Culture

Arlington, Va., August 16, 2018 - The consequences of healthcare-associated infections (HAIs) reach well beyond patients' physical health, souring social relationships, and leading some healthcare providers (HCP) to distance themselves from affected patients, according to a qualitative, systematic review published in the American Journal of Infection Control (AJIC), the journal of the Association for Professionals in Infection Control and Epidemiology (APIC).

To properly address patients' needs and concerns, researchers at Glasgow Caledonian University in Scotland, and colleagues, conducted a meta-synthesis of qualitative research, looking at 17 studies from five different countries addressing five common types of HAIs, focusing on patient experiences of both colonization and infection from bacteria that commonly cause HAIs.

The authors of this meta-synthesis urge HCP to consider the social circumstances that color patient experiences, including feeling shameful and dirty, and the responses of those around them, especially those of HCP.

According to the analysis, many patients experienced an emotional response to their diagnosis and described "feeling dirty," "having the plague," or "feeling like a leper." While emotional responses varied based on type of HAI, patients with nearly all colonization or infection types reported a fear of transmitting their infection to others. This fear affected patients' personal and workplace relationships. Some patients, particularly those colonized by MRSA, also expressed concern about working in certain professions because of their condition and a fear of rejection by coworkers.

Patients who were able to speak to infection preventionists reported receiving constructive information and feeling reassured about their condition, whereas patients who did not, reported feeling dismissed by staff members.

"Having an HAI is a significant event in the patient's care journey and subsequent life that is influenced by biology, society and context," said Kay Currie, PhD, the paper's lead author. "Understanding the patient experience can help HCP to interact and respond in a constructive way, providing more effective support during this challenging time in a patient's healthcare experience."

The analysis also found:

Concerns about interaction with HCP or restriction to healthcare treatment were particularly prominent among patients with infections caused by resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) or Extended-Spectrum Beta-lactamases (ESBL). The studies highlight patient reports of exclusion from rehabilitation classes, requirements to wait until the end of clinic appointments to be seen, or restrictions on attending clinics.

Many patients with HAIs reported changing their personal hygiene behavior, taking precautions to prevent the transmission of infection, including undergoing extensive cleaning at home and advising family members on hygiene measures.

Many patients reported interactions in a climate that induced fear and uncertainty, particularly when frontline HCP lacked knowledge of the causes and consequences of HAIs and could not provide the patient with adequate information. This finding highlighted the sociocultural context in which the infection or colonization occurs.

"As one in every 25 hospitalized patients in the United States is diagnosed with an HAI, it is critical to understand the long-lasting impact of such infections, not just from a physical perspective, but also from a social and emotional perspective," said 2018 APIC President Janet Haas, PhD, RN, CIC, FSHEA, FAPIC. "This qualitative review provides valuable insight into the patient perspective and how healthcare professionals can more effectively interact with their patients to enhance recovery in all areas of their lives."

GALVESTON, Texas - A new study from The University of Texas Medical Branch at Galveston has uncovered why some people that have brain markers of Alzheimer's never develop the classic dementia that others do. The study is now available in the Journal of Alzheimer's Disease.

Alzheimer's disease, the most common form of dementia, affects more than 5 million Americans. People suffering from Alzheimer's develop a buildup of two proteins that impair communications between nerve cells in the brain - plaques made of amyloid beta proteins and neurofibrillary tangles made of tau proteins.

Intriguingly, not all people with those signs of Alzheimer's show any cognitive decline during their lifetime. The question became, what sets these people apart from those with the same plaques and tangles that develop the signature dementia?

"In previous studies, we found that while the non-demented people with Alzheimer's neuropathology had amyloid plaques and neurofibrillary tangles just like the demented people did, the toxic amyloid beta and tau proteins did not accumulate at synapses, the point of communication between nerve cells," said Giulio Taglialatela, director of the Mitchell Center for Neurodegenerative Diseases. "When nerve cells can't communicate because of the buildup of these toxic proteins that disrupt synapse, thought and memory become impaired. The next key question was then what makes the synapse of these resilient individuals capable of rejecting the dysfunctional binding of amyloid beta and tau?"

In order to answer this question, the researchers used high-throughput electrophoresis and mass spectrometry to analyze the protein composition of synapses isolated from frozen brain tissue donated by people who had participated in brain aging studies and received annual neurological and neuropsychological evaluations during their lifetime. The participants were divided into three groups - those with Alzheimer's dementia, those with Alzheimer's brain features but no signs of dementia and those without any evidence of Alzheimer's.

The results showed that resilient individuals had a unique synaptic protein signature that set them apart from both demented AD patients and normal subjects with no AD pathology. Taglialatela said that this unique protein make-up may underscore the synaptic resistance to amyloid beta and tau, thus enabling these fortunate people to remain cognitively intact despite having Alzheimer's-like pathologies.

