Obtaining a medical marijuana card may pose a risk for those who use cannabis products to treat pain, anxiety, or depression, according to a Massachusetts General Hospital study.

In a significant minority of individuals, researchers found those at greatest risk of developing the addictive symptoms of cannabis use disorder (CUD) were seeking relief from anxiety and depression, suggesting the need for stronger safeguards over the dispensing, use, and professional follow-up of people who legally obtain cannabis through medical marijuana cards (MMC).

The findings were published in JAMA Network Open.

“There have been many claims about the benefits of medical marijuana for treating pain, insomnia, anxiety, and depression, without sound scientific evidence to support them,” says lead author Jodi Gilman, with the Center for Addiction Medicine at MGH. “In this first study of patients randomized to obtain medical marijuana cards, we learned there can be negative consequences to using cannabis for medical purposes. People with pain, anxiety or depression symptoms failed to report any improvements, though those with insomnia experienced improved sleep.” Particularly disturbing to Gilman was the fact individuals with symptoms of anxiety or depression — the most common conditions for which medical cannabis is sought — were most vulnerable to developing cannabis use disorder. CUD symptoms include the need for more cannabis to overcome drug tolerance and continued use despite physical or psychological problems caused by the cannabis.

“Medical” cannabis has surged in popularity as 36 states and the District of Columbia have commercialized its use (as of December 2021) for myriad health conditions through medical marijuana cards. These cards require written approval of a licensed physician who, under the current system, is typically not the patient’s primary care provider but a “cannabis doctor” who may provide authorization to patients with only a cursory examination, no recommendations for alternative treatments, and no follow-up. Indeed, the medical marijuana industry functions outside regulatory standards that apply to most fields of medicine.

MGH researchers began their trial in 2017 with 269 adults (average age of 37) from the Greater Boston area who were interested in obtaining a medical marijuana card. One group was allowed to get MMCs immediately, while the second group, designed to serve as a control, was asked to wait 12 weeks before obtaining a card. Both groups were tracked over 12 weeks. The team found that the odds of developing CUD were nearly two times higher in the MMC cohort than in the wait list control group, and that by week 12, 10 percent of the MMC group had developed a CUD diagnosis, with the number rising to 20 percent in those seeking a card for anxiety or depression.

“Our study underscores the need for better decision-making about whether to begin to use cannabis for specific medical complaints, particularly mood and anxiety disorders, which are associated with an increased risk of cannabis use disorder,” says Gilman.

Regardless of the specific health condition for which cannabis is sought, Gilman believes that regulation and distribution of cannabis to people with medical marijuana cards must be greatly improved. “There needs to be better guidance to patients around a system that currently allows them to choose their own products, decide their own dosing, and often receive no professional follow-up care.”

Gilman is associate professor of psychiatry at Harvard Medical School. Senior author A. Eden Evins, is the Cox Family Professor of Psychiatry at HMS.

The study was funded by the National Institute on Drug Abuse.

Harvard pandemic experts monitoring the global spread of the Omicron subvariant BA.2 say that early tracking in the U.S. suggests a milder impact than the dramatic case surge some nations have experienced.

Jacob Lemieux, an instructor in medicine at Harvard Medical School and infectious disease specialist at Massachusetts General Hospital, said that many regions of the world have seen large BA.2 outbreaks, but that the effects vary widely. In Hong Kong, for example, BA.2 led to a major surge in cases and what Lemieux described as a “complete loss of control over the epidemic.” In South Africa — which suffered a severe wave of Omicron, technically BA.1 — BA.2 almost completely replaced the COVID variant, but without cases rising substantially.

One possibility for BA.2 in the U.S. “is that we see almost nothing at all associated with the transition to BA.2 prevalence,” said Lemieux, who is the co-lead of the viral variants program for the Massachusetts Consortium on Pathogen Readiness, which held a media briefing on Monday. “That’s what happened in South Africa, where there was a severe BA.1 wave. BA.2 took over and there continued to be a low level of transmission, but there was no surge.”

For the longest time, your milk choices were whole, 2%, 1%, and fat-free (or skim). Today, refrigerator shelves at grocery stores are crowded with plant-based milks made from nuts, beans, or grains, and include favorites like almond, soy, coconut, cashew, oat, and rice. Yet the fertile ground of the plant-milk business continues to sprout new options, such as pistachio, pea, and even potato milk. It seems if you can grow it, you can make milk out of it.

