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Columbia Engineering researchers report that they have developed a “cloaking” system that temporarily hides therapeutic bacteria from immune systems, enabling them to more effectively deliver drugs to tumors and kill cancer cells in mice. By manipulating the microbes’ DNA, they programmed gene circuits that control the bacteria surface, building a molecular “cloak” that encapsulates the bacteria.
“What’s really exciting about this work is that we are able to dynamically control the system,” said Tal Danino, associate professor of biomedical engineering, who co-led the study in collaboration with Kam Leong, Samuel H. Sheng Professor of Biomedical Engineering. “We can regulate the time that bacteria survive in human blood, and increase the maximum tolerable dose of bacteria. We also showed our system opens up a new bacteria delivery strategy in which we can inject bacteria to one accessible tumor, and have them controllably migrate to distal tumors such as metastases, cancer cells that spread to other parts of the body.”
For the study published today by Nature Biotechnology, the researchers focused on capsular polysaccharides (CAP), sugar polymers that coat bacterial surfaces. In nature, CAP helps many bacteria to protect themselves from attacks including immune systems. “We hijacked the CAP system of a probiotic E. coli strain Nissle 1917,” said Tetsuhiro Harimoto, a PhD student in Danino’s lab who is the study’s co-lead author. “With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch.”
An Effective On/Off Switch
To do this, the researchers engineered a new CAP system, which they call inducible CAP, or iCAP. They control the iCAP system by giving it an external cue — a small molecule called IPTG — that allows for programmable and dynamic alteration of the E. coli cell surface. Because iCAP alters bacterial interactions with immune systems (such as blood clearance and phagocytosis) in a directed manner, the team found that they could control the time to which bacteria can survive in human blood, by tuning how much IPTG they give to the iCAP E. coli.
Using Bacteria For Therapy
While using bacteria for therapy is a new, alternative approach to treating a broad array of cancers, there are a number of challenges, in particular, their toxicity. Unlike many traditional drugs, these bacteria are alive and can proliferate within the body. They are also detected by the body’s immune systems as foreign and dangerous, causing high inflammatory response — too much bacteria means high toxicity due to over-inflammation — or rapid bacteria elimination — too little bacteria means no therapeutic efficacy.

