With 'batwing' mastopexy, more women can undergo nipple-sparing mastectomy

Peer-Reviewed Publication

WOLTERS KLUWER HEALTH

August 31, 2022 – Nipple-sparing techniques can provide better outcomes for women undergoing breast reconstruction after mastectomy – but due to complication risks, these approaches are often not offered to women with sagging or larger breasts. For this group of patients, a 'batwing' incision may provide a safer option to nipple-sparing mastectomy (NSM), reports a study in the September issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). Plastic and Reconstructive Surgery® is published in the Lippincott portfolio by Wolters Kluwer

"Our findings show that a simultaneous batwing mastopexy can be safely performed at the time of immediate breast reconstruction, while providing comparable complication rates and improving the aesthetic outcome," comments ASPS Member Surgeon Hahns Y. Kim, MD, of Loma Linda University Medical Center.

Batwing mastopexy offers safe approach to NSM in women with ptosis or larger breasts

Nipple-sparing procedures are an increasingly popular alternative for women undergoing mastectomy. In these techniques, the surgeon preserves the nipple and surrounding tissues (nipple-areola complex, or NAC) for use in immediate breast reconstruction using implants. Preserving the NAC allows for a more natural-looking reconstruction, leading to higher patient satisfaction.

However, NSM is generally not offered to women with sagging (ptosis) of the breasts or larger breasts, reflecting concerns about suboptimal aesthetic outcomes and increased risk of complications. The batwing incision – so called because it consists of two semicircular incisions above the nipple, connected by angled "wings" on either side of the NAC – enables the surgeon to perform breast lift (mastopexy) at the same time as mastectomy.

Dr. Kim and colleagues report their experience with batwing mastopexy for NSM in 80 women. About half of patients were undergoing preventive mastectomy due to high genetic risk of breast cancer. Outcomes were compared to those of 244 patients undergoing standard implant-based reconstruction, without preserving the NAC. Women selected for batwing mastopexy had larger breasts and a greater degree of ptosis.

Study participants

An average of 16 months after mastectomy and immediate reconstruction, the two groups of women had similar outcomes. At least one complication occurred in 23.8% of operated breasts in the batwing mastopexy group and 27.5% of the standard reconstruction group. Some minor complications, including hematoma (blood collections) and seroma (fluid collections), were less frequent in the batwing mastopexy group.

Necrosis (tissue death) of the skin or nipple – a more serious complication – was also less frequent in the batwing mastopexy group: 6.3% versus 11.5%. The rate of revision surgery (including fat grafting to improve the aesthetic results) was lower after batwing mastopexy (23.7% versus 30.3%). Other factors such as obesity and smoking were risk factors for skin/nipple necrosis or major infections, but batwing mastopexy was not.

New evidence can improve patient outcomes

The study shows that "complication rates in patients undergoing a simultaneous batwing mastopexy were comparable to those undergoing standard immediate implant-based reconstruction," the researchers write. Although the batwing technique is not new, the study provides new evidence that it may provide good aesthetic outcomes with no increase in complications in women with larger breasts or ptosis.

 

That's especially important, as it may allow surgeons to increase the number of patients who are offered NSM for breast cancer treatment or prevention. "A simultaneous batwing mastopexy may serve as an aesthetic enhancement for breast cancer patients undergoing immediate reconstruction," Dr. Kim and coauthors conclude. They emphasize the need for further studies to obtain higher-level evidence to help select patients who may benefit from this procedure.

Click here to read “The Batwing Mastopexy in Immediate Implant-Based Breast Reconstruction: An Aesthetic Enhancement for Patients with Cancer“

DOI: 10.1097/PRS.0000000000009380

###

About Plastic and Reconstructive Surgery

For over 75 years, Plastic and Reconstructive Surgery® (http://www.prsjournal.com/) has been the one consistently excellent reference for every specialist who uses plastic surgery techniques or works in conjunction with a plastic surgeon. The official journal of the American Society of Plastic Surgeons, Plastic and Reconstructive Surgery® brings subscribers up-to-the-minute reports on the latest techniques and follow-up for all areas of plastic and reconstructive surgery, including breast reconstruction, experimental studies, maxillofacial reconstruction, hand and microsurgery, burn repair and cosmetic surgery, as well as news on medico-legal issues.

About ASPS

The American Society of Plastic Surgeons is the largest organization of board-certified plastic surgeons in the world. Representing more than 7,000 physician members, the society is recognized as a leading authority and information source on cosmetic and reconstructive plastic surgery. ASPS comprises more than 94 percent of all board-certified plastic surgeons in the United States. Founded in 1931, the society represents physicians certified by The American Board of Plastic Surgery or The Royal College of Physicians and Surgeons of Canada.