So, are these new alternatives better nutritionally than the other plant milks — or just more of the same?

A few facts about plant-based milks

Plant-based milks are all made the same way: nuts, beans, or grains are ground into pulp, strained, and combined with water. You end up with only a small percentage of the actual plant — less than 10 percent for most brands. Nutrients like vitamin D, calcium, potassium, and protein are added in varying amounts. “Still, many alternative milks have similar amounts of these nutrients compared with cow’s milk,” says Walter Willett, professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health.

Plant-based milks are considered “greener” than dairy and emit fewer greenhouse gases during production. However, growing some of these plants and making them into milk requires great quantities of water. Most plant-based milks are low-calorie. On average, though, these milk products cost more than dairy.

Nutrition, calories, and other benefits of newer plant-based milks

Here’s a closer look at three new members of the alternative-milk family.

Pistachio milk is not green like the nut, but rather an off-brown color. Because it contains little actual pistachio, you miss out on the nuts’ essential vitamins and minerals, like thiamin, manganese, and vitamin B6. Yet pistachio milk contains less than 100 calories per cup, which is similar to skim cow’s milk and other plant-based milks. One extra benefit of pistachio milk is that it’s a bit higher in protein than other plant milks (which can be light in the protein department compared with cow’s milk).

Pea milk is created from yellow field peas, but has no “pea-like” flavor. Its color, taste, and creamy consistency are close to dairy, so people may find it more appealing than the sometimes-watery texture of other plant milks. Pea milk has a decent protein punch — at least 7 grams per serving — and each serving adds up to about 100 calories. It also requires less water in production than other plant milks and has a smaller carbon footprint than dairy.

Potato milk looks more like regular dairy milk than other plant milks because of the potato’s starchy nature. It’s arguably the most eco-conscious plant milk because growing potatoes requires less land and water than dairy and other plants. Potato milk also is low-calorie: 80 to 100 per serving.

This is an excerpt from an article that appears on the Harvard Health Publishing website.

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Matthew Solan is the executive editor of Harvard Men’s Health Watch.

Insights into how cancer cells adapt and rewire their metabolism to achieve growth and survive were accompanied by a call for tools to study this on a nearly single-cell level, according to a new paper in Nature Communications.

In the 1920s, Otto Warburg observed that cancer cells metabolically adapt their glucose pathway in unusual ways. Normally, glucose — the main nutrient needed for cells to function — is sent to the cell’s mitochondria to be broken down for energy, a process that requires oxygen. However, cancer cells appear to rapidly increase their glucose uptake and directly ferment it into lactate, even in the presence of oxygen and functional mitochondria.

“He called it aerobic glycolysis, but we know it as the Warburg effect,” says author Raul Mostoslavsky, scientific co-director of the Mass General Cancer Center and the Laurel Schwartz Professor of Oncology (Medicine) at Harvard Medical School. For nearly 15 years researchers have been trying to explain why cancer cells do this.

In this paper, Mostoslavsky’s team studied colon cancer tumors to learn more. They developed a fluorescent reporter that stained only a marker of glycolysis in cells of the tumor. Using this reporter and a mass spectrometry imaging approach developed by collaborator Nathalie Agar of Brigham and Women’s Hospital, the researchers found that not all cells within the colon cancer cell relied on Warburg glycolysis.

“We found that this metabolic adaptation does not happen in the whole tumor, only in a heterogeneous group that were not dividing,” says Mostoslavsky. His team had published this heterogeneous feature in squamous cell carcinoma but this is the first time it has been shown in colon cancer, and in non-dividing cells.

“What really surprised us is that when we stained the tumor cells with a marker of cell proliferation, they were mutually exclusive,” adds Mostoslavsky. Within fully transformed colon cancers, the cells that were doing Warburg glycosis were not dividing.

“This completely challenges the dogma of the Warburg effect,” he adds. For the past 10 to 15 years, most researchers working in cancer metabolism have held that cancer cells do Warburg glycolysis to send glucose for biomass production, or rapid proliferation. “Instead, we found that the main reason they were doing it was to reduce reactive oxygen species, or ROS.” Reactive oxygen species damage cells during glucose breakdown and energy production: “The cells do Warburg metabolism to protect against accumulation of ROS.”

