Novel device measures stiffness and stickiness of red blood cells

Researchers have created a versatile device that measures two important properties of red blood cells that are relevant for sickle cell and other diseases: deformation and adhesion.

The team, from Case Western Reserve University (CWRU) in Cleveland, OH, describes the innovative device - a microfluidic platform with a computer algorithm that does the math - in a paper published in the journal Technology.

Sickle cell disease is a group of inherited red blood cell disorders. People with the disease have abnormal hemoglobin - the protein that carries oxygen - in their red blood cells. The abnormal hemoglobin is called sickle hemoglobin.

Red blood cells containing normal hemoglobin are flexible and shaped like a doughnut with a thin flat area in the middle instead of a hole. This allows them to squeeze round bends in blood vessels and through smaller ones to deliver vital oxygen to tissues and organs.

However, sickle hemoglobin has a tendency to form stiff rods inside the red blood cell - changing it into the crescent or sickle shape that gives the disease its name.

Red blood cells containing sickle hemoglobin are less flexible than normal red blood cells and also tend to be stickier. These two features increase the risk that they will cause a blockage in a blood vessel and impede the delivery of oxygen to nearby tissues and organs.

When such a blockage occurs, it causes a sudden and severe attack of pain - called a pain crisis - that is typical of sickle cell disease. Pain crises occur without warning and often require hospitalization for effective treatment.

In extreme cases, the blockage of blood vessels in sickle cell disease can lead to widespread organ damage and early death.

Currently, the only way to cure sickle cell disease is with a stem cell transplant. But unfortunately, most patients are either too old for a transplant or do not have a relative with a good enough genetic match to receive transplantable stem cells from.

Effective treatments exist and these can reduce symptoms and prolong life. Early diagnosis and regular monitoring to prevent complications also helps.
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Potential monitor of disease progression

By assessing the extent of stiffness and stickiness, or the "dynamic deformability and adhesion," of red blood cells, the new microfluidic device offers great potential as a way to monitor progression of sickle cell disease, note the researchers.

They say the device could also help with research and developing new treatments for sickle cell disease.

Other ways to measure stiffness and stickiness in red blood cells - such as atomic force microscopy and optical tweezers - do exist, but they do not lend themselves to working with whole blood in a clinical setting, say the researchers.

They note their device can assess the stiffness of a single red blood cell, and also, by mimicking blood vessel properties, assess the stickiness of red blood cells from whole blood of sickle cell patients.

Lead investigator Umut Gurkan, an assistant professor in CWRU's Department of Mechanical and Aerospace Engineering, says:

"The microfluidic system developed here has the potential to be used in a high-throughput manner with an integrated automated image processing algorithm for measurement of RBC [red blood cell] deformability and adhesion in patients' blood."

The authors explain that healthy red blood cells undergo reversible deformation when they circulate around the body in blood vessels. They respond to "fluid shear stresses" extremely fast - they can bend and regain their shape in the space of 100 milliseconds.
'Interplay between dynamic deformability and increased adhesion'

To assess dynamic deformability of red blood cells, the researchers used what they call a dynamic deformability index (DDI), which they define as "the time-dependent change of the cell's aspect ratio." Essentially, a cell's DDI is a measure of how quickly it springs back to its normal shape after experiencing flow shear stress.

In their paper, the team describes a range of tests where they measured the DDI of deformable and non-deformable red blood cells.

The researchers also compared adhesion of deformable and non-deformable red blood cells from blood samples taken from sickle cell patients. They tested the stickiness of the cells under different flow shear stresses - both within and outside ranges experienced in normal blood vessels.

They found that at flow shear stresses "well above the physiological range," non-deformable sickle red blood cells were much stickier than deformable sickle red blood cells, "suggesting an interplay between dynamic deformability and increased adhesion" of red blood cells when blood vessel blockage occurs.

The team suggests the device may also be useful for studying the deformation of cells that could be relevant in other diseases - such as diabetes, malaria and the bone marrow disorder polycythemia vera.