"We don't yet fully understand the exact mechanism(s) responsible for this protection," said Taglialatela. "Understanding such protective biological processes could reveal new targets for developing effective Alzheimer's treatments."

On Avoiding Deep Dementia
Norman L. Cantor

To avoid prolonged dementia, the author has written an advanced directive to prohibit the provision of life-sustaining interventions, including hydration and nutrition, should he reach a self-defined point of cognitive debilitation. But if that point is reached, he would be unable to comprehend the reasoning that motivated the advanced directive, and he might enjoy life despite having dementia. Still, surrogate decision-makers and caregivers would have a moral and legal obligation to implement his advanced directive, argues Cantor, a professor emeritus of law at Rutgers University School of Law. Competent individuals should be given control over directing the types of life-sustaining treatments they receive if they develop dementia.

Other Voices: Three commentaries raise concerns about advance directives that limit care for people with dementia.

Are Obese Children Abused Children?
Maura Priest

In 2010, a South Carolina mother was charged with criminal neglect after her 14-year-old son reached 555 pounds, in the first U.S. felony case involving childhood obesity. But this article discusses important ethical and legal distinctions between negligent and abusive caretakers and caretakers of obese children. The former intentionally harm or fail to protect the children under their care, while caretakers of obese children may act in well-intentioned though misguided ways. And environmental, social, and genetic factors are also significant contributors to childhood obesity. Since allowing a child to become obese falls into a different moral and legal category from abusing or neglecting a child, the solutions to protect obese children must be different from those to protect abuse and neglect victims. Priest is an assistant professor of philosophy at Arizona State University and an affiliate researcher at the University of Cologne.

Discriminatory Demands by Patients
Philip M. Rosoff

Many in health care are concerned, even appalled, when patients demand physicians, nurses, and other caregivers of a particular gender or race. While there is evidence that patients from groups that have been victims of discrimination may have better health outcomes if they have clinicians of the same background or gender, how does one distinguish requests that are potentially beneficial from those that are simply discriminatory? Which requests should be honored, and which should be denied? The answers are not straightforward, writes Philip M. Rosoff, a professor of pediatrics and medicine at Duke University School of Medicine and an adjunct professor of clinical science at North Carolina State University College of Veterinary Medicine.

A new study suggests that long-term exposure to secondhand smoke during childhood increases the risk of chronic obstructive pulmonary disease (COPD) death in adulthood. The study also suggests secondhand smoke exposure as an adult increases the risk of death not only from COPD but also several other conditions.

Secondhand smoke is known to have adverse effects on the lung and vascular systems in both children and adults. But it is unknown whether childhood exposure to secondhand smoke is associated with mortality in adulthood. To explore the issue, American Cancer Society epidemiologists led by W. Ryan Diver, MSPH, examined associations of childhood and adult secondhand smoke exposure with death from all causes, ischemic heart disease, stroke, and chronic obstructive pulmonary disease among 70,900 never-smoking men and women from the Cancer Prevention Study II Nutrition Cohort. Study participants, primarily ages 50 to 74 at the beginning of the study, answered questions about their secondhand smoke exposure during childhood and as adults and were followed for 22 years.

Those who reported having lived with a daily smoker throughout their childhood had 31% higher mortality from chronic obstructive pulmonary disease compared to those who did not live with a smoker. In a calculation done for this release, Diver says the increase in COPD mortality corresponds to about 7 additional deaths per year per 100,000 never-smoking study participants. Although the study counted only deaths, the increase in fatal COPD implies that living with a smoker during childhood could also increase risk of non-fatal COPD.

In addition, secondhand smoke exposure (10 or more hours/week) as an adult was associated with a 9% higher risk of all-cause mortality, a 27% higher risk of death from ischemic heart disease, a 23% higher risk of death from stroke, and a 42% higher risk of death from COPD.

"This is the first study to identify an association between childhood exposure to secondhand smoke and death from chronic obstructive pulmonary disease in middle age and beyond," said Diver. "The results also suggest that adult secondhand smoke exposure increases the risk of chronic obstructive pulmonary disease death. Overall, our findings provide further evidence for reducing secondhand smoke exposure throughout life."

Continued growth in global demand for palm oil is expected to mean an expansion in oil palm plantations in Africa. The continent offers the low-lying tropical ecosystems oil palm prefers, hence an opportunity for States, businesses and local farmers to generate income. However, the lessons learned from Southeast Asia, where most oil palm plantations are located, prompted the international team to assess the potential impact on primates of an expansion in oil palm cultivation in Africa.

