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Behind the Scenes, McKinsey Guided Companies at the Center of the Opioid Crisis

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Supported byContinue reading the main storyBehind the Scenes, McKinsey Guided Companies at the Center of the Opioid CrisisThe consulting firm offered clients “in-depth experience in narcotics,” from poppy fields to pills more powerful than Purdue’s OxyContin.Send any friend a storyAs a subscriber, you have 10 gift articles to give each month. Anyone can read what you share.Chris Hamby and The reporters pored over a trove of more than 100,000 documents to investigate McKinsey’s unknown work for opioid makers.June 29, 2022, 6:15 p.m. ETIn patches of rural Appalachia and the Rust Belt, health authorities were sounding alarms that a powerful painkiller called Opana had become the drug of choice among people abusing prescription pills.It was twice as potent as OxyContin, the painkiller widely blamed for sparking the opioid crisis, and was relatively easy to dissolve and inject. By 2015, government investigations and scientific publications had linked its misuse to clusters of disease, including a rare and life-threatening blood disorder and an H.I.V. outbreak in Indiana.Opana’s manufacturer, the pharmaceutical company Endo, had scaled back promotion of the drug. But months later, the company abruptly changed course, refocusing resources on the drug by assigning more sales representatives.The push was known internally as the “Sales Force Blitz” — and it was conducted with consultants at McKinsey & Company, who had been hired by Endo to provide marketing advice about its chronic-pain medicines and other products.

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McKinsey Settlement Documents