This research showed that indeed Warburg glycolysis is real and functional in cancer cells as a needed adaptation. “But it’s not for the reason we used to think,” says Mostoslavsky. “This means we need to rethink how we are studying cancer metabolism.” Much of the advancements made in the past 10 years studying cancer metabolism come from mass spectrometry analysis of metabolomics, which require many cells. The problem is a lack of means for analyzing cellular heterogeneity.

“If metabolic adaptation happens in some cancer cells or not in others, you will not be able to determine that with the current technologies that exist,” he says. “We now know Warburg glycolysis is a heterogeneous feature happening in tumors so we need to develop tools that will allow us to investigate tumors in a single-cell fashion.”

In this paper, the team relied on a novel mass spectrometry imaging tool developed to achieve data almost at a single cell resolution. Says Mostoslavsky: “It is clear that cancer metabolism is highly heterogeneous so we will need new tools like this to study and define these metabolic features in tumors.”

Other authors of the study include Carlos Sebastian, Christina Ferrer, Maria Serra, Jee-Eun Choi, Nadia Ducano, Alessia Mira, Manasvi Shah, Sylwia Stopka, Andrew Perciaccante, Claudio Isella, Daniel Moya-Rull, Marianela Vara-Messler, Silvia Giordano, Elena Maldi, Niyata Desai, Diane Capen, Enzo Medico, Murat Cetinbas, Ruslan Sadreyev, Dennis Brown, Miguel Rivera, Anna Sapino, and David Breault.

This work was supported by grants from the National Institutes of Health, FPRC 5 per mille 2011 MIUR, FPRC 5 per mille 2014 MIUR, RC 2018 Ministero della Salute, and the European Union’s Horizon 2020 Research and Innovation Program.

This was adapted from a Massachusetts General Hospital press release.

A large study challenges the theory that light alcohol consumption benefits heart health, suggesting instead it may be attributed to other lifestyle factors common among light to moderate drinkers.

Published in JAMA Network Open, the research was led by a team from Massachusetts General Hospital and the Broad Institute of MIT and Harvard.

The study included 371,463 adults with an average age of 57 years and an average alcohol consumption of 9.2 drinks per week. All were participants in the U.K. Biobank, a large-scale biomedical database and research resource containing in-depth genetic and health information.

Consistent with earlier studies, investigators found that light to moderate drinkers had the lowest heart disease risk, followed by people who abstained from drinking. People who drank heavily had the highest risk. However, the team also found that light to moderate drinkers tended to have healthier lifestyles than abstainers — such as more physical activity and vegetable intake, and less smoking. Taking just a few lifestyle factors into account significantly lowered any benefit associated with alcohol consumption.

The study also applied the latest techniques in a method called Mendelian randomization, which uses genetic variants to determine whether an observed link between an exposure and an outcome is consistent with a causal effect — in this case, whether light alcohol consumption causes a person to be protected against cardiovascular disease.

“Newer and more advanced techniques in ‘non-linear Mendelian randomization’ now permit the use of human genetic data to evaluate the direction and magnitude of disease risk associated with different levels of an exposure,” says senior author Krishna G. Aragam, a cardiologist at MGH and an associate scientist at the Broad Institute. “We therefore leveraged these new techniques and expansive genetic and phenotypic data from biobank populations to better understand the association between habitual alcohol intake and cardiovascular disease.”

When the scientists conducted such genetic analyses of samples taken from participants, they found that individuals with genetic variants that predicted higher alcohol consumption were indeed more likely to consume greater amounts of alcohol, and more likely to have hypertension and coronary artery disease.

The analyses also revealed substantial differences in cardiovascular risk across the spectrum of alcohol consumption among both men and women, with minimal increases in risk when going from zero to seven drinks per week, much higher risk increases when progressing from seven to 14 drinks per week, and especially high risk when consuming 21 or more drinks per week. Notably, the findings suggest a rise in cardiovascular risk even at levels deemed “low risk” by national guidelines from the U.S. Department of Agriculture (i.e. below two drinks per day for men and one drink per day for women).

