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Researchers who studied antibody responses in 30,000 patients with mild-to-moderate COVID-19 report that the patients' antibodies were relatively stable for at least five months. Although the results do not yet provide conclusive evidence that these levels protect from reinfection, Ania Wajnberg and colleagues say they "believe it is very likely that they will decrease the odds ratio of reinfection and may attenuate disease in the case of breakthrough infection." As the number of daily COVID-19 cases worldwide continues to mount, the nature of the humoral immune response, which includes an antibody response, remains uncertain. Assessing the antibody response in mild and asymptomatic cases is of particular importance since these cases constitute the majority of infections. In March 2020, the Mount Sinai Health System in New York City began to screen individuals for antibodies to SARS-CoV-2 to recruit volunteers as donors for convalescent plasma therapy. By 6 October, Mount Sinai had screened 72,401 individuals, with a total of 30,082 individuals testing positive, many of whom showed notable IgG antibody responses. Wajnberg and colleagues studied this cohort to dissect the longevity and potency of their anti-SARS-CoV-2 antibody responses. Using a well-established assay, they evaluated neutralizing effects of the antibodies, critical to understanding possible protective effects. They report that spike binding as measured by the assay is roughly correlated with virus neutralization. To evaluate longevity of the antibody response, the authors recalled 121 plasma donors. In these patients, they found stable antibody titers for a period approximating five months. The authors note their findings contradict other work suggesting antibody responses do not have much longevity, including work published in June 2020 that showed waning titers eight weeks after virus infection. However, among other differences, the antibodies measured in that report targeted a different viral antigen. This may suggest the stability of the antibody response over time depends on the target antigen, the authors say. They plan to follow their cohort over longer intervals to help inform if and how enduring antibody responses protect from reinfection. "We believe it is imperative to swiftly perform studies to investigate and establish a correlate of protection from infection with SARS-CoV-2." This could inform policy regarding the COVID-19 pandemic, they say, and would be beneficial to vaccine development efforts.

MINNEAPOLIS - Women with epilepsy who take the antiseizure drug valproic acid while pregnant are at more than double the risk of having children with autism spectrum disorder and nearly double the risk of having children with attention deficit hyperactivity disorder (ADHD), according to a study in the October 28, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Clinical recommendations warn against the use of valproic acid in pregnancy if possible due to associations with birth defects and other health conditions in children, but valproic acid is also a first-line treatment for generalized seizures and may be the best option for optimal seizure control," said study author Brian D'Onofrio, Ph.D., of Indiana University in Bloomington. "We looked at three medications and found that women who reported using valproic acid in the first three months of pregnancy had more than twice the risk of their children having autism and nearly twice the risk of their children having ADHD than women with epilepsy who were not taking any antiseizure drugs during pregnancy."

The study looked at 14,614 children born to women with epilepsy between 1996 and 2011. About 23% of those women reported using antiseizure medication in their first trimester. The three most used drugs were carbamazepine, taken by 10% of the women, lamotrigine, taken by 7% of the women, and valproic acid, taken by 5% of the women.

Using medical records, researchers identified which children were later diagnosed with autism or ADHD.

Of the children exposed to valproic acid, 36 out of 699 developed autism by the age of 10 years, compared to 154 out 11,298 who were not exposed to any antiseizure medication during gestation. A total of 54 out of 699 children whose mothers took valproic acid during their pregnancies developed ADHD by the age of 10, compared to 251 out of 11,298 who were not exposed.

After adjusting for factors like the severity of the epilepsy, women who reported using valproic acid during the first trimester had a 2.3 times greater risk of having children diagnosed with autism and a 1.7 times greater risk of children diagnosed with ADHD than women who reported using no antiseizure medications.

Researchers found that the women who took lamotrigine and carbamazepine had no increased risk of their children developing autism or ADHD.

"Our findings add to the growing body of evidence that suggests certain antiseizure medications may be safer than others during pregnancy," D'Onofrio said. "While we did not find that the drugs directly caused autism or ADHD, our study expands upon prior work on birth outcomes by demonstrating a link between valproic acid and longer-term problems. Our findings suggest that women who use antiseizure medications, particularly valproic acid, should weigh potential harm to the fetus, as well as ongoing seizure management, in their decision-making with their doctors if they are considering becoming pregnant."

A limitation of the study is that researchers were not able to rule out all alternative explanations for associations, such that these findings should not be seen as entirely conclusive.

The use of bariatric surgery to treat severe obesity in adolescents, and the racial disparities in access to that treatment, were analyzed in a retrospective study published in Annals of Surgery by researchers at The University of Texas Health Science Center at Houston (UTHealth).

Nearly 19% of children and adolescents in the U.S. are obese. Because many obese children become obese adults, childhood obesity can be linked to mortality and morbidity in adulthood, making it one of the leading causes of death in the U.S. Ethnic minority groups have the highest rates of severe obesity in the country.

"It's no surprise that childhood obesity has been a challenge in this country from both a public health and clinical standpoint for decades," said Sarah Messiah, PhD, MPH, lead author of the study and professor of epidemiology, human genetics, and environmental sciences at UTHealth School of Public Health in Dallas. "What is most alarming is that over the past five to 10 years, we have seen an increase in those who have severe obesity. This group of patients is growing at three times the pace of adolescents who are obese."