About Wolters Kluwer

Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the clinicians, nurses, accountants, lawyers, and tax, finance, audit, risk, compliance, and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with advanced technology and services.

Wolters Kluwer reported 2021 annual revenues of €4.8 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 19,800 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students in effective decision-making and outcomes across healthcare. We support clinical effectiveness, learning and research, clinical surveillance and compliance, as well as data solutions. For more information about our solutions, visit https://www.wolterskluwer.com/en/health and follow us on LinkedIn and Twitter @WKHealth.

For more information, visit www.wolterskluwer.com, follow us on Twitter, Facebook, LinkedIn, and YouTube.

---

JOURNAL

Plastic & Reconstructive Surgery

Disclaimer: AAAS and EurekAlert! are n

Canada Ranks 8th for Safest Countries for Women to Travel in Solo: Study

Sharon Miki Chan - Monday


a woman wearing an orange hat looks at lake and mountains© Pexels


We already know that Canada is a beautiful place to live, but it looks like it’s also one of the safer places for women to travel solo in — according to a new travel study.

Luggage storage company Bounce conducted a Women’s Solo Travel Safety study, which analyzed more than 30 countries globally based on factors including:
The percentage of women who have experienced violence.
The rate of female homicide victims per 100,000 victims
Safety index scores
The percentage of women who feel safe walking alone at night
Attitudes toward violence against women
Laws on domestic violence
The global gender gap index score
Overall safety score out of 10

On this list, Canada ranked eighth. Interestingly, one factor that contributed to this land’s rank, according to the study’s report, was that “the number of women who have suffered violence from a partner is a good indicator of the attitudes toward violence against women in a country, and the nation with the lowest rate is Canada.”

You may also like: The world’s coolest street in 2022 is located in Canada.
What is the safest country for women to travel solo in?

The Republic of Ireland topped the list as the safest country for women to travel solo, with the report noting that Ireland ranked “amongst the top-scoring nations for almost all of the eight factors analyzed” and that “the Emerald Isle scores particularly highly for the laws it has in place to protect women from violence, as well as when it comes to local attitudes toward violence against women.”

By way of comparison, Canada scored 6.67 out of 10 for its overall safety for women travelling solo, compared to 7.88 out of 10 for top-ranking Ireland or 2.25 out of 10 for last-ranking Columbia.

Austria, Norway, Slovenia and Switzerland rounded out the remaining countries in the top five.

See also: Dreaming of travelling to Europe solo? These 5 tips may help.

N.S. mass shooting probe told cultural shift needed to address gender-based violence

Wednesday

HALIFAX — A broad cultural shift is needed to seriously address gender-based and domestic violence in Canada, a panel of experts on Wednesday told the inquiry into the 2020 mass shootings in Nova Scotia.


During a wide-ranging roundtable discussion, the inquiry — called the Mass Casualty Commission — heard that the situation won’t change unless more funding, education, support and political will is applied to the societal problem. The inquiry is investigating how a gunman with previous domestic assault accusations drove a replica police car and murdered 22 people in Nova Scotia in April 2020.

Katreena Scott, a professor and clinical psychologist at Western University, said men who perpetrate violence need more support and services. “Very often we don’t know and we don’t see and we don’t recognize risk factors and warning signs of abuse perpetration,” Scott said.

She said that in Ontario, research has shown that a majority of perpetrators of femicides exhibited risk factors that were missed by authorities, including obsessive behaviour and violent histories with former partners. Scott said that people who witness gender-based violence or who suspect someone they know may be a victim often don't know how to help or where to get help.

“We often then lean away and guard the impact of abusive behaviours or at worst we blame the victim for their own victimization,” she said. “What we do is we empower perpetrators to continue to behave abusively.”

Scott noted that around 20 per cent of abusers are most likely to repeat their violent behaviour once they are in the justice system, which then fails to address the problem. Intervention with high-risk men needs to be more intense, and they need to be monitored closely once they enter the system, she said.

Scott said funding is needed to grow a “suite of service options” that is flexible to meet the needs of men and maintain the core goal of keeping women and children safe. “Men do access services; they will reach out when offered the opportunity. Change is possible — we should expect change and we need to act on it,” she said.

The Nova Scotia shooting rampage that began on April 18, 2020, was preceded by a domestic assault by gunman Gabriel Wortman against his spouse, Lisa Banfield. The inquiry has gathered evidence indicating he used coercive tactics against her throughout their 19-year relationship, as well as against other women.

“I think we have very few tools in the criminal justice system or outside … to deal with men like the perpetrator in this mass casualty,” said Sue Bookchin, of the feminist Be the Peace Institute. “He was not somebody who would have reached out for help.”