The discovery that the relationship between alcohol intake and cardiovascular risk is not a linear one but rather an exponential one was supported by an additional analysis of data on 30,716 participants in the Mass General Brigham Biobank. Therefore, while cutting back on consumption can benefit even people who drink one alcoholic beverage per day, the health gains of cutting back may be more substantial — and, perhaps, more clinically meaningful — in those who consume more.

“The findings affirm that alcohol intake should not be recommended to improve cardiovascular health; rather, that reducing alcohol intake will likely reduce cardiovascular risk in all individuals, albeit to different extents based on one’s current level of consumption,” says Aragam.

The study’s lead author was Kiran J. Biddinger, and additional authors included Connor A. Emdin, Mary E. Haas, Minxian Wang, George Hindy, Patrick T. Ellinor, Sekar Kathiresan, and Amit V. Khera.

Funding was provided by the National Institutes of Health and the American Heart Association.

An operation called a radical prostatectomy has long been a mainstay of prostate cancer treatment. Offered most often to men whose cancer has not yet begun to spread, it involves removing the entire prostate gland, and can be performed in different ways. With the traditional “open” method, surgeons remove the prostate through an 8- to 10-inch incision just below the belly button. Alternatively, surgeons can perform a robot-assisted radical prostatectomy. With this approach, miniaturized robotic instruments are passed through several much smaller incisions in the patient’s abdomen. Surgeons control these instruments remotely while sitting at a console.

At least 85 percent of all radical prostatectomies in the United States today are performed robotically. But how do those high-tech surgeries compare with the traditional open method?

Most studies show no major differences between the procedures in terms of patient survival or their ability to control prostate cancer over the long term. Robotic prostatectomies ostensibly offer quality-of-life advantages for urinary function and sexual health. However, the supporting evidence comes mostly from doctors’ reports, insurance claims-based data, or studies too small to generate definitive conclusions.

Now, results from a much larger comparative study provide needed clarity.

During the study, researchers from Harvard-affiliated hospitals and other academic medical centers in the United States followed 1,094 men who were treated with radical prostatectomy between 2003 and 2013. All the men had newly-diagnosed cancer that was confined to the prostate gland. Among them, 545 men had an open radical prostatectomy, while the remaining 549 men had a robot-assisted operation. Then at two-, six-, 12-, and 24-month intervals, the men responded to questions about their urinary and bowel functioning, ability to engage in sexual activity, energy levels, and emotional state.

What the study found

According to the results, both methods were equally effective at removing cancer from the body, and post-surgical complications between them occurred relatively infrequently. However, there were some short-term differences between the two approaches. For instance, the robotically-treated men had shorter lengths of hospital stay (1.6 days versus 2.1 days on average), and they also reported lower pain scores after surgery. Men who underwent robotically-assisted surgery also reported fewer complications such as blood clots (10 men versus three men), urinary tract infections (33 men versus 23 men), and bladder neck contracture, which is a treatable condition that occurs when scarring in the bladder outflow makes it hard to urinate. In all, 45 men experienced a bladder neck contracture after open surgery, compared to nine men treated with the robotic method.

This is an excerpt from an article that appears on the Harvard Health Publishing website.

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Charlie Schmidt is the editor of the Harvard Medical School Annual Report on Prostate Diseases.

President Biden’s recently announced cancer “moonshot” has been described as merely a reboot of the original, unveiled by President Obama in 2016 to much fanfare. But specialists say the effort is not just more of the same, but a reassessment, with new goals and a welcome focus on prevention.

Harvard experts expressed relief that Biden didn’t follow in the footsteps of some campaigns and pledge to eliminate cancer entirely. At a time when scientific truth and accuracy are being questioned, they said, unrealistic goals only further erode the public’s trust in science.

They agreed, however, that one of the project’s chief objectives — halving the cancer death rate — is possible. Optimism stems from dramatic advances over the past two decades in understanding cancer biology, which has translated into more effective treatments. These breakthroughs include precision therapies, which target specific differences between tumor and normal cells in individual patients, and immunotherapy, which activates the body’s defense mechanisms against the disease.

“These new classes of treatments are the two big lessons of the last 20 years, and those are pretty remarkable,” said George Demetri, a professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute and co-director of the Ludwig Center at Harvard. “And I can guarantee you that there’ll be at least two more big ones in the next 20 years.”