Pediatricians often suggest lifestyle modifications such as changes in diet to reduce calorie intake and increased physical activity. However, dietary and behavioral changes alone have not been proven to be successful in treating children and adolescents with severe obesity.

Messiah and other researchers suggested in the paper that bariatric surgery, commonly known as weight loss surgery, in combination with lifestyle changes, could be the best option for treating severely obese adolescents.

"The American Academy of Pediatrics supports the use of bariatric surgery in adolescents because evidence shows that it works and is safe. Pharmaceutical treatment options are very limited and have mixed results, and unfortunately for those who are already severely obese, lifestyle changes won't be enough," Messiah said.

Bariatric surgery is a minimally invasive surgery that alters the stomach or intestines to help obese patients lose weight.

By obtaining data from the American Society for Metabolic and Bariatric Surgery, researchers found that although obese adolescents are turning to weight loss surgery as a way to lose a significant amount of weight, many of those who are severely obese, especially Hispanic and Black adolescents, are not being offered that treatment option.

"There is a big disconnect between those who are getting the surgery and those who need it. Research has shown that this is a safe and effective way to help these children get their life on track, but the issue is bariatric surgery is not being utilized to treat obesity among ethnic minority groups," Messiah said.

According to the study, more than 10% of Hispanic and Black youth suffer from severe obesity in the U.S., yet their rates of completing weight loss surgery are well below that of white youth. Data used by researchers show that in 2018, 68.5% of youth who completed bariatric surgery were white, versus 18.5% Hispanic and 15.5% Black youth.

"More pediatricians need to refer these patients to surgeons if they are a good candidate to help get their patients on a healthier path," Messiah said.

Although bariatric surgery is an invasive treatment option, and perhaps not an agreeable weight loss solution for many youth and their families, Messiah says it is an evidence-based safe option. "Research shows that readmission into hospitals post-surgery due to any complications is low. Out of surgeries performed between 2017 and 2018, only 3.4% of youth patients were readmitted to the hospital," Messiah said.

Despite potential risks, Messiah said adolescents face diabetes, heart disease, asthma, high blood pressure, and psychological issues including anxiety, depression, and low self-esteem that studies have found are associated with severe obesity in youth.

Most recently, studies have shown that both adult and pediatric patients with obesity are at a high risk of severe illness or death if they were to contract COVID-19.

"The bottom line is, most adolescents will not lose the weight on their own, and utilizing bariatric surgery is a safe and effective way to help treat this problem before it is too late," Messiah said. "We need to start intervening earlier so that they can enter adulthood healthier."

Research out in this week's issue of JAMA confirms the success of a treatment for persistent atrial fibrillation (AFib) that combines the standard treatment, catheter ablation, with a separate infusion of ethanol, or alcohol, to the vein of Marshall. Miguel Valderrabano, M.D., division chief, cardiac electrophysiology, Houston Methodist, designed the procedure, first using it successfully in 2008. Earlier this year, he presented these findings at the annual meeting for the American College of Cardiology.

Atrial fibrillation refers to an abnormal and irregular heart rhythm, which can lead to stroke, blood clots and heart failure if left untreated. As a treatment, catheter ablation uses electrical energy to reset the heartbeat. While effective for some, in many patients, the procedure must be repeated multiple times to achieve positive results. The Vein of Marshall Ethanol for Untreated Persistent Atrial Fibrillation (VENUS) trial enrolled 343 patients, with 155 of them receiving the combination treatment. At the six and 12-month mark, 49% of those patients remained free from atrial fibrillation. At the same interval, only 38% of patients who received catheter ablation alone had the same results. AFib is the most commonly diagnosed arrhythmia.

The prevalence of AFib in the United States ranges from 2.7 million to 6.1 million, according to the Centers for Disease Control and Prevention.

Findings from the multi-center trial prove that the combination approach is an effective first-line treatment and could be incorporated as the standard of care. For patients, it increases their chances of requiring only one procedure to return to health, eliminating the stress and worry that can accompany frequent surgical procedures.

DALLAS, Oct. 28, 2020 -- Current smokers faced nearly three times the risk of premature death from cardiovascular disease compared with people who never smoked, with the risk being higher among those who began smoking during childhood, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Smoking continues to cause an estimated 100,000 deaths from cardiovascular disease every year in the U.S. Currently, there are about 25 million people who smoke daily including 5 million who became regular smokers before the age of 15.

Earlier research in Cuba found a correlation between childhood smoking and a higher risk for premature death overall. In this new study, investigators set out to determine if the findings were generalizable in other populations by conducting a similar analysis of U.S. data focused on death from cardiovascular disease.

"It was surprising to see how consistent these findings were with our earlier research and with other studies from around the world, including from the U.K., Australia and Japan, among others, both in terms of the substantial risks associated with smoking and with the health benefits of quitting smoking," said lead study author Blake Thomson, M.Phil., D.Phil., an epidemiologist at the University of Oxford in Oxford, England. "The age at which a person begins smoking is an important and often overlooked factor, and those who start smoking at a young age are at especially high risk of dying prematurely from cardiovascular disease. However, quitting can substantially reduce that risk, especially for those who quit at younger ages. Getting people to quit smoking remains one of the greatest health priorities globally."