To prevent tragedies like the Nova Scotia shootings, children should be taught in schools about gender-based violence and about how to better handle their emotions and build healthy relationships.

“If we did it this way in schools, we could shift the perceptions of an entire generation,” said Bookchin.

Kristina Fifield, of the Halifax-based Avalon Sexual Assault Centre, said more education and accountability needs to occur in workplaces, while she said those in power need to put a higher priority on addressing gender-based violence.

Fifield said government funding needs to stop being “reactionary” and instead be tailored to specific needs. “The one-size-fits-all approach does not work for perpetrators of violence and it does not work for victims and survivors."

This report by The Canadian Press was first published Aug. 31, 2022.

Keith Doucette, The Canadian Press

Nova Scotia to require the collection of race-based data from police stops

Yesterday 

HALIFAX — Nova Scotia’s Justice Department is committing to the collection of race-based data by police, in an effort to determine if Black, Indigenous and other racialized communities are disproportionately targeted by law enforcement.



The department said Thursday it is accepting all the recommendations by a committee established to review ways of gathering race-based information from police. In a news release, Justice Minister Brad Johns said there is "no place for racism in our justice system."

"It must be addressed at every level," Johns said. "These recommendations will guide the development of a data-collection model for police stops that will help ensure police practices and interactions are free from discrimination."

The provincial government said the data is being collected to determine whether some racial groups are being stopped and questioned more often than others. Gathering race-based data, the province said, can help police improve their interactions with African Nova Scotians and Indigenous Peoples, in particular.

The committee was struck as a result of a provincially commissioned study of random police stops — known as street checks — by criminologist Scott Wortley in March 2019. Wortley’s review found that African Nova Scotians were about six times more likely to be the subjects of random police stops than their representation in the population would predict.

He condemned the practice by the Halifax regional police and by the local RCMP, saying it targeted young Black men and created a "disproportionate and negative'' impact on African Nova Scotian communities.

Since 2019, police in Nova Scotia have not been allowed to conduct street checks.

The committee that recommended the new data-collection policy included representatives from the African Nova Scotian Decade for People of African Descent Coalition, Halifax Regional Police, the Nova Scotia Chiefs of Police Association, Cape Breton Regional Police, the Nova Scotia Human Rights Commission and the provincial Department of Justice, among others.

Vanessa Fells, director of operations at the African Nova Scotian Decade for People of African Descent Coalition, said in a telephone interview the commitment is "the beginning of something."

However, she said she hoped the data will be released to the communities most affected by street checks and that the new policy will lead to changes in how police behave.

"How they will be transparent and release the data to this community is a very important step," Fells said.

"If there are issues like racial profiling, then this could help us identify those, and we can identify where it is happening."

"It should show up in the data. Why are you (a police officer) stopping this person? Are you (police officers) doing this for legal reasons, or are you just doing it just because you saw this person walking in a neighbourhood you didn't think they should be in?" she said.

The committee defined a "police stop" as a situation during which an officer stops a person — whether the person is on foot or in a vehicle — when the officer believes there is a reasonable suspicion the person has recently engaged in, or will engage in, a crime, or has information relevant to an investigation or that may help prevent crime.

Race-based data collected in these instances is described by the committee as "a mechanism to monitor the equitable delivery of policing services."

The committee says police stops are not considered situations during which police interact with the public at community meetings or when citizens request police assistance. Traffic checkpoints or situations when police are canvassing an area during an investigation are also not considered police stops.

The government said its next steps in the process include reviewing current data-collection systems used by police agencies and working with communities and police to come up with a way to gather race-based data.

This report by The Canadian Press was first published Sept. 1, 2022.

Michael Tutton, The Canadian Press

Ethnicity, poverty, low community involvement linked to lasting loneliness

Long-term isolation may lead to depression, declines in physical function, says UCSF-Northwestern study

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Most people are at risk for periodic loneliness, but for midlife and older adults who identify as Hispanic/Latinx, or who live in poverty, loneliness may be less likely to resolve over time. 

In a study in which 641 participants, whose average age was 63, were interviewed by phone over the course of about 18 months during the pandemic, researchers at UC San Francisco and Northwestern University found that 16% suffered from persistent loneliness. An additional 22% were initially lonely but adapted over time, the researchers reported in their study publishing in the Journal of the American Geriatrics Society earlier this month.

When the researchers looked at those participants whose feelings of loneliness dissipated as the pandemic progressed, they found 53% of white participants fit in this category, versus 18% of Hispanic/Latinx participants. Similarly, those living above poverty level were more likely to experience decreasing loneliness compared with those living in poverty: 71% and 29%, respectively. 

