Author Archives: admin

Asymmetrex Director Comments on Positive Attributes of Private … – PR Web (press release)

By adminJune 9, 2017Stem Cell Clinic

Many more patients are estimated to receive stem cell treatments in private clinics than in clinical trials.

Boston, MA (PRWEB) June 08, 2017

In a new early view article published in the online Journal of Stem Cell Research and Medicine, James L. Sherley, M.D., Ph.D., founder and director of Asymmetrex, LLC, asks the question, Why are patients scared away from private stem cell clinics? (May 6, 2017). Sherley presents a critical assessment of the warnings pronounced by federal agencies and professional organizations, like the National Institutes of Health (NIH) and the International Society for Stem Cell Research (ISSCR), against private clinics providing stem cell treatments. He argues that new treatments in private clinics are, for the most part, not very different than stem cell treatments in clinical trials authorized by the Food and Drug Administration (FDA).

In his comment, Sherley chides the NIH, ISSCR, and alarmist commentators for portraying private stem cell clinics, as a group, as unethical, and even dangerous to patients, without good evidence to support their claims. He provides examples to show that many operational elements of stem cell treatments in private clinics are not unlike FDA-authorized clinical trials. Both stem cell treatment settings have strengths and weaknesses. Sherleys position is that, In their missions to serve patients, the NIHs and ISSCRs efforts would seem to be better spent informing patients how to obtain the best care in either setting. In earlier writings and presentations, he has also urged decision-makers to develop policies for collecting, organizing, and studying stem cell treatment data from private clinics. Since the number of patients treated in private clinics is now estimated to far exceed the number in clinical trials, Sherley has argued that excluding this valuable experience by vilifying it is a tragic loss to stem cell medical research and patients.

A crucial way in which FDA-authorized clinical trials and private stem cell treatment clinics are not different is their past lack of a means to determine the dose and quality of stem cell treatments. In his published comment, Sherley notes that none of the anti-private clinic alarmists acknowledges this deficiency that also impacts the worth of stem cell clinical trials. In fact, this need even limits the quality of some approved stem cell therapies like umbilical cord blood stem cell transplant.

Asymmetrex has recently developed a technological solution for the half century-old problem of specifically counting tissue stem cells. With the companys new technology, it is now possible to determine the dose and quality of therapeutic tissue stem cell preparations. Asymmetrex is positioned to become the certifying agency for the dose and quality of tissue stem cells used in approved treatments and either FDA-authorized clinical trials or private stem cell clinic treatments. Sherley predicts that adoption of this shared certification process will promote a more reasoned assessment of the contributions that private stem cell clinics are and can make to accelerating progress in stem cell medicine.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrexs focus is employing its technological advantages to develop and market facile methods for monitoring adult stem cell number and function in stem cell transplantation treatments and in pre-clinical assays for drug safety.

Share article on social media or email:

View original post here:
Asymmetrex Director Comments on Positive Attributes of Private ... - PR Web (press release)

Looking Back: June 9, 2017 – Fairbanks Daily News-Miner

By adminJune 9, 2017Stem Cell Clinic

10 YEARS AGO

June 9, 2007 Alaskas congressional delegation continues to support legislation that would give the federal government more opportunities to fund embryonic stem cell research.

Rep. Don Young voted in favor of the Stem Cell Research Enhancement Act of 2007 on Thursday, which would make federal funds available to research projects using excess embryonic stem cells that have been donated to an in vitro clinic, and would otherwise be discarded.

The House voted 247-176 in favor of the bill, which has been sent to President Bush.

25 YEARS AGO

June 9, 1992 Fairbanks Mayor Wayne Nelsons sweeping four-part plan to cut the costs of city government and generate revenues survived its introduction to the city council Monday.

The council voted unanimously to advance ordinances calling for the closure of the Fairbanks Fire Department, the creation of a city-run lottery, the appointment of a revenue commission and the opening of the citys labor negotiations to the public.

50 YEARS AGO

June 9, 1967 Fairbanks could receive live television programming from communication satellites within 18 months, Alaskas broadcasters were told yesterday.