By advocating for acupuncture and other treatments, she helped countless patients weather the pain of chemotherapy and radiation.Barrie R. Cassileth, whose efforts to bring treatments like acupuncture and massage into mainstream cancer care helped countless patients weather the pain of chemotherapy, radiation and terminal illness, died on Feb. 26 at an assisted-living home in Beverly Hills, Calif. She was 83.Her granddaughter Rachel Greenspan said the cause was complications of Alzheimer’s disease.Dr. Cassileth, who founded the Integrative Medicine Service at Memorial Sloan Kettering Cancer Center in New York City, drew a bright line between alternative medicine, which she often dismissed as quackery, and what she called complementary medicine, which attempts to alleviate the symptoms of cancer and its treatments.Such care might also be casually considered “alternative,” like acupuncture, massage and herbs, but Dr. Cassileth insisted that the difference lay in the science: The approaches had been rigorously studied, and they showed actual medical benefits.And, just as important, she never offered them in place of conventional medicine, let alone as a cure, a practice she called “grotesquely outrageous” in The New York Times in 1998. “It is malpractice on the part of public health services to offer an untested, unscientific method as a real alternative.”Dr. Cassileth first came into the public eye as a sharp critic of alternative medicine in the late 1970s and ’80s, when nontraditional approaches to cancer were the stuff of best-selling books and daytime talk shows.A study that she and several colleagues published in The New England Journal of Medicine in 1985 showed that differences in personality among patients with advanced cancer did not change outcomes. Patients who showed grit and determination, they found, died just as quickly as patients who showed stoic resignation to the disease.“For every anecdote about a cancer patient with a good attitude who lived, I can give you 200 about those who had good attitudes and died,” she told The Los Angeles Times that year.She was especially concerned about licensed medical practitioners who advised their patients to seek treatment outside the mainstream. She raised the alarm when a survey conducted in the early 1990s showed that 9 percent of cancer patients did not pursue conventional treatments — a number that later included Steve Jobs, the co-founder of Apple, who at first tried to fight the disease with dietary supplements and juices.“He had the only kind of pancreatic cancer that is treatable and curable,” she told USA Today in 2013. “He essentially committed suicide.”But Dr. Cassileth was also quick to note the limits of her own research, and to assert her openness to the possible efficacy of treatments outside the mainstream. She was both a member the American Cancer Society’s Subcommittee on Questionable Methods of Cancer Management and an adviser to the National Institutes of Health’s Office of Alternative Medicine, now called the National Center for Complementary and Alternative Medicine.She took a historical perspective. Cancer was once considered incurable, and so the focus of treatment was limited to palliative care, helping ease a patient’s pain. But with the rise of chemotherapy and radiation and the growing possibility of survival, comfort and quality of life took a back seat. Her mission, she said, was to bring that back, using evidence-based, noninvasive treatments.“She was a legend in our field,” Dr. Ting Bao, the director of integrative breast oncology at Memorial Sloan Kettering, said in an interview.Barrie Joyce Rabinowitz was born on April 22, 1938, in Philadelphia. Her father, Albert Rabinowitz, owned a company that manufactured socks; later, he and her mother, Rosalind (Kaizen) Rabinowitz, ran a company that designed and installed kitchens.She is survived by her siblings, Stephen Rabinowitz and Ruth Rabinowitz; her daughters, Jodi Cassileth Greenspan and Wendy Cassileth; her son, Gregory Cassileth; and six grandchildren.She attended Bennington College in Vermont and spent a summer teaching art in Pownal, a village near the Massachusetts border. Working out of a one-room schoolhouse, she befriended the parents of two of her students. The mother, Ms. Rabinowitz soon learned, had terminal cancer, and the experience of watching her suffer focused her interests on helping alleviate such pain.She graduated with a degree in social sciences in 1959, a year after marrying Peter Cassileth. They later divorced. Her second marriage, to H. Taylor Vaden, a communications executive, also ended in divorce. Her third husband, Richard Cooper, a hematologist, died in 2016.Dr. Cassileth received a master’s degree in psychology from Albert Einstein University and a Ph.D. in medical sociology in 1978 from the University of Pennsylvania, where her husband, Peter, was an oncologist.As part of her doctoral program, she worked closely with adult leukemia patients. After being hired at Pennsylvania as an assistant professor, she helped establish one of the first palliative cancer care programs in the country.She later taught at Duke, Harvard and the University of North Carolina before being approached in 1999 by Memorial Sloan Kettering, where one of the benefactors, Laurance Rockefeller, was leading an effort to create an integrative care program.What started as a one-woman show in one small office grew to a staff of about 60 people, with its own four-story building, largely thanks to Dr. Cassileth’s leadership. In 2003, she was the founding president of the Society for Integrative Oncology.Today, thousands of cancer patients at Memorial Sloan Kettering, and in similar programs nationwide, benefit from complementary care — the result, Dr. Cassileth always insisted, of advances in conventional medical care.“Quality of life has only become an issue,” she told The Washington Post in 2000, “since enough patients have been around long enough to worry about quality of life.”

Heavy alcohol use is associated with missing work, but the scope of that relationship has not been well understood. Now, based on survey data from more than 110,000 U.S. adults with full-time jobs, researchers at Washington University School of Medicine in St. Louis have quantified the extent of the problem.
Among U.S. adults working full time, an estimated 9% — almost 11 million full-time workers — met the diagnostic criteria for alcohol use disorder, a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse consequences in one’s social life, work life or health.
The findings are published online March 17 in the journal JAMA Network Open.
Analyzing the survey data, the researchers found that people with severe alcohol use disorder reported missing 32 days of work each year because of illness, injury or simply skipping work, more than double the number of workdays missed by individuals without alcohol use disorder. In all, workers with alcohol use disorder missed more than 232 million work days annually.
“Alcohol use disorder is a major problem in the United States and a big problem in many workplaces, where it contributes to a significant number of workdays missed,” said senior investigator Laura J. Bierut, MD, the Alumni Endowed Professor of Psychiatry. “The problem likely has worsened during the pandemic, and we need to try to do more to ensure that people can get the help they need to deal with alcohol use disorder. The new data also point to an economic incentive for employers and policymakers to address the issue.”
Bierut and her colleagues analyzed data gathered from 2015 through 2019 via the National Survey on Drug Use and Health. The survey is administered every year by the Substance Abuse and Mental Health Services Administration, which asks individuals over age 12 about their use of alcohol and other drugs over the previous 12 months.

