A Short Story: “Grandpa’s Gift of Germany” Part One

Grandpa’s Gift of GermanyPart One  by A, K, Buckroth

Oh My Gosh! I’m going. I’m really, really going!

This huge decision of mine to visit Germany came about due to the death of my grandfather. His quick demise through heart failure saddened my spirit, my heart, the core of my being. Our times spent together, the private, personal conversations we shared remain invaluable and unforgettable.

“What would you like to do, Andrea?” he seriously asked me, looking me in the eyes during a visit to my grandparents home in Hyde Park, Massachusetts.

“I’d like to travel, Grandpa. I’d like to visit Germany, maybe Poland too. Find some family roots, ancestors….”

A recent high school graduate, I was eighteen when Grandpa and I had that conversation. Pondering that happy scene, I remember sitting on the swing in my grandparents back yard.

*     *     *

Riiiing. Riiiing,” went the telephone, shattering my thoughts. This was an unexpected call from Grandpa’s attorney. He wanted me to meet with him to discuss my grandfather’s will. Evidently, I was chosen as a beneficiary. Once there, I learned that Grandpa left me some money – $5,000 to be exact. Specifications in receiving this gift mentioned that I visit Germany, a once distant dream I had shared with Grandpa those eight years ago. As a history buff, this country deeply intrigued me due to ancestral roots.

Getting over the shock of this “present,” feeling richer for it, my research for a trip to Germany began. Suddenly affordable through Grandpa’s bestowal, my limitless imagination, excitement, determination with courage became strong.

At the age of twenty-six ─ attractive, single, smart, independent ─ my college graduation lead me to a career as an Executive Assistant for four years. My salary was acceptable, my apartment was humbly comfortable, best of all, my employer allowed me two weeks paid vacation time. Two weeks!  Paid!

So many preparations to make. What to do first?! Where will I stay? What about a passport? Find and speak with a travel agent – √. Change United States currency into German Marks – √. Learn the language ─ enough to find a restroom, ask for directions, figure out a food menu, locate train stations, the use of Germany’s transportation network; to politely greet, speak plainly, complimentary, and simply to townsfolk – √. Wowee.

After gathering numerous compelling and informational travel brochures about Germany through my membership with an auto club, I had to calm down enough to organize this trip, to focus on where I wanted to go. All of the brochures displayed magnificent pictures of castles, museums, inviting landscapes, shopping centers, restaurants ─ anything and everything a visitor would enjoy. My excitement was overwhelming. This became a commitment ─ a commitment to myself.

First, accommodations.

Robert immediately came to mind. Robert Elman, U. S. Army Captain, stationed in Aschaffenburg, Germany. He and I discussed this possibility ─ I remembered his personal invitation to me ─ when he came home on leave the last time. Through that, I decided to contact him.      Although we had a friendly yet casual relationship beginning in high school lasting through adolescence (my high school prom, his military cotillion, movies and fast food dates, working together at a local grocery) I had to contact his parents for his present address.

Residing in the same city, I knocked on their door without an invitation. They greeted me with whole hearted and joyous enthusiasm.

“Andrea, it’s been a while since we’ve seen you. Come in come in!” the exuberance of seeing them again brought tears to my eyes. I truly did not know what to expect. This charming couple recalled my youthful days with their son. Delightfully, Robert’s contact information became available to me without any qualms.

To BeContinued….

Destination The World NCPA Anthology 2020, Volume Two, © 2020. “Grandpa’s Gift Of Germany” page 22. Available at Amazon.com.

Good ‘Science’ Wednesday! RE: Sickle Cell Disease

As posted to my facebook pages September 8, 2021, it is shared here”

Mother and daughter team up to fight bias and discrimination in treatment for people with sickle cell disease

by Kevin McCormack

“Adrienne Shapiro and Marissa Cors are a remarkable pair by any definition. The mother and daughter duo share a common bond, and a common goal. And they are determined not to let anyone stop them achieving that goal.

“Marissa was born with sickle cell disease (SCD) a life-threatening genetic condition where normally round, smooth red blood cells are instead shaped like sickles. These sickle cells are brittle and can clog up veins and arteries, blocking blood flow, damaging organs, and increasing the risk of strokes. It’s a condition that affects approximately 100,000 Americans, most of them Black.

“Adrienne became a patient advocate, founding Axis Advocacy, after watching Marissa get poor treatment in hospital Emergency Rooms.  Marissa often talks about the way she is treated like a drug-seeker simply because she knows what medications she needs to help control excruciating pain on her Sickle Cell Experience Live events on Facebook.

“Now the two are determined to ensure that no one else has to endure that kind of treatment. They are both fierce patient advocates, vocal both online and in public. And we recently got a chance to sit down with them for our podcast, Talking ‘Bout (re) Generation. These ladies don’t pull any punches.

“Enjoy the podcast.

“CIRM is funding four clinical trials aimed at finding new treatments and even a cure for sickle cell disease.

An Irish Wog by A. K. Buckroth

Although a “wog” denotes a negative, racial connotation in Australia, Britain, Ireland, and Scotland, this story projects quite the opposite. For good reason, I changed this adjective into a verb. To me it means “walking and running = wogging or a wog-run” for walking intermittently with running.

“Running?” you ask. Yes indeed, running.

