Publisher Health

Researchers have developed a new statistical model that predicts which cities are more likely to become infectious disease hotspots, based both on interconnectivity between cities and the idea that some cities are more suitable environments for infection than others. Brandon Lieberthal and Allison Gardner of the University of Maine present these findings in the open-access journal PLOS Computational Biology.
In an epidemic, different cities have varying risks of triggering superspreader events, which spread unusually large numbers of infected people to other cities. Previous research has explored how to identify potential “superspreader cities” based on how well each city is connected to others or on each city’s distinct suitability as an environment for infection. However, few studies have incorporated both factors at once.
Now, Lieberthal and Gardner have developed a mathematical model that identifies potential superspreaders by incorporating both connectivity between cities and their varying suitability for infection. A city’s infection suitability depends on the specific disease being considered, but could incorporate characteristics such as climate, population density, and sanitation.
The researchers validated their model with a simulation of epidemic spread across randomly generated networks. They found that the risk of a city becoming a superspreader increases with infection suitability only up to a certain extent, but risk increases indefinitely with increased connectivity to other cities.
“Most importantly, our research produces a formula in which a disease management expert can input the properties of an infectious disease and the human mobility network and output a list of cities that are most likely to become superspreader locations,” Lieberthal says. “This could improve efforts to prevent or mitigate spread.”
The new model can be applied to both directly transmitted diseases, such as COVID-19, or to vector-borne illnesses, such as the mosquito-borne Zika virus. It could provide more in-depth guidance than traditional metrics of risk, but is also much less computationally intensive than advanced simulations.
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

Aedes aegypti are the primary vector for mosquito-borne diseases such as dengue fever. However, the effects of climate change-related weather anomalies on mosquito populations is not well understood. A study published in PLOS Neglected Tropical Diseases by Cameron Nosrat at Stanford University, United States and colleagues suggests that early interventions may prevent disease transmission even as extreme climate events may increase the abundance of Ae. aegypti populations.
Temperature and rainfall have significant impacts on Ae. aegypti abundance, and climate change will likely intensify the frequency of extreme climate events such as floods, droughts, heat waves and cold waves. To better understand the specific effects of weather anomalies on the dynamics of vector-borne disease transmission, researchers conducted a retrospective cohort study to determine the impact of extreme rainfall and temperature on mosquito abundance and the risk of dengue infections in Kenya. Using satellite-derived climate data, the authors classified extreme climate events rainfall and temperatures as in the upper or lower 10% of historical averages. The researchers then monitored Aedes aegypti abundance using trapping methods and new dengue fever cases via blood samples collected from a cohort of 7,653 children.
Flood seasons contributed to significantly higher Ae. aegypti egg and adult abundance. However, extreme climate events and greater Ae. aegypti abundance did not correlate to an increased number of confirmed dengue fever cases. Human behaviors can modify the relationship between mosquito abundance and disease transmission, and influence infection risk. Preventative measures in the study sites may have contributed to reductions in dengue transmission. A major limitation of the study was the lack of long-term Kenya climate data; however, the authors believe their study effectively examines the influence of weather anomalies on various life stages of Ae. aegypti abundance.
According to the authors, “Dengue is the fastest-growing mosquito-borne disease in the world, and as climate change accelerates, many vulnerable populations will continue to be disproportionately impacted by this virus. Having shown floods to result in significantly increased dengue vector abundance, we hope to encourage actionable interventions to limit infection risk in light of these extreme climate events.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

Dogs infected with the Leishmania parasite smell more attractive to female sand flies than males, say researchers.
The study published in PLOS Pathogens is led by Professor Gordon Hamilton of Lancaster University.
In Brazil, the parasite Leishmania infantum is transmitted by the bite of infected female Lutzomyia longipalpis sand flies.
Globally over 350 million people are at risk of leishmaniasis, with up to 300,000 new cases annually. In Brazil alone there are approximately 4,500 deaths each year from the visceral form of the disease and children under 15 years old are more likely to be affected.
Leishmania parasites are transmitted from infected dogs to people by sand flies when they bite. Visceral leishmaniasis affects the internal organs and is fatal if not treated.
As only female sand flies transmit the parasite, researchers wanted to understand if infection made dogs more attractive to the insect.
Professor Gordon Hamilton of Lancaster University said: “In this study we showed that infected dog odour is much more attractive than uninfected dog odour to the female sand flies. Only the females can transmit the pathogen and male sand flies, which do not transmit the parasite, are not affected by the changed odour.
“This clear-cut difference in attraction of female and male sand flies suggests that the females are preferentially attracted by parasite infected hosts and this could lead to enhanced infection and transmission opportunities for the parasite.”
The researchers had previously found that dogs infected with Leishmania parasites smelled different compared to uninfected dogs.
Professor Hamilton said: “Domestic dogs are the reservoir of infection, therefore understanding how the infection affects the attractiveness of dogs to the insect vector is important in understanding the epidemiology of the disease and offers opportunities for new control and diagnostic methodologies.”
Story Source:
Materials provided by Lancaster University. Note: Content may be edited for style and length.

