I was going to inspect consisting of a globe-shaped leafy ball, known as a “drey,” wedged amidst branches, also used in winter but more often during the warmer months. The account mentioned that most dreys consisted of a single chamber although occasionally they make two chambers — the equivalent of a foyer leading into the living room.

Working my way up the tree I reached the destination and with a little bit of anxiety bordering on trepidation stuck my hand into the nest and felt around. Fortunately no one was home, which is what I expected since several bangs on the main trunk next to the drey had elicited no response. I quickly realized I had a two chamber nest.

The entrance chamber was the smaller of the two and I could feel a partial wall separating the two. The back chamber was about 50% bigger than the size of a curled squirrel (say that tens time fast!) I was surprised by how solid the nest felt and how thick the walls were (they can contain more than 20 layers of leaves; one researcher tickled apart the wall of a drey and found 26 leafy layers).

The thick wall of a squirrel nest serves two vital functions — helping to keep rain out and body warmth in and the leafy layered wall exceeds in doing both. The leaves act like shingles on a roof and their overlapping positioning helps to prevent water from infiltrating the nest. Similarly, the leaves help to retain heat and many experiments have documented their thermal benefits, by keeping internal nest temperatures high when occupied by the squirrel. In one study in Finland researchers found that once a red squirrel entered a drey it quickly warmed up, making the temperature inside the nest 60 to 80 degrees warmer than the surrounding air.

The latin or scientific name for the grey squirrel is Sciurus carolinensis; the genus name means “shadow tail,” a reference to the shadow the tail makes when its arched over the back of the squirrel, a common position when the animal is eating. The species name relates to Carolina, where the first squirrel was presumably first discovered and described to science.

Grey squirrels live up to their name, being grey in coloration, but if you get a chance to view a squirrel up close you’ll see the pelage is a bit more colorful. Occasionally while birding I’ll train my binoculars on a nearby squirrel and I am always taken by their subtle beauty, enrobed as they are in muted earth tone colors. The squirrel’s underside is white and it’s face, tail, and armpit is diffused with brown. There’s a flecking of black, white, and brown or tan peppered throughout the grey fur. Melanistic (all black) and albinistic (all white) squirrels occur with melanistic being the more common of the two rare pelages, but even these blacks squirrels make up less than one percent of the population. I remember, as a child,when visiting my aunt who lived in Rye, New York seeing a population of black squirrels that lived in the forest next to a golf course.

When it comes to managing their food supply rodents generally display two types of behaviors: scatter hoarding or centralized or “larder” hoarding, with grey squirrels practicing the former (chipmunks employ the latter). If you watch grey squirrels in the fall you’ll see them carrying acorns and other nuts burying them (or caching them) in dozens of locations. This behavior suggests they possess very good memories, which they indeed do, since 95 to 99% of the cached nuts are recovered and eaten.

I recently watched acorn caching involving a squirrel on my front lawn. The squirrel walked slowly and then stopped to paw the earth, followed by some sniffing, the way a squirrel assesses the suitability of the site in the grass in which to hide the acorn. It did this three or four times apparently unhappy with something about each of the sites until it finally met the right set of squirrelly conditions at a site near a tall holly tree. Scratching quickly with its front paws the squirrel quickly buried the acorn. Its scattered larder was now one acorn larger.

Grey squirrels are quite adept at differentiating acorns from different oak species; they “know” that acorns from white oaks germinate in the fall while those of red oaks do so in the following spring and, not surprisingly, eat the white oak acorns first while storing acorns from red oaks. Another advantage to this strategy, besides eating acorns that would be lost to germination if they tried to store them, comes from the fact that tannin levels in red oak acorns (tannin is the ingredient that makes your lips pucker when drinking red wine) lessens over time, making the acorns less bitter and more palatable.

We’re not sure if squirrel lips pucker when eating tannic acorns but I do know they develop a large stained moustache while and after eating black walnuts. Despite the impending facial smudge they’ll develop, they look like the definition of contentment as they hold the prized walnut in their paws and proceed to gnaw through the green husk to get to the walnut shell and meat that lays within.

We have another squirrel species that roams the forest of Long Island: the Southern Flying Squirrel. Strictly nocturnal, this little living fabric of “flying” carpet can be seen at bird feeding stations where it’s especially fond of suet. Of course, they don’t fly but rather glide from one tree to another, using an extended fold of skin on each side of its body connecting front and back legs. Their flattened tail helps to serve as a rudder and brake.