Maj. Gen. George P. Sampson, USA-Ret., vice president for operations with Communications Satellite Corp., described the rapidly developing future of satellite communication to a luncheon meeting of the Alaska Broadcasters Association here yesterday.

75 YEARSAGO

June 9, 1942 The million miles which Al Jolson has been promising since 1909 to walk for one of his mammys smiles was never closer to an accurate figure today.

At least 900,000 miles, by his own calculation, from the spot where he knows the sun shines best the dynamic song and patter man of stage, screen, and radio strolled the streets of Fairbanks, making mental notes of his first view of life in Alaska while marking time before the first performance of his Keep em Smilin tour of the Territorys Army encampments.

Before most of the men in Uncle Sams new Army were born Al Jolson was already dubbed one of the greatest dominators in the theater. And, years before that, he had shucked off the name he brought with him to the United States from his native Russia as a boy of seven Asa Yoelson and turned his aspirations from that of becoming a cantor.

Read the original here:
Looking Back: June 9, 2017 - Fairbanks Daily News-Miner

Parkinson’s target of China’s first clinical trial using embryonic stem … – Genetic Literacy Project

By adminJune 9, 2017Embryonic Stem Cells

In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinsons disease and inject 4 million immature neurons derived from human embryonic stem cells into their brains.

This will mark the start of the first clinical trial in China using human embryonic stem (ES) cells, and the first one worldwide aimed at treating Parkinsons disease using ES cells from fertilized embryos. In a second trial starting around the same time, a different team in Zhengzhou will use ES cells to target vision loss caused by age-related macular degeneration.

It will be a major new direction for China, says Pei Xuetao, a stem-cell scientist at the Beijing Institute of Transfusion Medicine who is on the central-government committee that approved the trials. Other researchers who work on Parkinsons disease, however, worry that the trials might be misguided.

Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, is concerned that theChinese trials use neural precursors[, which] can turn into other kinds of neurons, and could accumulate dangerous mutations during their many divisions, says Loring. Not knowing what the cells will become is troubling.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Trials of embryonic stem cells to launch in China

Visit link:
Parkinson's target of China's first clinical trial using embryonic stem ... - Genetic Literacy Project

China plans embryonic stem cell trials for Parkinson’s and blindness – BioNews

By adminJune 9, 2017Embryonic Stem Cells

Two teams of doctors in China are to administer embryonic stem cell therapy from fertilised human embryos to treat different degenerative diseases.

One trial testing ESC therapy in Parkinson's diseasewill be the first clinical trial of human embryonic stem cells (ESCs) in China, as well as the first trial in the world to examine ESCs for the treatment of Parkinson's, according to a report in Nature News. Both studies will be led by stem cell specialist Dr Qi Zhou at the First Affiliated Hospital of Zhengzhou University.

The only previous study of this type started in Australia last year:patients with the degenerative disease are being treated with cells derived from parthenogenetic embryos. These stem cells were harvested from unfertilised eggs induced into embryonic development, sidestepping many of the ethical issues with using viable embryos. ESCs are pluripotent stem cells taken from the inner cell mass of human embryos and have the potential to develop into any of the 200-plus specialised cell types in the adult body.

In Parkinson's disease, a specialised type of brain cell that produces the neurotransmitter dopamine are lost. Dr Zhou's team will inject four million immature cells derived from ESCs into the striatum area of patients' brains with the aim of reducing symptoms. This follows an unpublishedfour-year study led by Dr Zhou which showed promising results in 15 monkeys.

A second team will treat patients with age-related macular degeneration (AMD), in which vision is compromised by the loss of pigmented retinal epithelia in the eye. Building on pre-clinical trials carried out in South Korea and the US, ESC-derived retinal epithelial cells will be injected into the retinas of AMD patients in a bid to stop the disease progressing.

Using ESCs intreatment is controversialon ethical grounds, as well as fears that they could cause tumours. Some scientists are concerned that theParkinson's patients are being injected with cells thatmay not become the desired type of neurone. 'Not knowing what the cells will become is troubling.' said Dr Jeanne Loring at the Scripps Research Institute, California.However, pre-clinical work for the Australian trial found that 97 percentof the ESC-derived precursor cells developed into dopaminergic neurons.