A campaign by McKinsey and Endo to push the company’s chronic-pain products, including Opana.The untold story of McKinsey’s work for Endo was among the revelations found by The New York Times in a repository of more than 100,000 documents obtained by a coalition of state attorneys general in a legal settlement related to McKinsey’s opioid work.Much has been disclosed over the years about McKinsey’s relationship with Purdue Pharma, including the consulting firm’s recommendation that the drug maker “turbocharge” its sales of OxyContin. But The Times found that the firm played a far deeper and broader role in advising clients involved in the opioid crisis than was publicly disclosed.The McKinsey records include more than 15 years of emails, slide presentations, spreadsheets, proposals and other documents. They provide a sweeping and detailed depiction of a firm that became a trusted adviser to companies at the core of an epidemic that has claimed half a million American lives.While the firm held remarkable sway at Purdue, it also advised the largest manufacturer of generic opioids, Mallinckrodt. It worked with Endo on marketing Opana and helped it grow into a leading generics manufacturer. It advised Johnson & Johnson, whose subsidiary Tasmanian Alkaloids was the largest supplier of the raw materials extracted from poppies used to make many top-selling opioids. Then, as the full brunt of the epidemic became apparent, it counseled government agencies on how to address the fallout.McKinsey’s opioid clients already wanted to grow their businesses. What the firm offered was know-how and sophistication, the documents show, and, as it noted in one presentation, “in-depth experience in narcotics.”The Massachusetts attorney general, Maura Healey, who helped craft the settlement, said in a statement that “as Americans were dying from the opioid epidemic, McKinsey was trading on its reputation and connections to make the crisis worse.” She added that the newly released documents “expose McKinsey’s role in the opioid crisis and will inform policymakers’ efforts to prevent this from happening again.”Drawing on reams of data and proprietary tools, McKinsey vetted deals and advised on corporate strategy. It developed tactics for dealing with regulators and helped secure approval for new products.The firm helped clients adopt more aggressive sales strategies, which, on at least two occasions, led companies to shift resources to more potent products. It profiled and targeted physicians, in some instances trying to influence prescribing habits in ways that federal officials later warned heightened the risk of overdose.And when opioid prescriptions began to decrease during a government crackdown, the records show, McKinsey devised new approaches to drive sales.McKinsey agreed to provide the documents to the attorneys general last year as part of a nearly $600 million settlement in which it admitted no wrongdoing. The firm has since apologized for its advice to opioid makers but, in a statement on Wednesday, suggested that its work with companies other than Purdue was “much more limited” and that it “did not counsel or recommend to Endo that it promote Opana more aggressively.”“We recognize the terrible consequences of the opioid epidemic and have acknowledged our role in serving opioid manufacturers,” said a McKinsey spokesman. “We stopped that work in 2019, have apologized for it and have been focused on being part of the solution.”An Endo spokeswoman declined to comment on the company’s work with McKinsey, citing litigation. She instead referred to a company statement saying that in September 2016 Endo had “stopped promoting opioid products to health care professionals” and eliminated its opioid-focused sales force.Mallinckrodt declined to comment. Johnson & Johnson, in a statement, maintained that all its actions were appropriate, while Purdue said that it was focused on ending bankruptcy proceedings so it could reorganize into a new, more “public-minded” company that would “deliver billions of dollars of value” toward abating the opioid crisis and compensating victims.‘Opana Patients’Dr. Steven Butler, a kidney specialist serving a largely rural stretch of East Tennessee, helped with an unusual case in fall 2012. A woman in her 20s had arrived at the Holston Valley Medical Center in Kingsport with an array of symptoms — she was anemic, and her kidneys appeared to be failing — that resembled a rare blood disorder.A few days later, another patient with similar symptoms arrived at the hospital. Then a third. Dr. Butler called the Tennessee Department of Health, which launched an investigation. Over the following months, more patients appeared.As they underwent time-consuming treatments, some acknowledged they had dissolved and injected a pill whose name Dr. Butler had never heard before: Opana ER.The Opioid CrisisFrom powerful pharmaceuticals to illegally made synthetics, opioids are fueling a deadly drug crisis in America.An Unrelenting Surge: ​​Deaths from drug overdoses again rose to record-breaking levels in 2021. Here is how to talk to your family about the threat opioids pose.Youth Deaths: Young people are turning to social media to find prescription pills. But drugs found this way are often laced with deadly doses of fentanyl.A Settlement: Purdue Pharma reached a deal with a group of states that long resisted the structure of the original bankruptcy plan. Here is what the agreement means.Detailing Tragedies: As part of the settlement, families who lost loved ones to opioid addiction were allowed to address the owners of Purdue Pharma in court.“Locally, it became a very well-described phenomenon,” he recalled. “They were just called ‘Opana patients,’ as though that was a real common thing.”The tangled path that led to Opana’s rise illustrates McKinsey’s deep involvement in the opioid business, with its work for one client rippling out with consequences for others.Years earlier, the firm had helped usher the drug onto the market, advising Endo’s partner, Penwest Pharmaceuticals, on its launch in 2006. Two years later, the documents show, McKinsey performed a project for Purdue that paved the way for Endo to extend Opana’s reach.Purdue was seeking approval from the Food and Drug Administration for a new version of OxyContin that would be more difficult to snort or inject. After the F.D.A. denied its application in 2008, Purdue enlisted McKinsey’s help. The consultants interviewed a former drug dealer about OxyContin abuse, oversaw scientific studies, prepared regulatory documents and coached company officials on how to deal with the F.D.A., which had been a McKinsey client. The agency gave its approval in 2010, and later allowed Purdue to claim the new pills were resistant to abuse.Soon, OxyContin sales declined — while Opana sales rose. In an internal document, Endo attributed the uptick in part to “patient dissatisfaction with new OxyContin formulation.” Data on abuse showed similar trends: a decline for OxyContin and a rise for Opana.Endo later developed a new version of Opana it wanted to promote as abuse-resistant. The F.D.A. found that the new pills “demonstrated a minimal improvement in resistance to tampering by crushing,” and that they were “readily abusable” by injection. The agency allowed the drug to enter the market in early 2012, but without being labeled as resistant to abuse.Cooking Opana in order to inject it, on a stove in West Virginia.Mark TrentWithin months, Dr. Butler saw his first Opana patient. In October 2012, both the F.D.A. and the Centers for Disease Control and Prevention put out health alerts about the blood syndrome. Then another cluster appeared, in North Carolina, and other cases in Arkansas, Florida, Pennsylvania and South Carolina.To make matters worse, according to the F.D.A., the new version of Opana drove many users to switch from snorting to injecting, considered a riskier form of abuse. The likely cause of the blood disorder, researchers determined, was the very substance that Endo had added to make the pills harder to crush. When dissolved and injected, it could trigger rapid red blood cell destruction and organ damage.Rajiv De Silva, formerly of McKinsey, took over Opana’s manufacturer, Endo, in 2013.BusinesswireAs concerns about Opana grew, Endo hired a new chief executive in 2013: Rajiv De Silva, a former leader within McKinsey’s pharmaceutical practice who soon tapped the firm to help chart a growth strategy.A few months after Mr. De Silva took over, McKinsey helped Endo execute a complicated maneuver known as a “tax inversion” — a legal form of tax avoidance that the Obama administration would decry as an “abuse” of the system. For tax purposes, the Pennsylvania company was now based in Ireland, where the rate was substantially lower.Endo’s offices in Dublin. With the help of McKinsey, it moved its headquarters out of the U.S. for tax purposes.Paulo Nunes dos Santos for The New York TimesThe move, which sent Endo’s stock price climbing, was “a tax play to set up doing a lot of deals,” according to a 2014 email from a McKinsey partner named Dr. Arnab Ghatak, who also helped lead the firm’s work with Purdue.Endo went on a buying spree and would soon become one of the largest U.S. manufacturers of generic opioids.‘The Narcotics Franchise’The production of pills by companies like Endo and Purdue depended on a complex and tightly regulated global supply chain stretching from the fields of Tasmania to factories in the American heartland.Here, too, was McKinsey.Long before a patient in the United States filled a prescription for OxyContin, a farmer on another continent harvested a poppy rich in a substance called thebaine. Tasmanian Alkaloids, the Johnson & Johnson subsidiary, controlled the majority of this market.From far-flung fields and extraction facilities, the raw materials made their way to American processing plants. The top U.S. producers at this stage were another Johnson & Johnson subsidiary, Noramco, and Mallinckrodt, the big generics manufacturer.The documents reveal McKinsey’s work advising them behind the scenes. By the firm’s own account, it had deep expertise in the international trade of legal narcotics. “We serve the majority of the leading players,” the consultants wrote in a 2009 memo.That year, the firm oversaw a project for Johnson & Johnson titled “Maximizing the Value of the Narcotics Franchise.” In a presentation set against an image of a poppy field, the consultants advised the company on how it could invest to further strengthen its already-dominant position or sell the business if the price was right.

