Body

Following a dietary weight loss program can be difficult. Many factors trigger diet lapses, which can lead to weight loss failure. Experts disagree on whether physical activity increases risk or protects against diet lapses. While some studies show exercise leads to overeating by increasing appetite and/or a person’s justification for eating, other studies show exercise regulates hunger and may help reduce overeating.

Researchers from the Center for Weight, Eating and Lifestyle Science (WELL Center) in the College of Arts and Sciences at Drexel University found exercise to be a protective factor in a study where participants in a weight loss program, who were following a reduced-calorie diet, engaged in exercise in their real-world environments.

“Almost all behavioral weight loss programs prescribe exercise because of its health benefits and because it expends energy or ‘burns calories,’” said Rebecca Crochiere, a graduate student in the College of Arts and Sciences and lead author of the study. “Interestingly, our study suggests that exercise may also aid in adhering to a reduced-calorie diet, perhaps through improved regulation of appetite or eating behavior. It adds another reason to engage in exercise if one is seeking weight loss.”

The study found that exercise was protective against overeating. When participants did not engage in exercise, the risk of overeating in the following hours was 12 percent. Whereas when participants engaged in 60 minutes of exercise, the risk of overeating was cut by more than half, to five percent.

For every additional 10 minutes of exercise a participant engaged in, the likelihood of overeating decreased by one percent in the few hours following exercise.

Researchers collected data from 130 participants using novel methods, like ecological momentary assessments, or brief surveys, that were delivered to participants’ smartphones multiple times a day to measure overeating and hip-worn fitness trackers to measure exercise.

“These findings can help researchers to better understand when participants who are seeking weight loss are at risk of overeating,” said Crochiere. “It can inform the development of treatments that prevent overeating and facilitate weight loss.”

Crochiere cautioned these findings represent patterns observed across the sample as a whole; a goal for future research is to investigate if the effect of exercise on eating behavior differs from person to person.

The results also hinted that the effect of exercise on eating behavior may depend on the intensity of the exercise, with light (versus moderate-to-vigorous) physical activity showing the strongest protective effects against overeating, though more research is needed to support this finding, said Crochiere.

The study, “Is Physical Activity a Risk or Protective Factor for Subsequent Dietary Lapses Among Behavioral Weight Loss Participants?” was published January 2020 in Health Psychology. It was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Co-authors include Elizabeth Lampe, graduate student; Stephanie Manasse, PhD; Meghan Butryn, PhD; Evan Forman, PhD, all of Drexel University; Stephanie Kerrigan, PhD, of Yale University; and Ross Crosby, PhD, of the Neuropsychiatric Research Institute.

Although this study has concluded, the WELL Center continues to recruit for other weight management studies, including a study investigating effective cognitive and behavioral components of weight loss. For more information, visit drexel.edu/weightloss.

Journal

Health Psychology

DOI

10.1037/hea0000839

What The Study Did: Researchers examined how often homicide was the cause of death among women in Louisiana who were pregnant or up to one year postpartum compared with other causes.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Maeve E. Wallace, Ph.D., of the Tulane University School of Public Health and Tropical Medicine in New Orleans, is the corresponding author.

(doi:10.1001/jamapediatrics.2019.5853)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

What The Study Did: Researchers calculated the average cost of recommended initial HIV antiretroviral therapy (ART) regimens in the U.S. from 2012 to 2018 and analyzed how this cost has changed over the years. High ART costs are one of the factors that can lead to poor HIV treatment and outcomes in the U.S.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Rochelle P. Walensky, M.D., M.P.H., of Massachusetts General Hospital in Boston, is the corresponding author.

(doi:10.1001/jamainternmed.2019.7108)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Montreal, February 3, 2020 -- Most people living with HIV control the virus thanks to antiretroviral therapy (ART). Although this medication is highly effective, the presence of latent viral reservoirs in their bodies means they require lifelong therapy. Studies have demonstrated that immunotherapy combining two anti-HIV antibodies can also suppress HIV, similar to ART. Now an international team of researchers from the University of Montreal Hospital Research Centre (CRCHUM), the Rockefeller University (United States) and the University of Cologne (Germany) has shown that the use of these antibodies during ART interruption has an effect on the immune system of HIV-infected individuals.