In 2015, China announced new regulations for stem cell therapies aiming both to enable legitimate human trials, and curb administration of unapproved treatments. Zhou's clinical trials will be fully compliant, using government-certified ESC lines and the clinicians have been granted approval by a central government committee for their use.

Committee member Dr Pei Xuetao, a stem-cell scientist at the Beijing Institute of Transfusion Medicine, called the study a'major new direction for China'. Other groups of scientists are already planning trials for the testing of ESC therapy for other targeted treatments, such as encouraging growth and repair following spinal cord injuries.

Read more from the original source:
China plans embryonic stem cell trials for Parkinson's and blindness - BioNews

Similarities in human and pig embryos provide clues to early stages of development – Phys.Org

By adminJune 9, 2017Embryonic Stem Cells

June 8, 2017 Developing human primordial germ cells (each small green and red cell is a PGC). Credit: Walfred Tang/Surani lab

Scientists have shown how the precursors of egg and sperm cells the cells that are key to the preservation of a species arise in the early embryo by studying pig embryos alongside human stem cells.

In research published today in Nature, researchers at the University of Cambridge and the University of Nottingham demonstrate how pig embryos and human embryonic cells show remarkable similarities in the early stages of their development. By combining these two models, they hope to improve our understanding of the origins of diseases such as paediatric germ cell tumours and fetal abnormalities.

Primordial germ cells, the precursors of eggs and sperm, are among the earliest cells to emerge in human embryos after implantation, appearing around day 17, while the surrounding cells go on to form the rest of the human body. However, little is understood about how they originate. Currently, the law prohibits culture of human embryos beyond 14 days, which prevents investigations on this and subsequent events such as gastrulation, when the overall body plan is established.

Now, researchers have used a combination of human and pig models of development to shed light on these events. They have shown for the first time that the interplay between two key genes is critical for the formation of the germline precursors and that this 'genetic cocktail' is not the same in all species.

First, by using human pluripotent embryonic stem cells in vitro, scientists led by Professor Azim Surani at the Wellcome Trust/Cancer Research UK Gurdon Institute established a model that simulates genetic and cellular changes occurring up to gastrulation. Human pluripotent embryonic stem cells are 'master cells' found in embryos, which have the potential to become almost any type of cell in the body.

As these stem cells can be multiplied and precisely genetically manipulated, the model system provides a powerful tool for detailed molecular analysis of how human cells transform into distinct cell types during early development, and which changes might underlie human diseases.

The work shows that when an embryo progresses towards gastrulation, cells temporarily acquire the potential to form primordial germ cells, but shortly afterwards lose this potential and instead acquire the potential to form precursors of blood and muscle (mesoderm) or precursors of the gut, lung and the pancreas (endoderm). The model also tells us that while the genes SOX17 and BLIMP1 are critical for germ cell fate, SOX17 subsequently has another role in the specification of endodermal tissues.

For an accurate picture of how the embryo develops, however, it is necessary to understand how cells behave in the three-dimensional context of a normal embryo. This cannot be achieved by studies on the most commonly used mouse embryos, which develop as egg 'cylinders', unlike the 'flat-disc' human embryos. Pig embryos, on the other hand, develop as flat discs (similar to human embryos), can be easily obtained, and are ethically more acceptable than working with non-human primate (monkey) embryos.

Researchers from the University of Nottingham dissected whole flat discs from pig embryos at different developmental stages and found that development of these embryos matches with the observations on the in vitro human model, as well as with non-human primate embryonic stem cells in vitro. For example, pig germ cells emerge in the course of gastrulation just as predicted from the human model, and with the expression of the same key genes as in human germ cells. Human and pig germ cells also exhibit key characteristics of this lineage, including initiation of reprogramming and re-setting of the epigenome modifications to our DNA that regulate its operations and have the potential to be passed down to our offspring which continues as germ cells progress towards development into sperm and eggs.