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McKinsey Settlement Documents

A presentation McKinsey prepared for Johnson & Johnson, whose subsidiaries played key roles in the opioid supply chain.For Mallinckrodt, McKinsey consultants walked factory floors and monitored production data, recommending how the company might coax greater yields from the same base of raw materials and speed up manufacturing lines.In 2016, McKinsey prepared Mallinckrodt for negotiations with companies that sourced generic drugs for Walmart and CVS, and advised on dealing with the Drug Enforcement Administration. The D.E.A. had set production limits to prevent an oversupply of pills, and McKinsey counseled Mallinckrodt on how it could use logistical tactics to secure a higher quota while maintaining a “friendly relationship” with the agency.“To suggest this work was intended to undermine relevant laws or regulations would be false,” the McKinsey spokesman said.McKinsey consultants also took jobs at the opioid manufacturers themselves. A partner in the firm’s pharmaceutical practice, Frank Scholz, became Mallinckrodt’s senior vice president of global operations in 2014 and later was promoted to president of its generics business.But it was the arrival of Mr. De Silva at Endo that brought a particular opportunity for McKinsey. In late 2014, the company asked the consultants to provide advice on structuring the company’s sales force. This soon evolved into a more detailed project in an area where McKinsey excelled: how to dispatch hundreds of sales representatives to maximum effect.Shifting to OffenseMcKinsey had a playbook for seemingly any problem a pharmaceutical company might face, from production snags to generic competition to inquisitive regulators. But the firm had a particular penchant for sales and marketing.In the years leading up to its work on Opana, McKinsey had built increasingly powerful tools for getting the right messages in front of the right physicians, and the firm had honed them in numerous opioid-marketing projects, including two for Johnson & Johnson.While the broad strokes of these efforts have been known, the documents provide an unprecedented look inside McKinsey’s tool kit. The records related to the firm’s work for Purdue are particularly detailed, providing insight into the strategies that consultants used for other companies.In 2009, the firm recommended a technique known as segmentation. The best marketing campaigns — whether for food, cars or electronics — divided consumers into segments based on how they acted and thought, then developed tailored messages to win them over, the consultants said.In Purdue’s case, the customer was a physician with a license to prescribe controlled substances, and the product was OxyContin.The consultants interviewed dozens of physicians and solicited the views of hundreds more in a survey. Four groups of doctors emerged, each with a distinct profile. The consultants then developed messages to appeal to each group’s practical and emotional needs.