In a study published in Nature Medicine, the researchers describe how injection of these potent anti-HIV antibodies, known as neutralizing antibodies, is associated with enhanced T cell responses that specifically recognize the virus. T cells are important white blood cells (lymphocytes) that help control chronic infections like HIV. This study shows an unsuspected interaction and a potential influence between the two arms of the human immune system: humoral immunity (antibodies) and cell-mediated immunity (T cells).

"It is really a proof of concept," said Dr. Daniel E. Kaufmann, a CRCHUM researcher and a professor at Université de Montréal. "Here, we analyzed blood samples from participants in a clinical trial conducted by our collaborators that used laboratory-produced monoclonal antibodies to block the virus. All participants maintained viral suppression for at least 15 weeks after the ART therapy was stopped."

He added: "We observed what happened to other immune cells that target the virus. In this study, we documented the increase of the T cell immune response on nine HIV-infected study participants. But are these T cell responses more effective at controlling HIV than before this intervention? This remains to be demonstrated."

A Phase 1b clinical trial

Two days before their ART therapy was stopped, nine individuals living with HIV and harbouring viruses sensitive to antibodies received a first injection of a cocktail of two antibodies. Recruited by the international research team, this cohort of individuals received new injections of antibodies after three and six weeks of follow-up. Blood tests were carried out every week to check if the virus returned.

Using sophisticated cell analysis techniques, Julia Niessl, the study's first author and a doctoral student in Kaufmann's lab, observed that the activity level of CD4 and CD8 T cells responding specifically to HIV was augmented during the period of antibody therapy combined with ART interruption.

Antibodies work differently than drugs. They are not passive; in addition to blocking the virus, they "engage" the immune system and influence it.

"In the future," said Kaufmann, "this kind of antibody therapy will be studied in larger clinical trials for HIV prevention or treatment, as antibodies are very well tolerated by humans and can efficiently block the virus for many weeks."

According to the World Health Organization, approximately 37.9 million people were living with HIV at the end of 2018.

A study at The University of Texas MD Anderson Cancer Center showed that circulating tumor cells (CTCs), a form of liquid biopsy, was independently associated with melanoma relapse, suggesting CTC assessment may be useful in identifying patients at risk for relapse who could benefit from more aggressive therapy following primary treatment.

Results from the study were published in Clinical Cancer Research, a journal of the American Association for Cancer Research. Although CTCs can be detected in melanoma patients, there is limited data regarding their significance in stage III (node-positive) disease. This prospective study was based on earlier research that found CTCs in a significant number of breast cancer patients, which was associated with relapse, independent of other existing methods for determining prognosis.

"Our findings are significant, given that there is a need for blood-based biomarkers to guide clinical decision making for stage III melanoma patients," said Anthony Lucci, M.D., professor of Breast Surgical Oncology and Surgical Oncology, and study lead. "There currently are no blood tests available to help doctors accurately tell which patients are likely to relapse, and should be given therapy, and which are low risk, and could be observed."

The researchers assessed CTCs during the patient's first clinic visit, and relapse-free survival was compared between patients with one or more CTCs, versus those with no CTCs. CTCs were observed in 90 out of 243 patients enrolled in the study.

"Our analysis demonstrated that CTC detection was significantly associated with a decrease in relapse-free survival at six months, and persisted at a 54-month longer-term follow-up," said Lucci. "The data from this study provides support for the future pursuit of liquid biopsy techniques to help identify patients most likely to benefit from adjuvant systemic therapy."

Lucci added that this is vital given that there currently is no clear consensus on when to recommend immunotherapy for node-positive melanoma patients. Despite the development of new targeted and immune therapies to treat melanoma, many patients either do not respond to these therapies or develop resistance to therapy within six to eight months. Because such therapies also can have side effects, avoiding treatment in patients at low risk for relapse may prevent overtreatment.

SILVER SPRING, Md. - A new study led by scientists at the Walter Reed Army Institute of Research has shown for the first time that a single dose of an experimental Zika vaccine in a dengue-experienced individual can boost pre-existing flavivirus immunity and elicit protective cross-neutralizing antibody responses against both Zika and dengue viruses. Findings were published today in Nature Medicine.

Researchers analyzed the antibody responses of a dengue-experienced volunteer who participated in a Phase 1 clinical trial of the WRAIR-developed Zika purified inactivated virus vaccine. They identified a potent cross-reactive antibody called MZ4 that demonstrated a potent ability to neutralize the Zika virus as well as the dengue virus serotype-2 strain. In addition, MZ4 protected against Zika and dengue in a mouse model of infection.