The researchers plan to study red blood cell stiffness and stickiness in more sickle cell disease patients so they can link the two properties with other disease and patient characteristics.

As the technology for making them becomes cheaper and more widely available, more and more researchers are using microfluidic devices in all kinds of ways to investigate, diagnose and perhaps even treat disease.

For example, Medical News Today recently learned how an "IVF chip" incorporating microfluidics with imaging techniques enabled researchers to film a single sperm fusing with an egg cell.

And in May 2015, another article described how scientists are using microfluidic technology to develop new immunotherapy vaccines. Using microfluidic technology, they can squeeze immune system B cells so their membranes develop temporary holes through which antigens that program specific immune responses can be inserted.

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Are cooling caps the solution to prevent hair loss during chemotherapy?

Hair loss—one of the most-feared side effects of cancer treatment—may have met its match. Scientists have known since the 80s that cooling a person's scalp can prevent significant hair loss during chemotherapy. A cooling device called DigniCap was approved for women with breast cancer by the U.S. Food and Drug Administration in 2015. This cap was tested in a clinical trial at UCLA led by Dr. Sara Hurvitz, director of hematology and oncology breast cancer program at UCLA's Jonsson Comprehensive Cancer Center. 

Two studies  found that the cap was effective; results showed that women lost less than 50 percent of their hair. The trial Hurvitz participated in paved the way for physicians to help people with cancer overcome one of the most visible signs of treatment.

How did scientists come up with the idea of cooling the scalp to help save the hair of a woman who has cancer, and how long did the development process take?
The idea to cool the scalp during chemotherapy infusion to reduce hair loss is not a new one. It has been in place for over three decades and evaluated by several other companies. There are other devices in use clinically. This is the first one to be FDA approved.

How did your research play a role in the FDA approval of this cooling cap?
We participated in the clinical trial that led to the FDA approval of this device. We enrolled and treated multiple patients on this study who were undergoing standard chemotherapy for early stage breast cancer.

How does the cooling cap actually work?
Cooling the scalp slows down blood flow to the hair follicles during the infusion of chemotherapy, which in turn limits the delivery of chemotherapy to the scalp. This lessens the toxic effects of chemotherapy on the hair follicle, thus limiting hair loss. Several devices utilize ice caps that are cumbersome to store and to manage. The device we evaluated is a tight-fitting cap, much like a bathing cap, that is attached to a cooling machine and worn during chemotherapy and for an hour or two after chemotherapy. This machine avoids the need to use a freezer or change caps during treatment.


Why do you think this cooling cap is beneficial for women going through treatment?
Hair loss from chemotherapy causes a major impact on quality of life for many women with early stage breast cancer. The hope is that reduction in or prevention of hair loss will reduce the emotional stress associated with a cancer diagnosis.

Why is it that some women still lose their hair after using the cooling cap?
Hair loss is not completely prevented in the majority of patients with scalp cooling, but half of patients are able to keep more than 50 percent of their hair with cooling (whereas nearly all patients who take curative chemotherapy without cooling cap use will lose over 50 percent of their hair). This allows a woman to look more like herself during chemotherapy. Hair also tends to fill in and look normal more quickly after chemotherapy has completed, compared to women who did not use scalp cooling.

What is the future of the cooling cap and could it prevent hair loss in people with other cancer types as well as men who have cancer?
Different devices are being evaluated in clinical trials in a variety of cancer types. This could certainly be utilized by male cancer patients as well. 

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Smart, traceable drug delivery can make cancer therapy more effective

In today’s era, an easy way to track any location is to navigate through GPS. Similarly, smart and trackable drug delivery systems can improve efficiency of cancer treatment. Imaging techniques can help visualize the drug carrier and monitor its delivery to the target tissues. However, a single visualization technique is usually not enough to track the drug with precision. Indian scientists have now designed multifunctional, smart and trackable drug delivery systems.

Researchers have developed multifunctional gold nano-structure that can be used in cancer imaging and therapy.

Nano-systems can simultaneously transfer drug and allow imaging of tumor. However, it is very critical to differentiate the drug carrier system from surrounding tissues and the targeted area.