Using data collected between 1997 and 2014, from the annual U.S. National Health Interview Survey, researchers examined the medical histories, lifestyle habits and demographics of smokers and nonsmokers. The study included 390,929 adults, ages 25 to 74 years (average age of 47), 56% female. Occasional smokers were excluded from the study. Current smokers were grouped by the age at which they began smoking.

During the follow-up period, 4,479 people died before the age of 75 from heart disease or stroke. After adjusting for potential confounding variables, such as age, education, alcohol consumption, region and race, researchers found:

58% were never smokers; 23% were ex-smokers; and 19% were current smokers;

Among current smokers, 2% had started smoking before age 10, and 19% began smoking between ages 10 and 14; and

Those who quit smoking by the age of 40 reduced their excess risk of premature death from cardiovascular disease by about 90%.

Quitting smoking at any age offered benefits, and the earlier a person quit, the better, according to the findings. The analysis found that when compared to peers who had never smoked:

Smokers who quit between ages 15 to 34 had about the same risk of dying from heart disease or stroke;

Those who quit between ages 35 to 44 had about a 20% higher risk;

Those who quit between ages 45 to 54 had about a 60% higher risk;

Those who quit between ages 55 to 64 had about a 70% higher risk of death from heart disease or stroke; and

Those who were current smokers had nearly three times the risk of dying prematurely from heart disease or stroke.

"Preventing the next generation from smoking can save lives, but we must also emphasize that quitting smoking can save lives now, and in the years to come," said Thomson. "Simply put, health policies should aim to prevent young people from smoking and should clearly communicate the benefits of quitting to those who do smoke, ideally as young as possible, and before the onset of serious illness."

"This study adds to the body of evidence that starting to smoke at younger ages can significantly increase the risk of death from cardiovascular disease. It validates the American Heart Association's position that smoking is a serious health hazard, that effective multi-episode counseling and medical therapies for cessation should be available to all and that stopping smoking should be an urgent priority for smokers of all ages, especially the young," said Rose Marie Robertson, M.D., FAHA, deputy chief science and medical officer of the Association.

"This data precedes the explosion in e-cigarette use in the U.S., and similar long-term outcomes from vaping can only be assessed over time. However, health risks have begun to emerge, and we know that vaping among teens is a precursor to smoking combustible cigarettes for many," said Robertson, who is also co-director of the Association's Tobacco Center of Regulatory Science.

Thomson said more research is needed to better clarify the mechanisms by which prolonged smoking from childhood affects cardiovascular risk. Future research should also further examine the association between early smoking initiation and death from other causes, such as respiratory diseases and cancers, and in other populations.

FOR IMMEDIATE RELEASE

In a new medical records analysis of racial disparities in end-of-life care, researchers at Johns Hopkins Medicine and three collaborating institutions report that Black patients voluntarily seek substantially more intensive treatment, such as mechanical ventilation, gastronomy tube insertion, hemodialysis, CPR and multiple emergency room visits in the last six months of life, while white patients more often choose hospice services.

This finding, researchers say, demonstrates the extent of different choices that are made in seeking end-of-life care despite an overall increase nationwide in the U.S. toward the use of hospice care regardless of diagnosis, especially in noncancer deaths.

"What's unique about our study is that we show this disparity is persistent -- not decreasing over time -- and appears to be fairly general because it is not specific to a few diseases such as cancer," says David L. Roth, Ph.D., director of the Johns Hopkins Center on Aging and Health (COAH) and a co-author of the study. These persistent disparities may impact the quality of end-of-life experiences differently for Black and white Americans and underline the importance of advance care planning and advance directives -- things that other studies have shown are less likely to be in place for Black Americans.

In a report on the study published online Aug. 24 in the Journal of the American Medical Association Network Open, the investigators note that the increasing use of hospice services in the last six months of life is seen as a positive trend -- reducing emergency department visits, repeated hospital stays, and intensive, invasive life-preserving procedures such as intubation/mechanical ventilation, tracheostomies and feeding tubes. For the study, researchers analyzed data from the ongoing, population-based REasons for Geographical and Racial Differences in Stroke (REGARDS) study coordinated by the University of Alabama at Birmingham and funded by the National Institutes of Health. Between 2003 and 2007, REGARDS enrolled more than 30,000 participants in the United States, ages 45 or older, to better understand why Southerners and Black Americans have higher rates of stroke, and related diseases that affect brain health, than other Americans. By design, REGARDS has an oversampling of Black Americans and residents of the "stroke belt" in the Southeastern United States (including Alabama, Arkansas, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina and Tennessee), to gain more information about the racial and geographical health disparities and mortality rate differences that exist.

For the current study, Roth and his colleagues identified REGARDS participants who defined themselves as either Black or white Americans, who died between 2013 and 2015 due to natural causes (excluding sudden death), and whose records were linked to Medicare claims. They examined patients who received hospice care for three or more days in the last six months of life, and if these people had multiple hospitalizations, made any emergency department visits, or were given intensive medical procedures during the same time period. Ultimately, their study population contained 1,212 participants (31.2% Black and 48% female, with a mean age of 81).

The researchers found that 34.9% of Black study participants who died used hospice services over the study period, compared with 46.2% of white participants. Black Americans were significantly less likely than white Americans to use three or more days of hospice. Also, Black Americans were more likely to have multiple emergency room visits and hospitalizations, or to undergo intensive treatments in the last six months of life -- regardless of the cause of death. This was especially true for noncancer deaths.