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McKinsey Settlement Documents

McKinsey, drawing on data analyses, made personality profiles of doctors to fuel opioid sales.McKinsey identified a particular opportunity in doctors who were hesitant to prescribe OxyContin because of worries about abuse, addiction and possible scrutiny from the D.E.A. These physicians often tried to treat chronic pain with less powerful drugs.Persuading them to switch to OxyContin could be worth hundreds of millions of dollars, McKinsey advised. To do this, McKinsey proposed tactics to “raise physician comfort levels through appropriate education and support.” Sales representatives, McKinsey said, should reassure doctors that many of their colleagues prescribed OxyContin and that the drug need not be reserved for extreme pain.In 2014, the F.D.A. introduced new labeling requirements for OxyContin and similar opioids, limiting their use to cases of severe chronic pain in which less risky treatments had proved ineffective. But McKinsey’s strategy had long since been rolled out.Another McKinsey approach, known as targeting, tried to identify doctors who would provide the greatest return on sales representatives’ time.Purdue, dissatisfied with dipping OxyContin sales in 2013, had enlisted McKinsey’s help. Revenues were down, the consultants advised, in large part because of government actions to tamp down the opioid epidemic. Doctors were writing prescriptions for fewer tablets and lower doses, and wholesalers and pharmacies were imposing new controls.Fentanyl Overdoses: What to KnowCard 1 of 5Devastating losses.

Histone deacetylase (HDAC) inhibitors are a class of drugs used in oncology. An international research team involving scientists at the Technical University of Munich (TUM), Cornell University in Ithaca (USA), the German Cancer Research Center (DKFZ) in Heidelberg and Martin Luther University of Halle-Wittenberg has now investigated the effects of some HDAC drugs in more detail. The scientists researched whether those epidrugs affect proteins other than the HDACs which they are designed to inhibit.
“To do so, target deconvolution by chemical proteomics is the method of choice. Hence, we first made new chemical tools — the so called affinity matrices — that would allow us to systematically profile the HDACs,” explains Dr. Guillaume Médard, group leader for chemical proteomics at the TUM chair of Proteomics and Bioanalytics led by Prof. Bernhard Küster.
Profiling HDAC drugs by chemical proteomics
“I profiled 53 drugs and most of them, but not all, hit their intended HDAC target,” stated Severin Lechner, a doctoral candidate at the TUM School of Life Sciences. “There were, however, some surprises. Drugs used in hundreds of scientific studies were not as selective as it had been assumed. Many had additional targets that were not previously known.
These results highlight the power of proteomic approaches, as they can probe the binding to thousands of proteins at once. Finally, the team identified several molecules with outstanding selectivity, making them the inhibitors of choice for future scientific studies.
The target landscape of HDAC drugs
“The most unexpected finding was that MBLAC2 is off-target for half of the profiled molecules,” Lechner continues. This protein is not well characterized. Coincidentally, the team of Prof. Maurine Linder in Cornell researched on it at the same time. The two groups collaborated and confirmed that the protein is indeed hindered in performing its function in presence of the drugs.
Working with the group of Prof. Michael Pfaffl at TUM, Lechner examined the hinted unexplained phenotypic effects of some drugs and proved that MBLAC2 inhibition or knock-down leads to an accumulation of extracellular vesicles in the extracellular space. Extracellular vesicles are small membrane-bounded particles secreted by cells and transported through the whole body to transmit biomolecules and information between cells and tissues.
Fundamental research to make tomorrow’s epidrugs
“We are excited because we have uncovered a new player in this field of biology that notably encompasses exosomes, which play crucial roles in neurology, immunology and oncology,” explains Médard. “We are now designing molecules that only hit MBLAC2 so that we can probe this obscure protein in a range of model systems.”
This study will be useful to those who want to use HDAC inhibitors for probing biology or for therapeutic use. It helps in choosing the right chemical tool. It is also a valuable set of data for medicinal chemists who need to understand how chemical structures relate to potency and selectivity to make tomorrow’s epidrugs.
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Materials provided by Technical University of Munich (TUM). Note: Content may be edited for style and length.