Even as vaccines are becoming more readily available in the U.S., protecting against the asymptomatic and pre-symptomatic spread of the virus (SARS-CoV-2) that causes COVID-19 is key to ending the pandemic, say two Georgetown infectious disease experts.
In their Perspective, “SARS-CoV-2 Transmission Without Symptoms” published March 18 in the journal Science, Angela L. Rasmussen, PhD, and Saskia V. Popescu, PhD, MA, faculty affiliates of the Center for Global Health Science and Security at Georgetown University Medical Center, make the case that symptomless transmission silently drives viral spread and is key to ending the pandemic.
“Determining the true transmission capability of asymptomatic and pre-symptomatic cases is inherently complex, but knowledge gaps should not detract from acknowledging their role in the spread of SARS-CoV-2,” the authors write.
“We can’t rely on vaccination alone to control the pandemic,” says Rasmussen. “Vaccines are great for protecting people against disease, but we don’t yet know how well they work to protect against transmission.”
Rasmussen says that from a biological perspective, it would be unlikely that a vaccine that protects well against disease would not protect against infection. “But just like the vaccines don’t offer a hundred percent protection against getting sick, they also aren’t a hundred percent likely to protect against transmission.”
In addition, while vaccines reportedly will become widely available in the U.S. by summer, that is not the case in the rest of the world where the pandemic continues unabated.
“Asymptomatic and pre-symptomatic transmission poses a unique challenge for public health and infection prevention mitigation efforts,” says Popescu. “Ultimately this is something we will need to continuously keep our eye on as we move into the next phase of the COVID-19 pandemic and a reduction of disease due to vaccinations.”
Rasmussen and Popescu conclude, “Until there is widespread implementation of robust surveillance and epidemiological measures that allow us to put out these smokeless fires, the COVID-19 pandemic cannot be fully extinguished.”
Story Source:
Materials provided by Georgetown University Medical Center. Note: Content may be edited for style and length.