"Rapid-onset countermeasures are needed to protect military personnel, travelers and residents in areas where emerging infections such as Zika and dengue viruses are already widespread and expanding," said Dr. Kayvon Modjarrad, who leads the U.S. Army Zika vaccine program, directs the Emerging Infectious Diseases Branch at WRAIR and is one of the lead authors on the paper. "These results demonstrate the potential for MZ4 to be part of the prevention toolbox for these diseases."

The individual's immune profile was compared to trial volunteers who had no previous exposure to dengue virus. While the volunteer with prior dengue exposure experienced a sharp increase in antibodies that neutralize Zika and dengue viruses, following just one dose of the ZPIV vaccine, the dengue-naïve trial participants required two vaccinations to reach a similar magnitude of Zika antibody responses. Additionally, no cross-reactive antibody response to dengue virus.

"These new findings indicate that an effective Zika vaccine could both boost dengue virus immune responses and generate potent Zika neutralizing antibodies that might have unique potential as a prevention tool in regions where both dengue and Zika are prevalent," said Dr. Shelly Krebs, a B cell researcher at WRAIR and senior author of the paper.

Building on these findings, researchers used samples from another Phase 1 study of the ZPIV vaccine currently being conducted in Puerto Rico, where there is a higher risk of exposure to flaviviruses, a family of viruses that includes Zika, dengue, Japanese encephalitis, yellow fever and West Nile viruses. WRAIR researchers found that vaccination with ZPIV in Puerto Rican individuals with prior flavivirus-experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.

Asymptomatic Zika infections can lead to severe birth defects and neurologic complications. The ZPIV vaccine candidate was developed by WRAIR based on the same inactivated flavivirus vaccine technology the Institute used to create its Japanese encephalitis vaccine, which was licensed in the U.S. in 2009. Three Phase 1 human clinical trials have shown ZPIV to be safe and well-tolerated in healthy adults and that it induced a robust immune response (Modjarrad et al., 2018). WRAIR's Zika efforts are ongoing, overseen by the Institute's Emerging Infectious Diseases Branch.

PITTSBURGH, Feb. 3, 2020 - A marker for heart disease risk considerably worsens as women transition through menopause, according to a new analysis from the largest and longest running study of women's health in midlife, the Study of Women's Health Across the Nation (SWAN). Black women experience this accelerated decline earlier in menopause than their white counterparts.

According to the research team, led by scientists at the University of Pittsburgh Graduate School of Public Health, the findings add to growing evidence that menopause is a critical time for changes in cardiovascular health and underscore the importance of women and their doctors focusing on heart health during the menopausal transition. The results are reported online and will appear in the March issue of Arteriosclerosis, Thrombosis, and Vascular Biology, a journal of the American Heart Association.

"Midlife is not just a period where women have hot flashes and experience other menopausal symptoms," said senior author Samar R. El Khoudary, Ph.D., M.P.H., associate professor of epidemiology at Pitt Public Health. "It's a time when their cardiovascular disease risk is increasing as we see significant changes in multiple clinical measures of their physical health."

El Khoudary and her team used a subset of data from SWAN Heart, an ancillary study that enrolled women from Pittsburgh and Chicago between 2001 and 2003 and included two examinations of early markers of cardiovascular health over time. Ultimately, 339 women were included in this study, 36% black and the rest white.

The study focused on how arterial stiffness changes as women transition through menopause. Arterial stiffness refers to the elasticity of arteries and is measured by looking at how fast blood flows through arteries. Stiffer arteries can lead to dysfunction in how well the heart pumps and moves blood, and damage to the heart, kidneys and other organs.

The researchers tracked the women through SWAN for up to 12.5 years, or until they reached menopause, allowing them to confidently anchor the arterial stiffness measure to the menopausal transition.

On average, as women went through menopause, their arterial stiffness increased by about 0.9% up to one year before their last menstrual period to about 7.5% within one year before and after their last period, a considerable acceleration. The black women in the study experienced greater increases in arterial stiffness earlier in the transition than white women, more than a year before menopause. The findings held after adjusting for numerous factors that could affect heart health, including waist circumference, blood pressure, lipids, smoking status, physical activity levels and financial stress.