Many years ago I worked in a nature preserve and one day went to look at some white baneberry growing along a trail I knew was developing fruits (also known as doll’s eyes due to the resemblance of the fruits to the eyes once used in old fashioned porcelain dolls, white baneberry is in the buttercup family). As I neared the plants I noticed, at the base of a large chestnut oak on the other side of the trail, a small brownish object. Inspecting it I realized it was a freshly dead flying squirrel. I sadly wondered if the squirrel had misjudged the location of the tree or got carried by the wind and collided with the tree with such force that it caused its demise.

While I’ll never know what killed that flying squirrel so many years ago, I do know the cause of many squirrel deaths today— roadkill. Grey Squirrels routinely cross roads that are within their territory; unfortunately, they have no awareness of cars as lethal objects. In one study a state wildlife biologist counted 390 dead squirrels along a fifty mile stretch of highway in New Hampshire.

As I drive Long Island roads I’m constantly alert for squirrels bounding out from the road shoulder (and other wildlife like box turtles); so far so good — while I’ve had a number of close calls with darting squirrels I haven’t hit one.

I’m very grateful I haven’t hit a squirrel with my car and even more grateful of the experience I had, climbing an oak tree half a century ago, since it was the catalyst for developing a lifelong fondness of squirrels.

A resident of Setauket, John Turner is conservation chair of the Four Harbors Audubon Society, author of “Exploring the Other Island: A Seasonal Nature Guide to Long Island” and president of Alula Birding & Natural History Tours.

Photos courtesy of Pixabay

Photo from Pixabay

‘Beaujolais wines are deliciously fresh to the palate. They charm you with their delicacy, tenderness, and lightness.’

Curnonsky {Maurice Edmond Sailland} French writer, 1872-1956

By Bob Lipinski

Bob Lipinski

Beaujolais Nouveau (known as Beaujolais Primeur in France) is the “new” Beaujolais wine that has been fermented to capture the ultimate in lightness and freshness besides its intense grapy aromas and flavors.

Beaujolais is a grape-growing district below the southern part of Burgundy, between Lyon and Mâcon. It is about 35 miles long and between seven and nine miles wide. Beaujolais is both the name of the place and the wine made there and was named after the village of Beaujeu. Beaujolais is made from grapes coming from the appellations of Beaujolais and Beaujolais-Villages within the district.

Beaujolais is made from a red grape called Gamay, which produces light, fresh and fruity wines wherever it grows in the world. The wine owes its easy drinkability to a winemaking process called carbonic maceration (called whole berry fermentation). This technique preserves the fresh, fruity quality of the wine, without extracting bitter tannins from the grape.

Beginning in 1951, the official release date of Beaujolais Nouveau was November 15. However, in 1985 the release date was changed to the third Thursday in November regardless of the specific date.

This youthful wine has limited aging potential; therefore, it is enjoyed within a short time after fermentation. Nouveau is at its best when it first appears on the market. After one year it is tired and with few exceptions should be forgotten.

Beaujolais are fresh, fruity, uncomplicated, light-bodied wines. They are excellent wines for warm weather when fuller-bodied red wines may overpower. For best results serve Beaujolais Nouveau chilled at about 55 degrees Fahrenheit.

Beaujolais Nouveau should have the fresh, full, fruity bouquet and flavor of blackberries, candy-apple, cherries, plums, raspberries, red lollipops, strawberries, spices, violets, and an overwhelming freshness. On the palate, Beaujolais should be young, lively, and joyous.

Some cheeses to enjoy with this particular wine are Beaufort, Bel Paese, Camembert, Charolais, Cheshire, Feta, Fontina, Raclette, Tomme de Savoie, and Triple-Crèmes. Beaujolais Nouveau pairs well with salads, fried chicken, light chicken and turkey dishes, pork, artichokes, ratatouille, eggs, ham, salmon, swordfish, tuna, hamburgers (cheeseburgers), pizza, hot dogs, chestnuts, salami, picnic foods, and chocolate.

Brands of Beaujolais Nouveau worth searching for include Georges Duboeuf, Louis Jadot, Jean-Paul Thevenet, Louis Tete, Mommessin, Domaine Dupeuble, and Jean Foillard.

Bob Lipinski is the author of 10 books, including “101: Everything You Need To Know About Whiskey” and “Italian Wine & Cheese Made Simple” (available on Amazon.com). He conducts training seminars on Wine, Spirits, and Food and is available for speaking engagements. He can be reached at www.boblipinski.com OR [email protected].