Because of my sense of goodwill toward fundraising for worthy causes, the American Diabetes Association (“ADA”) was no different. I had made life-changing commitments by walking numerous miles through different city streets in different states over numerous years doing coast-to-coast fundraising for a cure of several different human diseases. However, this organization had something big on its desk to offer money-raising runners and walkers, diabetics and non-diabetics.

Through an open invitation, interested peers gathered for a tri-monthly ADA meeting in a plush, downtown Los Angeles, California hotel conference room to discuss, learn, and hear about positive advancements in the care and treatment of this disease, with lunch included. I was in.

During this meeting, a special announcement attracted my attention. “This year we will sponsor a marathon in Ireland to raise research money,” a speaker bellowed to the audience of at least 30 interested individuals. This meeting began the organizing of the ADA’s first participation in a 26.2 mile run, walk, skip jump, rubber-on-hardtop-or-concrete marathon. “Eager participants in this “Friendly Marathon in Dublin, Ireland should sign up immediately,” she told us.

How exciting!

Dublin, Ireland? Never having been there, I became so intrigued that I signed up on the spot. I paid the registration fee. Oh, what had I done?! Was I serious? Could I do this? Sure I could. I sensed this wonderful opportunity would be personally empowering.

“For those interested,” the speaker continued, “you’ll find more information packets on the back tables. Please help yourselves.”

Before she stopped talking, I approached that back table and gathered multiple explanatory brochures, flyers, business cards and whatever information I could carry.

Thus began my personal training. I had participated in 5k and 10k fundraising walks for Cancer, Heart Disease, Alzheimer’s, Multiple Sclerosis, Alopecia, Leukemia, etc. Now, I began pounding the pavement for diabetes. Training started in February and lasted through September. With California sunshine on my back, my prepping began after work each day with a two-mile walk, which extended a little longer each day. I looked forward to this routine. Each day I grew stronger, leaner. I felt good in this new body!

Having received more of the required registration forms, an ADA administrator contacted me by phone with an invitation to another luncheon to be held in Santa Monica, California.

“…My name is Barbara Ann, and I’d like to welcome you to the marathon fundraising efforts with the ADA. So far, thirteen people have signed up for sure. Have you ever participated in a marathon?”

“No, I haven’t and I have a lot of questions.”

“Good, good,” she responded. “Save them for the luncheon in two weeks. I’m hoping all thirteen of you will have many of the same concerns. I’ll cover them all. Are you excited?”

“Yes, I sure am,” I blurted along with the others.

“Good. I’ll let you go for now. See you in a couple weeks! Bye.”

She sounded friendly enough. My questions would just have to wait.

The main purpose of the Santa Monica plan was for registrants to meet each other. Anxious, I happily drove the hour to get there. After a meatball and spaghetti lunch with a green leaf salad and iced tea, Barbara Ann encouraged each of the thirteen of us to not only get our passports in order, but to invest in good running shoes, foot tape for toes and upper foot bones, and a water bottle carrier. We were each given a white t-shirt emblazoned with the words “TEAM DIABETES” in red along with a red tank top reading the same in white letters and a navy-blue canvas duffle bag embroidered with the phrase “American Diabetes Association” in bright red. The plan was for all of us to meet at the Santa Monica Pier each Saturday to learn how to stretch properly, breathe properly and increase our mileage as a team.

At a Sports Authority retailer, I purchased a belted-waist water bottle holder, safety sunglasses to avoid dust and insects in my eyes, feet-wrapping tape, appropriate, high-soled, supportive sneakers, and white cotton socks. The sunny Southern California coast became my initial practice wog. I called my routine “wogging” for walking intermittently with running.

Trekking 17.5 miles beginning in Wilmington, California on the concrete sidewalk toward the shores of the Pacific Ocean in 3.5 hours, I passed through Harbor City, Lomita, Torrance, Redondo Beach, Hermosa Beach, all the way to Manhattan Beach. Although I wanted to go even further to Venice Beach, I did not, knowing that I still had to turn around eventually and go home. With this trek confidentially under my cap, I knew I was ready. At the age of 43, I had relearned how to take care of myself to participate in this goal, seeking a worldwide cure for the pandemic of diabetes.

On two separate occasions, different individuals blocked my pathway, causing me to veer into the street. “Wait, wait a minute, pretty lady,” a grungy-looking, middle aged man said. “I want to talk to you. I see you running by every day.”

Politely stopping, I kept a yard’s length between us. Panting slightly, sipping my water, I quickly asked “What? What is it?”

“Can I have some of your water? Or is that vodka?” he chuckled out loud bending backwards in his foolish delight. “You’re gorgeous. What’s your name?”

A bit frightened by this confrontation, I didn’t reply but hurriedly resumed my pace, veering back onto the sidewalk. I started thinking about people becoming a safety hazard. Gosh, I hope he isn’t waiting for me on my way back. He wasn’t, thank goodness.

The second time, in Lomita, a straggly, unkempt middle-aged woman blocked my path waving her arms to stop me. “Jesus Christ!” I yelled. “Get out of my way!” And I kept going. She hollered something at my back about wanting some food and liking my sneakers. Oh my Gosh! I thought. I’m going to get clubbed over the head for my shoes!  Due to these confrontations, I changed my direction ‒ forward and back ‒ never seeing either of those characters again. Whew!