In the study, the researchers set out to identify 'areas of compromise' in which oil palm cultivation would be most productive while having little impact on primates. They concluded that such areas were rare across Africa, covering only 0.13 to 3.3 million hectares (Mha).

There are only 3.3 million hectares available with little impact on primates

In total, according to the study, 273 Mha of land could be planted with oil palm in Africa: 84 Mha with low yields, 139 Mha with average yields and just 50 Mha with high yields, in view of local soil and climate criteria and assuming crops are solely rain-fed with intermediate use of inputs. "If we combine these figures with the data on primate vulnerability, oil palm could only be grown with little impact on primates on 3.3 Mha. That figure drops to 0.13 Mha if we only consider high-potential land" , says Ghislain Vieilledent, CIRAD ecologist and co-author of the study. Those figures of 3.3 Mha and 0.13 Mha correspond to just 6.2% and 0.2% respectively of the demand for additional land by 2050, given that 53 Mha of additional land is forecast to be needed by then.

There may be mitigation strategies, but the impact remains high

"One potential mitigation strategy would be to identify alternative trajectories for agricultural expansion, using 'smart' criteria to minimize and and delay the loss of primate home range as much as possible," says Ghislain Vieilledent. The researchers compared two income-driven oil palm expansion scenarios and two conservation-driven scenarios. The income-driven scenarios would see the most productive and accessible land converted to oil palm cultivation first. In the conservation-driven scenarios, it is land with low carbon stocks and low primate vulnerability that would be converted first. The researchers showed that even in a scenario seeking to minimize the impact on primates, five species, on average, would lose 1 ha of habitat for every 1 ha of land converted to oil palm cultivation.

Levers to help mitigate the impact of oil palm cultivation

"Levers for the successful conservation of African biodiversity do exist," says Ghislain Vieilledent. "One way could be to increase yields in existing plantations by using high quality seed and adopting better agricultural practices." Initiatives such as the Round Table on Sustainable Palm Oil (RSPO) should also be supported, with a strengthening of the environmental component of this certification. Another possible solution lies in reducing future demand for palm oil in the northern hemisphere by raising consumer awareness and seeking alternatives to biodiesel. However, given the population growth expected across Africa over the next 30 years and the increased food consumption which will inevitably accompany it, the effects could be limited. There is already momentum for change and the researchers hope their findings will contribute to this.

Primates are a good indicator of biodiversity

The researchers focused on primates because they are a good indicator of overall biodiversity. "There is a correlation between primate diversity and the richness of species in other taxonomic groups. They play an important role in seed dispersal and in maintaining the composition of forest ecosystems," explains CIRAD ecologist Ghislain Vieilledent. Populations of many primate species are in decline: 37% of primate species in mainland Africa and 87% of species in Madagascar are under threat of extinction according to International Union for Conservation of Nature (IUCN) criteria. In this study, the distribution of 193 African primate species was taken into account (at a resolution of 10 x 10 km) along with their vulnerability (IUCN conservation status).

Mathematics can help public health workers better understand and influence human behaviours that lead to the spread of infectious disease, according to a study from the University of Waterloo.

Current models used to predict the emergence and evolution of pathogens within host populations do not include social behaviour.

"We tend to treat disease systems in isolation from social systems, and we don't often think about how they connect to each other, or influence each other," said Chris Bauch, co-author and a professor in the Department of Applied Mathematics at Waterloo. "This gives us a better appreciation of how social reactions to infectious diseases can influence which strains become prominent in the population."

By adding dynamic social interactions to the models already used for disease outbreaks and evolution, researchers could better anticipate how a virulent pathogen strain may emerge based on how humans attempt to control the spread of the disease. This new addition to disease modelling could allow scientists to better prevent undesirable outcomes, such as more dangerous mutant strains from evolving and spreading.

The social modelling could impact public health responses to emerging infectious diseases like Ebola and Severe Acute Respiratory Syndrome (SARS). Human behaviour during these outbreaks often changes dramatically during the outbreak. People may start using face masks, or stop using them prematurely. Also, public fear of the pathogens may end up driving the wrong type of behaviour if the public's information is incorrect. The modelling could help public health responses navigate and better channel these kinds of population responses,

Bauch and his co-author Joe Pharaon formulated the new mathematical model to study the influence of social behaviour on the competition between pathogen strains with different virulence. Using computer simulations, they analyzed how the model behaved under various possible scenarios that might occur to populations to explore the logic of the hypothesis that social behaviour plays a role in the evolution of the strain.

"Human behaviour plays a big role in the spread and evolution of an infectious disease," said Pharaon,a PhD candidate at Waterloo's Faculty of Mathematics. "The model we formulated was a general model, but it could be adapted with more biological detail and structure for more specific pathogens."

