martes, 25 de noviembre de 2014

HAN Archive - 00373|Health Alert Network (HAN)

HAN Archive - 00373|Health Alert Network (HAN)



CDC. Centers for Disease Control and Prevention. CDC 24/7: Saving Lives. Protecting People.



Fatal Gastrointestinal Mucormycosis in an Infant Following Ingestion of Contaminated Dietary Supplement – Connecticut, 2014

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This is an official
CDC HEALTH ADVISORY



Distributed via the CDC Health Alert Network
November 25, 2014, 13:45 ET (1:45 PM ET)
CDCHAN-00373

Summary

The Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and Connecticut Departments of Public Health and Consumer Protection are investigating a fatal case of gastrointestinal (GI) mucormycosis caused by Rhizopus oryzae in a premature infant. The infant received ABC Dophilus® Powder, a dietary supplement product containing viable microbial ingredients purchased from Solgar, Inc., Leonia, New Jersey. The product claimed to have “probiotic” properties and is marketed for infants and children. Subsequent testing of the same lot of unopened Solgar ABC Dophilus® Powder revealed contamination with Rhizopus oryzae. The purpose of this HAN advisory is to provide awareness about this fatal case of GI mucormycosis following ingestion of a contaminated dietary supplement and to provide guidance to state health departments and health care providers. Please disseminate this information to healthcare workers in neonatal intensive care units, hospital pharmacies, pediatricians, and primary care providers, as well as to microbiology and pathology laboratories.

Background

Mucormycosis is a rare infection caused by mold in the order Mucorales, including Rhizopus spp. GI mucormycosis is a very rare manifestation of this disease and occurs when mucormycosis involves the GI tract causing signs and symptoms such as:
  • Abdominal pain
  • Abdominal distension
  • Nausea
  • Vomiting
These symptoms are thought to occur primarily when a susceptible person ingests the fungus, and they usually occur in immunocompromised individuals.
In October 2014, a hospital in Connecticut notified CDC and the Connecticut Department of Public Health of a fatal case of gastrointestinal mucormycosis in a preterm infant of 29 weeks’ gestation. The infant received lot 074 024 01R1 of ABC Dophilus® Powder for four days, beginning on day one of life. ABC Dophilus® Powder is a product intended to contain three bacteria, Bifidobacterium lactis, Streptococcus thermophilus, and Lactobacillus rhamnosus.The product was purchased from Solgar, Inc., Leonia, NJ, and is marketed specifically for infants and children. This product and other dietary supplements thought to have probiotic effects have been used in preterm infants on the basis of a recent Cochrane review supporting their use for prophylaxis against necrotizing enterocolitis (NEC), a possible complication in preterm infants. ABC Dophilus ® Powder is intended for use as a dietary supplement and, as such, is not regulated as a drug by the FDA.  FDA has not evaluated the safety of this product for any intended use and has not evaluated the veracity of any claims of probiotic or other health benefits.
This infant subsequently developed clinical signs and symptoms of NEC. Surgical exploration of the infant’s abdomen revealed complete GI ischemia from esophagus to rectum, a portion of necrotic bowel was resected. Following surgery, the infant developed multiple areas of vascular occlusion, a finding not associated with NEC. Shortly thereafter, the infant died.
Histopathologic results from the infant’s necrotic bowel showed angioinvasive fungal infection, consistent with mucormycosis. immunohistochemical staining of the tissue block performed locally and at CDC was positive when tested with a monoclonal antibody known to react with several mucormycete fungal agents. Sequencing of fungal DNA recovered from the tissue block at CDC identified the fungus as Rhizopus oryzae, a known cause of mucormycosis.
The hospital initiated an investigation into the infant’s death, including evaluation of the Solgar ABC Dophilus® Powder product. Local testing of unopened bottles of lot 074 024 01R1 Solgar ABC Dophilus® Powder revealed contamination with mold, confirmed to be Rhizopus oryzae at CDC. On November 14, 2014, Solgar Inc. issued a voluntary recall (http://www.fda.gov/Safety/Recalls/ucm423219.htm) of ABC Dophilus® Powder lots 074024-01R1, 074024-01, and 074024-02 (all with expiration dates of 7/31/15). This recall notice includes the instructions that “Consumers who have purchased Solgar ABC Dophilus® Powder are urged not to consume the product.” This product was distributed to 29 states, Puerto Rico, the United Kingdom, and Israel through pharmacies, retail stores, wholesalers, and online retailers.
Investigation into this fatal case of GI mucormycosis following ingestion of contaminated Solgar ABC Dophilus® Powder is ongoing. National case finding efforts are underway to identify additional cases of GI mucormycosis following ingestion of this contaminated dietary supplement.
Recommendations
  • Solgar ABC Dophilus® Powder should not be used, especially in infants who may be especially susceptible to infection.
  • In considering the use of any dietary supplement, clinicians should consider that the FDA does not regulate these products as drugs.
Clinical Care
  • Clinicians evaluating:
    • Preterm infants for necrotizing enterocolitis OR
    • Infants who have signs or symptoms of gastrointestinal mucormycosis such as abdominal pain, abdominal distension, nausea, or vomiting
Should review whether Solgar ABC Dophilus® Powder was used as part of the infants’ care.
  • If Solgar ABC Dophilus® Powder was consumed by the patient within the previous 30 days, clinicians should consider consultation with an infectious disease physician to assist in an assessment which may include the following:
    • Aggressive evaluation for a source of infection, including surgical exploration.
    • Empiric treatment with antifungals active against mucormycete infections.
Reporting
  • Clinicians and public health officials are asked to notify their state or local health departments if they learn of cases or deaths in the following categories that have occurred since November 1, 2013:
    • Confirmed or suspected cases of infants with gastrointestinal mucormycosis (diagnosed via culture or histopathology).
OR
    • Unexplained infant deaths within 30 days after ingesting Solgar ABC Dophilus® Powder.
For more information:
Please consult the CDC website for this investigation: http://www.cdc.gov/fungal/rhizopus-investigation.html