During the second Santa Monica meet-up, two of my younger teammates beat my time. I was appalled! Heck, a few of my teammates even ran up and down 27 concrete steps during these practices. I was jealous yet did not bust my butt to kill myself. I wanted to enjoy this experience.

Over the following seven months, I raised the required $3,000 plus, including the $672 roundtrip flight cost. My ego became inflamed once again and I was un-shy to ask for monetary donations from the restaurants I had passed daily. Employees and managers of numerous public establishments had seen and wondered about me. One seafood restaurant gave me a check for $50; another Bar & Grill gave me a check for the same. Other checks were made out to the ADA. Onward bound!

On and on, my pleas for help for a cure of diabetes brought monetary success. Family, friends, neighbors, acquaintances of friends, medical doctors, etc. – I asked almost everyone I met or came in contact with. Blessings and good wishes poured in along with cash and personal checks! I was going to be part of the cure for this baffling disease. I knew it in my heart and soul!

Sure, not everyone believed in my hopes and dreams for a cure of diabetes, but I remained upbeat, positive, and pressed forward.

Scheduled for October 30th, this “Friendly Marathon” brought me a delightful, anticipatory planned flight to the other side of the world.  My excitement overflowed through this overall participation and my having made such a huge commitment.

Taking a pre-planned two-week, paid vacation from work, I left Los Angeles International Airport (LAX) on October 25th for the 12-hour flight to Dublin International Airport (DUB), and arrived on October 26th.  During the flight, I witnessed the awesome time change in the sky, from very dark for seconds to a bright dawn that continued in the same five seconds. Awesome! My spirit was aflutter with this experience. This endeavor was meant to be, I knew it.

Upon landing, the scent of rain filled the air, immediately invigorating and awakening my senses to the surroundings. Not having reviewed weather reports before leaving California, I thought I had all I needed. This early-bird arrival allowed me to get to my Dublin city hotel with plenty of time to get settled in and become familiar with my surroundings: restaurants, shops, theatre, etcetera. I was psyched and ready for my first marathon in an unfamiliar and strange country.

The following day, leaving the comfort of the Jury’s Royal Hotel room, I wandered its lobby collecting various pamphlets of sights to see as a tourist. Despite reading the colorful and delightful variations of many different brochures with interesting venues, I knew I was here for one thing – the marathon. I was already living a dream just being here without the enticement of touristy ventures. I was glad to have brought my old faithful hooded, winter butt-covering coat since the weather was unusually bitter cold and rainy. The country was experiencing “the worst storm in fifty years.” Having to purchase a knit cap big enough to cover my ears for warmth along with woolen gloves in the hotel’s gift shop, I carefully bounded through the surrounding neighborhood within walking distance of the hotel. I wrapped my sock-covered feet in plastic bags for extra warmth and resilience in my sturdy rubber boots. Numerous people walked the streets in long wool coats, covering their heads and faces with scarves and hats for protection from the non-stop cold wind and heavy rains.

Grey hues in the sky matched the light gray and brown cobblestone streets and walkways. Cobblestones. I was used to seeing such a thing in movies, but coming up close and personal with having to walk on them became mandatory. They were unavoidable yet delightfully different at the same time, although a bit cumbersome to walk upon.

The hotel restaurant’s numerous hot meals whetted my appetite. Irish Stew with lamb or beef, vegetables and potatoes; bacon and cabbage with a side of brown bread; something called a “rasher” and something else called a “Blaa.” Prime rib with mashed potatoes, brown gravy and green beans ‒ sounded tasty, safe and familiar ‒ along with a leafy salad was available as well. Mm. Something called a “Colcannon” that consists of a bowl of potatoes mashed with milk, butter, scallions and kale; another available item called a “Carvery” would take too long to explain. The warm, freshly home-made lamb stew was a great choice on my first visit on this cold and wet weather day.

I realized it was October 28th meaning I had actually lost a day due to jet-lag. I wondered about the other ADA team member marathon participants, hoping to meet with them. I sighted only one team member from the Santa Monica runs who stayed in the same hotel. Come to find out, others were in different hotels scattered around Dublin, not to arrive until later.

6:00AM, October 30th, marathon day, I taxied with two other marathoners to our designated starting point. Although the rain calmed to a drizzle, during this exciting set-up and meet-‘n-greet, plastic trash bags were offered as body covers to the racers as wet gear protection with racing numbers safety-pinned to the fronts and backs.

I was ready!

Many times during this long, Ireland, walk-run, I purposely slowed down to admire Ireland’s beauty: ancestral, ivy draped stone buildings, wildly rushing streams, and the tremendous amount of bars as we wogged out of the city. Separated by speed, in no hurry and often left behind, I wogged alone. Realizing this, I decided to become a tourist after six hours, when I accomplished the 20-mile mark, a sharp, right knee pain gave me reason to stop.

That’s it, I thought. I fulfilled my promises to myself, the diabetics of the world and the ADA. Climbing aboard a readied and pre-planned ambulance for a return ride to the hotel, I certainly was not the only one to stop early. We were each wet from the inside out due to the rain and sweat, so the warmth of the ambulance was most welcoming.