The combined human-pig models for early development and cell fate decisions likely reflect critical events in early human embryos in the womb. Altogether, knowledge gained from this approach can be applied to regenerative medicine for the derivation of relevant human cell types that might be used to help understand and treat human diseases, and to understand how mutations that perturb early development can result in human diseases.

Dr Ramiro Alberio, from the School of Biosciences at the University of Nottingham, says: "We've shown how precursors to egg and sperm cells arise in pigs and humans, which have similar patterns of embryo development. This suggests that the pig can be an excellent model system for the study of early human development, as well as improving our understanding of the origins of genetic diseases."

Dr Toshihiro Kobayashi in the Surani lab at the Gurdon Institute, adds: "We are currently prevented from studying human embryo development beyond day 14, which means that certain key stages in our development remain a mystery. The remarkable similarities between human and pig development suggest that we may soon be able to reveal the answers to some of our long-held questions."

Explore further: Mapping pluripotency differences between mice, monkeys, and humans

More information: Toshihiro Kobayashi et al. Principles of early human development and germ cell program from conserved model systems, Nature (2017). DOI: 10.1038/nature22812

Journal reference: Nature

Provided by: University of Cambridge

Not too shabby, humans. New research shows that certain primate stem cells have pluripotency superior to some types derived from mice. The study, published in Nature, maps how pluripotency differs among mice, monkeys, and ...

Researchers at the Babraham Institute have investigated the early stages of the development of cells called primordial germ cells and developed strategies to generate 'lookalike' cells in the lab. The generation of human ...

Scientists at the University of Cambridge working with the Weizmann Institute have created primordial germ cells - cells that will go on to become egg and sperm - using human embryonic stem cells. Although this had already ...

An important international summit on human gene editing recently recommended that researchers go ahead with gene editing human embryos, but keep revisiting how and when such modifications would be appropriate in the clinic. ...

Scientists at the University of Cambridge have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells - the body's 'master cells' - and a 3D scaffold on which they can grow.

Researchers at Karolinska Institutet have identified cell surface markers specific for the very earliest stem cells in the human embryo. These cells are thought to possess great potential for replacing damaged tissue but ...

(Phys.org)A small team of researchers from Austria and Sweden has found that ravens are able to remember people who trick them for at least two months. In their paper published in the journal Animal Behavior, the group ...

Sex-changing fish exhibit differences in androgen receptor (AR) expression in muscles that are highly sensitive to androgens (male sex hormones) and essential for male courtship behavior, according to a Georgia State University ...

It's well known that young babies are more interested in faces than other objects. Now, researchers reporting in Current Biology on June 8 have the first evidence that this preference for faces develops in the womb. By projecting ...

Paleontologists investigating the sea bed off the coast of southern California have discovered a lost ecosystem that for thousands of years had nurtured communities of scallops and shelled marine organisms called brachiopods.

A Cornell study, published May 26 in the journal Nature Ecology and Evolution, describes how shifts in diets in Europeans after the introduction of farming 10,000 years ago led to genetic adaptations that favored the dietary ...

Wild capuchin monkeys readily learn skills from each otherbut that social learning is driven home by the payoff of learning a useful new skill. It's the first demonstration of "payoff bias" learning in a wild animal, and ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Abused pup receives cutting-edge stem cell therapy | fox5sandiego … – fox5sandiego.com

By adminJune 9, 2017Uncategorized

Please enable Javascript to watch this video

SAN DIEGO Abused orphan pup "Dwyane," who has severe disfigurements, is on the road to recovery after stem cell therapy by a Poway-based company.

The one-year-old puppy was reportedly kicked, beaten and forced to wear a wire muzzle before he was rescued in Tijuana.

Last month, he was taken to Helen Woodward Animal Center in Rancho Sante Fe. Since then, the dog has undergone several procedures, including a hip surgery Tuesday.

Animal hospital officials said Dwaynes work isnt over yet, as he still needs major reconstruction to his elbow and additional facial surgeries to help him breathe easier.

There is no risk involved because we use the dog's own tissue to isolate the stem cell, said Dr. Jeffrey Schaffer with VetStem of Poway.