The Centers for Disease Control and Prevention (CDC) protects people's health and safety by preventing and controlling diseases and injuries; enhances health decisions by providing credible information on critical health issues; and promotes healthy living through strong partnerships with local, national and international organizations.

DEPARTMENT OF HEALTH AND HUMAN SERVICES

HAN Message Types

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  • Health Advisory: Provides important information for a specific incident or situation; may not require immediate action. Example: HAN00346
  • Health Update: Provides updated information regarding an incident or situation; unlikely to require immediate action. Example: HAN00342
  • Info Service: Provides general information that is not necessarily considered to be of an emergent nature. Example: HAN00345
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This message was distributed to state and local health officers, state and local epidemiologists, state and local laboratory directors, public information officers, HAN coordinators, and clinician organizations.
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Additional Resources

New Opportunity: Apply for the Performance Partnership Pilot

SAMHSA
New Opportunity: Apply to the Performance Partnership Pilots Program
Monday, December 1, 2014 | 3:30 p.m. Eastern Time
Today, five Federal agencies are coming together to offer communities support in overcoming the obstacles they face in achieving better outcomes for disconnected youth. For the next 100 days, States, tribes, and municipalities can apply to become a Performance Partnership Pilot (P3) program. These pilot communities will test innovative, cost-effective, and outcome-focused strategies for improving results for disconnected youth.
You're invited to register for an upcoming webinar on Monday, December 1, 2014, at 3:30 p.m. Eastern Time to learn more about P3.

About the P3 Program
The P3 program enables up to 10 pilot communities to blend funds that they already receive from different discretionary programs administered by the U.S. Departments of Education, Labor, and Health and Human Services; the Corporation for National and Community Service; and the Institute for Museum and Library Services. P3 allows communities the flexibility to overcome barriers and aligns program and reporting requirements so applicants can propose the most effective ways to use these dollars. In addition, pilot communities will receive start-up grants of up to $700,000.
Government and community partners already invest considerable attention and resources to meet the needs of America's disconnected youth. However, practitioners, youth advocates, and program administrators on the front lines of service delivery have told us that achieving powerful outcomes is still sometimes inhibited by obstacles. Those obstacles include difficulty coordinating across the multiple systems that serve youth. P3 responds directly to these challenges by offering more flexibility in exchange for better outcomes.
Questions? Contact disconnectedyouth@ed.gov.