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy, characterized by progressive muscle wasting and weakness and caused by abnormally repetitive DNA segments that are transcribed into toxic molecules of RNA. Instead of ferrying a gene’s instructions for translation into proteins, these RNA molecules accumulate in cells, disrupting cellular machinery.
Rett syndrome (RS) is a rare genetic neurological disorder that affects the way the brain develops, resulting in progressive loss of motor skills and language early in life.
Writing in the June 29, 2022 online issue of Science Translational Medicine, researchers at University of California San Diego School of Medicine used three-dimensional brain organoids — self-organized tissue grown from stem cells that mimics neurological functions — to discover fundamental similarities between DM1 and RS, and perhaps therapeutic opportunities.
“We turned to 3D brain organoids that simulate the developing human cortex to study the effects of the CTG repeat expansion on neuronal processes,” said first author Kathryn Morelli, PhD, a fellow in the lab of senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine.
“It’s a model that can be made from induced pluripotent stem cell lines from real DM1 patients that carry these toxic RNA aggregates. It mimics cortical development in utero.”
Unlike other types of muscular dystrophy, patients with DM1 often exhibit progressive neurocognitive symptoms, with learning and social impediments that can appear similar to autism spectrum disorders. Recent clinical data has shown that the higher the number of inherited DNA repeats, the earlier the onset of symptoms — and the greater the impact of the disease on the central nervous system.

Researchers have gained ground in understanding unique immune cells equipped to remember the identities of malicious invaders. The researchers developed a new atlas that describes tissue-resident memory T cells in diverse tissue settings, boosting the prospects of the development of immune defense strategies to enhance immunity at sites vulnerable to infection.
Scientists exploring how our immune system responds to pathogens and cancers have ramped up their attention to CD8+ T cells, which are deployed in response to infections and malignancies and equipped to remember the identities of malicious invaders.
While some of these critical “memory” cells circulate throughout the body, others are known to remain lodged within bodily organs to guard entry sites as part of an entrenched, long-term defense system. A new study led by biologists at the University of California San Diego offers fresh insights on these specialized cells, known as CD8+ tissue-resident memory T cells. Published June 27 in Nature Immunology, the study is led by Postdoctoral Scholars Max Heeg and John Crowl (now a scientist at Outpace Bio) in Professor Ananda Goldrath’s laboratory in UC San Diego’s School of Biological Sciences and provides a framework for understanding how tissue-resident memory T cells adapt to distinct tissue environments. The researchers developed a new atlas that describes tissue-resident memory T cells in diverse tissue settings, boosting the prospects of the development of immune defense strategies to enhance immunity at sites vulnerable to infection.
“By identifying the unique transcriptional pathways and regulators of tissue-resident memory T cells, we can discover novel targets that inform strategic design of vaccines to provide the greatest protection among ‘first responders’ in the tissues where pathogens and tumors begin their expansion,” said Goldrath, who holds the Tata Chancellor’s Endowed Professorship in the Department of Molecular Biology.
While several studies have examined memory cells as they either circulate or become entrenched in organ tissue, little had been known about the role that the surrounding tissue environments play in the process. When an infection takes hold, the immune system activates CD8+ T cells and directs them to infected tissues to survey cells for pathogens. Once the infection clears, the number of pathogen-specific CD8+ T cells declines, but a small number of cells remain as a type of long-term sentry system to bolster immunity against future infections.
The new study examined tissue-resident memory T cells residing in mouse organs such as the kidney, spleen, small intestine and liver. The collective results from across these disparate tissue environments generated insights into how each T cell population is governed by unique processes based on the “tissue of residence.”
Finally, the scientists raise the possibility that future extensions of this research could come in the form of customized engineered therapies: “…these findings collectively raise the possibility of ‘programming’ tissue-tailored immune responses, where immune cells that promote or regulate inflammation could be transcriptionally engineered for trafficking to, retention in and function within a particular tissue.”
The coauthors of the Nature Immunology study are: John Crowl, Maximilian Heeg, Amir Ferry, Justin Milner, Kyla Omilusik, Clara Toma, Zhaoren He, John Chang and Ananda Goldrath.
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Materials provided by University of California – San Diego. Original written by Mario Aguilera. Note: Content may be edited for style and length.