"Despite tremendous growth in palliative care and hospice use in the United States, our work highlights a pressing need to address racial disparities in end-of-life care," says study lead author Katherine Ornstein, Ph.D., M.P.H., director of research for the Institute of Care Innovations at Home at Mount Sinai and associate professor of geriatrics and palliative medicine at Mt. Sinai's Icahn School of Medicine in New York.

The study team recommends that more sustained efforts be made to reduce disparities in end-of-life-care through efforts to better educate and train health care providers and to promote the discussion of personal values and treatment preferences for the end of life in Black populations.

In addition to evidence that has shown that hospice care is more medically beneficial to patients in the end of life, hospice care, the researchers say, may also cost less than emergency or invasive treatments at the end stages of a person's life. A 2013 study found $2,561 in savings to Medicare for each patient enrolled in hospice 53-105 days before death, compared with a matched, nonhospice control. Even higher savings were seen with more common, shorter enrollment periods: $2,650, $5,040 and $6,430 per patient enrolled 1-7, 8-14 and 15-30 days prior to death, respectively.

What The Study Did: This randomized clinical trial compared the change in pain severity among adults with chronic low back pain who received electroacupuncture or a placebo treatment.

Authors: Jiang-Ti Kong, M.D., of the Stanford University School of Medicine in Stanford, California, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.22787)

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, conflict of interest and financial disclosures, and funding and support.

The loss of huge ice masses can contribute to the warming that is causing this loss and further risks. A new study now quantifies this feedback by exploring long-term if-then-scenarios. If the Arctic summer sea-ice were to melt completely, a scenario that is likely to become reality at least temporarily within this century with ongoing greenhouse gas emissions from burning fossil fuels, this could eventually add roughly 0.2°C to global warming. It is, however, not in addition to IPCC projections of future warming since these already take the relevant mechanisms into account. Still, the scientists could now separate the effects of the ice loss from other effects and quantify it.

The 0.2°C are substantial, given that global mean temperature is currently about one degree higher than in pre-industrial times, and governments worldwide agreed to stop the increase well below two degrees.

"If global ice masses shrink, this changes how much of the sunlight that hits Earth's surface is reflected back into space. Decreasing ice cover in the Arctic exposes more of the darker ocean water that absorbs more energy," says Nico Wunderling, lead author of the study. "This is referred to as albedo feedback. It's like wearing white or black clothes in summer. If you wear dark, you heat up more easily." Further factors include for instance the increase of water vapour in the atmosphere due to the warming if more ice is melting. Warmer air can hold more water vapour, and water vapour increases the greenhouse effect. The basic mechanisms are well-known since long, but the Potsdam scientists were able to actually calculate the overall amount of warming that can be triggered by global ice loss.

"This is not a short-term risk. Earth's ice masses are huge, which makes them very important for our Earth system as a whole - it also means that their response to anthropogenic climate change, especially that of the ice sheets on Greenland and Antarctica, unfolds on longer timescales. But even if some of the changes might take hundreds or thousands of years to manifest, it's possible we trigger them within just a couple of decades," says Ricarda Winkelmann who leads the research group.

The scientists did comprehensive computer simulations. The effects are not always straightforward: for instance, if a massive ice cover on land is shrinking, there can still be snow - which still reflects the sunlight, just like the ice did. This is why, if the mountain glaciers and the ice on Greenland and West Antarctica would all disappear, the additional warming directly caused by the ice loss would likely be just an additional 0.2 degrees on top of the 0.2 degrees due to Arctic summer sea-ice melting. "Yet every tenth of a degree of warming counts for our climate," says Winkelmann. "Preventing Earth system feedback loops, or vicious circles, is thus more urgent than ever."

Researchers have improved the assessment of consistency in meta-analysis. The improved consistency measure considers statistical power, and it has potential to alter the interpretation of meta-analyses. The new measure was published in European Journal for Philosophy of Science.

Meta-analysis refers to combining results of several studies mathematically. Especially, medicine considers meta-analyses as the highest level of evidence. If a meta-analysis recommends a treatment, the treatment most probably becomes established.

Meta-analysis must be consistent per se. Conventional measures of consistency straightforwardly favour large studies and do not consider statistical power as a source of inconsistency. Statistical power denotes the ability of a study to detect statistically significant results, such as effects of a treatment.

"Repeating a study with high statistical power is more difficult than repeating a study with low statistical power. Our proposed measure of inconsistency emphasises this aspect," says Data Manager Ari Voutilainen from the University of Eastern Finland, one of the four developers of the measure.

"If a meta-analysis combines studies that differ from each other with respect to statistical power, the meta-analysis is inconsistent, even if within-study variances are low. Moreover, it is important that studies with the highest statistical power have the strongest effect on the results of a meta-analysis. Our proposed measure accentuates the meaning of statistical power also from this viewpoint."

Scientific journals publish approximately half a million meta-analyses annually. Consequently, the improved consistency measure can have a substantial effect on research in general.