Today, we gave the injection of the stem cells in the hip and then a slow one through the vein," said Dr. Patricia Carter, chief veterinarian at Helen Woodward Animal Center. "Then we gave him something that made him unsleepy, but hes still recovering from the surgery two days ago.

Dwayne is a warrior and shows his love to those who have love to give.

He is adorable, sweet and with everything that is going on, he wants to give you kisses and love, Schaffer said.

Over $40,000 has been donated to Dwayne for medical costs from around the world, including Paris. He also has had plenty of people giving well wishes and dropping off toys at the animal hospital.

The animal center posts updates on Dwayne and other orphan pets on itswebsite.

Continued here:
Abused pup receives cutting-edge stem cell therapy | fox5sandiego ... - fox5sandiego.com

Chinese cell therapy effective in small multiple myeloma trial | Reuters – Reuters

By adminJune 9, 2017Uncategorized

By Deena Beasley | CHICAGO

CHICAGO A small trial conducted in China found that an experimental therapy using altered cells to recruit the body's immune system to attack cancer can induce remission in most patients with advanced multiple myeloma, a blood plasma cancer.

The study of 35 patients tested a chimeric antigen receptor T-cell (CAR-T) therapy developed by China's Nanjing Legend Biotech Co.

The drug candidate, known as LCAR-B38M, targets a protein called BCMA found on cancerous blood plasma cells - the same target being pursued by Bluebird Bio Inc and Celgene Corp with their CAR-T called bb2121.

CAR-T therapies require a complicated process of extracting immune system T cells from an individual patient, altering their DNA to sharpen their ability to spot and kill cancer cells, and infusing them back into the same patient.

The American Society of Clinical Oncology, which featured the data here at its annual meeting, said that out of 19 trial patients followed for more than four months, 14 reached complete remission. One patient had a partial response and four patients reached "very good partial remission," but the cancer did get worse in one of those patients.

Multiple myeloma "is a disease you can treat pretty well with other drugs, but this could be long-term remission," said Dr. Bruce Johnson, chief clinical research officer at Boston's Dana-Farber Cancer Institute and ASCO's incoming president.

Eighty five percent of trial patients experienced cytokine release syndrome (CRS), a potentially life-threatening inflammatory condition, but researchers said the side effect was temporary and manageable in most patients. Two people had severe CRS, but recovered after treatment with Actemra, an anti-inflammatory drug.

The study is being conducted at Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

The largest investor in Nanjing Legend Biotech is Genscript Biotech, a multinational provider of contract research services to pharmaceutical companies and others, according to Dr. Frank Fan, chief scientific officer at Nanjing Legend.

He said the company plans to enroll a total of 100 patients in the Chinese trial and to start a similar trial in the United States in early 2018.

"At ASCO I will hope to find collaborators in the U.S.," Fan told Reuters. "We are open for collaboration at different levels."

So far two companies have filed for U.S. approval of CAR-T drugs targeting a different protein called CD19. Kite Pharma Inc expects the Food and Drug Administration to decide by Nov. 29 whether to approve axicabtagene ciloleucel for advanced non-Hodgkin lymphoma, a cancer that starts in white blood cells.

The FDA is also reviewing Novartis AG's tisagenlecleucel-T for pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia.

(Reporting by Deena Beasley; Editing by Phil Berlowitz)

WASHINGTON As the United States battles a growing opioid abuse crisis, the Food and Drug Administration on Thursday asked Endo International Plc to withdraw from the market its long-lasting opioid painkiller, Opana ER, sending Endo's shares down more than 12 percent.

GENEVA A polio outbreak has been confirmed in an area of Syria partly held by Islamic State, the first re-emergence of the virus in Syria since 2014, the Global Polio Eradication Initiative and the World Health Organization said on Thursday.