Once showered, comfortable, and full of some delicious Colcannon, I began to plan for the rest of my stay. The following day, I stiffly walked to Dublin’s nearby ‘rail tour/bus’ office for a meandering, half-day trip into the Wicklow Mountains, the ancient and monastic home of St. Kevin, along coastal scenery, and into Glendalough and The Vale of Clara. Due to the continuous heavy rains with flooding in areas, the tour bus carefully slowed down, causing the tourist company’s scheduled events to change. I didn’t care. I felt safe, happy, warm. For 24Ł, this experience could not be passed up.

Heading back to Dublin, this tour bus coasted through Cork, Limerick (home of author Frank McCourt), and through the cities of Cashel, Cahir and Clonmel. We passed miles and miles and acres and acres of bright green, healthy grasslands nourishing goats, cows, sheep, lambs, lambs and more lambs. Hmm, I couldn’t help but wonder if the delicious lamb stew I had the day before had come from this beautiful pasture.

The early morning of November 1st found me on a tour bus to the historic city of Kilkenny. I greatly enjoyed a different yet delightfully delicious stew in the Witch’s House’ Restaurant/Pub before crossing the street to a jewelry store. Yes, a delicate pair of emerald earrings came into my possession. Continuing along the east coast, the tour continued to the Waterford Crystal Factory, which is spectacular. I learned the ingredients in making lead crystal wares are a certain type of sand, potash, and red-lead. Most interesting ─ and expensive ─ but I sent home a beautiful, lead-crystal, cut-glass whiskey decanter along with a decorative vase of the same design.

On November 2nd, I made the tough decision to wander the streets of Dublin alone. After checking my expense account from the former purchases, I was good to go. Walking through the continuous rain along with numerous other people, I felt comfortable blending right in and happily found a gift shop where I purchased an Ireland shaped magnet to add to my prodigious ‘refrigerator magnet’ collection. I roamed the outer and inner grounds of Trinity College, and continued to the beatific Christ Church Cathedral near the Dublin Castle. Tired and cold, I hopped onto a convenient city bus back to Jury’s Court. Buses were available every 15 minutes.

The next day, November 3rd, I purchased another bus ticket at 7 AM for a day trip to a place called The Burren, known for its scenic landscapes; onto The Cliffs of Moher, that included breakfast; then to Galway Bay, with a lunch stop at a seafood pub. There was enough time to enjoy a pint of Guinness beer while befriending another passenger with small talk of home. Back at the Jury’s Hotel after 10 PM, exhaustion put me to bed fully clothed.

By now I was out of clean clothes, so I found the hotel’s laundry useful. Purchasing ‘slots’ at the information desk, I was directed to the laundry area, ready to use the machines, and bought vending machine laundry detergent. Never having done this in my own country, I chalked this up to another experience. This time also allowed me to relax and rest my knee by using a hotel towel full of machine ice on my knee. That helped.

Finally, the rain stopped on November 5th. Hallelujah! This day, another point of interest offered Italian Gardens, Tower Valley, Japanese Gardens, Winged Horses, Triton Lake, a Pets Cemetery, Dolphin Pond, Walled Gardens, and Bamber Gate ─ all in one place. The history of these grounds begins in the 1840s, taking “one hundred men twelve years to complete.” I did not view all these areas because my intermittent knee pain caused me to rest on the tour bus. No matter. Bus driver Owen and I befriended each other for the duration. His thin frame topped off with fluffy white, thick curly hair, remained seated in the driver’s seat as he fondly spoke of growing up on the island. His light blue eyes sparkled through his stories. I intently listened to his smooth Irish brogue.

After a restful, peaceful sleep, November 6th greeted me with light grey rains as opposed to the former days of torrential downpours. My spirit remained heightened for the days’ plans: a train ride past The Giant’s Causeway, through the Glens of Antrim, and onto viewing the Wild Atlantic Coast but not for long. The downpours returned. This trip had to be halted due to a fallen tree blocking the train tracks. Another passenger invited to play dominoes, and we pleasantly passed the time. Stuck on that train for I can’t remember how many hours, I fell asleep at one point after being told that the food ran out. Oh well. I remained happy to be where I was ─ in Ireland.

Finally, another train pulled, or slowly dragged, the original passenger train all the way back to Connolly Station in Dublin. Gosh I had never experienced that that kind of rescue before.

The whole trip was definitely something to write home about. I truly cannot state which was my favorite site or favorite experience. It was all good. Would I wog it again? Yes indeed!

Just sharin’ a lighthearted story, right? I hope you enjoyed it! #buckroth

Destination The World NCPA Anthology 2020, Volume One, © 2020. “An Irish Wog” page 34. Available at Amazon.com.

 

“Biohackers to Share How To Make Insulin With the Public”

“A hundred years ago, scientists began researching how to make insulin using pancreases from dogs and cattle. Insulin has been used to treat people suffering with diabetes ever since, but it wasn’t until the 80s that genetic engineering allowed for the widespread distribution of this life-saving medicine.

“In a healthy human body, insulin is a hormone created by the pancreas that controls glucose levels in the bloodstream. But a diabetic’s body doesn’t naturally produce insulin, which means the body can’t store glucose for later use as energy in fat cells.