An opt-out organ donation register is unlikely to increase the number of donations, according to a new study from Queen Mary University of London.

The researchers say donors should actively choose to be on the register by opting-in to ensure they genuinely want to donate their organs and to limit families from refusing the donation of their deceased relatives' organs.

An opt-out system automatically registers everyone and presumes consent to donate so if you do not want to you must take yourself off the register, whereas an opt-in system requires explicit consent to donate and indicates willingness.

However most organ donation legislative systems, whether opt-in or out, include a clause that allows the final decision to donate to be made by family members.

NHS Blood and Transplant reported in 2016 that more than 500 families vetoed organ donations since April 2010 despite being informed that their relative was on the opt-in NHS Organ Donation Register*. This translated into an estimated 1,200 people missing out on potential life-saving transplants.

Plans to introduce an opt-out system in England by 2020 have recently been announced by the government, but the researchers suggest this will create ambiguity and will not reduce veto rates.

In three experiments†, American and European participants from countries that have either a default opt-in or default opt-out system were presented with a fictional scenario and asked to take on the role of a third party to judge the likelihood that an individual's 'true wish' was to actually donate their organs, given that they were registered to donate.

Overall, regardless of which country the participants came from, they perceived the donor's underlying preference to donate as stronger under the default opt-in and mandated choice systems as compared to the default opt-out and mandatory donor systems.

The study was published in Journal of Experimental Psychology: Applied.

Lead author Dr Magda Osman, from Queen Mary University of London, said: "We show it's harder to judge the underlying wishes of the deceased if they were on an opt-out and mandatory donation register. Why? Because making a free choice indicates what your preference is. If you don't actively choose and you are listed as a donor on the register, then it isn't clear if you really wanted to donate your organs. This matters because if in the event of death your relatives have to decide what to do, they may veto the organ donation if they can't tell for sure what your underlying wishes were."

Dr Yiling Lin, also from Queen Mary University of London, added: "There are plans to launch an opt-out organ donation system in England, but what we show is that this system is unlikely to increase actual rates of organ donation or reduce veto rates, all it will do is increase the number of people on the organ donation register."

In 2017/18 there were 6,044 people in the UK waiting for a transplant while 411 patients died while waiting on this list**. Similarly, this year in the US there are 114,000 people on the waiting list to receive an organ and it is estimated that 20 people die each day while waiting on the list***.

To address problems like these, behavioural interventions, such as nudges, have been used to provide practical solutions that are based on psychological and behavioural economic research.

An example of a nudge is an automatic default, such as the ones often used in organ donation legislative system. The rationale behind an automatic default is that it can bridge the gap between a good intention and the effort needed to implement that intention into practice.

Dr Osman said: "Our findings are important because they challenge the efforts of many nudge enthusiasts to promote the use of opt-out defaults in organ donation."

She added: "To help increase actual rates of organ donation, we need more transplant coordinators working with families to help them understand the issues before being faced with a monumental and distressing decision.

"We also need to offer people a way to indicate explicitly what they wish to do. This should involve an expressed statement of intention if their wish is to donate, or an expressed statement of intention if there is an objection to donate. This reduces the ambiguity in trying to infer what one wanted to do when it comes to donating their organs."

A study of more than 1 million pregnancies in Finland reports that elevated levels of a metabolite of the banned insecticide DDT in the blood of pregnant women are linked to increased risk for autism in the offspring. An international research team led by investigators at Columbia University’s Mailman School of Public Health and the Department of Psychiatry published these results in the American Journal of Psychiatry. The study, conducted in collaboration with investigators at the University of Turku and the National Institute of Health and Welfare in Finland, is the first to connect an insecticide with risk for autism using maternal biomarkers of exposure.

Researchers identified 778 cases of childhood autism among offspring born from 1987 to 2005 to women enrolled in the Finnish Maternity Cohort, representing 98 percent of pregnant women in Finland. They matched these mother-child pairs with control offspring of mothers and offspring without autism. Maternal blood taken during early pregnancy was analyzed for DDE, a metabolite of DDT, and PCBs, another class of environmental pollutants.

The investigators found the odds of autism with intellectual disability in offspring were increased by greater than twofold for the mother’s DDE levels in the top quartile. For the overall sample of autism cases, the odds were nearly one-third higher among offspring exposed to elevated maternal DDE levels. The findings persisted after adjusting for several confounding factors such as maternal age and psychiatric history. There was no association between maternal PCBs and autism.

While DDT and PCBs were widely banned in many nations over 30 years ago, including the U.S. and Finland, they persist in the food chain because their breakdown occurs very slowly, as long as several decades, resulting in continuing exposure to populations. These chemicals are transferred across the placenta in concentrations greater than those seen in the mother’s blood.