The small intestine is ground zero for survival of animals. It is responsible for absorbing the nutrients crucial to life and it wards off toxic chemicals and life-threatening bacteria.
In a new study published March 18 in the journal Science, Yale researchers report the critical role played by the gut’s immune system in these key processes. The immune system, they found, not only defends against pathogens but regulates which nutrients are taken in.
The findings may provide insights into origins of metabolic disease and malnutrition that is common in some undeveloped regions of the world.
“We were surprised that the immune system was so involved in nutrition,” said first author Zuri Sullivan, a former graduate student in the immunology department at Yale and now a Howard Hughes Medical Institute Hanna H. Gray postdoctoral fellow at Harvard. “And the study lays the groundwork for understanding how this reciprocal interaction works.”
Working in the lab of senior author Ruslan Medzhitov, Yale’s Sterling Professor of Immunobiology and an investigator at the Howard Hughes Medical Institute, Sullivan became interested in how the diets of humans and other animals can dramatically change the organization of their digestive tracts. For instance, the digestive systems of carnivores and herbivores are organized differently to accommodate their specialized diets. Omnivores have the most complex system, which must adapt to a diverse diet of proteins, fats, and carbohydrates depending upon what’s available in the environment.
Sullivan, Medzhitov, and a group of colleagues decided to study how the large numbers of immune cells present inside intestinal tracts might influence nutrition. For instance, a specific immune system signaling molecule, known as interleukin-22 (IL-22), plays a key role in combatting bacterial pathogens such as those that cause food poisoning. The presence of IL-22 also seems to prevent the uptake of certain nutrients in the digestive system when pathogens are present.
In a series of experiments, the researchers discovered that a specific group of immune system cells — gamma delta T cells — can suppress expression of interleukin-22 in mice and allow the cells on the intestinal wall to activate digestive enzymes and nutrient transporters.
In addition to providing insights into malnutrition in some parts of the world — where bacterial infections lead to chronic expression of IL-22 and suppress the uptake of nutrients. The findings might also eventually help researchers develop ways to combat high rates of metabolic diseases, such as Type 2 diabetes and obesity in the developed world, Sullivan said.
Story Source:
Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Males and females, generally speaking, experience and respond to pain differently, but scientists have yet to understand all the brain circuits involved in these differences. Now, new research from the UNC School of Medicine lab of Thomas Kash, PhD, shows how neurons use dopamine to regulate pain differently in male and female mice.
The discovery, published in the journal Neuron, could help the scientific community devise better pain management strategies, particularly for women, who are disproportionally affected by pain throughout their lifespans.
“We focused on this neural pathway because our previous work and that of others show that specific neurons release dopamine to regulate pain responses,” said Kash, the John R. Andrews Distinguished Professor of Pharmacology. “Unfortunately, that research was done only in male mice. So we decided to look at both male and female mice, and what we found was very surprising.”
Dopamine, long known as the brain’s pleasure chemical, can actually regulate a wide variety of behaviors. The dopamine neurons that Kash and his lab looked at had previously been shown to be important for both the rewarding properties and the pain-relieving properties of heroin. Beyond this, several studies have shown that these neurons can regulate attention, suggesting a link between drug abuse, pain, and attention.
Previously, using male mice, the Kash lab found that dopaminergic neurons played a key role in how opiates dampen pain, likely through the release of dopamine and glutamate. In the new experiments, his lab focused on a neural pathway starting at the midbrain region called the periaqueductal grey, including part of the dorsal raphe. That brain region is involved in behavioral adaptation — how animals learn to respond to their environment. The neurons that make dopamine in that region operate in conjunction with a brain structure called the bed nucleus of the stria terminalis, or BNST, forming a neural pathway.
“We found that activating this pathway reduced pain sensitivity in male mice, but made female mice move more, especially in the presence of something capturing their attention,” said first author Waylin Yu, PhD, a former graduate student in the Kash lab and current postdoctoral researcher at UC San Francisco. “We think this is because of the different ways males and females respond to pain.”
In particular, these experiments seem to indicate that dopamine helps males simply not feel as much pain, while in females, dopamine helps the mice focus attention elsewhere while in the presence of pain.
More research is needed, but the Kash lab research shows that activating specific neural projections to the BNST reduces acute and persistent inflammatory pain, providing further evidence that dopamine signaling can enhance the blocking of pain stimuli, thus counteracting severe pain.
“We hope to investigate how this pathway can regulate more emotional behaviors associated with chronic pain, and then also look at the dynamics of the system, such as how this pathway works in real time during behavior measurements,” Kash said. “These neurons are also implicated in the actions of opioids such as morphine, so we plan to investigate that domain, as well.”
The National Institutes of Health funded this research.

In cancer immunotherapy, cells in the patient’s own immune system are activated to attack cancer cells. CAR T cell therapy has been one of the most significant recent advances in immunotherapies targeted at cancer.
In CAR T cell therapy, T cells are extracted from the patient for genetic modification: a chimeric antigen receptor (CAR) is transported into the cells using a viral vector, helping the T cells better identify and kill cancer cells. When the antigen receptor cells identify the desired surface structure in the patient’s cells, they start multiplying and killing the target cells.
CAR T cell therapy was introduced to Finland in 2018, and the treatment form has been used in support of patients suffering from leukaemia and lymphomas.
So far, the application of CAR T cell therapy to solid tumours has been difficult: targeting the therapy at just the tumour is difficult when the cancer type is not associated with any specific surface structure. In many cancer types, there is an abundance of a specific protein on the tumour’s surface, but as the protein also occurs in low numbers in normal tissue, CAR T cell therapy is not able to discriminate between target protein levels. This is why genetically modified cells are quick to attack also healthy cells and organs, which can result in fatal adverse effects associated with the treatment.
A study recently published in the Science journal has found a solution to applying CAR T cell therapy to solid tumours as well: through collaboration, American and Finnish researchers identified a new way of programming CAR T cells so that they only kill cancer cells, leaving alone healthy cells that have the same marker protein as cancer cells.
New technique based on ultrasensitive identification of HER2 cells, further investigation underway
HER2 is a protein characteristic of, among others, breast cancer, ovarian cancer and abdominal cancers. The protein can also occur in great numbers on the surface of tumour cells, since, as a result of gene amplification, HER2 expression can be multiplied in tumours.
A new CAR T cell engineering technique developed by the researchers is based on a two-step identification process of HER2 positive cells. Thanks to the engineering, the researchers were able to produce a response where CAR T cells kill only the cancer cells in the cancer tissue.
“Our solution requires the preliminary identification of the surface structures associated with the cancer. When the preliminary recognition ability that induces the CAR construct is adjusted to require a binding affinity that is different from the affinity used by CAR to direct the killing of these cells, an extremely accurate ability to differentiate between cells based on the amount of target protein on their surface can be programmed in this two-step ‘circuit’ which controls the function of killer T cells,” says Professor of Virology Kalle Saksela from the University of Helsinki.
Further studies for the application of the technique are already ongoing. Postdoctoral Researcher Anna Mäkelä, who works at Professor Saksela’s laboratory, is coordinating a project funded by the Academy of Finland investigating the use of CAR T cell therapy on various cancer types and their surface structures.
“We are very excited about these results, and we are currently developing the technique so that it could be used to treat ovarian cancer. As the work progresses, the aim is to apply the technique itself and the targeting molecules of CAR constructs even more broadly to malignant solid tumours. Our goal is to develop ‘multi-warhead missiles’, against which cancer cells will find it difficult to develop resistance,” Mäkelä says.
Story Source:
Materials provided by University of Helsinki. Note: Content may be edited for style and length.