Safety Communications > UPDATED Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication

Safety Communications > UPDATED Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication

An updated safety communication has been issued for Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy.
Today, the U.S. Food and Drug Administration is taking immediate steps to help reduce the risk of spreading unsuspected cancer in women being treated for uterine fibroids. In an updated safety communication, originally issued in April 2014, the FDA warns against using laparoscopic power morcellators in the removal of the uterus (hysterectomy) or fibroids (myomectomy) in the vast majority of women.

UPDATED Laparoscopic Uterine Power Morcellation in Hysterectomy and Myomectomy: FDA Safety Communication

The following information updates our April 17, 2014 communication.
Date Issued: Nov. 24, 2014
Audience:
  • Health Care Providers
  • Medical Professional Associations
  • Cancer Advocacy Organizations
  • Health Care Facilities/Hospitals
  • Women with Symptomatic Uterine Fibroids who are Considering Surgical Options
  • Manufacturers of Devices used for Minimally Invasive Surgeries
Medical Specialties: Pathology, Internal Medicine, Nursing, Obstetrics/Gynecology, Oncology, Obstetrics/Gynecological Surgery; General Surgery
Product: 
Laparoscopic power morcellators are medical devices used during different types of laparoscopic (minimally invasive) surgeries. These can include certain procedures to treat uterine fibroids, such as removing the uterus (hysterectomy) or removing the uterine fibroids (myomectomy). Morcellation refers to the division of tissue into smaller pieces or fragments and is often used during laparoscopic surgeries to facilitate the removal of tissue through small incision sites.
Purpose: 
When used for hysterectomy or myomectomy in women with uterine fibroids, laparoscopic power morcellation poses a risk of spreading unsuspected cancerous tissue, notably uterine sarcomas, beyond the uterus. The FDA is warning against using laparoscopic power morcellators in the majority of women undergoing hysterectomy or myomectomy for uterine fibroids. Health care providers and patients should carefully consider available alternative treatment options for the removal of symptomatic uterine fibroids.
Summary of Problem and Scope: 
Uterine fibroids are noncancerous growths that develop from the muscular tissue of the uterus. Most women will develop uterine fibroids (also called leiomyomas) at some point in their lives, although most cause no symptoms1. In some cases, however, fibroids can cause symptoms, including heavy or prolonged menstrual bleeding, pelvic pressure or pain, and/or frequent urination, requiring medical or surgical therapy.
Many women choose to undergo laparoscopic hysterectomy or myomectomy because these procedures are associated with benefits such as a shorter post-operative recovery time and a reduced risk of infection compared to abdominal hysterectomy and myomectomy2. Many of these laparoscopic procedures are performed using a power morcellator.
Based on an FDA analysis of currently available data, we estimate that approximately 1 in 350 women undergoing hysterectomy or myomectomy for the treatment of fibroids is found to have an unsuspected uterine sarcoma, a type of uterine cancer that includes leiomyosarcoma. At this time, there is no reliable method for predicting or testing whether a woman with fibroids may have a uterine sarcoma.
If laparoscopic power morcellation is performed in women with unsuspected uterine sarcoma, there is a risk that the procedure will spread the cancerous tissue within the abdomen and pelvis, significantly worsening the patient’s long-term survival. While the specific estimate of this risk may not be known with certainty, the FDA believes that the risk is higher than previously understood.
Because of this risk and the availability of alternative surgical options for most women, the FDA is warning against the use of laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids.
Limiting the patients for whom laparoscopic morcellators are indicated, the strong warning on the risk of spreading unsuspected cancer, and the recommendation that doctors share this information directly with their patients, are part of FDA guidance to manufacturers of morcellators. The guidance strongly urges these manufacturers to include this new information in their product labels.