"SWAN is a unique source of data on changes in women's health over several decades, and this is the latest in a long line of research by our team and others that indicates the menopausal transition is a very important time for heart health," said lead author Saad Samargandy, M.P.H., a Ph.D. student at Pitt Public Health. "While there are limitations to our study, including that a sizeable minority of the women had their arterial stiffness measured at only one time point, we were still able to see that major changes to cardiovascular disease risk happen around menopause."

This study follows several others that link the menopausal transition to the accumulation of heart fat, changes in cholesterol, inflammation and coronary artery calcification, among other heart disease risk factors.

"Our study is not able to tell us why we're seeing these changes during the menopausal transition," El Khoudary said. "But we speculate that the dramatic hormonal changes accompanying menopause might play a role by increasing inflammation and affecting vascular fat deposition, a hypothesis that we would like to test in future studies."

Clinical trials will be needed to test if lifestyle interventions, such as changes to diet or physical activity; medications, such as statins or hormone replacement therapy; or even increased screening and tracking of measures of heart health could be beneficial as women go through menopause, she said.

"But we can say, right now, that women should be made aware that their cardiovascular health is likely to worsen as they go through menopause," El Khoudary said. "Therefore, frequent monitoring of cardiovascular risk factors may be prudent, particularly in black women who are at even greater risk earlier in the menopausal transition."

The invention of vaccines for disease prevention is often cited as one of the miracles of modern medicine. New research from Simon Fraser University suggests that tailoring vaccines based on geography and other factors could substantially reduce overall rates of bacterial disease.

Professor Caroline Colijn, who holds a Canada 150 Research Chair in Mathematics for Evolution, Infection and Public Health, is among lead researchers on the study published today in Nature Microbiology.

Colijn collaborated with Professor Jukka Corander of the University of Oslo and Dr. Nick Croucher from the MRC Centre for Global Infectious Disease Analysis at Imperial College London.

The trio proposes new methods for choosing the best vaccine to fight and eliminate certain bacterial strains, which could help minimize rates of pneumococcal disease, an infection that can cause serious illness such as pneumonia, sepsis and bacterial meningitis.

"Designing the best vaccine is important because when we vaccinate against some strains, other strains can come in and replace those strains," says Colijn. "If new strains are as bad as the ones we have replaced through vaccinations, that can undermine our vaccination efforts."

Citing existing concerns in the medical community around the replacement of bacterial strains in vaccines, Colijn says her latest research goes a step further. Researchers propose using genomic data and mathematical modelling to design vaccines for the specific geographic location where they will be used.

The study simulated the performance of vaccines over time to assess the risk of vaccine-targeted strains being replaced by other potentially dangerous strains. Through this predictive modelling approach, the researchers identified new vaccine designs that could help reduce overall rates of disease.

"It's only recently that we have been able to do bacterial genomics on the scale that we require for this work," says Colijn. "This was made possible by our ability to combine sequencing technologies with computational modelling in a new way."

These data modelling methods, when applied to pneumococcus, also help identify which options are best for minimizing disease in different age groups, or reducing the frequency of antibiotic resistant-infections.

Researchers are already considering whether these findings could be applied to other bacterial pathogens such as E. coli.

Both Corander and Croucher are also Associate Faculty at the Wellcome Sanger Institute, which could play a pivotal role in accelerating future vaccine discovery and design using these techniques.

WHY IT MATTERS:

According to ImmunizeBC, vaccines have saved more lives in Canada than any other medical intervention in the past 50 years.

The World Health Organization estimates that vaccines prevented at least 10 million deaths between 2010 and 2015, and many millions more lives were protected from illness by them.

CHICAGO--February 3, 2020--Shift workers are at a significantly increased risk for sleep disorders and metabolic syndrome, which increases a person's risk for heart disease, stroke and type 2 diabetes mellitus. Individuals, employers and physicians can all take steps to mitigate these risks, according to a clinical review in The Journal of the American Osteopathic Association.

Researchers say night-shift workers are especially prone to developing sleep disorders and metabolic syndrome. The risks increase even more for those who work irregular or rotating shifts.

"The strength of our economy and safety of our society depend heavily on night shift workers," says Kshma Kulkarni, OMS III at Touro University College of Osteopathic Medicine, and lead study author. "It is critical we address the health issues facing people in this line of work."