“We think of these chemicals in the past tense, relegated to a long-gone era of dangerous 20th Century toxins,” says lead author Alan S. Brown, MD, MPH, professor of Epidemiology at Columbia University’s Mailman School of Public Health and of Psychiatry at Columbia University Medical Center. “Unfortunately, they are still present in the environment and are in our blood and tissues. In pregnant women, they are passed along to the developing fetus. Along with genetic and other environmental factors, our findings suggest that prenatal exposure to the DDT toxin may be a trigger for autism.”

The researchers offer two reasons for their observation that maternal exposure to DDE was related to autism while maternal PCB exposure was not. First, maternal DDE is associated with low birthweight, a well-replicated risk factor for autism. In contrast, maternal PCB exposure has not been related to low birthweight. Second, they point to androgen receptor binding, a process key to neurodevelopment. A study in rats found DDE inhibits androgen receptor binding, an outcome also seen in a rat model of autism. In contrast, PCBs increase androgen receptor transcription.

A lineage of type 1 dengue virus found in Brazil is able to prevail over another even though it multiplies less in vector mosquitoes and infected human cells. This discovery was made under the scope of a Thematic Project supported by the São Paulo Research Foundation - FAPESP involving several Brazilian institutions as well as a university in the United States.

According to the study, the lineage activates a weaker immune response in the patient and is less strongly combated. As a result, the virus is able to multiply more in the organism and is more likely to be transmitted to others via infected mosquitoes, so that this lineage supersedes the other owing to its significantly greater overall capacity to multiply in mosquitoes and patients.

The researchers studied lineages 1 and 6 (L1 and L6) of type 1 dengue, which affect the population of São José do Rio Preto, São Paulo State, Brazil. Their findings showed that while L1 had a superior capacity to multiply in mosquitoes and cells, L6 was able to minimize and even deactivate the human immune response, so that this lineage ended up replacing L1.

"There were three approaches to investigating the situations in which dengue virus multiplies and to explain why one lineage supersedes another. Our research brought to light a new phenomenon that explains how a virus survives in a population," said Maurício Lacerda Nogueira, a professor at the São José do Rio Preto Medical School (FAMERP), head of its Dermatological Disease Department's Virology Research Laboratory, and co-author of an article that published the results of the study in PLOS Neglected Tropical Diseases . Nogueira also chairs the Brazilian Society for Virology.

"However, knowing whether the virus multiplies more or less in mosquitoes or human cells isn't enough to understand why one lineage replaces another. We also need to know how the virus interacts with the human organism as a whole," said Nogueira.

The study produced vital new knowledge for the production of dengue vaccines. "A global understanding of how the virus interacts with the population helps us understand how vaccines work and is fundamental to our ability to design them," he said.

Type 1 dengue virus has been circulating in Brazil since the mid-1980s. Three lineages (L1, L3 and L6, all belonging to the same genotype) were introduced at different times. L6 was initially observed in São José do Rio Preto, where it began circulating in 2008. L1 was first identified in the city in 2010. These two lineages cocirculated for a period.

L1 was expected to display a higher capacity to multiply in cells and in the vector mosquito, Aedes aegypti, since it arrived after L6 and its viral fitness appeared to be superior to that of L6. L1 was therefore expected to replace L6 as the dominant strain, but it began to decline in 2013 and eventually disappeared.

This fact contradicted existing scientific knowledge about the prevalence of one lineage over another - a phenomenon called clade replacement (a clade is a branch of a phylogenetic tree comprising all organisms that have evolved from a common ancestor).

Clade replacement occurs if a lineage multiplies more in human cells after being introduced than another lineage that was already living in the same environment, or if a lineage that arrives later multiplies more in the mosquito. In both cases, the lineage that supersedes the other is said to have a higher level of viral fitness.

Epidemiological fitness

A third explanation arose from a 2015 study conducted in Puerto Rico, where a lineage of dengue virus was found to have a lower level of viral fitness than the lineages that were already in the environment yet eventually replaced them. Scientists discovered that this lineage inhibited the interferon system, which acts as the first line of defense against viruses in mammals (interferons are a complex of proteins that interfere with viral replication and protect cells from infection). This phenomenon is called epidemiological fitness - the capacity of a virus to become dominant in the field during epidemic outbreaks.

In the Brazilian case, none of this happened. The researchers first sequenced the genomes of the two viral lineages, which were found to have 47 different amino acids. Despite this significant genetic distance, L6 won the competition between them.

"Based on the information available at the time, it was assumed that L6 multiplied better and therefore became dominant, but when we looked at contaminated human and monkey cells, we found that L1 multiplied ten times more on average than L6," said the coordinator for the FAPESP Thematic Project.