Go here to see the original:
Chinese cell therapy effective in small multiple myeloma trial | Reuters - Reuters

Berkeley Stem Cell Center – Research UC Berkeley

By adminJune 9, 2017Stell Cell Research

The Berkeley Stem Cell Center supports research and teaching in stem cell biology, engineering, and medicine at UC Berkeley, Lawrence Berkeley National Laboratory, and Children's Hospital and Research Center at Oakland. Activities sponsored by the Center include seminars, roundtables, and an annual retreat. The Center's CIRM funded Shared Stem Cell Research Laboratories in Stanley Hall and LSA provide investigators with fully equipped stem cell tissue culture and flow cytometry facilities and outstanding technical expertise. Its CIRM Center of Excellence, located in the Li Ka-Shing Center for Biomedical and Health Sciences, provides additional state of the art laboratory space and core facilities for tissue culture and flow cytometry, as well as molecular and cellular and whole animal imaging. Through its CIRM training program, the Center annually awards stem cell research fellowships to 16 highly talented pre-doctoral, postdoctoral, and physician scientists in training. The Siebel Stem Cell Institute - UC Berkeley supports stem cell research collaborations between Berkeley Stem Cell Center and Stanford University investigators, and provides funding to bring notable visiting scholars to campus.

See the article here:
Berkeley Stem Cell Center - Research UC Berkeley

Scientists Starting Dangerous Embryonic Stem Cell Trials With Cells That Could Mutate in Patients – LifeNews.com

By adminJune 9, 2017Stell Cell Research

China will begin trialling the use of embryonic stem-cells (ES) to treat Parkinsons disease and macular degeneration, in a move that has met with criticism from international experts.

The trials, which come in the wake of new stem-cell regulations introduced in China in 2015, will test the efficacy of injecting ES-derived cells into damaged areas of the brain and eyes.

In one trial, ES-derived neuronal-precursor cells will be injected into the areas of the brain affected by Parkinsons disease in attempt to regenerate dopamine-producing tissue. In another trial, the ES-derived retinal cells will be injected into eyes of people with age related macular degeneration. It is believed that the retinal cells may be able to replace cells damaged as a result of epithelial tissue degeneration.

It will be a major new direction for China, Pei Xuetao, a stem-cell scientist at the Beijing Institute of Transfusion Medicine who is on the central-government committee that approved the trials, told Nature.

Keep up with the latest pro-life news and information on Twitter.

Other researchers who work on Parkinsons disease, however, worry that the trials might be misguided.

Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, who is also planning stem-cell trials for Parkinsons, is concerned that the Chinese trials use neural precursors and not ES-cell-derived cells that have fully committed to becoming dopamine-producing cells. Precursor cells can turn into other kinds of neurons, and could accumulate dangerous mutations during their many divisions, says Loring. Not knowing what the cells will become is troubling.

Lorenz Studer, a stem-cell biologist at the Memorial Sloan Kettering Cancer Center in New York City, says that support is not very strong for the use of precursor cells. I am somewhat surprised and concerned, as I have not seen any peer-reviewed preclinical data on this approach, he told Nature.

LifeNews Note: This appeared at Bioedge.org and is reprinted with permission.

More:
Scientists Starting Dangerous Embryonic Stem Cell Trials With Cells That Could Mutate in Patients - LifeNews.com

Using Stem Cells to Heal Broken Bones – Healthline

By adminJune 8, 2017Stem Cell Medical Center

A promising new method for regenerating bones using the body's own stem cells may possibly eliminate the need for bone grafts.

When a fracture will not heal, people are typically left with two options.

One is bone grafting, the other is surgery.

A new treatment that uses gene and stem cell therapies could promise success with a less-invasive procedure.

Researchers led by a team from Cedars-Sinai Medical Center in Los Angeles, tested the therapy on laboratory animals and found that it triggered bones to regrow their own tissue.

If it is found safe in humans, the process could replace bone grafting as the gold standard treatment.

We are just at the beginning of a revolution in orthopedics, Dan Gazit, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a statement.

The study was published in the journal Science Translational Medicine.

Bone grafts can result in gaps between fracture edges, and often require surgery to relocate bone from other places in the body to fill in the spaces.

Bone can come from the patient or a cadaver.

But healthy bone isnt always available, and surgeries can lead to other complications.