A significant portion of the workforce

Kulkarni says 17.7% of the U.S. labor force works outside the hours of 6 am and 6 pm. She adds that shift workers are central to the travel, hospitality and ecommerce industries, as well as the 24-hour support needed from nurses, physicians and first-responders, like police and firefighters.

One study found 9% of night-shift nurses developed metabolic syndrome, compared to only 1.8% of day shift nurses. Other studies have noted that risks gradually increase with accumulated years of shift work.

Working nights disrupts individuals' circadian rhythm, the body's internal clock responsible for neural and hormonal signaling. Once a person's circadian rhythm is desynchronized from their sleep/wake cycle, they will likely experience disturbances in hormonal levels, including increased cortisol, ghrelin and insulin and decreased serotonin, among others.

The cascade of hormonal changes is what prompts the development of metabolic disorders and causes people to develop multiple chronic conditions. Kulkarni recommends the following measures to prevent serious health issues associated with shift work.

It starts with sleep

The first essential step for night shift workers is to establish consistent sleeping hours, says Kulkarni.
Employers can help by eliminating rotating shifts that disrupt sleep patterns even further. They can also schedule shifts to start before midnight and last no more than 11 hours to help workers adjust and stabilize their new circadian rhythm.

She adds that workers can maximize their rest by following some basic tips:

Sleep in a 7- to 8-hour block every 24 hours, ideally at the same time each day

Schedule the main block of sleep as close to evening or night as possible to minimize circadian disruption

Take an additional nap for 20 to 120 minutes earlier in the day to prevent fatigue

Controlling light exposure

Exposure to light promotes wakefulness in general, so researchers recommend night shift workers increase their light exposure prior to and throughout their shifts. In addition, employers can install high-intensity lights (~3,000 lux) to simulate daylight exposure and assist circadian adaptation.

Conversely, when coming off shift, workers should minimize their blue light exposure. Blue light is prominent in electronic screens and can delay melatonin production. Research shows avoiding blue light 2 to 3 hours before sleep can improve sleep quality. Kulkarni says workers can stay off their devices and/or wear orange tinted goggles to block out blue light.

Diet and exercise

Prior studies have shown shift workers are more likely to eat snacks higher in sugar and saturated fat while consuming less protein and vegetables, and more likely to skip meals. Kulkarni points out that diet is even more critical for people at risk for metabolic disorder and recommends the following to improve nutrition:

Eat three meals a day at close to the same time each day, with more calories consumed earlier in their wake cycle

Make sure meals and snacks primarily incorporate protein and vegetables

Employers can assist by offering nutritious options in vending machines and break rooms, and by scheduling regular breaks earlier in the shift.

Similarly, exercise plays an outsized role in the health of shift workers, and can help reestablish the circadian rhythm. Kulkarni recommends shift workers exercise at a similar time each day, at least 5 hours before they go to bed. In addition, they should incorporate aerobic exercise into their physical activity, as it has specifically been indicated to improve sleep quality.

"It's true that getting enough sleep, eating right and exercising are critical to everyone's health," says Kulkarni. "However, the nature of shift work is so disorienting and discordant with those principles, we really need to help people in those jobs strategize ways to get what they need."

Lupus is a chronic autoimmune disease that can damage any part of the body. When it causes inflammation in the kidneys (called lupus nephritis), they cannot properly remove waste from the blood or control body fluids. Without treatment, nephritis can lead to scarring and permanent damage of the kidneys, and possible final renal failure. In this case, patients need to undergo dialysis and possibly a kidney transplant. Currently, lupus nephritis patients are treated with nonsteroidal anti-inflammatory drugs and immunosuppressors, which are unsatisfactory and have side effects. Therefore, new therapeutic agents with higher potency, selectivity and safety are needed.

The research group, on immuno-inflammatory processes and gene therapy of the Bellvitge Biomedical Research Institute (IDIBELL), has published in the prestigious journal Kidney International, a study that demonstrates the immunomodulatory therapeutic capacity of a molecule present in our blood, called C4BP (?-). These results, validated in two animal models of lupus nephritis, represent a very promising advance for patients. Also, the applicability of this discovery is being evaluated in other autoimmune disorders, such as colitis and rheumatoid arthritis. Until now, satisfactory results have been obtained.