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association, Acta Pharmaceutica Sinica B (APSB) is a monthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences -- including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

Featured papers in this issue are:

Deficiency of anti-inflammatory cytokine IL-4 leads to neural hyperexcitability and aggravates cerebral ischemia-reperfusion injury by authors Xiaoling Chen, Jingliang Zhang, Yan Song, Pan Yang, Yang Yang, Zhuo Huang and Kewei Wang

(https://doi.org/10.1016/j.apsb.2020.05.002). In this paper, the authors describe a previously unknown mechanism by which IL-4 deficiency causes neural hyperexcitability and enhances neuronal excitatory transmissions. Supplementing IL-4 might be beneficial for improvement of functional recovery after brain ischemia injury.

Functional nano-vector boost anti-atherosclerosis efficacy of berberine in Apoe(?/?) mice by authors Xiaolei Ma, Tingting Zhang, Zhigang Luo, Xiaolin Lia, Miao Lin, Rui Li, Peng Du, Xiaoyou Yu, Chen Ma Pengju Yan, Jin Su, Lulu Wanga, Yuhuan Lic and Jiandong Jiang

(https://doi.org/10.1016/j.apsb.2020.03.005). The authors investigated BT1500M, which increased gut-absorption and intra-cellular uptake of berberine, modulated AMPK and NF-kB expression, and improved dyslipidemia and inflammation induced by high fat diet. The endothelial injury and subsequent macrophage infiltration and cholesteryl ester gathering in the aortic arch were decreased, resulting in the inhibition of artery plaque build-up.

Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors by authors Liying Ma, Haojie Wang, Yinghua You, Chaoya Ma, Yuejiao Liu, Feifei Yang, Yichao Zheng and Hongmin Liu

(https://doi.org/10.1016/j.apsb.2020.02.006). The authors designed and synthesized series II compounds (14a-w) based on the flavin adenine dinucleotide (FAD) similarity strategies. Further mechanism studies showed that compound 14q is an FAD competitive LSD1 inhibitor, which inhibits cell migration and invasion by reversing epithelial to mesenchymal transition (EMT).

Other articles published in the issue include:

Review articles

Recent advances of antibody drug conjugates for clinical applications

Pengxuan Zhao, Yuebao Zhang, Wenqing Li, Christopher Jeanty et al.

https://doi.org/10.1016/j.apsb.2020.04.012

Targeting necroptosis in anticancer therapy: mechanisms and modulators

Ying Wu, Guoqiang Dong, Chunquan Sheng

https://doi.org/10.1016/j.apsb.2020.01.007

Original articles

Icariside ?, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation

Zhilei Wang, Guang Xu, Hongbo Wang, Xiaoyan Zhan et al.

https://doi.org/10.1016/j.apsb.2020.03.006

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription

Ze Wang, Haihua Shang, Yazhuo Li, Chen Zhang et al.

https://doi.org/10.1016/j.apsb.2020.05.012

First small-molecule PROTACs for G protein-coupled receptors: inducing α1A-adrenergic receptor degradation

Zhenzhen Li, Yuxing Lin, Hui Song, Xiaojun Qin et al.

https://doi.org/10.1016/j.apsb.2020.01.014

Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum

Kun Zhang, Yu Zhao, Zheng Zhang, Mengyao Zhang et al.

https://doi.org/10.1016/j.apsb.2020.06.011

Identification of bioactive anti-angiogenic components targeting tumor endothelial cells in Shenmai injection using multidimensional pharmacokinetics

Chongjin Zhong, Chao Jiang, Suiying Ni, Qizhi Wang et al.

https://doi.org/10.1016/j.apsb.2019.12.011

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Kena Zhao, Tao Guo, Caifen Wang, Yong Zhou et al.

https://doi.org/10.1016/j.apsb.2020.04.015

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability

Lingyan Zhang, Mifang Li, Quan Zhou, Meng Dang et al.

https://doi.org/10.1016/j.apsb.2020.05.003

Remote loading paclitaxel-doxorubicin prodrug into liposomes for cancer combination therapy

Jiang Yu, Yingli Wang, Shuang Zhou, Jinbo Li et al.

https://doi.org/10.1016/j.apsb.2020.04.011

A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

Xinyu Hou, Chenting Shou, Muye He, Jiajun Xu et al.

https://doi.org/10.1016/j.apsb.2020.04.010

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Kuan Jiang, Junyi Chen, Lingyu Tai, Chang Liu et al.

https://doi.org/10.1016/j.apsb.2020.03.002

Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination

Xuehao Tian, Penglong Wang, Tong Li, Xuemei Huang et al.

https://doi.org/10.1016/j.apsb.2019.12.014

Understanding the role of antibiotic use patterns and patient transfers in the emergence of drug-resistant microbes is essential to crafting effective prevention strategies, suggests a study published today in eLife.

Antimicrobial resistance is a growing global health threat, but preventing it takes smart choices at the local level. The current findings, originally posted on bioRxiv*, provide insights on how antibiotic use patterns and patient transfers in hospitals drive the emergence of resistance, and suggest a new approach for tailoring prevention strategies to an individual hospital or ward.

"Hospitals continue to be important hotspots for antimicrobial resistance because of the confluence of frequent antibiotic use, fragile patients and the potential for highly resistant pathogens to spread through hospital wards when patients are transferred," explains lead author Julie Shapiro, Postdoctoral Fellow at the CIRI, Centre International de Recherche en Infectiologie, University of Lyon, France.