The development of an embryo is a well-orchestrated string of processes, ensuring correct formation and positioning of vital organs of the growing organism. At the molecular level, these processes are controlled in a precise manner by switching on or off specific factors such as genes or proteins. Any errors in these processes could result in physical defects or disease in the newborn organism.
A team of scientists from the National University of Singapore (NUS) led by Assistant Professor Xue Shifeng from the Department of Biological Sciences has discovered a new way to interpret unsolved Mendelian diseases — diseases inherited from either parent due to gene mutations in the developing egg or sperm — through studying the inheritance of a protein known as SMCHD1 which is coded by the SMCHD1 gene. Mutations in the SMCHD1 gene can cause diseases such as facioscapulohumeral muscular dystrophy (FSHD) which is a muscle degenerative disorder, and Bosma arhinia microphthalmia syndrome (BAMS) which causes abnormalities of the nose and eyes.
The researchers found that SMCHD1 from mothers controls the expression of a group of genes in offspring, known as the HOX genes, which determines the position of body parts in an embryo along the axis from its head to tail. The researchers also found that the inactivation of SMCHD1 in female zebrafish results in alterations to HOX gene expression leading to skeletal defects in their offspring.
The study led by NUS researchers, in collaboration with A*STAR, Yale-NUS and Aix-Marseille University, was published in Nature Communicationson 23 June 2022.
Inheritance of mother’s genes and structural defects
In mammals, SMCHD1 plays a key role in X-inactivation in females, a process where one of the copies of the X chromosome is randomly selected and disabled. This makes it challenging to study the role of the SMCHD1 gene inherited from mothers because inactivating the SMCHD1 gene is lethal for female mammals.

A large multicenter, randomized clinical trial revealed no difference in the risk of endotracheal intubation requirement at 30 days between awake prone positioning and standard positioning for patients with COVID-19 who suffered from acute hypoxemic respiratory failure, according to research published in JAMA by researchers at UTHealth Houston.
Given the concern of limited resources during the COVID-19 pandemic, awake prone positioning, in which a non-intubated patient lies face down, was adopted as an intervention for patients with respiratory failure. When a patient is lying face down, the diseased portion, which is usually the posterior part of the lung, is no longer compressed due to gravity, which was thought to improve the overall oxygenation within the lungs.
“Prior to the COVID-19 pandemic, it had been reported sporadically as a rescue measure, in very few case reports in different parts of the world,” said Sujith Cherian, MD, associate professor of medicine with McGovern Medical School at UTHealth Houston and director of quality for pulmonary and critical care medicine at Harris Health Lyndon B. Johnson Hospital. “This strategy was a measure in several countries, and even recommended by several medical societies, to use as a measure to improve the oxygenation to see if it would reduce the need for invasive mechanical ventilation.”
With the absence of any evidence-based strategy to guide this approach, Cherian, principal investigator of the study, and co-investigator Rosa Estrada-y-Martin, MD, professor of medicine with McGovern Medical School, wanted to see what the effects were on reducing the need for being on a ventilator. Estrada-y-Martin is also medical director of pulmonary and critical care medicine at Harris Health LBJ, the site of the Houston arm of the study.
“Many patients that require ventilators with COVID-19 pneumonia didn’t survive at the beginning of the pandemic,” said Estrada-y-Martin. “So, the idea was, what happens if we try to do something before they have to go to a ventilator?”
In addition to Harris Health LBJ, the only site in the U.S., the study was conducted at 20 other hospitals in Canada, Kuwait, and Saudi Arabia. It included adults who required at least 40% oxygen or non-invasive positive pressure ventilation and had not received invasive mechanical ventilation. The 400 patients were randomized to either the intervention group (205 participants; prone position 8-10 hours per day) or the control group (195 participants; no prone positioning). The primary outcome was endotracheal intubation within 30 days of randomization. The risk of endotracheal intubation did not significantly differ between groups (34% for prone versus 40% non-prone group) at 30 days, and the risk of mortality at 60 days was similar between the two groups (22.4% for prone versus 23.6% non-prone).
“Throughout my observation of the patients recruited for the study, it was becoming more obvious to me that the strategy helped only some patients, and it had a limited role in preventing patients from requiring mechanical ventilation,” said Cherian. “It will probably come as a surprise to several physicians because of just how widespread this measure was adopted in several countries all over the world. Moreover, one must keep in mind that it cannot be adopted as a uniform strategy in all patients and careful evaluation is necessary to identify who may benefit from this strategy. ”
Story Source:
Materials provided by University of Texas Health Science Center at Houston. Original written by Halle Jones. Note: Content may be edited for style and length.