“Because of this, the fat cells break down and over-produce keto acids — the organic compounds responsible for converting glucose into energy — leading to acid levels that are too high for the liver to withstand. Should a diabetic not have access to insulin, this acid imbalance can trigger diabetic ketoacidosis, a life-threatening condition. This is why monitoring insulin levels and using medicine is critical to survival for diabetics.

“Today, over seven million Americans with diabetes use at least one form of insulin to treat the disease, but many are at risk of not getting the care they need. The American Diabetes Association reported that 25% of patients have turned to self-rationing their medication to deal with its ever-increasing price tag.”

“Why is Insulin So Expensive?

“The standard process for how to make insulin involves growing it in common bacteria, such as E. coli or yeast, with the help of an amino acid sequencing machine. It’s estimated that a vial of insulin costs pharmaceutical companies five to six dollars to manufacture, but because of a complicated web of regulations those companies are able to sell vials for $180-400.

“Rising costs are nothing new. Insulin prices tripled from 2002 to 2013, and doubled between 2012 and 2016. To put this into perspective, in 1996 a vial of Humalog produced by Eli Lilly cost $21. Today, it’s priced at $324 despite the cost of production remaining steady. For those who rely on several vials per month, expenses can quickly end up in the thousands.

“In the U.S. pharmaceutical industry, 90% of the global insulin market is owned by three companies: Novo Nordisk, Eli Lilly, and Sanofi. These companies essentially have a monopoly on the market; there is simply no competition to drive the price down. And further, their price increases have remained consistent with one another over time.

“Every person with type I diabetes relies on insulin to survive, and many are willing to spend whatever it takes to get their necessary dosage. Big pharma is clearly taking advantage of this vulnerable part of the population, gorging themselves by charging astronomical costs and pricing out those who can’t afford to keep up”.

“Biohackers to Share How To Make Insulin With the Public”

“A group of dedicated biohackers believes that making insulin more accessible requires taking the monopoly away from the big three pharmaceutical companies that produce it. So they’ve started the Open Insulin Foundation, a non-profit with plans to develop the world’s first open-source insulin production model.

“The team consists of dozens of volunteers led by founder Anthony DiFranco, a type I diabetic. They’re now able to produce the microorganisms needed for insulin with a bioreactor. They’re also working to develop equipment that can purify the proteins produced by the bioreactor.

“With open-source hardware equivalent to proprietary bioreactors, the foundation hopes to give labs across the world access to the equipment needed to produce the insulin protein on a small scale.

“Very few people really have any concrete ideas about how to solve these problems,” says DiFranco. “At the level of the technical fundamentals, it’s clear that we can do this. And if we can, we must.”

“But the process hasn’t been easy. For six years, DiFranco’s team has attempted to reverse-engineer the production of insulin with volunteer-led experiments at their community labs in cities like Oakland, Baltimore, and Sunnyvale, CA.

“Today, they’re beginning to see hopeful signs of a major breakthrough — like getting an FDA-approved protocol for making injectables. The team estimates that costs will be 98% cheaper than big pharma, reaching prices as low as $5-15 per vial. The best part? They’re willing to give away their plans for how to make insulin for free.

“Our plan is to have a system for local production that can operate anywhere in the world that there is a need for it,” explains DiFranco. Open Insulin has already partnered with community labs, academic institutions, patient advocacy groups, and NGOs across the country and beyond.

“They hope their work eventually leads to the distribution of insulin in countries that don’t currently have access to it. “There was a time for being angry,” says DiFranco. “Now that we can actually see an end to this soon, it’s not anger anymore. It’s just determination.”

Found on Facebook.com, Monday, August 25, 2021. Posted by Christine Alm. Thank you Christine!

Just sharin’.  A. K. Buckroth

The color of your Urine and what it may tell about You!

“Historically, looking at urine has been a way for doctors to gauge a person’s health, especially before other types of testing were available. If you’ve had diabetes for a long time or know someone who has, you’ll know that urine testing was a way to figure out how well controlled (or uncontrolled) a persons’ diabetes was — this was done in the days before blood glucose meters were available. Now, of course, we have more sophisticated tools to convey glucose information. But urine still has its place. In fact, the color, smell and consistency of your urine can give you and your doctor helpful information about what might be going on in your body.”

What is urine?

“Urine is a waste product that contains breakdown products from food, drinks, medicines, cosmetics, environmental contaminants and by-products from metabolism and bacteria. Amazingly, urine contains more than 3,000 compounds — much more than what’s found in other body fluids, such as saliva or cerebrospinal fluid. The kidneys do a remarkable job of filtering and concentrating to help get these compounds out of the body (you can understand why keeping your kidneys healthy is so important). So, what is your urine telling you?”

If your urine is…

Bright yellow

“This may look alarming, especially when your urine seems to be glowing in the dark. But don’t worry — the bright yellow color is likely due to vitamins, specifically, B vitamins and beta carotene.

Green or blue

“Green or blue urine seems like something straight out of a science fiction movie, but the color is very likely due to certain medicines that you’re taking, such as amitriptyline, indomethacin (brand names Indocin, Indocin SR, Tivorbex) or propofol (Diprivan). Your urine might also be green or blue due to food dyes or, possibly, a urinary tract infection (UTI).