COVID-19 disproportionately affects men compared with women, raising the possibility that a hormone like progesterone may improve clinical outcomes for certain hospitalized men with the disease. New research from Cedars-Sinai published online in the journal Chest supports this hypothesis.
The pilot clinical trial, involving 40 men, is believed to be the first published study to use progesterone to treat male COVID-19 patients whose lung functions have been compromised by the coronavirus. While the findings are promising, larger clinical trials are needed to establish the potential of this experimental therapy, the investigators said.
The study was prompted by multiple reports that men are at higher risk of mortality and severe illness from COVID-19 than are women, according to Sara Ghandehari, MD, director of Pulmonary Rehabilitation in the Women’s Guild Lung Institute at Cedars-Sinai and principal investigator for the trial.
“As an ICU doctor, I was struck by the gender disparity among COVID-19 patients who were very sick, remained in the hospital and needed ventilators,” she said. In addition, some published research had indicated that premenopausal women, who generally have higher progesterone levels, had less severe COVID-19 disease than did postmenopausal women, who have lower progesterone levels. While the bodies of both men and women naturally produce progesterone, women produce much more of the hormone during their reproductive years.
Protective Effect from Female Hormones
Ghandehari hypothesized that the gender differences in disease outcomes might be due, in part, to a protective effect from female hormones. In particular, preclinical studies elsewhere had pointed to progesterone as having certain anti-inflammatory properties. This finding suggested progesterone might be useful in dampening a sometimes-fatal immune response, known as a “cytokine storm,” that can worsen lung damage and attack other organs in COVID-19 patients.

From swallowing pills to injecting insulin, patients frequently administer their own medication. But they don’t always get it right. Improper adherence to doctors’ orders is commonplace, accounting for thousands of deaths and billions of dollars in medical costs annually. MIT researchers have developed a system to reduce those numbers for some types of medications.
The new technology pairs wireless sensing with artificial intelligence to determine when a patient is using an insulin pen or inhaler, and flags potential errors in the patient’s administration method. “Some past work reports that up to 70% of patients do not take their insulin as prescribed, and many patients do not use inhalers properly,” says Dina Katabi, the Andrew and Erna Viteri Professor at MIT, whose research group has developed the new solution. The researchers say the system, which can be installed in a home, could alert patients and caregivers to medication errors and potentially reduce unnecessary hospital visits.
The research appears in the journal Nature Medicine. The study’s lead authors are Mingmin Zhao, a PhD student in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL), and Kreshnik Hoti, a former visiting scientist at MIT and current faculty member at the University of Prishtina in Kosovo. Other co-authors include Hao Wang, a former CSAIL postdoc and current faculty member at Rutgers University, Aniruddh Raghu, a CSAIL PhD student.
Some common drugs entail intricate delivery mechanisms. “For example, insulin pens require priming to make sure there are no air bubbles inside. And after injection, you have to hold for 10 seconds,” says Zhao. “All those little steps are necessary to properly deliver the drug to its active site.” Each step also presents opportunity for errors, especially when there’s no pharmacist present to offer corrective tips. Patients might not even realize when they make a mistake — so Zhao’s team designed an automated system that can.
Their system can be broken down into three broad steps. First, a sensor tracks a patient’s movements within a 10-meter radius, using radio waves that reflect off their body. Next, artificial intelligence scours the reflected signals for signs of a patient self-administering an inhaler or insulin pen. Finally, the system alerts the patient or their health care provider when it detects an error in the patient’s self-administration.
The researchers adapted their sensing method from a wireless technology they’d previously used to monitor people’s sleeping positions. It starts with a wall-mounted device that emits very low-power radio waves. When someone moves, they modulate the signal and reflect it back to the device’s sensor. Each unique movement yields a corresponding pattern of modulated radio waves that the device can decode. “One nice thing about this system is that it doesn’t require the patient to wear any sensors,” says Zhao. “It can even work through occlusions, similar to how you can access your Wi-Fi when you’re in a different room from your router.”
The new sensor sits in the background at home, like a Wi-Fi router, and uses artificial intelligence to interpret the modulated radio waves. The team developed a neural network to key in on patterns indicating the use of an inhaler or insulin pen. They trained the network to learn those patterns by performing example movements, some relevant (e.g. using an inhaler) and some not (e.g. eating). Through repetition and reinforcement, the network successfully detected 96 percent of insulin pen administrations and 99 percent of inhaler uses.
Once it mastered the art of detection, the network also proved useful for correction. Every proper medicine administration follows a similar sequence — picking up the insulin pen, priming it, injecting, etc. So, the system can flag anomalies in any particular step. For example, the network can recognize if a patient holds down their insulin pen for five seconds instead of the prescribed 10 seconds. The system can then relay that information to the patient or directly to their doctor, so they can fix their technique.
“By breaking it down into these steps, we can not only see how frequently the patient is using their device, but also assess their administration technique to see how well they’re doing,” says Zhao.
The researchers say a key feature of their radio wave-based system is its noninvasiveness. “An alternative way to solve this problem is by installing cameras,” says Zhao. “But using a wireless signal is much less intrusive. It doesn’t show peoples’ appearance.”
He adds that their framework could be adapted to medications beyond inhalers and insulin pens — all it would take is retraining the neural network to recognize the appropriate sequence of movements. Zhao says that “with this type of sensing technology at home, we could detect issues early on, so the person can see a doctor before the problem is exacerbated.”