Autoimmune diseases are caused by a malfunction of the immune system, which attacks the own cells and tissues becoming an aggressor instead of a protector. The complement pathway is one of the components of the innate system. This, among other functions, protects the body from pathogenic organisms. The IDIBELL team, led by Dr. Josep M. Aran, has demonstrated a new activity for one of the forms of complement inhibitor protein C4BP (?-). Specifically, it has been shown that it is able to reprogram myeloid cells (a type of white blood cell), transforming its proinflammatory and immunogenic activity to anti-inflammatory and tolerogenic activity.

The C4BP protein (?-) can both, be isolated from human serum, or obtained artificially (recombinantly) by culturing eukaryotic cells that express it. In mice that reproduce human lupus nephritis, it has been shown that the administration of C4BP (?-) greatly improves the symptomatology of the disease, especially when is compared to the therapeutic action of classical immunosuppressants. In addition, it has no side effects and is also effective against dermatitis, another condition derived from lupus.

What The Study Did: Naloxone is a medication used to reverse an opioid overdose, and this study looked at how an Ohio law that allowed pharmacists to dispense naloxone without a prescription was associated with dispensing rates.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Pamela C. Heaton, Ph.D., of the University of Cincinnati in Ohio, is the corresponding author.

(10.1001/jamanetworkopen.2019.20310)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

What The Study Did: National data from 895,000 adults were used to examine how state regulations regarding electronic cigarettes were associated with their use among U.S. adults.

Authors: Wei Bao, Ph.D., of the University of Iowa College of Public Health in Iowa City, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(10.1001/jamanetworkopen.2019.20255)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Washington (Jan. 31, 2020) - Even though mortality from congenital heart disease (CHD) has declined over the last three decades as diagnosis and treatments have advanced, the chances for a child to survive a CHD diagnosis significantly differs based on the country where he or she is born.

This eye-opening finding is drawn from the first comprehensive study of congenital heart disease across 195 countries, prepared using data from the Global Burden of Diseases, Injuries and Risk Factors Study 2017 (GBD), and recently published in The Lancet.

"Previous congenital heart estimates came from few data sources, were geographically narrow and did not evaluate CHD throughout the life course," write the authors, known collectively as the 2017 GBD Congenital Heart Disease Collaborators. Co-lead author Meghan D. Zimmerman, M.D., worked on the study while completing her pediatric cardiology and American Heart Association Global Health Fellowships at Children's National Hospital, and two pediatric cardiologists from Children's National, Cardiology Associate Chief Craig Sable, M.D., and Gerard Martin, M.D., medical director of Global Services, provided leadership and oversight of this paper. The remaining collaborators are from more than 45 institutions around the world, spanning cardiology, public health and schools of medicine on every continent.

This is the first time the GBD study data was used along with all available data sources and previous publications--making it the most comprehensive study on congenital heart disease burden to date. Key differences between this study and prior estimates include:

Anatomic groupings of CHD by type, rather than simply categorized as moderate, severe or critical.

Inclusion of new data sources, including data from screening programs, congenital registries, administrative data and data sources in mortality and survival.

A control mechanism to account for cases of CHD that remit on their own to reduce the risk of overestimating prevalence.

Inclusion of all cases of congenital heart disease, including those with chromosomal or genetic anomalies such as Trisomy 21 that often co-occur.

This more comprehensive data set led to findings that showed lower predicted long-term survival, higher remission, and lower prevalence than previous studies that extrapolated evidence from studies of high-income countries. However, it also means these new estimates are a more accurate representation of the current global state of affairs. Overall, the study found:

A 34.5% decline in deaths from congenital disease between 1990 to 2017.

Nearly 70% of deaths caused by CHD in 2017 (180,624) were in infants less than one year old.

Most CHD deaths occurred in countries within the low and low-middle socio-demographic index (SDI) quintiles.

Mortality rates get lower as a country's SDI rises.

Birth prevalence of CHD was not related to a country's socio-demographic status, but overall prevalence was much lower in the poorest countries of the world. This is because children in these countries do not have access to life saving surgical services.

Nearly 12 million people are currently living with CHD globally, 18.7% more than in 1990.

The burden of CHD is not fully realized by just looking at prevalence and mortality. The measure "Years of Life Lost" provides deeper insight into the staggering burden of CHD, taking into account both absolute mortality and age at death.