The next hypothesis was that L6's higher viral fitness might be due to its higher multiplication rate in the mosquito. The researchers therefore infected captive mosquitoes (bred for use in scientific experiments) orally, having them feed by biting a membrane that contained mouse blood contaminated with dengue virus L1 and L6. "Again, L1 multiplied ten times better than L6 in the mosquito," Nogueira said.

The researchers then investigated the possibility that the captive mosquitoes were somehow different from those found in the environment. In a new experiment, mosquito eggs were collected in the environment and hatched in the laboratory. The result was the same: L1 continued to be more efficient than L6 in terms of multiplication, although studies showed that patients infected with L6 had a far higher viral load than those infected with L1.

This evidence left the epidemiological fitness hypothesis, as had been the case in Puerto Rico, where a dengue virus that encoded interferon-inhibiting RNA had been found. Interference was not confirmed in the Brazilian case. "We then realized we were dealing with a mechanism that differed from the three known ones," Nogueira said.

To solve the mystery, the researchers began studying the immunological aspects of the virus's interaction with the organism. Using computational prediction systems, they found that L1 was far more likely than L6 to activate B and T lymphocytes, the main cellular components of the adaptive immune response.

Next, in studies involving mice and cells donated by people infected with the virus, the scientists succeeded in stimulating and measuring the activation of the response by B cells and T cells, observing that L6 activated a weaker response than L1. They also measured the level of cytokines present in the patients' serum. Cytokines are signaling molecules that mediate and regulate immunity.

"Generally speaking, we observed that L1 multiplies much better but also strongly activates the immune system in both humans and mice," Nogueira said. "In other words, L1 induces a very robust response against the virus by the organism, whereas L6 multiplies less but either inhibits the immune response or stimulates it little or not at all, so the organism takes longer to recognize the virus."

As a result, the number of L6 viruses in the human organism is tenfold the number of L1 viruses on average, found the FAPESP-supported study. They also observed that L1 multiplies much more in the mosquito and replicates far more locally when it infects a person. This vigorous replication triggers strong activation of B and T cells, leading to an increase in cytokines, and this strong immune response inhibits systemic replication by the virus in the organism. As a result, the viral load is lower and dissemination to mosquitoes is reduced, so that fewer people will be infected by L1.

Despite the lower capacity of L6 to multiply in the mosquito and at the site of initial replication after a person is bitten, it produces only weak activation of B and T cells and stimulates the secretion of cytokines that inhibit the immune response instead of stimulating it.

"So systemic replication in people is much greater," Nogueira said. "This means the number of viruses in the population is higher, and more mosquitoes will be infected. We therefore concluded that the epidemiological fitness of L6 is higher than that of L1, whereas the viral fitness of L1 is higher than that of L6."

The research lasted two and a half years and involved a group of 24 scientists at several Brazilian higher education institutions in addition to FAMERP - Oswaldo Cruz Foundation, the Federal Universities of Rio de Janeiro (UFRJ) and Minas Gerais (UFMG), and São Paulo State University (UNESP) - as well as foreign collaborator Nikos Vasilakis, also a coauthor of the article and a researcher at the Center for Tropical Diseases, University of Texas Medical Branch, in Galveston (USA).

"Using epidemiological, phylogenetic, molecular and immunological analysis, the authors of the research showed that differences in the host's immune response determine the dynamics of circulation in two lineages of dengue virus found in the city, suggesting that the factors that influence the dynamics of dengue transmission are far more complex than was previously thought," Vasilakis said.

There's nothing like a good laugh to lighten a mood, especially when the atmosphere is serious -- like it can be in a science classroom.

Using humor in the classroom has been shown to positively impact student learning, but what if an instructor simply isn't funny? Or what effect does it have on students if a teacher tells an offensive joke?

In a first-of-its-kind study published today in the journal PLOS ONE, researchers from Arizona State University found that students appreciate when instructors tell jokes in science class, but that female and male students differ in what topics they find funny or offensive.

Researchers from the School of Life Sciences surveyed students from 25 college science courses about their perceptions of instructor humor. Of the 1,637 respondents, 99 percent say they appreciate instructor humor and believe it improves the classroom experience. Many students also say humor decreases stress, enhances the relationship between students and instructor, and helps them remember what is taught in class.

Researchers were fascinated by the high number of students who valued humor.

"I went into [this study] thinking that maybe we shouldn't be joking in the classroom, but I left the study thinking that instructors should use humor as a way to better connect with students," said Sara Brownell, associate professor in the school and senior author of the paper. "But, as might seem obvious, we need to be careful with what we're joking about because we found the topics that instructors are joking about can have different effects on different students."