“Transient loneliness is common throughout the lifespan and while distressing in the short-term, it can often motivate individuals to reconnect with social relationships or the community,” noted first author Ashwin A. Kotwal, MD, assistant professor of medicine in the UCSF Division of Geriatrics. 

This motivation to reconnect with social relationships or to get involved in local activities may be one factor driving the transition from loneliness to decreasing loneliness, according to the researchers. Just 26% of participants who had overcome their earlier loneliness were socially isolated, versus 40% for those who remained lonely. 

The researchers used data from the COVID-19 & Chronic Conditions study, which had enrolled participants from five research projects in Chicago. Participants had completed six interviews at three-month intervals. They had at least one chronic condition, such as high cholesterol, high blood pressure, diabetes, stroke or cancer. Approximately half were white, 30% were Black and 20% were Hispanic/Latinx, and 61% were female. In addition to the participants who were persistently lonely or formerly lonely, 29% said they experienced occasional loneliness and 33% reported that they were never lonely. 

Social Distancing May Hit Hispanic/Latinx Households Harder 

In explaining why those identifying as Hispanic/Latinx were more likely to suffer from prolonged loneliness, the authors acknowledged that the heterogeneity of this population limits any generalizations. However, “culturally important familism” had been disrupted by social distancing during the pandemic, which meant intergenerational households accustomed to being together were segregated. Restrictions in community events and religious services may also have contributed to prolonged loneliness.

For those living in poverty, connecting virtually to friends and family during the pandemic, as well as obtaining quality masks, antigen tests and air purifiers, may have been prohibitive. They may also have been “disproportionately impacted by reduced access to transportation and closure of community-based activities,” the authors stated.

While the most virulent phase of the pandemic may be over, persistent loneliness continues to be a risk for some people, said Kotwal. 

“Individuals already experiencing socially or medically disrupting circumstances, such as chronic illness, widowhood, late life disability or mental health concerns, may experience greater barriers to coping with loneliness,” he said, adding that prolonged loneliness can lead to psychological distress and depression, and in the long-term functional decline, poor cardiovascular health and even death. 

 “Several promising interventions exist to address loneliness. These include peer support interventions, friendship lines, technology classes and intergenerational volunteers. These programs should be maintained or expanded,” he said. 

Authors: Senior author is Rachel M. O’Conor, PhD, MPH, of the Center for Applied Health Research on Aging at Feinberg School of Medicine at Northwestern University. Co-authors are Stephanie Batio, MS, Michael S. Wolf, PhD, MPH, and Julia Yoshino Benavente, MPH, of Northwestern University; Kenneth E. Covinsky, MD, MPH, and Carla M.  Perissinotto, MD, MHS, of UCSF. 

Funding: This research was supported by a grant from the National Institute on Aging (R01AG030611-S1) and Claude D. Pepper Older American Independence Center Coordinating Center Multi Center Collaborative grant (U24AG059693; P30AG044281; P30AG059988). Dr. Ashwin Kotwal’s effort on this project was supported by grants from the National Institute on Aging (K23AG065438; R03AG064323). Dr. O’Conor is supported by a training grant from the National Institute on Aging (K01AG070107).

Disclosures: Please refer to the paper. 

 

About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is ranked among the top 10 hospitals nationwide, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland, Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit https://www.ucsfhealth.org/. Follow UCSF Health on Facebook or on Twitter

###

Follow UCSF
ucsf.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf

---

JOURNAL

Journal of the American Geriatrics Society

DOI

10.1111/jgs.18010 

ARTICLE TITLE

Persistent loneliness due to COVID-19 over 18 months of the pandemic: A prospective cohort study

ARTICLE PUBLICATION DATE

25-Aug-2022

Manitoba says no statutory Orange Shirt holiday this year as talks continue

WINNIPEG — The Manitoba government is still planning to make the National Day for Truth and Reconciliation an official statutory holiday but says it's too late for the change to take effect this year.

© Provided by The Canadian Press

"It would be very disrespectful of everybody to introduce something at this point," Labour Minister Reg Helwer said Wednesday.

"We did have legislation we were working on, and went through consultation with labour and business — and continuing consultation with First Nations and other groups — and that pointed out to me that we need much more advice from many people on how this should run."

The day — also known as Orange Shirt Day — was established in honour of the experience of Phyllis Webstad, whose gift of clothing from her grandmother was taken away on Webstad's first day at a residential school.

The federal government recently made the day, which falls on Sept. 30, a statutory holiday for its workers and federally regulated workplaces. The Northwest Territories government followed suit with an announcement in July.

Manitoba Premier Heather Stefanson said earlier in the summer that her Progressive Conservative government might follow in time for this year. But with less than a month to go, provincially regulated businesses have not been told they must give staff the day off.