Although imaging-guided local drug administration has been used widely to treat cancer but it is still very difficult to achieve accurate drug delivery if single imaging technique is used. Designing nano-structures with multi-imaging functionality wherein one imaging system can complement another allows better visualization, assistance and delivery of drug.

“We have designed a Nano-IRIS consisting of gold nano-rattles surrounded by layer of solid silica and mesoporous silica. The nanostructure looks similar to that of an iris of the human eye,” explained the leader of the research team.

Gold nano-rattles are similar to a toy rattle, consisting of a solid gold core encapsulated within thin gold shell. ‘Raman reporters’ were loaded into these porous gold nano-rattles, which allow tissue imaging through Surface- enhanced Raman Spectroscopy (SERS).

In order to load doxorubicin - a fluorescent anti-cancer drug - the gold nano-rattle was coated with mesoporous silica layer. “Since gold reduces the fluorescence of the drug when placed in its proximity, the gold nano-rattle was first coated with solid silica followed by mesoporous silica, onto which the drug is loaded. This increases the distance between gold and the drug and thereby, retains the fluorescence of the drug,” said the researcher.

Raman and fluorescence imaging confirmed the uptake and landing of the drug in breast cancer cells. The uptake and chemotherapeutic potential of the Nano-IRIS was corroborated by the cell death in breast cancer cells. “The challenging part of the study was synthesis of such a complicated system,” he said. The group is now planning further studies and exploring chemotherapy combined with photo-thermal therapy for enhancing the therapeutic efficacy.

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Breastfeeding for more than 6 months leads to smaller waist circumference

Turns out, breastfeeding for more than six months is independently associated with smaller waist circumference in the decade after delivery among women. Pregnancy contributes to an accumulation of abdominal adiposity, which is an indicator of cardiometabolic dysfunction in later life.

During a recent study, the researchers assessed the relationship between waist circumference measured at follow-up and self-reported history of breastfeeding duration. Propensity score approaches were incorporated into the study to account for systematic differences between women who did and did not breastfeed.

The novel use of propensity score methods enabled the researchers to minimise the possibility of bias in the likelihood of breastfeeding due to overall healthier lifestyles. Additional analyses that consider the lifetime duration of breastfeeding is proposed in order to advance understanding of the cumulative effect of breastfeeding on maternal central adiposity. 

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'Tummy tuck' reduces back pain after childbearing

Besides restoring the pre-pregnancy shape of the abdomen, abdominoplasty or "tummy tuck" -- a surgical operation involving the removal of excess flesh from the abdomen -- can improve back pain and urinary incontinence after childbearing, a study says. 
 
Many women seek tummy tuck surgery to restore the shape and appearance of the abdomen after childbearing, but the new study, published suggests that it also improves two of the most common physical complaints experienced by women after labour and delivery.

"Abdominoplasty has a proven functional benefit as well as a cosmetic benefit," said lead author.

The study covered 214 women undergoing abdominoplasty with repair of the abdominal muscles at nine plastic surgery centres. 

The women's average age was about 42 years, with an average of 2.5 deliveries.

Before and after surgery, the women completed questionnaires rating their disability from back pain and urinary incontinence.

In the preoperative questionnaires, about 51 per cent of women had moderate to severe disability from back pain, while urinary incontinence was a "significant concern" for 42.5 per cent.

On follow-up questionnaires at six weeks and six months, scores for both problems showed major improvement, the study said. 

At six months, only nine per cent of patients still had moderate disability from back pain. Urinary incontinence remained a significant problem for less than two per cent of women, the findings showed. 

"By reducing the problems of back pain and incontinence, abdominoplasty with rectus repair leads to a better life for women after childbearing," the author  said. 