What if a science instructor tells a joke that's not funny?

The study found that even if teachers tell jokes that fall flat - jokes that students don't find funny - it did not change the students' attention to course content or their relationship with the instructor.

However, if a teacher tells a joke that is offensive and unfunny, more than 40 percent of students say it decreases their ability to pay attention to course content and negatively affects whether an instructor is seen as relatable. Although this can hurt all students, it may have a larger impact on women.

This study found that men and women in science classrooms differed on what topics they thought were funny or offensive. In the survey, science students were presented with hypothetical topics professors could joke about. Male students were more likely to find hypothetical jokes told by the instructor about gender, sexual orientation, religious identity and race funny, while women were more likely to find these same hypotheticals offensive. However, both men and women find three topics to be funny and not offensive: science, college and television.

"More and more studies are starting to paint a picture that the classroom environment is really important for student learning," said Brownell. "Science classrooms and the instructors teaching the science are typically described by students as boring, unapproachable and difficult. So, science instructors who try to be funny can create better learning environments, as long as they are not offensive."

What does this mean for instructors?

"They need to think twice about the type of humor they use," said Katelyn Cooper, lead author and postdoctoral researcher in Brownell's lab. "Is it a joke about cute animals? Probably OK. A pun about science? Probably OK."

Student researchers

One unusual aspect of this study is that it was carried out by 16 undergraduate and graduate students enrolled in a class that focused on biology education research. Advertised as a project-based course, the entire class worked on the research project during one semester. The students worked as investigators on the project -- formulating the initial research idea, collecting and analyzing data, and editing the final manuscript.

Taija Hendrix, an undergraduate student researcher at the time of the study, said by taking the course, she was able to see the entire process of research from the very beginning. Hendrix said the possibility of being published was exciting.

"This class brought together students from all across the School of Life Sciences, some of whom I probably wouldn't have worked with, but in this course, we were all able to work together towards a common goal," said Hendrix. "The instructors told us they wanted our research to be published. For me, this idea was incredible that something I did would be read not only by other students, but scientists. The idea of contributing to the scientific literature before officially being a scientist myself wasn't something I thought I would have the privilege to do. Because of this course I was able to."

Hendrix graduated in May of 2018 with her bachelor's in biological sciences. She is now teaching high school science classes in Avondale, Arizona, and plans on using plenty of humor to help

Journal

PLoS ONE

Years after the end of the Human Genome Project (HGP), which mapped the human genetic blueprint, its contributions to science and scientific culture are still unfolding. Ioannis Pavlidis, Eckhard Pfeiffer Professor of Computational Physiology at the University of Houston, UH doctoral student Dinesh Majeti and Alexander Petersen, professor of management at the University of California Merced, report in Science Advances that HGP scientists not only laid the groundwork for scientific breakthroughs for decades to come, but - because they worked together - brought to the mainstream a collaboration model that changed science's cultural norms.

"One of the key factors of the success was the way it incorporated cross collaboration between biologists, computer scientists and other disciplines," said Pavlidis.

"Research was organized around a new model, the consortium model, where scientists from different fields and in different localities worked for years toward a common goal."

Since Galileo first peered into a telescope and DaVinci sketched out human anatomy, the business of science has been populated by independent endeavors. Systematic team efforts were transient exceptions. For centuries that image of the loner scientist was not updated, nor did it need to be - until now.

Pavlidis and Petersen report that after the sequencing of the human genome was completed in 2003, the consortium model did not go away, and scientists never returned to their silos. It was a clear departure from norms.

Researchers from biology, computing and other disciplines kept building consortia, unlocking the genetic secrets of fauna and flora, and in the process transforming the ability to understand, predict and edit life.

"In an era where science has been professionalized, one cannot fully appreciate the reasons for genomics' success unless you look at the effect it had on the researchers' careers," said Petersen.

To investigate this, the authors assembled a dataset that included biographic and funding information for over 4,000 faculty in 155 biology and computing departments in the United States, including information for their 400,000+ publications co-authored with a network of nearly 500,000 collaborators.

Using big data and counterfactual modeling, the team demonstrated that biology and computing researchers who crossed disciplinary boundaries collaborating with each other on genomics grounds had more successful careers than their mono-disciplinary colleagues.

"Their cross-disciplinary publications had superior impact and the same patterns were found to be true at the international literature level," said Petersen. Specifically, genomic articles with mixed authorship from biology and computing, or genomic articles with mixed biology and computing content, had significantly stronger impact compared to alternatives.

Petersen and Pavlidis believe that as cross-disciplinary work continues, scientific advancements will follow suit.

"If we continue to do this and have well-timed and well-designed funding efforts, as the Human Genome Project had, then I think we can put scientific progress on steroids," said Pavlidis.