Helwer said consultations with Indigenous groups on how to mark the day are still ongoing. He also said businesses would need more advance notice than 30 days.

"It would be very uncomfortable for business to spring that on them."

The Winnipeg Chamber of Commerce is supporting the idea of a statutory holiday. Some 70 per cent of members who participated in a recent survey favoured the change.

The Opposition New Democrats pushed for a bill to enact the statutory holiday months ago.

Chamber president Loren Remillard said he understands the province needs more time to ensure the holiday is not just a day off work but an opportunity to reflect on reconciliation.

"No one wants to see this holiday just be a day off with no learning that comes as a result," Remillard said.

"It's not our place to say how to best recognize truth and reconciliation. It's a partnership, but that must be something that is informed and driven by Indigenous voices and leadership."

This report by The Canadian Press was first published Aug. 31, 2022.

Steve Lambert, The Canadian Press

‘YES Oklahoma’ project aims to improve American Indian representation in cancer research

Grant and Award Announcement

UNIVERSITY OF OKLAHOMA

 

IMAGE: THE PROJECT, “NATIVE AMERICAN YOUTHS ENJOY SCIENCE - YES OKLAHOMA,” WILL DEVELOP A PROGRAM TO IMPROVE THE REPRESENTATION OF AMERICAN INDIAN STUDENTS IN BIOMEDICAL AND CANCER RESEARCH. view more 

CREDIT: PROVIDED BY THE UNIVERSITY OF OKLAHOMA

The National Cancer Institute of the National Institutes of Health has awarded the University of Oklahoma an expected $2 million over five years to develop a program to improve the representation of American Indian students in biomedical and cancer research. 

“American Indian professionals are underrepresented in scientific fields, particularly those in biomedical research, and near-absent in cancer research,” said the project’s director, Cecil M. Lewis Jr., Ph.D. “This discrepancy impacts community health; there is a substantial health disparity in cancer impacting American Indians, particularly cancer types where regular screening, early detection and access to health care have a large impact. A more robust health care workforce and infrastructure, one with strong ties to communities, should reduce these rates.”

Lewis is a professor of anthropology in the Dodge Family College of Arts and Sciences at OU. The project’s co-directors are Cara Monroe, Ph.D., research scientist for OU’s Center for the Ethics of Indigenous Genomics Research; Rajagopal Ramesh, Ph.D., professor of pathology in the OU College of Medicine, and associate director for education and training at the OU Health Stephenson Cancer Center; and Kent Smith, Ph.D., (Comanche/Chickasaw), professor of anatomy and cell biology at the Oklahoma State University Center for Health Sciences and associate dean for the Office of American Indians in Medicine and Science that serves both the OSU-CHS Tulsa campus and the OSU College of Osteopathic Medicine at the Cherokee Nation.

Lewis said the program will provide a research training strategy in which American Indian high school students will engage in hands-on scientific research, with a strong emphasis in cancer research. Two different cohort groups, one of students and one of Oklahoma teachers, will support community building and sustainability of the student training pipeline.

YES Oklahoma Scholars, eligible high school juniors and seniors, will have the opportunity to participate in an intensive summer research experience and earn college credit. YES Oklahoma Teachers, middle and high school teachers from partner schools across the state, will participate in a summer training event that includes curriculum development, as well as salary and compensation benefits. Students enrolled in these teachers’ classes, a third beneficiary group called YES Oklahoma Trainees, also benefit from the teachers’ participation by taking part in the curriculum.

Lewis said the grant also provides support for graduate student training and mentorship at OU and the OSU Center for Health Sciences.

“Together, the directors, scholars, teachers, trainees and graduate students, along with associated communities and tribes, will form the YES Oklahoma Outreach Team, providing education in cancer prevention focused on families and communities,” Lewis said. “The YES Oklahoma program will directly impact over 76 scholars and teachers annually, and the combined outreach events will indirectly impact thousands of underserved students, teachers, families and community members.”

This project is a partnership between the University of Oklahoma’s Norman campus, OU Health Stephenson Cancer Center on the OU Health Sciences Center campus, and the OSU Center for Health Sciences, among other centers and programs. The grant proposal received letters of support by the tribal president of the Wichita and Affiliated Tribes, the Kiowa Tribe Higher Education Program, and the chairman of the Comanche Nation, as well as superintendents representing partnering schools in Oklahoma and more than 20 Oklahoma faculty mentors in biomedical related sciences. The YES Oklahoma proposal received a perfect review score, referred to as an “Impact 10,” by the NIH review panel, a rare triumph for grant proposals and strong demonstration of the potential impact of partnership between Oklahoma institutes and tribal partners.