A delta breakthrough infection generates a potent and broad neutralizing antibody response in double vaccinated individuals, according to new research. The findings were published this week in mBio, an open-access journal of the American Society for Microbiology.
In the new study, researchers collected sera from individuals attending St. Thomas’ Hospital in London who tested positive for COVID-19 and had received 2 doses of either the Pfizer or AstraZeneca vaccines. They measured how much antibody the person produced and whether the antibodies were able to prevent infection of cells by different SARS-CoV-2 variants of concern.
The researchers found that in vaccinated individuals, there was a rapid and robust IgG recall response following breakthrough infection. This antibody response had broad neutralizing activity against current variants of concern, including omicron. The neutralization potency was 4.5-fold reduced against omicron compared to delta whereas it was 28.9-fold reduced for people who were unvaccinated.
“Overall, a breakthrough infection effectively boosts the vaccine response, which could provide broad protection against current variants of concern,” said co-author Katie Doores, Ph.D., Reader in the Department of Infectious Diseases, King’s College London, in the United Kingdom. “Recent studies show a third vaccine dose dramatically increases the neutralizing antibody response, particularly against omicron. Our data suggests a delta breakthrough infection can also act as an effective booster. This study provides insights into population immunity in double COVID-19 vaccinated individuals where SARS-CoV-2 transmission levels remain high.”
Dr. Doores said they are now studying the immune response in more detail by isolating monoclonal antibodies from individuals experiencing breakthrough infections.
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Materials provided by American Society for Microbiology. Note: Content may be edited for style and length.

A world-first treatment for Creutzfeldt-Jakob disease (CJD), developed by scientists at the Medical Research Council (MRC) Prion Unit at UCL, has shown “very encouraging” early results following its use in six patients at University College London Hospitals (UCLH) NHS Foundation Trust.
CJD is a rare but devastating disease that causes brain damage and for which there is currently no licensed treatment. It is always fatal and most patients sadly die within a few months of diagnosis.
Researchers at the MRC Prion Unit at UCL have developed a monoclonal antibody, called PRN100, which was given to six UCLH patients with CJD between October 2018 and July 2019.
The results, published in the Lancet Neurology, show the treatment is safe and able to access the brain. In three patients, disease progression appeared to stabilise when dosing levels were in target range.
Given the small number of patients treated, researchers say the findings should be regarded as preliminary and further studies are needed to draw more comprehensive conclusions.
None of the six patients experienced side effects while receiving the treatment but all sadly died as a result of their condition.

Neurosurgery experts from Cambridge have led the largest ever study examining the surgical management of traumatic brain injuries, highlighting regional inequalities in both major causes and treatment of such injuries.
The Global Neurotrauma Outcomes Study, funded by the NIHR, is published in The Lancet Neurology and provides data to assist in decision making and improving outcome for patients with traumatic brain injury globally.
The paper focuses on types of cases, the way they are managed, and death rates, and was compiled using data submitted by 159 hospitals in 57 countries to a central database, which the researchers then analysed. The researchers stratified countries into four tiers (very high, high, medium, low) according to their Human Development Index (HDI), which takes account of factors like life expectancy, education, and income.
The prospective study determined that patients in the low HDI tier were often young and tended to suffer skull fractures due to assault but were classified as ‘mild’ traumatic brain injury (TBI).
In the medium and high HDI tiers, patients were also young, but most had moderate to severe TBI caused by a road traffic collision and extradural haematoma — a bleed on the outside of the dura mater, the membrane covering of the brain.
In the very high tier, patients tended to be older and presented with a moderate or severe TBI associated with a fall and acute subdural haematoma — a bleed on the inner surface of the dura mater.