Recommendations for Health Care Providers:
  • Be aware of the following new contraindications recommended by the FDA;
    1. Laparoscopic power morcellators are contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or post-menopausal, or are candidates for en bloc tissue removal, for example through the vagina or mini-laparotomy incision. (Note: These groups of women represent the majority of women with fibroids who undergo hysterectomy and myomectomy.)
    2. Laparoscopic power morcellators are contraindicated in gynecologic surgery in which the tissue to be morcellated is known or suspected to contain malignancy.
  • Be aware of the following new boxed warning recommended by the FDA:
    The FDA warns that uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer, and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.
  • Carefully consider all the available treatment options for women with uterine fibroids.
  • Thoroughly discuss the benefits and risks of all treatments with patients. Be certain to inform the small group of patients for whom laparoscopic power morcellation may be an acceptable therapeutic option that their fibroid(s) may contain unexpected cancerous tissue and that laparoscopic power morcellation may spread the cancer, significantly worsening their prognosis. This population might include some younger women who want to maintain their fertility or women not yet peri-menopausal who wish to keep their uterus after being informed of the risks.
Recommendations for Women:
  • Ask your health care provider to discuss all the options available to treat your condition. There are risks and benefits associated with all medical devices and procedures and you should be aware of them.
  • If your doctor recommends laparoscopic hysterectomy or myomectomy, ask him/her if power morcellation will be performed during your procedure, and to explain why he or she believes it is an appropriate treatment option for you.
  • If you have already undergone a hysterectomy or myomectomy for fibroids, tissue removed during the procedure is typically tested for the presence of cancer. If you were informed these tests were normal and you have no symptoms, routine follow-up with your physician is recommended. Patients with persistent or recurrent symptoms or questions should consult their health care provider.
  • A number of additional surgical treatment options are available for women with symptomatic uterine fibroids including traditional surgical hysterectomy (performed either vaginally or abdominally) and myomectomy, laparoscopic hysterectomy and myomectomy without morcellation, and laparotomy using a smaller incision (minilaparotomy). All treatments carry risk, and you should discuss them thoroughly with your health care provider.
FDA Actions:
The FDA has taken the following actions in light of scientific information that suggests that the use of laparoscopic power morcellators may contribute to the spread and upstaging of unsuspected uterine cancer in women undergoing hysterectomy and myomectomy for fibroids:
  • The FDA conducted a review of published and unpublished scientific literature, including patients operated on from 1980 to 2011 to estimate the prevalence of unsuspected uterine sarcoma and uterine leiomyosarcoma in patients undergoing hysterectomy or myomectomy for presumed benign fibroids (leiomyoma). This analysis led us to believe that the prevalence of unsuspected uterine sarcoma in patients undergoing hysterectomy or myomectomy for presumed benign leiomyoma is 1 in 352 and the prevalence of unsuspected uterine leiomyosarcoma is 1 in 498. Both of these estimates are higher than the clinical community previously understood.
  • Convened a meeting of the Obstetrics and Gynecological Medical Device Advisory Panel in July 2014. The panel discussed patient populations in which laparoscopic power morcellators should not be used, mentioning specifically patients with known or suspected malignancy. The panel also discussed mitigation strategies such as labeling, and suggested that a boxed warning related to the risk of disseminating unsuspected malignancy would be useful.
  • Issued an Immediately In Effect (IIE) guidance that asks manufacturers of new and existing laparoscopic power morcellators to include two contraindications and a boxed warning in their product labeling. This information warns against using laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy and recommends doctors share this information with their patients.
  • Published safety information related to these devices and alternative treatment options for the treatment of fibroids available on its website to help people better understand the risks of laparoscopic power morcellators.
In addition to the most recent contraindications and boxed warning, the FDA continues to consider other steps that may further reduce such risk—such as encouraging innovative ways to better detect uterine cancer and containment systems designed specifically for gynecological surgery.
The FDA will continue to review adverse event reports, peer-reviewed scientific literature, and information from patients, health care providers, gynecologic and surgical professional societies, and medical device manufacturers.
Reporting Problems to the FDA: 
Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices. If you suspect that a morcellator and/or specimen bag has malfunctioned or contributed to a serious injury or adverse outcome, the FDA encourages you to file a voluntary report through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
Health care professionals employed by facilities that are subject to the FDA's user facility reporting requirementsshould follow the reporting procedures established by their facilities.
Federal law requires hospitals to report some adverse events related to medical devices. Specifically, federal regulations require user facilities to report a suspected medical device-related death to both the FDA and the manufacturer. User facilities must also report a medical device-related serious injury to the manufacturer or to the FDA if the medical device manufacturer is unknown.
With regard to the spread of unsuspected cancer when using laparoscopic power morcellation for hysterectomy or myomectomy in women with symptomatic uterine fibroids, the FDA considers this to be reportable as a serious injury.
Other Resources:
References:
  1. NIH Fact Sheet on Uterine Fibroids. March 2013. Available athttp://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=50
  2. Nieboer TE, Johnson N, Lethaby A, et al. Surgical approach to hysterectomy for benign gynecological disease. Cochrane Database Syst Rev. 2009;(3):CD003677.
  3. Ibid.
Contact Information: 
If you have questions about this communication, please contact the Division of Industry and Consumer Education (DICE) at DICE@FDA.HHS.GOV, 800-638-2041 or 301-796-7100.