"In high income countries like the United States, we diagnose some heart conditions prenatally during the 20-week ultrasound," says Dr. Martin, a pediatric cardiologist at Children's National Hospital who contributed to the study. "We catch others right after birth with a pulse oximetry screening for critical congenital heart disease. We can operate to correct a critical issue within the first week of life. And now our CHD kids are growing and thriving through adulthood and having families of their own."

"For children born in middle- and low-income countries, these data draw stark attention to what we as cardiologists already knew from our own work in these countries--the lack of diagnostic and treatment tools leads to lower survival rates for children born with CHD," adds Dr. Sable. "This is one of the most significant publications I have been a part of as it highlights the substantial loss of life to CHD in infancy around the globe."

The authors write, "The UN has prioritized reduction of premature deaths from heart disease, but to meet the target of 'ending preventable deaths of newborns and children under 5 years of age,' health policy makers will need to develop specific accountability measures that address barriers and improve access to care and treatment."

The study also includes a 400-page appendix breaking down each area by type of congenital anomaly, world region and country.

Antiretroviral drugs are the gold standard for the treatment of HIV infection. They are highly effective in suppressing replication of the virus but require lifelong daily application and can be associated with side effects. Due to the high mutability of HIV and its capacity for rapid adaptation, combinations of antiretroviral agents are required to prevent the development of drug re-sistance and treatment failure.

Broadly neutralizing antibodies targeting HIV

Broadly neutralizing antibodies are a focus of ongoing research on novel op-tions for the treatment and prevention of HIV infection. Their mode of action substantially differs from regular antiretroviral drugs, as antibodies target the virus through specific binding of HIV surface proteins.

Clinical trials have demonstrated the potential of broadly neutralizing antibod-ies by reducing the viral load in the blood of HIV-infected individuals. Similar to antiretroviral drugs, however, the effects of single antibodies were only temporary because of the development of viral resistance.

Identification of the highly potent antibody 1-18

Scientists at the University Hospital Cologne have now identified a novel anti-body called 1-18 that targets HIV. This antibody is highly potent and showed activity against 97% of the tested HIV variants. „1-18 is therefore among the best HIV neutralizing antibodies described to date", says Dr. Philipp Schom-mers, resident physician at the Department I of Internal Medicine and one of the first authors of the article.

In collaboration with colleagues at the California Institute of Technology (Pas-adena, USA), the researchers identified the mode of action of antibody 1-18 in detail. 1-18 binds and inactivates a surface structure of HIV that is particu-larly relevant because it is essential for viral infection and replication.

Effective HIV therapy using antibody 1-18

The therapeutic efficacy of the newly identified antibody 1-18 was studied using a mouse model that allows recapitulation of HIV infection as it occurs in humans. In this model, other broadly neutralizing antibodies showed only short-term effects because of the rapid development of viral resistance. In contrast, treatment with the antibody 1-18 resulted in suppression of the viral load that was maintained for the duration of therapy. „These results indicate that development of viral resistance against the new antibody 1-18 is restrict-ed when compared to other antibodies", says Dr. Henning Grüll, resident phy-sician at the Institute of Virology and also first author of the work.

Due to its high potency, the scientists consider 1-18 a promising candidate for HIV immunotherapy. "In addition, 1-18 has great potential for preventing HIV infection by passive immunization", adds Prof. Dr. Florian Klein, lead and sen-ior author of the study. Clinical trials are now planned to further investigate antibody 1-18.

ANN ARBOR--With no way to reliably tell whether an athlete has a concussion, many may be playing with an undiagnosed injury. Likewise, 2 million people die every year because we don't have an early warning when brain cells are dying--and another 4 million experience cognitive disabilities.

Now, a team of doctors and engineers has developed a noninvasive way to measure whether brain cells are in distress using an infrared laser. Their device uses optical fibers to deliver pulses of infrared light to a person's forehead. This light can penetrate through the skin and skull to the brain without doing harm. It interacts with an important molecule for metabolism called cytochrome C oxidase, or CCO.

While existing technology can give real-time information on whether the brain is getting oxygen, this new device gives information about whether the brain cells are able to use that oxygen. This information could enable concussions to be diagnosed on the sidelines of an athletic event. Alternatively, it could provide rapid feedback as doctors adjust treatment in the ER, operating room or the intensive care unit.