Parkinson’s disease is a neurodegenerative disorder characterized by the destruction of a specific population of neurons: the dopaminergic neurons. The degeneration of these neurons prevents the transmission of signals controlling specific muscle movements and leads to tremors, involuntary muscle contractions or balance problems characteristic of this pathology. A team from the University of Geneva (UNIGE) has investigated the destruction of these dopaminergic neurons using the fruit fly as study model. The scientists identified a key protein in flies, and also in mice, which plays a protective role against this disease and could be a new therapeutic target. This work can be read in the journal Nature Communications.
Apart from rare forms involving a single gene, most Parkinson’s cases result from an interaction between multiple genetic and environmental risk factors. However, a common element in the onset of the disease is a dysfunction of mitochondria in dopaminergic neurons. These small factories within cells are responsible for energy production, but also for activating the cell’s self-destruct mechanisms when damaged.
The laboratory of Emi Nagoshi, Professor in the Department of Genetics and Evolution at the UNIGE Faculty of Science, uses the fruit fly, or Drosophila, to study the mechanisms of dopaminergic neuron degeneration. Her group is particularly interested in the Fer2 gene, whose human homolog encodes a protein that controls the expression of many other genes and whose mutation might lead to Parkinson’s disease via mechanisms that are not yet well understood.
In a previous study, this scientific team demonstrated that a mutation in the Fer2 gene causes Parkinson’s-like deficiencies in flies, including a delay in the initiation of movement. They had also observed defects in the shape of the mitochondria of dopaminergic neurons, similar to those observed in Parkinson’s patients.
Protecting neurons
Since the absence of Fer2 causes Parkinson’s disease-like conditions, the researchers tested whether — on the contrary — an increase in the amount of Fer2 in the cells could have a protective effect. When flies are exposed to free radicals, their cells undergo oxidative stress which leads to the degradation of dopaminergic neurons. However, the scientists were able to observe that oxidative stress no longer has any deleterious effect on the flies if they overproduce Fer2, confirming the hypothesis of its protective role.
“We have also identified the genes regulated by Fer2 and these are mainly involved in mitochondrial functions. This key protein therefore seems to play a crucial role against the degeneration of dopaminergic neurons in flies by controlling not only the structure of mitochondria but also their functions,” explains Federico Miozzo, researcher in the Department of Genetics and Evolution and first author of the study.
A new therapeutic target
To find out whether Fer2 plays the same role in mammals, the biologists created mutants of the Fer2homolog in mouse dopaminergic neurons. As in the fly, they observed abnormalities in the mitochondria of these neurons as well as defects in locomotion in aged mice. “We are currently testing the protective role of the Fer2 homolog in mice and results similar to those observed in flies would allow us to consider a new therapeutic target for Parkinson’s disease patients,” concludes Emi Nagoshi.
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Materials provided by Université de Genève. Note: Content may be edited for style and length.

Obesity and overweight are among the biggest health challenges of the 21st century, according to the World Health Organization (WHO). Almost 60 percent of Germans are considered overweight, while 25 percent are obese. Moreover, being overweight often triggers severe secondary diseases such as diabetes, arteriosclerosis, or heart attacks.
Immunological processes determine the course of this disease. As part of a new study, a group of LMU researchers led by Dr. Susanne Stutte and Professor Barbara Walzog has shown that a high-caloric diet, even for a period of only three weeks, has drastic effects on the immune system.
“A particular kind of immune cells known as plasmacytoid dendritic cells (pDCs) begins to accumulate in the visceral adipose tissue,” explains Stutte. This adipose tissue is located inside the abdomen and surrounds internal organs. With high caloric diet, small clusters of immune cells form tertiary lymphoid structures inside this fat, resulting in fatal immune responses.
“Now, these pDCs in visceral fat are in a constant state of alarm and release type-I interferon,” explains Walzog. This interferon usually mediates the control of infections, but here it triggers the metabolic syndrome: the metabolism derails and inflammatory markers rise. When the migration of pDCs into the fat is blocked, weight gain is reduced and the metabolic condition improves considerably.
The results of this study, which was carried out in collaboration with Harvard Medical School in Boston, could now contribute to the development of new approaches toward a therapeutic intervention of the metabolic syndrome.
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Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

Daytime napping among older people is a normal part of aging — but it may also foreshadow Alzheimer’s disease and other dementias. And once dementia or its usual precursor, mild cognitive impairment, are diagnosed, the frequency and/or duration of napping accelerates rapidly, according to a new study.
The study, led by UC San Francisco and Harvard Medical School together with Brigham and Women’s Hospital, its teaching affiliate, departs from the theory that daytime napping in older people serves merely to compensate for poor nighttime sleep. Instead, it points to work by other UCSF researchers suggesting that dementia may affect the wake-promoting neurons in key areas of the brain, the researchers state in their paper publishing March 17, 2022, in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
“We found the association between excessive daytime napping and dementia remained after adjusting for nighttime quantity and quality of sleep,” said co-senior author Yue Leng, MD, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences.
“This suggested that the role of daytime napping is important itself and is independent of nighttime sleep,” said Leng, who partnered with Kun Hu, PhD, of Harvard Medical School, in senior-authoring the paper.
Watch-Like Devices, Annual Evaluations Used to Measure Naps, Cognition
In the study, the researchers tracked data from 1,401 seniors, who had been followed for up to 14 years by the Rush Memory and Aging Project at the Rush Alzheimer’s Disease Center in Chicago. The participants, whose average age was 81 and of whom approximately three-quarters were female, wore a watch-like device that tracked mobility. Each prolonged period of non-activity from 9 a.m. to 7 p.m. was interpreted as a nap.