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7 Things Your Back Pain Is Trying to Tell You

Pain is our body's way of telling us that something is wrong. In the case of back pain, the root cause may be obvious - you may have been involved in a car accident, or lifted a box that was too heavy. Though it may also seem like a mystery. Nevertheless, if you dig a little, the root cause of your back pain could also be sorted out. So if you're unsure about why you are in agony, one of these 7 possible causes may be it: 

 

1. You're feeling stressed It should come as no surprise to learn that stress can cause tight muscles and knots in your neck and upper back. Anxiety may also cause you to have back spasms too. If you suspect that stress is causing you back pain, try to incorporate some relaxation techniques such as meditation and deep breathing into your routine. A weekly yoga class, or an intensive stretch will help reduce lower back pain. 

2. You're hooked on technology Hunching over a phone or tablet for several hours a day can cause what has now been termed, 'text neck'. Having a slumped neck and rounded shoulders adds an additional 60 pounds of weight on your spine, which can inadvertently change your posture and cause back pain. To prevent this from happening, try keeping your phone at eye level instead. 

3. You're not sitting properly Just as looking down at your smartphone can cause back problems, sitting down all day can wreck havoc on your spine too. Poor posture can cause lower back pain by increasing the amount of pressure or tension on the bones, joints, ligaments, and spinal discs. Improve your sitting posture by keeping your forearms parallel to the floor, your head in line with your torso, your feet flat on the floor or resting on a foot rest, your back fully supported and thighs parallel to the floor. 

4. You have a muscle imbalance elsewhere in your body Everything in your body is interconnected. Your back pain may be stemming from tight hamstrings or weak abdominal. If other muscle groups are weak, it can cause the muscles of the back to do more work than they should to keep the spine upright or moving correctly. Try working with a physical therapist to identify and correct the specific imbalances that are over-taxing your back.

 

5. You have a bulging or ruptured disc The disks between your vertebrae help cushion the spine and act as shock-absorbers. Over time, however, they can flatten or rupture due to natural aging, certain movements, or a family history of disc disease. While it doesn't always cause pain, when it does, it can be hugely uncomfortable. If a bulging disc is the culprit, doctors often prescribe over-the-counter medicine, hot and cold packs, and physical therapy. 

6. Something more serious is going on Pancreatitis, ulcers, or even a kidney infection could cause pain that radiates into the back. It may also be a result of an infection, osteomyelitis - an infection of the spine. Most back pains tend to resolve on their own in six weeks - but if yours has gotten worse then be sure to see a physician, particularly if it is accompanied by fever, numbness in the rectal area, and loss of bowel or bladder control. 

7. You just had a baby Statistics show that almost 80% of new moms suffer from lower back pain as a result of the stress placed on the body during pregnancy. Another cause may also be due to the habits that result from caring for a young baby, such as holding a baby on one side of the body, or hunching while nursing - which can lead to muscle imbalance, affecting the natural curve of your spine. Are you a new mom? Try be aware of maintaining good posture by alternating muscle groups so you're not constantly rocking, swaying, or bouncing your baby on one side. 

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C-section in first birth ups risk of stillbirth, ectopic pregnancy later

A new study has indicated that women who have a C-section in first delivery, might be at a slightly increased risk for ectopic pregnancy and stillbirth in future pregnancies.

 But, the researchers are quick to point out that the risk of the complication is very low.

The findings of the research have been based on the analysis of data from nearly 833,000 first-time mothers in Denmark. It was found that those whose baby was delivered by cesarean section had a 14 percent higher rate of stillbirth in their next pregnancy than those who had a vaginal delivery.

This means that the absolute risk increase comes out to be 0.03 percent, a significantly low value. In easier to understand terms, this implies that that for every 3,000 cesarean deliveries, there would be one extra stillbirth in future pregnancies.

Furthermore, women who had a cesarean delivery for their first baby were 9 percent more likely to have a future ectopic pregnancy than those who had a vaginal delivery, according to the researchers at University College Cork in Ireland and Aarhus University in Denmark.

The absolute increased risk for ectopic pregnancies comes out to be 0.1 percent, which means that for every 1,000 cesarean deliveries, there would be one extra ectopic pregnancy in future pregnancies.

However, having a cesarean delivery for a first baby did not increase women's risk of miscarriage in future pregnancies.

 

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