To help hospitals assess the best strategies for preventing the emergence of resistance, Shapiro and her colleagues employed a technique typically used in ecology to study the effect of antibiotic use and patient transfers on infections. They developed a computer model based on a year's worth of data around seven species of infection-causing bacteria, including drug-resistant strains, in 357 hospital wards in France.

"We found that the volume of antibiotic use at the hospital-ward level had a stronger influence on the incidence of more resistant pathogens, while patient transfers had the most influence on hospital-endemic microbes and those resistant to the last-line antibiotics carbapenems," Shapiro says.

They also found that the use of the penicillin antibiotic, piperacillin-tazobactam, was the strongest predictor of the emergence of bacteria that are resistant to the standard treatments for life-threatening blood infections. If this is confirmed in further studies, the authors suggest that the strategy of using piperacillin-tazobactam instead of carbapenems to prevent antimicrobial resistance may need to be reconsidered.

In fact, the study showed that the effects of antibiotic prescription and patient transfer patterns on the emergence of drug resistance varied among different microbes and types of infections, suggesting that a more individualised approach to preventing resistance is necessary.

"Our work highlights the need to tailor strategies against microbial resistance to specific pathogens," concludes senior author Jean-Philippe Rasigade, Associate Professor of Microbiology at the Hospices Civils de Lyon university hospital. "Applying the modelling techniques we used here to other healthcare settings could help inform local and regional antibiotic stewardship and infection control strategies."

PHILADELPHIA - Beth Reisboard, 76, was relieved in 2018 when she received the results from her annual mammogram: "Negative." But her OB-GYN suggested she have a second screening. Reisboard has dense breasts, which means there are certain cancers that mammography may not be sensitive enough to detect.

Surprised, Reisboard scheduled an appointment to undergo an abbreviated MRI at Penn Medicine. Twelve hours later, she received a call from the clinic -- they had found a tumor.

"By the time the cancer would have been picked up by a mammogram, it could have been stage two or three. By recommending a second screening, Dr. Ann Steiner saved my life," Reisboard said.

Reisboard is among the more than 400 asymptomatic women with dense breasts who underwent abbreviated magnetic resonance imaging (also called "fast MR" or AB-MR) at Penn Medicine between 2016 and 2019. In a retrospective study of these patients, all of whom had a negative 3-D mammogram within the previous 11 months, researchers in the Perelman School of Medicine at the University of Pennsylvania found that abbreviated MRI detected roughly 27 cancers per 1,000 women screened. By comparison, 3-D mammography detects about four to five cancers in 1,000 women screened, on average. The findings were published in the Journal of Clinical Oncology.

"Mammogram is the best tool we have to detect breast cancer, but it's not perfect. In women with fatty tissue, we can very easily detect cancer. But in women with very dense breasts, the sensitivity can be low as 30 percent," said Susan Weinstein, MD, an associate professor of Radiology at Penn. "We need to start thinking about how to better screen women with dense breasts, and AB-MR is an effective and feasible option."

Digital breast tomosynthesis (also called DBT or 3-D mammography) has become the new standard of care for breast cancer screening since it was approved by the U.S. Food and Drug Administration in 2011, detecting on average 25 percent more cancers per 1,000 women when compared to 2-D mammography. However, since DBT detects abnormalities on the basis of morphology, cancers in dense breast tissues may be obscured, and therefore be missed, on a standard mammogram.

To bring awareness to the limitations of mammography in dense breasts, breast dense notification legislation has been passed in 38 states and the District of Columbia, mandating that doctors notify patients if they have dense breasts, although the wording of the laws varies from state to state.

After a patient is notified about her breast density, the most common supplemental screening exam is ultrasound, which is readily available at most breast centers, according to Weinstein. However, ultrasound has limitations, and multiple studies have demonstrated a significantly higher cancer detection rate with contrast-enhanced MRI compared to an ultrasound screening.

The challenge is that breast MRI is a limited and expensive resource. It can require up to 16 sets of imaging, which can take up to 40 minutes to complete. Abbreviated MRI, by contrast, is a newer, shortened version of the screening. It requires only three sequences on average, making it a more accessible option for the 40 percent of women in the U.S. with dense breasts.

In 2016, the multidisciplinary ECOG-ACRIN Cancer Research Group launched a clinical trial of 1,444 women to compare abbreviated breast MRI with 3-D mammography. The research team -- led by Sloan Kettering and by Mitchell D. Schnall, MD, PhD, chair of Radiology at Penn Medicine -- found that among women with dense breasts undergoing screening, abbreviated breast MRI had a significantly higher rate of invasive cancer detection than 3-D mammogram. The results were published in JAMA in February 2020.

As the ECOG-ACRIN research trial was underway at Penn, the Department of Radiology decided to start offering abbreviated MRI to Penn Medicine patients as a supplemental screening option for those with dense breasts. In their retrospective study of the data from that time period, Weinstein and colleagues found 13 cancers in 475 patients who had a negative 3-D mammogram on the abbreviated MRI supplemental screening. An additional 13 cancers equates to more than 200 percent more cancers detected through abbreviated MRI than with 3-D mammography.