After the start of the SARS-C0V-2 pandemic, investigators from ResearchPath LLC and their collaborators at Rutgers University quickly dedicated resources to develop accurate and reliable COVID-19 testing. As variants emerged, they developed a PCR test that uses molecular beacons not only to diagnose COVID-19 infection, but also to identify the specific variant causing that infection. Their research appears in The Journal of Molecular Diagnostics, published by Elsevier. Their methodology is openly available so that it can be replicated by any facility that can run a PCR test.
“It is extraordinary to see that SARS-CoV-2 was not a monolithic infection with a predictable set of clinical features, but rather an ever-evolving disease for which the different strains produce unique clinical features that affect testing, symptoms, and even which organ systems can be attacked,” explained lead investigator Sanjay Tyagi, PhD, Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Identifying specific strains reveals important information such as the length of incubation period, length of contagious period, transmissibility, pathogenicity, and even changes in the predominant symptoms.
Information on strain types is generally reported by the international community or a few states with large populations that perform genetic sequencing. The deep sequencing needed to identify SARS-CoV-2 strains is accurate and can identify each mutation present in a sample, but it is costly, slow and requires specialized equipment. Yet knowledge of the strain type provides important information for public health professionals, policymakers, and individuals.
“Knowing that a highly contagious and dangerous strain is emerging in a local community could inform policymakers to initiate safety measures to limit spread,” said co-investigator Ashley Hill, MD, ResourcePath LLC, Sterling, VA, USA. “It can also serve as an early warning system for healthcare systems that need to plan for surges in ER visits and ICU care. Knowing which strain has infected a person can also help determine which treatments would be most beneficial.”
Using real-time PCR probes designed by Rutgers University and already used around the world for many purposes, Rutgers designed the Rutgers-RP RT-PCR assay to detect mutations in SARS-CoV-2 that have been shown to increase immune escape, avoid neutralization, and increase transmissibility. They pioneered the use of molecular beacons to identify specific genetic mutations. Molecular beacons are hairpin-shaped molecules that can be designed to selectively bind to a specific mutant sequence, avoiding wild-type sequences that often differ by a single nucleotide.
Nine mutations were selected for testing, and the beacon for each has differently colored dyes. Every original variant of concern — alpha, beta, gamma, delta, and omicron — has a unique combination of these mutations. and when the beacon binds to its target molecule, its distinct color can be detected by the assay.
Each beacon was tested individually to confirm its specificity to the assigned mutation. Then, the beacons were combined into a multiplex assay and tested by RT-PCR on 26 SARS-CoV2-positive patient samples that had previously been tested and identified with deep sequencing. Two samples were identified as the alpha variant, two as the epsilon variant, and eight as the delta variant. The multiplex assay was in full agreement with results from deep sequencing, with a sensitivity and specificity of 100%.
Researchers report that the test is also very adaptable. When omicron emerged, the investigators were able to design a beacon in less than a month to identify a mutation that is unique to omicron and is important for immune evasion. The investigators identified the omicron variant in 17 of 33 additional patient samples that had been previously tested, and the results were 100% in agreement.
“The tools we developed to track and identify new variants will be useful for this pandemic and for any unforeseen viruses or pathogens that may arise going forward,” said lead author Ryan J. Dikdan, BS, Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
“The SARS-CoV-2 virus is not done with us yet. We desperately need a worldwide monitoring system for the inevitable emerging strains that could be even more contagious or deadly,” the investigators said. “The Rutgers-RP RT-PCR variant assay could be widely deployed in laboratories around the world right now to monitor all the known variants of concern. The assay will be updated with new primer/probe sets for each new important variant that emerges.”
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Materials provided by Elsevier. Note: Content may be edited for style and length.