Demetri gives the original moonshot a mixed grade. The resources it provided have boosted research, resulting in new technologies such as a needlelike device that can be inserted into a tumor to test several drugs at once for effectiveness. But some things he thought essential and whose progress would be helped by federal support — like standardizing patient electronic records and increasing their portability between systems — have seen little improvement.

“Our ability to extract useful information from medical records is still woefully inadequate,” Demetri said. “The electronic medical records systems are better than chicken scratch on a piece of paper, but they still keep data in a very siloed way that is inefficient, unhelpful to research, and impossible to aggregate into a large-scale learning system.”

Cancer death rates have fallen steadily since peaking in 1990, dropping about a third from 216 cancer deaths per 100,000 to 145 per 100,000 in 2020. While possible, halving the age-adjusted death rate is by no means guaranteed, Demetri said. Cancer is a hugely complex and mysterious disease. Precision treatments, for example, can be amazingly effective, targeting patient-specific alterations in certain tumor subtypes with custom-designed drugs. But those same drugs may be ineffective on other tumors, even with the same type of cancer.

“Precision medicine, for about 15 percent or 20 percent of the patients, is really remarkable, but that leaves 85 percent of the patients saying, ‘Hey, Doc, I thought this was supposed to be a lot better than this,’” said Demetri, who was a working group member of Blue-Ribbon Panel that helped set priorities for the Obama initiative.

Demetri also isn’t a fan of the “moonshot” comparison. Though obviously a massive undertaking, the physics to land a human on the moon were known. The challenge for scientists was putting existing knowledge to work through engineering and scaling the results.

“With cancer research, there are still so many unknowns that you never really know where the next breakthrough is going to come from,” Demetri said. “What worries me about this moonshot messaging is that it sets up a public expectation: ‘Put this money here and in five years you’ll be invited to Cape Canaveral to see a big rocket go up,’ and everybody will be happy. Research doesn’t necessarily work that way in biomedical science discovery.”

While the analogy may be faulty from a scientific standpoint, the idea that progress against cancer will take moonshot-scale financial resources is not, according to Timothy Rebbeck, the Vincent L. Gregory Jr. Professor of Cancer Prevention at the Harvard T.H. Chan School of Public Health and director of the School’s Zhu Family Center for Global Cancer Prevention.

Rebbeck and Karen Emmons, professor of social and behavioral science at the Chan School, welcomed the emphasis on prevention in the Biden plan. Prevention has the potential to make a significant impact on mortality because, unlike treatment, there is already a lot of knowledge about how to prevent cancer. The problem — one that plagues many public health campaigns — is how to educate and motivate people to take action.

To boost prevention measures, the original moonshot created Implementation Science Centers around the country. Emmons heads one such program, the Chan School’s Implementation Science Center for Cancer Control Equity, where her projects include a collaborative effort to increase health care providers’ ability to refer patients for lung cancer screening and smoking cessation services.

As COVID numbers fall and mandates lift, the question remains: Is it possible to avoid trade-offs between returning to pre-pandemic lifestyles and an uptick in COVID-19-related deaths?

To find an answer, investigators at Massachusetts General Hospital, Boston Medical Center, and Georgia Tech conducted a simulation study that projected the future of the COVID-19 pandemic in every state.

The analysis, which is published in JAMA Health Forum, assumes the current pace of vaccination is maintained into the future, and models different dates of lifting mandates. In most states, relaxing masking mandates and other restrictions resulted in some “rebound” in COVID-19-related deaths; however, delaying the date of lifting mandates did little to lessen the eventual rise in deaths.

“The inevitable rebound in mortality was directly attributable to the Omicron variant — when we repeated the analysis, assuming the infectivity of the previous Alpha and Delta variants, the model did not project such rising mortality after relaxing mask mandates,” says co-first author Benjamin P. Linas, a professor of medicine at Boston University School of Medicine.

One of the strongest predictors of the extent of the rebound surge in mortality after relaxing mandates was the degree of immunity in the community at the time of lifting the mandate. Therefore, communities with a high percentage of residents who are vaccinated and/or who have had COVID-19 are likely to have lower death rates.