 

###

About the Project
The project, “Native American Youths Enjoy Science - YES Oklahoma,” is funded by the National Cancer Institute of the NIH, grant no. 1R25CA274172-01

About the University of Oklahoma Office of the Vice President for Research and Partnerships 

The University of Oklahoma is a leading research university classified by the Carnegie Foundation in the highest tier of research universities in the nation. Faculty, staff and students at OU are tackling global challenges and accelerating the delivery of practical solutions that impact society in direct and tangible ways through research and creative activities. OU researchers expand foundational knowledge while moving beyond traditional academic boundaries, collaborating across disciplines and globally with other research institutions as well as decision makers and practitioners from industry, government and civil society to create and apply solutions for a better world. Find out more at ou.edu/research.

About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. OU serves the educational, cultural, economic and health care needs of the state, region and nation. For more information visit www.ou.edu.

About Oklahoma State University Center for Health Sciences

Oklahoma State University Center for Health Sciences is a nationally recognized academic health center focused on teaching, research and patient care. Learn more at medicine.okstate.edu/

Drug effects of ketamine in mice can depend on the sex of the human experimenter

University of Maryland School of Medicine researchers demonstrated that a stress response in the brain is essential for ketamine’s antidepressant response in mice suggesting new ways to improve antidepressant therapy for patients who do not respond to it

Peer-Reviewed Publication

UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE

 

IMAGE: TODD GOULD, MD view more 

CREDIT: UMSOM

Many researchers who work with mice can tell you that mice behave differently depending on who is handling them. Anecdotal reports and some existing scientific reports indicate that mice tend to be more fearful and uptight around men, and relaxed and comfortable around women. Whether this behavior actually affects research results though, remains a sort of the elephant in the room that not many people seem to want to address.

Now, researchers at the University of Maryland School of Medicine (UMSOM) have shown that mice respond more to the antidepressant effects of the drug ketamine when administered by men and not by women. The group demonstrated that the response of mice detected in a specific region of their brain from handling by a man is essential for ketamine’s effect to work. Then, the researchers identified the mechanism behind this response.

The researchers say that while the influence of the sex of the scientist administering ketamine is not directly relevant to the human response to ketamine, the brain mechanism underlying their findings could help determine why some people do not respond to ketamine anti-depressant therapy and suggest ways to potentially make this therapy work better for those patients who do not respond well.

The findings were published on August 30 in Nature Neuroscience.

“Our findings in mice suggests that activating a specific stress circuit in the brain may be a way to improve ketamine treatment. Our thought is that you may be able to provide a more robust antidepressant effect if you combine the ketamine with activation of this brain region, either a drug that spurs this process in the brain or even some sort of specific stressor,” said Todd Gould, MD, Professor of Psychiatry at UMSOM.

Dr. Gould’s team anecdotally noticed that ketamine’s antidepressant-like effects only seemed to work consistently when male researchers administered the treatment to mice. The team reached out to other labs studying mouse responses to ketamine, who reported the same issues, but no one had yet systematically documented the phenomena and investigated the cause. At the time, most of Dr. Gould’s team was women and so figuring out why the experiments did not work when women performed them was essential to the team getting workable data, so they could move forward with project.

To look into this, they began by observing mouse preference for being around T-shirts or cotton swabs rubbed on the wrists, elbow, or behind the ear that came from men versus women. The mice preferred spending more time around T-shirts and cotton swabs that came from women rather than men. When the researchers used a chemical to block the smell of the mice, they no longer preferred women’s T-shirts or cotton swabs over men’s.

“Compared to humans, mouse sense of smell and their sensitivity to pheromones (airborne hormones) are more keenly developed, so it’s not surprising that they respond differently to many smells, including those of men compared to women,” said Dr. Gould.

Next, they confirmed the original anecdotal findings with a systematic experiment using many researchers to verify that mice responded to ketamine when administered men, but not by women. Then, the researchers wanted to understand the mechanism behind why the mice behave this way. The researchers investigated several factors potentially involved in mediating ketamine’s response in mice, but ultimately settled on one: corticotropin-releasing factor (CRF). CRF is located region of the brain, known as the hippocampus, responsible for learning and memory that had previously been associated with depression. When the researchers had women administer the ketamine along with an injection of CRF, the mice finally responded to ketamine as if they were being treated with an antidepressant.

“We think that some people may have higher or lower levels of CRF, and we believe that people do not respond well to ketamine antidepressant therapy might respond if we could administer the treatment with some CRF-related chemical that could induce ketamine’s effects,” said Polymnia Georgiou, PhD, a former postdoctoral fellow in Dr. Gould’s laboratory, who led the project. “Alternatively, we typically see the antidepressant effects of ketamine lasting 1-3 days, but with CRF administration, it is possible that we may be able to extend the effects to last longer with CRF.”