High-tech analysis of genetic data may yield new test for endometriosis

High-tech analysis of genetic data may yield new test for endometriosis

National Institutes of Health (NIH) - Turning Discovery Into Health

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Contact

Robert Bock
301-496-5133

High-tech analysis of genetic data may yield new test for endometriosis

NIH-funded study may offer alternative to surgical diagnosis
Using sophisticated computer-based technology to analyze genetic data obtained from uterine tissue, researchers have identified patterns of genetic activity that can be used to diagnose endometriosis, an often-painful condition that occurs when tissue that normally lines the inside of the uterus grows outside the uterus. The prototype diagnostic method, developed with funding from the National Institutes of Health, can not only distinguish endometriosis from other disorders of the uterus, but can also identify the severity of the disease.
The finding is the first step toward the eventual development of a test to diagnose endometriosis that wouldn’t require surgery. Currently, a surgical procedure known as laparoscopy is the only definitive way to diagnose and stage endometriosis that occurs on the pelvic lining and organs.
study by NIH researchers estimated that as many as 11 percent of women have endometriosis.
In their study, the researchers used a computer-based technology known as machine learning to analyze the gene activity of samples of tissue taken from the endometrium — the inner lining of the uterus. Machine learning allows computers to learn from an activity without being explicitly programmed. Biomedical researchers rely on the technology to analyze the interactions that take when information on large numbers of genes is translated into proteins, a process called gene expression. The method enabled the researchers to develop a highly accurate grouping system to distinguish samples that came from women with endometriosis from samples that came from women with other conditions affecting the uterus and pelvis, and samples that came from normal controls.
“Laparoscopy involves general anesthesia and making an incision in the abdomen,” said Louis DePaolo, Ph.D., chief of the Fertility/Infertility Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and a coauthor of the study. “These findings indicate that it may be possible to avoid the surgical procedure and diagnose endometriosis from a tissue sample obtained in the office setting without anesthesia.”
The study, appearing in the journal Endocrinology, was conducted by researchers at the University of California, San Francisco (UCSF) through the NIH Specialized Cooperative Centers Program in Reproduction and Infertility Research, funded by the NICHD. Additional support came from the University of California Office of the President.
In most cases, endometriosis results from retrograde menstruation, in which endometrial tissue flows backward, through the fallopian tubes and into the pelvic cavity, rather than out through the cervix, explained Linda Giudice, M.D., Ph.D., an obstetrician, gynecologist, and reproductive endocrinologist at UCSF and the lead author of the study. In women with endometriosis when the endometrial tissue enters the abdominal cavity it attaches to organs in the abdominal and pelvic cavities, such as the ovaries, the outside of the uterus, the intestines, or other organs or tissues. This tissue continues to follow the monthly menstrual cycle, and the resulting bleeding can cause inflammation, scarring, and pain. In the long term, endometriosis may lead to infertility.
The researchers used samples from the NIH/UCSF Human Endometrial Tissue and DNA Bank External Web Site Policy, established by Dr. Giudice. The samples in the bank came from women who were undergoing procedures involving the uterus or pelvis.
Dr. Giudice and her colleagues used DNA microarray technology to identify which genes were expressed (involved in making protein) in each woman’s endometrial tissue. They analyzed 148 samples: 77 from women with endometriosis, 37 from women without endometriosis but with other uterine/pelvic problems, and 34 from women without any uterine conditions (the control group).
Not only could the researchers distinguish between samples from endometriosis patients and those who did not have endometriosis, they could also tell the difference between samples from endometriosis patients and those from patients with other uterine disorders. Moreover, they could tell the difference between lesser and more advanced stages of endometriosis, and identify endometriosis at different points in the menstrual cycle.
“We’re looking ahead to potentially being able to do a test for endometriosis in the office, as opposed to general anesthesia in the operating room,” Dr. Giudice said. Such a procedure would likely involve inserting a tiny, thin plastic catheter through the cervix into the uterus to remove a sample of endometrial cells – a procedure that takes about 5-10 minutes, Dr. Giudice explained.
The NIH NICHD Reproductive Medicine Network has begun a multisite clinical trial that will test the method in a larger number of volunteers, Dr. De Paolo said.
In the endometrium of women with endometriosis, the researchers found distinct patterns of gene expression involving inflammation and in activating the immune system. The also observed specific patterns of gene expression involved in building new blood vessels. Women with uterine fibroids and other pelvic disorders also showed signs of immune activation, although the gene expression in these conditions differed from that in women with endometriosis.
For investigators seeking to further refine the method into a diagnostic test, the study, along with the genomic data the researchers identified, is available online at http://press.endocrine.org/doi/abs/10.1210/en.2014-1490?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed External Web Site Policy.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website athttp://www.nichd.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH...Turning Discovery Into Health®
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NIH scientists determine how environment contributes to several human diseases