“A difficult trade-off lies on the horizon,” says co-senior author Jagpreet Chhatwal, director of MGH’s Institute for Technology Assessment. “While there is ample evidence in our analysis that a March 2022 lifting date leads to rebound mortality in many states, the simulation also suggests that with the Omicron variant, whenever states do remove mandates will face the same difficult choice between increased COVID-19 mortality and the freedoms of returning to a pre-pandemic norm.

“The one intervention that can mitigate this impossible choice is ongoing COVID-19 vaccination with boosters,” adds Chhatwal, who is also an assistant professor at Harvard Medical School.

Even though a delay in lifting mask mandates or restrictions on social gatherings will likely not entirely prevent future surges in COVID-19-related deaths, the findings could potentially aid state public health officials as they weigh different options. “Arguments to remove restrictions must explicitly make the case for lifting restrictions within a cost-benefit framework examining the cost of restrictions versus the cost of COVID-19 mortality,” says co–first author Jade (Yingying) Xiao, a PhD student at Georgia Tech. “At the same time, those who favor maintaining restrictions must recognize that ‘just a little longer’ will not suffice.”

The researchers note that the highly transmissible Delta and Omicron variants will likely continue to take a major toll across the country, but if a less transmissible viral strain were to become dominant, rebounding morbidity and mortality rates would be substantially lower. “Were this the case, it would likely be possible to more safely remove restrictions at the beginning of the second quarter of 2022,” says co–senior author Turgay Ayer, director of Business Intelligence and Healthcare Analytics at the Center for Health and Humanitarian Systems at Georgia Tech.

Additional co-authors include Ozden O. Dalgic, Peter P. Mueller, Madeline Adee, and Alec Aaron.

Arthur C. Brooks wants people to lift people up. But the behavioral social scientist whose recent work has focused on helping people lead happier lives is worried that mixed messages from officials about whether to continue to work and learn remotely and keep a distance from friends has generated a culture of fear that is bringing us down in dangerous ways.

“People have learned to be afraid of each other,” said Brooks, the William Henry Bloomberg Professor of the Practice of Public Leadership at Harvard Kennedy School. “That’s a really damaging thing for a happy world, for a well-functioning society. The truth is, for most people, it’s probably a much, much bigger risk to us to isolate than it is to mix right now.”

Experts acknowledge that COVID does continue to be a significant concern for those with compromised immune systems or other health conditions that put them at greater risk for complications. While Brooks and number of other Harvard scholars agree that those with extenuating health circumstances need to proceed with more caution, they also say that for most healthy individuals — particularly those who are fully vaccinated — additional time spent socially distant from family and friends may worsen a growing national mental health problem.

Brooks, who said that the country had been facing a loneliness crisis well before COVID, noted that continuing to socially isolate has been linked to a spike in symptoms of clinical depression and a drop in a key chemical messenger that helps us feel good.

“Neurochemically, we’re missing out on the boost of oxytocin, which is the neuropeptide that functions as a hormone and aids in human bonding,” said Brooks. “It’s critical for a well-functioning, happy life, and you get it in abundance from the things that social isolation prevents: eye contact and touch.”

While many were optimistic early in the pandemic that virtual technologies might help keep levels of the hormone high, evidence suggests there’s little oxytocin being produced during conversations over Zoom, Skype, Facetime, or social media, said Brooks.

“These technologies are like the junk food of social life. You can kind of exist on them, but you’ll be pretty unhealthy pretty fast if this is your whole diet.”

Jennifer Gatchel, an assistant professor of psychiatry at Harvard Medical School, knows the threat of the pandemic is “still not at zero,” particularly for the elderly and the immunocompromised. There also remains the issue of those who end up suffering long-term symptoms, including fatigue, shortness of breath, and brain fog, even as a result of a mild case of COVID. Still she agrees about the importance of starting to reach out once again.

“There’s going to be an increasing risk of missing out on in-person interactions which in the long term promote and sustain relationships and connectedness,” she said. “I think recognizing that that risk may indeed be mounting and growing, and that ongoing isolation presents a known risk to physical health, is really critical.”

Research has shown that social isolation can have negative effects on health, significantly increasing the risk of premature death, depression, anxiety, heart disease, and other conditions. A recent study of more than 50,000 older women in the U.S. found those with greater social isolation and loneliness had a 13 percent to 27 percent higher risk of cardiovascular disease than women who had more connection. A similar report from 2016 that analyzed 23 different studies involving 181,000 adults found loneliness, social isolation, or both were associated with a 29 percent increased risk of heart attack and 32 percent greater risk of stroke.