Patients who regurgitate regularly but without any known cause may have a condition called rumination. Unfortunately, rumination is often confused with other gastrointestinal conditions, which means many patients may not be getting prompt treatment. But a new study by investigators at Massachusetts General Hospital (MGH) in Neurogastroenterology and Motility clearly describes this syndrome, how to distinguish it from other conditions, and how to treat it.
Rumination syndrome is a behavioral problem, in which patients effortlessly and repeatedly regurgitate food into their mouths while eating and sitting upright. It is a learned behavior that is classified as a disorder of the gut-brain interaction (DGBI). Many experts think that regurgitations develop as a habit involving an uncomfortable, mounting sensation or inner tension (similar to patients with tics) that results in contraction of the abdominal walls after eating. This pattern gets reinforced with positive associations (such as relief of anxiety and stress after regurgitation) as well as negative associations (such as the discomfort of trying to suppress the inner tension without regurgitating).
“This condition causes a lot of embarrassment and may stop people from eating with others,” explains Trisha Satya Pasricha, MD, co-lead author with Helen Burton Murray, PhD, both of MGH’s Division of Gastroenterology. “It is not well understood, and is often mistaken for other disorders.”
One reason rumination symptoms are missed is because they overlap with other DGBIs, such as functional dyspepsia (stomach pain or indigestion) or gastroparesis, which is when patients feel nauseous and full after eating just a small amount. Patients may incorrectly describe their symptoms as reflux or vomiting. As a result, the condition may go undiagnosed or misdiagnosed for a long period. That can lead to significant social constraint and possibly weight loss.
Pasricha and her colleagues screened 242 patients who were referred to specialists for gastric symptoms that could indicate they were experiencing rumination. The symptoms that brought these patients to a gastroenterologist included dyspepsia and gastroparesis.
Thirty-one of the 242 (12.8%) patients met criteria for rumination syndrome, which is determined using a gastric symptom scoring system. Almost half of those patients (48%) reported associated psychosocial impairment, meaning that they experienced difficulty in social situations because of their condition.
Comparing those patients with rumination and those without, there were no differences in race, gender, frequency of diabetes, or frequency of gastroparesis. “There is little demographically that distinguishes these patients other than their tendency to regurgitate when eating,” says Pasricha. “They are not more likely to have a history of an eating disorder or weight problems.”
However, the patients with rumination were more likely to also experience heartburn, particularly daytime symptoms. The researchers suggest that screening for heartburn and regurgitation could help identify more patients with this condition.
The treatment for rumination is behavioral and involves the practice of diaphragmatic, or deep, breathing. Two pilot trials have shown that this significantly improves gastroesophageal reflux. Comprehensive cognitive behavioral therapy for rumination syndrome (CBT-RS) is also recommended. CBT is an increasingly popular type of behavior therapy that helps people re-orient their thinking, teaching them new thought processes to replace old patterns that lead to self-harm and other poor outcomes.
Story Source:
Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.