Mohammed Islam, professor of electrical engineering and computer science, will present the study on Super Bowl Sunday at the Photonics West conference in San Francisco. He and his collaborators at Michigan Medicine, the School of Kinesiology and the College of Literature, Science, and the Arts told us about how the new technique works.

What kinds of patients could this help?

Steven Broglio, director of the Michigan Concussion Center and professor athletic training: Concussions in athletics have been in the spotlight for the previous decade, but soldiers are also at high risk. Concussion can happen to anyone.

At present, there is no one test that can diagnose a concussion. There's no scan, no blood test, no computer test. We currently rely on a clinical exam and interpretation by the medical provider, so the diagnosis is subjective. We believe this technology is the first step in changing that by measuring brain metabolism, potentially resulting in faster and more certain diagnoses.

The quicker you identify a concussion, the faster you can begin the recovery process of resting and gradually returning to normal activity. Research in the last 10 years has shown that resting sooner can shorten recovery time, helping people get back to school, work and military duty.

Rachel Russo, a trauma and emergency surgeon and clinical lecturer: This device could guide the treatment of more serious brain injuries and other conditions that put the brain at risk. In its broadest application, it could help patients whose blood pressure falls so much that there isn't enough blood flow to keep cells functioning normally. This can happen when a person is very ill or because they have lost too much blood. We need to keep them in the 'Goldilocks zone'--their blood pressure has to be high enough to supply oxygen to the cells and low enough to discourage bleeding in injured tissues.

In the ER and the intensive care unit, or ICU, patients are sometimes kept in medical comas while they heal from traumatic brain injuries. This would be the first device that could measure how well their brain cells are doing right in the hospital room.

What does measuring cytochrome C oxidase tell you?

Ioulia Kovelman, associate professor of psychology: It can tell us if the tissue is healthy and is metabolizing or "eating" properly--such as a brain of a healthy individual versus the brain of a person who suffered a concussion or has Alzheimer's disease, amyotrophic lateral sclerosis (ALS) or other types of brain dysfunction or trauma.

Russo: CCO decreases when cells are in distress. One of the challenges is that we don't know if there's a universal threshold that signals a problem, the way we have normal ranges for different markers when we run a blood count. This is one of the areas we want to explore in the future.

But even without a threshold for action, we believe we could observe how a patient's cell metabolism changes over time and correlate that with other vital signs. This could give us an early indication of how they are recovering and whether more aggressive treatment is needed.

How does the device measure CCO?

Islam: There is a part of CCO that is excited by light with wavelengths between 750 nanometers and 900 nanometers. If you pluck a string on a violin, you hear its resonant frequency. CCO has, if you like, a string that we pluck with our laser, and we see the resonant frequency in the light we record.

Why hasn't it been done before?

Islam: Previous experiments used infrared lamps, but the signal from the CCO is not very distinct. Hemoglobin, which tells us about the blood oxygen levels, also responds to the range of wavelengths we use to probe CCO, and it is 10 to 20 times more plentiful in human tissue. We needed a stronger signal from the CCO to distinguish it from the hemoglobin and other molecules in the body, and we got that stronger response by using a laser that is nearly 10 times brighter than the lamps.

That increased brightness, along with measurement techniques to suppress noise during the measurements, was critical to enabling the conclusive measurements of CCO during cognitive attention tests with a portable, noninvasive device. Such attention tests are often used with concussion patients.

What did your experiments show?

Kovelman: In our study, we asked participants to complete an attention task developed by Daniel Weissman, a professor of psychology, cognition and cognitive neuroscience. This task can be used to study healthy attention, such as attention development in children or attention dysfunction in individuals who might have a brain injury or concussion.

As individuals were completing this attention task, we saw an increase in oxygenated blood flow to their frontal lobe--the part of the brain that sits behind our forehead and is essential to being able to attend. Along with the increase in oxygenated blood flow, we also saw a change in the brain's CCO redox state--in other words, as oxygen supply increased, so did the consumption of the oxygen by the neurons of the frontal lobe that were busy attending to the task. This means that our new method can effectively measure brain metabolism, an index of brain function.

All cells use oxygen and energy, not just in the brain. Can this device look for trouble in other organs?

Russo: We think it can. We would have to adjust the depth of the measurement, but we may be able to observe other organs at risk of failure--for example, the heart, lungs or kidneys.