A class of viruses known to cause severe diarrheal diseases — including the one famous for widespread outbreaks on cruise ships — can grow in the salivary glands of mice and spread through their saliva, scientists at the National Institutes of Health have discovered. The findings show that a new route of transmission exists for these common viruses, which afflict billions of people each year worldwide and can be deadly.
The transmission of these so-called enteric viruses through saliva suggests that coughing, talking, sneezing, sharing food and utensils, and even kissing all have the potential for spreading the viruses. The new findings still need to be confirmed in human studies.
The findings, which appear in the journal Nature, could lead to better ways to prevent, diagnose, and treat diseases caused by these viruses, potentially saving lives. The study was led by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
Researchers have known for some time that enteric viruses, such as noroviruses and rotaviruses, can spread by eating food or drinking liquids contaminated with fecal matter containing these viruses. Enteric viruses were thought to bypass the salivary gland and target the intestines, exiting later through feces. Although some scientists have suspected there may be another route of transmission, this theory remained largely untested until now.
Now researchers will need to confirm that salivary transmission of enteric viruses is possible in humans. If they find that it is, the researchers said, they may also discover that this route of transmission is even more common than the conventional route. A finding such as that could help explain, they said, why the high number of enteric virus infections each year worldwide fails to adequately account for fecal contamination as the sole transmission route.
“This is completely new territory because these viruses were thought to only grow in the intestines,” said senior author Nihal Altan-Bonnet, Ph.D., chief of the Laboratory of Host-Pathogen Dynamics at the NHLBI. “Salivary transmission of enteric viruses is another layer of transmission we didn’t know about. It is an entirely new way of thinking about how these viruses can transmit, how they can be diagnosed, and, most importantly, how their spread might be mitigated.”
Altan-Bonnet, who has studied enteric viruses for years, said the discovery was completely serendipitous. Her team had been conducting experiments with enteric viruses in infant mice, which are the animal models of choice for studying these infections because their immature digestive and immune systems make them susceptible to infections.
For the current study, the researchers fed a group of newborn mice that were less than 10 days old with either norovirus or rotavirus. The mouse pups were then returned to cages and allowed to suckle their mothers, who were initially virus-free. After just a day, one of Altan-Bonnet’s team members, NHLBI researcher and study co-author Sourish Ghosh, Ph.D., noticed something unusual. The mouse pups showed a surge in IgA antibodies — important disease-fighting components — in their guts. This was surprising considering that the immune systems of the mouse pups were immature and not expected to make their own antibodies at this stage.
Ghosh also noticed other unusual things: The viruses were replicating in the mothers’ breast tissue (milk duct cells) at high levels. When Ghosh collected milk from the breasts of the mouse mothers, he found that the timing and levels of the IgA surge in the mothers’ milk mirrored the timing and levels of the IgA surge in the guts of their pups. It seemed the infection in the mothers’ breasts had boosted the production of virus-fighting IgA antibodies in their breast milk, which ultimately helped clear the infection in their pups, the researchers said.
Eager to know how the viruses got into the mothers’ breast tissue in the first place, the researchers conducted additional experiments and found that the mouse pups had not transmitted the viruses to their mothers through the conventional route — by leaving contaminated feces in a shared living space for their mothers to ingest. That’s when the researchers decided to see whether the viruses in the mothers’ breast tissue might have come from the saliva of the infected pups and somehow spread during breastfeeding.
To test the theory, Ghosh collected saliva samples and salivary glands from the mouse pups and found that the salivary glands were replicating these viruses at very high levels and shedding the viruses into the saliva in large amounts. Additional experiments quickly confirmed the salivary theory: Suckling had caused both mother-to-pup and pup-to-mother viral transmission.
Research reported in this study was funded by the Division of Intramural Research of the NHLBI, part of NIH. Additionally, the research involved collaboration with two laboratories at the NIH National Institute of Dental and Craniofacial Research: the Adeno-associated Virus Biology and Utilization for Gene Transfer lab (ZIA-DE000695) and the Neuronal and Progenitor/Stem Cell Function During Salivary Gland Development lab (ZIA-DE00722).