Orange

“Certain medications, such as rifampin (Rifadin, Rimactane), sulfasalazine (Azulfidine, Azulfidine EN-Tabs, Sulfazine, Sulfazine EC), and phenazopyridine (Pyridium, used to treat UTIs, and others), laxatives, and some chemotherapy drugs can turn your urine orange. Orange urine may also be a sign of liver problems or dehydration.

Brown

“Brown or tea-colored urine can result from antimalarial drugs, certain antibiotics, and laxatives that contain senna or cascara. Fava beans, rhubarb and aloe can also darken your urine, as can some kidney and liver disorders, such as hepatitis and cirrhosis.

Red or pink

“Red or pink urine can be a sign of something serious…or not. Red urine may be due to the presence of blood, and that’s always somewhat concerning. Blood in the urine may be a sign of a UTI, enlarged prostate, a tumor, kidney or bladder stones, menstruation or injury to the urinary tract. It can also occur if you take blood-thinning medicine or aspirin. Less alarming causes of red urine are beets, berries and rhubarb.

Cloudy

“Cloudy urine can result from a UTI, vaginal infection, or dehydration. If the urine is more milky in appearance, that may be due to the presence of bacteria, mucus, fat, or red or white blood cells.

“By the way, “healthy” urine should be pale yellow or straw-colored in appearance.”

Just sharin’! A. K. Buckroth

“New post on The Stem Cellar”

City of Hope scientists use stem cells to develop ‘mini-brains’ to study Alzheimer’s and to test drugs in development

by Yimy Villa

Alzheimer’s is a progressive disease that destroys memory and other important mental functions. According to the non-profit HFC, co-founded by CIRM Board member Lauren Miller Rogen and her husband Seth Rogen, more than 5 million Americans are living with Alzheimer’s. It is the 6th leading cause of death in the U.S and it is estimated that by 2050 as many as 16 million Americans will have the disease. Alzheimer’s is the only cause of death among the top 10 in the U.S. without a way to prevent, cure, or even slow its progression, which is it is crucial to better understand the disease and to develop and test potential treatments.

It is precisely for this reason that researchers led by Yanhong Shi, Ph.D. at City of Hope have developed a ‘mini-brain’ model using stem cells in order to study Alzheimer’s and to test drugs in development.

The team was able to model sporadic Alzheimer’s, the most common form of the disease, by using human induced pluripotent stem cells (iPSCs), a kind of stem cell that can be created from skin or blood cells of people through reprogramming and has the ability to turn into virtually any other kind of cell. The researchers used these iPSCs to create ‘mini-brains’, also known as brain organoids, which are 3D models that can be used to analyze certain features of the human brain. Although they are far from perfect replicas, they can be used to study physical structure and other characteristics.

The scientists exposed the ‘mini-brains’ to serum that mimics age-associated blood-brain barrier (BBB) breakdown. The BBB is a protective barrier that surrounds the brain and its breakdown has been associated with Alzheimer’s and other age-related neurodegenerative diseases . After exposure, the team tested the ‘mini-brains’ for various Alzheimer’s biomarkers. These markers included elevated levels of proteins known as amyloid and tau that are associated with the disease and synaptic breaks linked to cognitive decline.

Research using brain organoids has shown that exposure to serum from blood could induce multiple Alzheimer’s symptoms. This suggests that combination therapies targeting multiple areas would be more effective than single-target therapies currently in development.

The team found that attempting a single therapy, such as inhibiting only amyloid or tau proteins, did not reduce the levels of tau or amyloid, respectively. These findings suggest that amyloid and tau likely cause disease progression independently. Furthermore, exposure to serum from blood, which mimics BBB breakdown, could cause breaks in synaptic connections that help brains remember things and function properly.

Image Description: Yanhong Shi, Ph.D.

In a press release from the Associated Press, Dr. Shi elaborated on the importance of their model for studying Alzheimer’s.

“Drug development for Alzheimer’s disease has run into challenges due to incomplete understanding of the disease’s pathological mechanisms. Preclinical research in this arena predominantly uses animal models, but there is a huge difference between humans and animals such as rodents, especially when it comes to brain architecture. We, at City of Hope, have created a miniature brain model that uses human stem cell technology to study Alzheimer’s disease and, hopefully, to help find treatments for this devastating illness.”

The full results of this study were published in Advance Science.

Dr. Shi has previously worked on several CIRM-funded research projects, such as looking at a potential link between COVID-19 and a gene for Alzheimer’s as well as the development of a therapy for Canavan disease.

“…to help combat immune related problems….”

New post on The Stem Cellar

Improving a special kind of cell to help combat immune related problems

by Yimy Villa

Regulatory T cells (Tregs) are a type of immune cell that play an extremely important role in maintaining stability in the body and preventing the body’s immune system from attacking its own cells and organs. This unique property makes Tregs extremely valuable to researchers as a potential treatment for immune related issues. One of these is autoimmune disease, which is a disease in which the body’s own immune system attacks healthy cells. Some examples of this are type 1 diabetes, multiple sclerosis, and lupus. Another immune related issue is graft vs. host disease (GvHD), which can occur after receiving a transplantation where the donated bone marrow or stem cells start attacking the recipient.