Mark T. Gladwin, MD, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean at UMSOM, said, “These are exciting new findings that underscore the importance of basic research to lay the foundation for future clinical innovations. Our investigators are leaders in the study of new approaches for the treatment for depression, such as ketamine. They also found an unexpected interaction between the sex of the mice studied and the sex of the scientist administering the drugs, highlighting the importance of evaluating unexpected effects of our experimental systems and approaches.”

This work was supported by National Institutes of Health’s National Institute on Mental Health (NIMH) (grants MH107615, MH086828, MH093897), the Veterans Administration (1I01BX004062), and the NIMH and National Institute of Aging Intramural Research Programs.

Author Carlos Zarate, MD, of the NIMH, is a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation. Authors Panos Zanos, PhD, former Assistant Professor of Psychiatry at UMSOM; Jaclyn Highland, PhD, former graduate student at University of Maryland; Ruin Moaddel, PhD, of the National Institute of Aging, Dr. Zarate, and Dr. Gould are co-inventors in patents and patent applications related to the pharmacology and use of (2R,6R)-HNK in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. Dr. Moaddel and Dr. Zarate have assigned their patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. Dr. Zanos, Dr. Highland, and Dr. Gould have assigned their patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that may be received by the University of Maryland, Baltimore. Dr. Gould has received research funding from Allergan and Roche Pharmaceuticals and has served as a consultant for FSV7 LLC, during the preceding three years.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

---

JOURNAL

Nature Neuroscience

DOI

10.1038/s41593-022-01146-x 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Experimenters’ sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor

ARTICLE PUBLICATION DATE

30-Aug-2022

COI STATEMENT

Author Carlos Zarate, MD, of the NIMH, is a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation. Authors Panos Zanos, PhD, former Assistant Professor of Psychiatry at UMSOM; Jaclyn Highland, PhD, former graduate student at University of Maryland; Ruin Moaddel, PhD, of the National Institute of Aging, Dr. Zarate, and Dr. Gould are co-inventors in patents and patent applications related to the pharmacology and use of (2R,6R)-HNK in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. Dr. Moaddel and Dr. Zarate have assigned their patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. Dr. Zanos, Dr. Highland, and Dr. Gould have assigned their patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that may be received by the University of Maryland, Baltimore. Dr. Gould has received research funding from Allergan and Roche Pharmaceuticals and has served as a consultant for FSV7 LLC, during the preceding three years.

Harnessing the power of saffron color for food and future therapeutics

Peer-Reviewed Publication

KING ABDULLAH UNIVERSITY OF SCIENCE & TECHNOLOGY (KAUST)

 

IMAGE: A KAUST TEAM HAS DEVISED A METHOD TO PRODUCE SAFFRON'S ACTIVE INGREDIENT FROM THE FRUIT OF AN ORNAMENTAL PLANT POPULAR IN CHINA, GARDENIA JASMINOIDES, SHOWN HERE ON THE LEFT. ON THE RIGHT IS SAFFRON, THE WORLD'S MOST EXPENSIVE SPICE. view more 

CREDIT: © 2022 KAUST.

Saffron is the world’s most expensive spice. Usually obtained from the stigma of Crocus sativa flowers, it takes 150,000–200,000 flowers to produce one kilogram of saffron. Now, KAUST researchers have found a way to use a common garden plant to produce saffron’s active ingredient, a compound with important therapeutic and food industry applications.

The color of saffron comes from crocins: water-soluble pigments derived from carotenoids by a process that is catalyzed by enzymes known as carotenoid cleavage dioxygenases (CCDs). Crocins also occur, albeit in much lower amounts, in the fruits of Gardenia jasminoides, an ornamental plant used in traditional Chinese medicine.

Crocins have high therapeutic potential, including their role in protecting neural cells from degradation, as well as their antidepressant, sedative and antioxidant properties. They also have an important role as natural food colorants.

Harvesting and processing hand-picked stigmas of saffron is very labor intensive. Moreover, saffron is only grown in limited areas of the Mediterranean and Asia. So, new biotechnological approaches to produce these compounds in large amounts are in great demand.

KAUST researchers identified a highly efficient carotenoid cleavage dioxygenase enzyme from Gardenia jasminoides that produces the crocin precursor crocetin dialdehyde. They have now established a system for investigating CCD enzymatic activity in plants and developed a multigene engineering approach for sustainable biotechnological production of crocins in plant tissues.