Currently, Penn Medicine is one of a handful of health systems nationwide to offer abbreviated MRI as a supplemental screening for breast cancer. The supplemental screening is available for patients with heterogeneously or extremely dense breast tissue, with a negative previous mammogram within the last 11 months and less than 20 percent lifetime risk for breast cancer. In Pennsylvania, abbreviated MRI had not been covered by insurance, but in July 2020, Governor Tom Wolf signed Senate Bill 595 into law, which requires insurers to cover supplemental screenings, including MRI, for women with dense breasts.

"As even more data comes out, there is going to be a lot of debate about how we should screen women with dense breasts, and how we should pay for it. It is important to keep in mind that, although we are detecting more cancers, we don't know the long-term benefits, such as survival rates," Weinstein said. "With further research, we will have more information in the future."

Reisboard, who was diagnosed with invasive lobular carcinoma, had her tumor removed and underwent radiation therapy in 2019. She is now cancer-free. For her, the message of her story is clear: "If your breasts are dense, you've got to talk to your doctor about having an MRI. I am walking, living proof of that."

When the Universe was only a tenth of its current age its galaxies experienced a growth spurt. It was this period that the scientists in the ALPINE project (1) focused on when they used ESO's ALMA (2) telescope to carry out the first ever large survey of distant galaxies. To their surprise, these galaxies observed in the early stages of their life were far more mature than expected. Their work is the subject of a series of articles published on 27 October 2020 in the journal Astronomy & Astrophysics, signed among others by members of the CNRS and Aix-Marseille Université (3).

Galaxies began to form very early in the history of the Universe. To study their infancy, it is therefore necessary to go back to the dawn of time, by observing very distant galaxies. The ALPINE project focused on a period between 1 and 1.5 billion years after the Big Bang, when the first galaxies experienced a phase of rapid growth. Although such distant galaxies have already been observed, this is the first time that so many of them have been studied systematically. Images of 118 massive (4) galaxies, obtained with the Hubble (visible light) and Spitzer (near infrared) space telescopes, as well as spectra acquired using the ground-based VLT and Keck telescopes, were supplemented by 70 hours of observation with ALMA at submillimetre wavelengths (between the infrared and radio waves).

ALMA can quantify dust, a sign of maturity in galaxies, and cold gas, which provides information about their rate of growth and the number of stars they can form, as well as the motion of this gas, thus revealing the dynamics of galaxies. And this turned up some surprising data. For a start, the observed galaxies proved to be very rich not only in cold gas, which fuels star formation, but also in dust, which is thought to be a by-product of stars at the end of their lives. So despite their young age, these galaxies had apparently seen the formation and death of a first generation of stars! The galaxies surveyed also exhibit an astonishing diversity of shapes: some are disordered, others already have a rotating disc that may end up as a spiral structure like the Milky Way, while yet others have been spotted in the process of merging. Another surprising observation is that certain galaxies appear to be ejecting gas, forming mysterious haloes around them. The survey thus raises a number of new questions about the early evolution of galaxies.

Empathy is talked about a lot these days. Against the backdrop of a global pandemic and a divisive political climate in the United States, calls for empathy have become louder and more urgent. We encourage empathy for those inflicted with COVID-19 and those struggling with unemployment. We reminisce about the empathy of public figures who have recently passed away. Both Democrats and Republicans have highlighted their own presidential candidate's empathy and accused the other side of lacking it.

But do we always want people to show empathy? Not so, said researchers from the University of California, Davis. A recently published paper suggests that although empathy is often portrayed as a virtue, people who express empathy are not necessarily viewed favorably.

"Empathy has become a sort of 'catch-all' for desirable personal qualities," said Y. Andre Wang, who is a doctoral candidate and lead author of the paper. "But people's views on empathy are actually more complicated.

"We found that what people think of empathizers depends on who is receiving their empathy. People don't necessarily like or respect those who show empathy toward morally questionable individuals," he added.

The paper, "Evaluations of Empathizers Depend on the Target of Empathy," was published online in September in the Journal of Personality and Social Psychology. It is co-authored by Andrew Todd, associate professor of psychology at UC Davis.

In a series of seven studies, researchers recruited more than 3,000 participants throughout the United States. They showed these participants various scenarios where someone is sharing a personal experience with another individual. In some studies, the personal experience was negative, such as stress from work problems; in other experiments, the experience was positive, such as a recent job promotion. The individual responded to this personal experience either with empathy or neutrally. Participants then rated their impressions of the responder, such as how much they liked the responder, and how warm they found the responder to be.

Who receives empathy?

But these studies had a twist: The character sharing the personal experience was portrayed either positively or negatively. For example, in one study, some participants learned that she worked for a white nationalist organization, and other participants learned that she worked for a children's hospital. In another study, the character sharing the personal experience was either pro-vaccination or anti-vaccination. (This particular study was conducted at the beginning of the COVID-19 pandemic.)

The researchers found that this portrayal mattered for their impressions of the empathizer: Participants liked and respected the empathizer, but only when the character receiving empathy was liked as well. When the character was disliked (as a white nationalist or an "anti-vaxxer"), participants did not like and respect the empathizer as much. In some studies, participants even preferred it when the responder condemned rather than empathized with the character.

"People are often encouraged to empathize with disliked others, but our findings suggest that they are not always viewed favorably for doing so," the researchers concluded.