For this reason, researchers at the La Jolla Institute for Immunology (LJI) and Emory University School of Medicine, partially supported by a CIRM training grant , have been working to generate stable induced Tregs (iTregs) for treating autoimmune diseases and rejection of a transplanted organ. The teams were led by LJI professor Anjana Rao, Ph.D, and Emory instructor Benjamin G. Barwick, Ph.D. The two team study showed evidence that vitamin C and and specific proteins called TET can be combined to give Tregs their life-saving power. Studies have previously found that vitamin C can enhance the activity of TET proteins and prompt the generation of stable iTregs under lab conditions.

For this study, the researchers also analyzed gene expression patterns as well as changes that altered the physical structure of DNA in the induced Tregs. The team found a major modification involving the DNA itself and showed that TET enzymes were also involved. All of these interactions can eventually change how cells “read” the DNA code. They also observed the alteration of DNA accessibility which depends on whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression.

In a news release, LJI instructor Xiaojing Yue, Ph.D elaborated on the results of this study.

“Vitamin C can be used to stabilize iTregs generated in vitro. We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation.”

The full study was published in EMBO reports.

“World Sickle Cell Day”

An Open Letter to CIRM for World Sickle Cell Day

“Dear CIRM,

World Sickle Cell Day is this Saturday June 19th. The goal of this day is to increase knowledge of the disease and understanding of the challenges faced.

“It is a day that I greet with very mixed feelings.  I’m of course extremely grateful to CIRM for the time and money spent looking for a cure.  The work of doctors, of researchers, the courage of families in the sickle cell community who are taking part in studies, and of course those of you who worked so hard for the original funding for CIRM, I applaud all of you, yet it’s hard to wait for a cure.

“While I wait I worry. I worry about my friends who are not getting good care.  They are the ones who can’t find a doctor to treat them, not able to take advantage of the medications that are already approved.  They are the ones who walk into the Emergency Room hoping for knowledgeable treatment while understanding that they may be accused of being a drug seeker,  turned away in excruciating pain. They are the ones who succumb after years of poor care.

“With sickle cell disease there is the same level of understanding about medical malpractice that we had of police brutality before George Floyd. We hardly remember Rodney King or Eric Garner. As a country we were aware that something was wrong but we tended to retreat in denial after each terrible headline.

“That’s where we are with sickle cell disease.  We may see a heart-wrenching story and watch televised reports with interest, but after all, it’s easier to live in disbelief, to think that medical care is not that bad, rather than understand that people are being dismissed and denied treatment. We call it structural racism without understanding what that term really means.

“While I wait I must acknowledge that change is coming.  We have a Sickle Cell Data Collection Project in California that helps us track healthcare for sickle cell disease. This is data that we can use to point to structural weakness and address health disparities.  NASEM, the National Academies of Science Engineering and Medicine, has published a huge report with significant suggestions for improving sickle cell care. Many scientists, researchers and advocates took part in this landmark study, detailing what has gone wrong in health care and how to improve the work. And of course we have CIRM. I am very thankful for the leadership and pioneering work of doctors Donald Kohn, Matthew Porteus and Joseph Rosenthal who are using their knowledge and experience in this fight.

“When we have successful research on stem cell transplants for sickle cell disease, many of us with sickle cell family members will want to relax, but we can’t forget those who may not be able to get a curative transplant. I hope Dr Niihara at Emmaus, and Dr. Love of Global Blood Therapeutics will continue their important work finding effective treatments. We must continue this fight on all fronts.

“World Sickle Cell Day will come again next year.  Let’s see what it brings.

“A sickle cell grandmother, “Nancy M. René.”

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Celebrating International Women’s Day!

Women who have changed, and are changing, the world

by Kevin McCormack

The problem with trying to write about something like Women’s History Month is where do you start? Even if you narrow it down to women in science the list is vast.

Marie Curie

I suppose you could always start with Maria Salomea Skłodowska who is better known as Marie Curie. She not only discovered radium and polonium, but she was also the first woman to win a Nobel Prize (in Physics). When she later won another Nobel (in Chemistry) she became the first person ever to win two Nobels and is still the only person ever to win in two different fields. Not a bad place to start.

Agnes Pockels

Or how about Agnes Pockels (1862–1935). Even as a child Agnes was fascinated by science but, in Germany at the time, women were not allowed to attend university. So, she depended on her younger brother to send her his physics textbooks when he was finished with them. Agnes studied at home while taking care of her elderly parents. Doing the dishes  Agnes noticed how oils and soaps could impact the surface tension of water. So, she invented a method of measuring that surface tension. She wrote a paper about her findings that was published in Nature, and went on to become a highly respected and honored pioneer in the field.

Jennifer Doudna (left) and Emmanuelle Charpentier: Photo courtesy Nature

Fast forward to today we could certainly do worse than profile the two women who won the 2020 Nobel Prize in Chemistry for their work with the gene-editing tool CRISPR-Cas9; Jennifer Doudna at the University of California, Berkeley, and Emmanuelle Charpentier at the Max Planck Unit for the Science of Pathogens in Berlin. Their pioneering work showed how you could use CRISPR  to make precise edits in genes, creating the possibility of using it to edit human genes to eliminate or cure diseases. In fact, some CIRM-funded research is already using this approach to try and cure sickle cell disease.