“The enzyme we have identified and the multigene engineering strategy could be used to establish a sustainable plant cell factory for crocin production in tissue culture of different plant species,” says lead author of the study Xiongie Zheng.

“Our biotechnological approach can also be used on crops, such as rice, to develop crocin-rich functional food.”

Team leader Salim Al-Babili says the study paves the way for efficient biotechnological production of crocins and other high-value compounds derived from carotenoids (apocarotenoids) as pharmaceuticals in green tissues as well as other starch-rich plant organs. It also highlights the contribution of functional diversification among CCD genes to the independent evolution of alternative apocarotenoid biosynthesis routes in different plants.

“Most of our knowledge about CCD enzymatic activity and substrate specificity comes from experiments using E.coli engineered to produce different carotenoids,” he says.

“Functional characterization in plants, for example by using a transgenic approach such as we have here, is important for deducing the role of CCDs in carotenoid metabolism and unravelling their real contribution to the carotenoid/apocarotenoid pattern.” 

The platform technology could be used to produce other important carotenoid-derived compounds, including widely used scents and colorants.

“It could be used to produce safranal and picrocrocin, for example, which give rise to the taste and characteristic aroma of saffron. These could be used as flavor additives and they also have a bioactive potential awaiting exploration,” adds Zheng.

---

JOURNAL

Plant Biotechnology Journal

DOI

10.1111/pbi.13901 

ARTICLE TITLE

Gardenia carotenoid cleavage dioxygenase 4a is an efficient tool for biotechnological production of crocins in green and non-green plant tissues

New way found to turn number seven plastic into valuable products

Peer-Reviewed Publication

WASHINGTON STATE UNIVERSITY

 

IMAGE: THE WSU RESEARCH TEAM, INCLUDING POSTDOCTORAL RESEARCHER YU-CHUNG CHANG, USED PLA PLASTIC WASTE TO CREATE A HIGH-QUALITY RESIN FOR 3D PRINTING. view more 

CREDIT: WSU

PULLMAN, Wash. — A method to convert a commonly thrown-away plastic to a resin used in 3D-printing could allow for making better use of plastic waste. 

A team of Washington State University researchers developed a simple and efficient way to convert polylactic acid (PLA), a bio-based plastic used in products such as filament, plastic silverware and food packaging to a high-quality resin. 

“We found a way to immediately turn this into something that’s stronger and better, and we hope that will provide people the incentive to upcycle this stuff instead of just toss it away,” said Yu-Chung Chang, a postdoctoral researcher in the WSU School of Mechanical and Materials Engineering and a co-corresponding author on the work.  “We made stronger materials just straight out of trash. We believe this could be a great opportunity.”

About 300,000 tons of PLA are produced annually, and its use is increasing dramatically.  

Although it’s bio-based, PLA, which is categorized as a number seven plastic, doesn’t break down easily. It can float in fresh or salt water for a year without degrading. It is also rarely recycled because like many plastics, when it’s melted down and re-formed, it doesn’t perform as well as the original version and becomes less valuable.

“It’s biodegradable and compostable, but once you look into it, it turns out that it can take up to 100 years for it to decompose in a landfill,” Chang said. “In reality, it still creates a lot of pollution. We want to make sure that when we do start producing PLA on the million-tons scale, we will know how to deal with it.” 

In their study, published in the journal, Green Chemistry, the researchers, led by Professor Jinwen Zhang in the School of Mechanical and Materials Engineering, developed a fast and catalyst-free method to recycle the PLA, breaking the long chain of molecules down into simple monomers – the building blocks for many plastics. The entire chemical process can be done at mild temperatures in about two days. The chemical they used to break down the PLA, aminoethanol, is also inexpensive.

“If you want to rebuild a Lego castle into a car, you have to break it down brick by brick,” Chang said. “That’s what we did. The aminoethanol precision-cut the PLA back to a monomer, and once it’s back to a monomer, the sky’s the limit because you can re-polymerize it into something stronger.”

Once the PLA was broken down to its basic building blocks, the researchers rebuilt the plastic and created a type of photo-curable liquid resin that is commonly used as printing “ink” for 3D printers. When it was used in a 3D printer and cured into plastic pieces, the product showed equal or better mechanical and thermal properties than commercially available resins. 

While the researchers focused on PLA for the study, they hope to apply the work to polyethylene terephthalate (PET), which is more common than PLA, has a similar chemical structure and presents a bigger waste problem. 

They have filed a provisional patent and are working to further optimize the process. The researchers are also looking into other applications for the upcycling method. 

---

JOURNAL

Green Chemistry

DOI

10.1039/D2GC01745H 

ARTICLE TITLE

A chemical approach for the future of PLA upcycling: from plastic wastes to new 3D printing materials