Over the last decade, researchers and staff working on Penn State’s INSIGHT study have trained new mothers in skills that — among other things — help newborns sleep more during the night. New research from Penn State’s Center for Childhood Obesity Research (CCOR) shows that second children in these families also slept longer.
New parents often want infants to sleep because the parents are tired, but sleep is critical to health and development. The researchers in CCOR study sleep because it affects whether children develop obesity. Sleep also affects a child’s capacity for emotional regulation and cognitive development. What is more, research shows that sleep deprived parents are more likely to develop depression and be involved in traffic accidents. Infant sleep can be important for the whole family’s health and well-being.
Responsive parenting
The INSIGHT study — an acronym for intervention nurses start infants growing on healthy trajectories — began in 2012 with CCOR researchers training 279 mothers of first-born infants in responsive parenting practices. Responsive parenting involves responding to children in a timely, sensitive, and age-appropriate manner, based on the child’s presenting needs.
In INSIGHT, the mothers were taught how to respond to infant behavior states like fussiness, alertness (feeding and interactive play), drowsiness, and sleeping. The training included several specific recommendations about bedtime routines and responding to nighttime waking.
Children in the INSIGHT intervention group slept longer each night and were more likely to soothe themselves to sleep than children in the control group. Significantly, these children also had lower body mass indices (BMIs) for the first three years of their lives.

A recent publication from researchers at the University of Kentucky explains the importance of identifying and understanding how differences between tissues and cells alter gene expression without changing the underlying genetic code.
Introductory biology classes teach that DNA is transcribed into RNA, which is then translated into proteins. However, many cellular processes affect how quickly transcription and translation occur. Gene expression looks at the differences in RNA concentrations within a cell, and it can help scientists know which genes are active within that tissue or cell.
“Changes in gene expression can significantly affect various diseases and disease trajectories,” said Justin Miller, Ph.D., assistant professor in the UK College of Medicine’s Department of Pathology and Laboratory Medicine.
Miller, who is also affiliated with the Sanders-Brown Center on Aging and Biomedical Informatics, says he and his colleagues previously developed the first algorithm to identify ramp sequences from a single gene sequence. Through their recent work, Miller and fellow UK co-authors Mark Ebbert, Ph.D., and Matthew Hodgman created an online version of that algorithm and showed that ramp sequences change between tissues and cells without changing the RNA sequence.
A ramp sequence is part of the RNA sequence that slows translation at the beginning of the gene by using codons (sequences of three DNA or RNA nucleotides) that are not easily translated. Ramp sequences counterintuitively increase overall gene expression by evenly spacing the translational machinery and preventing collisions later in translation.
In their recent publication in NAR Genomics and Bioinformatics, the researchers present the first comprehensive analysis of tissue- and cell type-specific ramp sequences and report more than 3,000 genes with ramp sequences that change between tissues and cell types, which correspond with increased gene expression within those tissues and cells.

New University of Otago research suggests the brain function of otherwise-healthy individuals exposed to event trauma has the ability to “bounce back” over time once the threat resolves.
Researchers led by Dr Katie Douglas at the University of Otago, Christchurch’s Department of Psychological Medicine, conducted a follow-up study on a group of Cantabrians, who had been exposed to trauma during the region’s earthquakes over a decade ago.
The original study, conducted two to three years after the earthquakes, showed participants who were exposed to trauma but didn’t develop psychological difficulties, still suffered from problems with aspects of cognitive function compared with non-exposed participants.
Dr Douglas says the new follow-up study, conducted 8 years post-quakes, shows the cognitive function of those trial participants is now normal compared with a group of people tested in Dunedin.
“This is good news as it offers preliminary evidence that there are no long-lasting effects on cognitive impairment after exposure to a traumatic event, at least in people who don’t develop a mental health condition. It suggests changes in their cognitive functioning and emotion processing may be related to exposure to continued threat in the environment, which improves when the threat resolves.”
The original 89 trial participants were recruited in response to articles, opinion pieces and community notices in newspapers and via word of mouth over the course of 13 months, from January 2013 to February 2014. All received a face-to-face assessment and completed diagnostic questionnaires to confirm they had received no earthquake-related psychiatric diagnoses or counselling.