In awarding the Nobel to Charpentier and Doudna, Pernilla Wittung Stafshede, a biophysical chemist and member of the Nobel chemistry committee, said: “The ability to cut DNA where you want has revolutionized the life sciences. The ‘genetic scissors’ were discovered just eight years ago but have already benefited humankind greatly.”

Barbara McClintock: Photo courtesy Brittanica

Appropriately enough none of that work would have been possible without the pioneering work of another woman, Barbara McClintock. She dedicated her career to studying the genetics of corn and developed a technique that enabled her to identify individual chromosomes in different strains of corn.

At the time it was thought that genes were stable and were arranged in a linear fashion on chromosomes, like beads on a string. McClintock’s work showed that genes could be mobile, changing position and altering the work of other genes. It took a long time before the scientific world caught up with her and realized she was right. But in 1983 she was awarded the Nobel Prize in Medicine for her work.

Katherine Johnson at her desk at Langley Research Center: Photo courtesy NASA /AFP

Katherine Johnson is another brilliant mind whose recognition came later in life. But when it did, it made her a movie star. Kind of. Johnson was a mathematician, a “computer” in the parlance of the time. She did calculations by hand, enabling NASA to safely launch and recover astronauts in the early years of the space race.

Johnson and the other Black “computers” were segregated from their white colleagues until the last 1950’s, when signs dictating which restrooms and drinking fountains they could use were removed. She was so highly regarded that when John Glenn was preparing for the flight that would make him the first American to orbit the earth he asked for her to manually check the calculations a computer had made. He trusted her far more than any machine.

Johnson and her co-workers were overlooked until the 2016 movie “Hidden Figures” brought their story to life. She was also awarded the Presidential Medal of Freedom, America’s highest civilian honor, by President Obama.

There are so many extraordinary women scientists we could talk about who have made history. But we should also remind ourselves that we are surrounded by remarkable women right now, women who are making history in their own way, even if we don’t recognized it at the moment. Researchers that CIRM funds, Dr. Catriona Jamieson at UC San Diego, Dr. Jan Nolta at UC Davis, Dr. Jane Lebkowski with Regenerative Patch technologies and so many others. They’re all helping to change the world. We just don’t know it yet.

If you would like to learn about other women who have made extraordinary contributions to science you can read about them here and here and here.

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Wait, there’s more science!

“Given the ongoing struggle to find new therapeutic cancer drug targets, I have long believed that a more rapid approach for discovery would consist of reversing the question,” stated Stine. “Rather than the conventional route of interrogating the tumor at the genomic and proteomic level in order to reveal disease-associated targets, why not ask the patient? The readout for differences in self and non-self antigens manifests itself in the form of antibodies, and our approach assumes that the answers to our drug and target discovery questions are contained within this response.” – J.T. Stine, Seattle Times, 2005

Applications in Humans

The statement above was the founding question addressed by Spaltudaq (today known as Theraclone Sciences).  The result of sampling a cancer patient’s immune repertoire led to the discovery of a broadly reactive and specific IgG antibody using the iSTAR method (a precursor to BLAST).

Discovery:

Screen normal/exposed and disease individuals for

  1. Neutralizing anti-infective antibodies (viral, bacterial)

  2. Tumor specific antibodies/epitopes from host B-cells

Immune monitoring

  1. Vaccine evaluations prior or during clinical trials – associate epitopes with efficacy

  2. Monitor immune response during tolerance block therapeutics such as anti-CTLA-4 or anti-PD1

Auto-immune patient B-cell screening

  1. Discover antibodies in auto-immune patient repertoire which can be therapeutic in other diseases where the eliciting target exists.

Applications in other mammals:

Discovery:

Immunize with tumor lines or clinical isolates

  1. Screen for novel tumor-specific or -selective epitopes or targets for naked antibody targeted ADCC

  2. Screen for novel internalization targets for antibody/drug conjugates

  3. Screen for functional antibodies that have a deleterious effect on tumor growth

Immunize with viral or bacterial targets

  1. Upfront functional screens can reveal novel or additional antibody epitope pairs for neutralization

  2. Use neutralization data to engineer more efficacious vaccines

Target extracellular domains of 7TM’s/GPCR’s

  1. The most “drugable” target is easily targeted with BLAST

  2. Discover antibodies that are agonists, antagonists or neutral

  3. Discover a more specific cell set to deplete due to the selective expression of GPCR’s on various cell types

An example of the use of BLAST in Type 1 diabetes (T!D) to interrogate the immunological history of their disease in order to determine the most relevant first-response cell surface proteins which were targeted on pancreatic islets cells by T-cells or other effector mechanisms.  A discovery here may lead to another use of BLAST which would consist of understanding the TCR’s responsible for this detection and selectively eliminating them with anti-TCR-specific antibodies.

Whole-cell immunization & BLAST

  1. Antibody generation in a massive scale

  2. Below is an example of the fraction of antibodies created en masse

BLAST

Functional Screen

Hit Selection

IgG Memory B-cells

Hits

Molecular

Reconstitution

V-gene

sequence

matching

  1. Reveals:

  2. v-gene epitope bias and overall immune response to target

  3. alternative target-specific hypermutated related sequences that may have other desirable properties that weren’t revealed in the screen and can now be synthesized