Empathy in the eye of the observer

Although empathy is widely studied, little is known about how people evaluate empathizers when they are not themselves the recipients of empathy. These findings have implications for how empathy operates in the current sociopolitical climate, where empathy is often touted as a solution to national divisions and strife.

"Is more empathy always better? Not according to our participants." Wang said. "Our findings suggest that people see empathy as a social signal. Whom you choose to empathize with shows whom you care about and what you stand for.

"Empathy is, of course, valuable. But it is not a panacea. If people who empathize across social divides are repudiated, then empathy might not always bridge those divides. Instead, it might even reinforce them."

Rye Brook, NY (Monday, October 26, 2020) - Patients participating in The Leukemia & Lymphoma Society's (LLS) groundbreaking precision medicine Beat AML Master Clinical Trial had superior outcomes compared to acute myeloid leukemia (AML) patients who opted for standard chemotherapy treatment, according to findings published today in the prestigious Nature Medicine journal.

The Beat AML trial achieved its primary endpoint by showing genomic analysis of the leukemia cells to identify AML subtypes can be completed within an unprecedented seven days, giving patients, caregivers and their doctors ample time to make a more personalized treatment decision without risking the patient's chance for survival.

In other key findings, the study demonstrated a paradigm shift in how patients diagnosed with AML should be treated, proving that using genetic information to match patients to targeted therapies leads to better survival rates than the traditional one-size-fits all treatment approach.

AML is an extremely fast-moving cancer of the marrow and blood, affecting 21,000 people in the U.S. a year, and killing 10,000. For decades patients have been given the same treatments almost immediately upon diagnosis because waiting allows the cancer cells to grow out of control. This standard of care involves either infusion of a combination of two chemotherapies, cytarabine and daunorubicin, or treatment with a so-called hypomethylating agent, a drug that unleashes signals allowing the cancer cells to die.

"The study shows that delaying treatment up to seven days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival compared to patients who opted for standard of care," said John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research of The Ohio State University, and one of the Beat AML leads and corresponding author of the study. "This patient-centric study shows that we can move away from chemotherapy treatment for patients who won't respond or can't withstand the harsh effects of the same chemotherapies we've been using for 40 years and match them with a treatment better suited for their individual case."

Going on the Offensive Against AML

Recognizing the urgent need to do better for AML patients, LLS launched this clinical trial in fall 2016 to test multiple novel targeted therapies at major cancer centers across the U.S., in newly diagnosed AML patients aged 60 and older. In a historic first for cancer clinical trials, LLS is the first non-profit health organization to sponsor a trial and hold the IND (Investigational New Drug) application from the U.S. Food and Drug Administration. Beat AML partnered with Foundation Medicine Inc. to employ next generation genomic sequencing to rapidly analyze the patients' cancer cells, and identify the patients' AML subtype so they can be given a targeted therapy within a safe timeframe.

"The breadth of this collaboration, with every clinician, cancer center, pharmaceutical partner and all of the many operations and technical support companies, all unified in working toward the common goal of building a new model for tackling this challenging disease, was truly inspiring," said Amy Burd, Ph.D., LLS vice president of research strategy, and first author on the paper.

Drs. Byrd and Burd were joined by Brian Druker, MD, Director, Knight Cancer Institute at Oregon Health & Science University, and Ross L. Levine, MD, Director of the Center for Hematologic Malignancies at Memorial Sloane Kettering Cancer Center, in leading a team of renowned academic researchers and other collaborators to plan, develop and launch Beat AML. To date, the trial, which is ongoing, has screened more than 1,000 patients at 16 cancer centers. The data presented in today's Nature Medicine publication represents patient enrollment during a slice of time between November 17, 2016 and January 30, 2018.

Compelling Data Findings

Of 487 patients with suspected AML who agreed to participate during that timeframe, 395 were found eligible for the trial. Screening and analysis was successfully completed within the seven-day timeline for 374, or 94.7 percent, of those patients. Ultimately, 224 of those patients opted to participate on one of the 11 study arms that were active during that period. The patients who didn't chose to join the study either opted for standard of care, palliative care, or an alternative clinical trial.

The median overall survival for patients in Beat AML was 12.8 months v. 3.9 months for patients opting for standard of care.

"The study is changing significantly the way we look at treating patients with AML, showing that precision medicine, giving the right treatment to the right patient at the right time, can improve short and long-term outcomes for patients with this deadly blood cancer," said Louis J. DeGennaro, Ph.D. president and CEO of LLS. "Further, Beat AML has proven to be a viable model for other cancer clinical trials to emulate."

Indeed, LLS recently launched its Beat COVID trial, leveraging rapidly the Beat AML infrastructure to quickly pivot to treat blood cancer patients who are infected with the COVID-19 virus. Studies show blood cancer patients are between 30-60% at risk of death if infected with the COVID-19 virus and Beat COVID is testing a drug called acalubrutinib (Calquence ®), already approved to treat several types of blood cancers. The drug shows promise in addressing deadly symptoms of Covid-19, such as inflammation of lungs and other vital organs. The trial is open to patients diagnosed with all types of blood cancers.

LLS is also planning other precision medicine trials modeled after Beat AML, including LLS PedAL, a global precision medicine trial for children with relapsed acute leukemia, on track to launch in summer 2021, and Stop MDS, a master trial for patients with myelodysplastic syndromes, a blood cancer that frequently progresses to AML.