NIH scientists determine how environment contributes to several human diseases

National Institutes of Health (NIH) - Turning Discovery Into Health



Institute/Center

Contact

Robin Arnette
919-541-5143


NIH scientists determine how environment contributes to several human diseases

Using a new imaging technique, National Institutes of Health researchers have found that the biological machinery that builds DNA can insert molecules into the DNA strand that are damaged as a result of environmental exposures. These damaged molecules trigger cell death that produces some human diseases, according to the researchers. The work, appearing online Nov. 17 in the journal Nature, provides a possible explanation for how one type of DNA damage may lead to cancer, diabetes, hypertension, cardiovascular and lung disease, and Alzheimer’s disease.
“Until this paper, no one had actually seen how the polymerase did it or understood the downstream implications.”
—Samuel Wilson, M.D.
Senior NIEHS researcher
Time-lapse crystallography was used by National Institute of Environmental Health Sciences (NIEHS) researchers to determine that DNA polymerase, the enzyme responsible for assembling the nucleotides or building blocks of DNA, incorporates nucleotides with a specific kind of damage into the DNA strand. Time-lapse crystallography is a technique that takes snapshots of biochemical reactions occurring in cells.
Samuel Wilson, M.D., senior NIEHS researcher on the team, explained that the damage is caused by oxidative stress, or the generation of free oxygen molecules, in response to environmental factors, such as ultraviolet exposure, diet, and chemical compounds in paints, plastics, and other consumer products. He said scientists suspected that the DNA polymerase was inserting nucleotides that were damaged by carrying an additional oxygen atom.
“When one of these oxidized nucleotides is placed into the DNA strand, it can’t pair with the opposing nucleotide as usual, which leaves a gap in the DNA,” Wilson said. “Until this paper, no one had actually seen how the polymerase did it or understood the downstream implications.”
DNA nucleotide damaged by oxidation
After the DNA polymerase (gray molecule in background) inserts a damaged nucleotide into DNA, the damaged nucleotide is unable to bond with its undamaged partner. As a result, the damaged nucleotide swings freely within the DNA, interfering with the repair function or causing double-strand breaks. These steps may ultimately lead to several human diseases. (Graphic courtesy of Bret Freudenthal)
Wilson and his colleagues saw the process in real time, by forming crystal complexes made of DNA, polymerase, and oxidized nucleotides, and capturing snapshots at different time points through time-lapse crystallography. The procedure not only uncovered the stages of nucleotide insertion, but indicated that the new DNA stopped the DNA repair machinery from sealing the gap. This fissure in the DNA prevented further DNA repair and replication, or caused an immediate double-strand break.
“The damaged nucleotide site is akin to a missing plank in a train track,” Wilson said. “When the engine hits it, the train jumps the track, and all of the box cars collide.”
Large numbers of these pileups and double-strand breaks are lethal to the cell, serving as a jumping off point for the development of disease. However, it can be a good thing if you are a researcher trying to destroy a cancer cell.
“One of the characteristics of cancer cells is that they tend to have more oxidative stress than normal cells,” said Bret Freudenthal, Ph.D., lead author of the paper and postdoctoral fellow in Wilson’s group. “Cancer cells address the issue by using an enzyme that removes oxidized nucleotides that otherwise would be inserted into the genome by DNA polymerases. Research performed by other groups determined if you inhibit this enzyme, you can preferentially kill cancer cells.”
Wilson and Freudenthal stressed that the quantities of oxidized nucleotides in the nucleotide pool are usually under tight control, but if they accumulate and start to outnumber undamaged nucleotides, the DNA polymerase adds more of them to the strand. Molecules that inhibit oxidation, known as antioxidants, reduce the level of oxidized nucleotides, and may help prevent some diseases.
NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH...Turning Discovery Into Health®