Conversely, human touch, other studies suggest, can slow the heartbeat and lower the blood pressure as well as the stress hormone cortisol. A 2018 study even indicated hugging could help ward off respiratory illness.

Robert Waldinger, a psychiatrist at Massachusetts General Hospital and director of one of the world’s longest-running studies of adult life, said deep, meaningful relationships have been linked with “both emotional well-being and physical health in numerous studies.” He singled out loneliness as “as powerful a predictor of declining health and well-being as smoking and obesity.”

“For the vaccinated and boosted, how do you weigh the small risk of COVID or long COVID versus the long, ongoing risk of languishing, this state of feeling not even depressed or anxious but just blah?“

— psychiatrist Robert Waldinger (pictured below)

Waldinger, who is also a psychiatry professor at HMS, said many of us able who are finally reconnect with our friends in person will likely feel “an upsurge in exhilaration.” It’s a positive emotional lift that “doesn’t happen quite the same way when we talk on the phone,” he added, “and I think the closer the relationship the stronger that effect.”

Waldinger pointed out that being with good friends also helps us feel more grounded. “My close friends really validate my sense of me and my connections in the world,” he said. “We are built to resonate with each other emotionally, and a lot of that, I think, is through being present together.”

But if togetherness is a key to healthy relationships and well-being, pandemic-enforced school closures have put tweens and teens at a particular disadvantage, said Karestan Koenen.

A drug widely used in HIV therapy has shown to stop disease progression in 25 percent of patients with fourth-line metastatic colorectal cancer.

Findings from the trial, published in Cancer Discovery, raise the possibility of an unexpected promising direction in cancer treatment, not just colorectal cancer. The drug used in the study was lamivudine, a reverse transcriptase inhibitor.

The trial included 32 patients with advanced metastatic colon cancer whose disease progressed despite four lines of previous cancer treatments. The first nine patients received the standard HIV-approved dose of lamivudine.

“After giving them only this one drug — nothing else — we saw signs of disease stability,” says co-senior author David T. Ting of the Mass General Cancer Center. After adjusting the dosing four-fold, another 23 patients received lamivudine therapy where it was highly tolerated.

The research team observed that 9 of the 32 patients, or 28 percent, had disease stability or mixed response at the end of the trial. “This provides evidence that an HIV drug can be repurposed as an anti-cancer therapy in metastatic cancer patients,” says Ting. While the research team did not see tumor shrinkage, the results are encouraging.

“If we see this kind of response with just one HIV drug, the next obvious trial is to see what else we can achieve with HAART, or highly active anti-retroviral therapy,” adds Ting, referring to the standard three-drug regime for HIV treatment.

The first clues to this unusual drug trial surfaced in Ting’s lab and those of his collaborators over the past 10 years. The team discovered that up to 50 percent of a tumor’s DNA was composed of “repetitive elements,” which were previously considered “junk DNA.”

“Only cancer cells produced these repetitive element, not healthy cells,” says Ting. Colorectal cancers produce abundant amounts of repetitive elements, as do cancers of the esophagus, lung, and several others. These repetitive elements spew out extraordinary levels of RNA which replicate in a viral-like life cycle through reverse transcription into what Ting describes at the repeatome.

The repeatome acts much like a virus does relying on reverse transcription to replicate itself and move in the genome. “It’s a way for cancers to change their genome to adapt to stress,” adds Ting, who had the idea to assess whether an HIV drug, such as lamivudine, might interfere with the process.

In their preclinical studies, Ting found that colorectal cancer cells were sensitive to lamivudine, reducing their ability to move. The team also discovered that the drug induced DNA damage and interferon responses, an indication that the drug triggered an inflammatory response in the tumor cells. Although not proven or evaluated in this trial, Ting theorizes that pairing reverse transcriptase inhibitor therapy with immunotherapy might encourage immune cells to become involved in these cancers.

Research shows that in a U.S. population of HIV patients receiving three-drug anti-retroviral therapy for life, their incidence of colon, breast, and prostate cancer was significantly less than the general population. Ting speculates this kind of therapy might prevent a cancer or a recurrence or turn a crushing metastatic disease into a chronic disease like HIV.