Reference

Freudenthal BD, Beard WA, Perera L, Shock DD, Kim T, Schlick T, Wilson SH. 2014. Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide. Nature; doi:10.1038/nature13886 [Online 17 November 2014].
Grant numbers:
Z01ES050158
Z01ES050161
ZICES043010
U19CA105010

Final Recommendation Statement: Vitamin D Deficiency: Screening - US Preventive Services Task Force

Final Recommendation Statement: Vitamin D Deficiency: Screening - US Preventive Services Task Force

U.S. Preventive Services Task Force banner



The U.S. Preventive Services Task Force released today a final recommendation statement on screening for vitamin D deficiency in adults. To view the recommendation and the evidence on which it is based, please go to http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/vitamin-d-deficiency-screening. The final recommendation statement can also be found in the November 25 online issue of Annals of Internal Medicine.

Close Friends May Be Key to Teens' Drinking: MedlinePlus

Close Friends May Be Key to Teens' Drinking: MedlinePlus

A service of the U.S. National Library of Medicine
From the National Institutes of HealthNational Institutes of Health






Close Friends May Be Key to Teens' Drinking

Larger peer group is less important when it comes to drinking or not, study says
By Robert Preidt
Friday, November 21, 2014
HealthDay news image
Related MedlinePlus Pages
FRIDAY, Nov. 21, 2014 (HealthDay News) -- Close friends have more influence on teens' alcohol use than their general peer group does, a new study says.
"We've known for a long time that friends and peers have an influence on individual alcohol use, but there are no common studies that distinguished between the broader peer group and the friend group's influence on those decisions," Jonathon Beckmeyer, an assistant professor at Indiana University's School of Public Health, said in a university news release.
Beckmeyer analyzed data gathered from 15-year-olds in a U.S. government study and found that the drinking habits of their close friends had a greater effect on their own alcohol consumption than did alcohol use among their peers.
For example, even if a teen believed that many other teens drank, they were less likely to have tried alcohol if they believed their friends didn't drink.
"We're spending our time changing perceptions of the broader peer group, but really what might be the more key determinant of teen alcohol use is what's going on in their own friend group," Beckmeyer said.
"Really working to encourage teens to make friendships with non-alcohol-using friends could be one of the more effective things parents can do to help," he suggested.
The study was presented Wednesday at the annual meeting of the American Public Health Association in New Orleans. Research from meetings is generally considered preliminary until it's been published in a peer-reviewed journal.
SOURCE: Indiana University, news release, Nov. 19, 2014
HealthDay
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