COLUMBUS, Ohio - Married people who fight nastily are more likely to suffer from leaky guts - a problem that unleashes bacteria into the blood and can drive up disease-causing inflammation, new research suggests.

It's the first study to illuminate this particular pathway between bad marriages and poor health, said lead author Janice Kiecolt-Glaser, director of the Institute for Behavioral Medicine Research at The Ohio State University Wexner Medical Center. The study appears in the journal Psychoneuroendocrinology.

"We think that this everyday marital distress - at least for some people - is causing changes in the gut that lead to inflammation and, potentially, illness," she said.

Researchers at Ohio State recruited 43 healthy married couples, surveyed them about their relationships and then encouraged them to discuss and try to resolve a conflict likely to provoke strong disagreement. Touchy topics included money and in-laws.

The researchers left the couples alone for these discussions, videotaped the 20-minute interactions and later watched how the couples fought. They categorized their verbal and non-verbal fighting behaviors, with special interest in hostility - things such as dramatic eye rolls or criticism of one's partner.

"Hostility is a hallmark of bad marriages - the kind that lead to adverse physiological changes," said Kiecolt-Glaser, a professor of psychiatry.

Then the researchers compared blood drawn pre-fight to blood drawn post-fight.

Men and women who demonstrated more hostile behaviors during the observed discussions had higher levels of one biomarker for leaky gut - LPS-binding protein - than their mellower peers. Evidence of leaky gut was even greater in study participants who had particularly hostile interactions with their spouse and a history of depression or another mood disorder.

Previous studies have drawn strong correlations between poor marriages and health woes.

"Marital stress is a particularly potent stress, because your partner is typically your primary support and in a troubled marriage your partner becomes your major source of stress," Kiecolt-Glaser said.

Research, including some previously conducted at Ohio State, has shown that marital discord can slow wound healing and drive up risk for inflammation-related diseases, including depression, heart disease and diabetes.

The new Ohio State study aimed to search for a novel biological pathway for why that might be.

By looking for the presence of a biomarker associated with bacteria in the bloodstream, the team was able to find evidence of leaky gut, a little-understood condition in which the lining of the intestines becomes more permeable, allowing for the release of partially digested food and bacteria into the bloodstream.

Participants, who ranged in age from 24 to 61 and had been married at least three years. The couples were also part of another Ohio State study looking at how the interactions between marital hostility and depression can lead to obesity.

In the leaky-gut study, the researchers found a strong, significant link between hostility and the biomarker LBP, which indicates the presence of bacteria in the blood. And there was a strong link between that biomarker and evidence of inflammation. Compared to participants with the lowest LBP, those with the highest LBP had 79 percent higher levels of C-reactive protein, the primary biomarker of inflammation.

The researchers also looked at another biomarker of bacteria, called soluble CD14, and at a handful of established inflammatory markers. They found evidence that the biomarkers of leaky gut corresponded to increases in inflammation.

Furthermore, hostile behaviors' effect on potentially problematic biomarker activity in the bloodstream was more significant for those participants who had a history of depression.

"Depression and a poor marriage - that really made things worse," Kiecolt-Glaser said. "This may reflect persistent psychological and physiological vulnerabilities among people who have suffered from depression and other mood disorders."

Michael Bailey, co-author of the study and part of Ohio State's Institute for Behavioral Medicine Research and The Research Institute at Nationwide Children's Hospital, said there is an established link between stress, the sympathetic nervous system and changes in the microbes in the gut.

"With leaky gut, the structures that are usually really good at keeping the gunk in our gut - the partially digested food, bacteria and other products - degrade and that barrier becomes less effective," he said.

And bacteria in the blood driving up inflammation could potentially contribute to poor mental health - creating a troubling loop, Bailey said.

The researchers pointed out that inflammation increases with age and that the average age in this study was 38, which might mean that the results would be more profound in older people.

Lifestyle changes that could contribute to decreased risk of gut-related inflammation include diets high in lean proteins, healthful fats, fruits, vegetables and whole grains, Kiecolt-Glaser said. Probiotics might also be useful, she said.

CORVALLIS, Ore. - Timber harvested illegally under fraudulent permits is undercutting conservation efforts in the Brazilian Amazon, new research by an international collaboration shows.

The findings represent a troublesome counterpunch to an overall decline in deforestation rates in the region and indicate high-value timber species such as ipe? may be at risk of overexploitation.

The study appeared today in Science Advances.

At 2.1 million square miles, the Amazon Rainforest is the world's largest intact forest, with the majority of it in Brazil.

The Amazon Basin is home to 10 percent of all known plant and animal species and stores 100 billion metric tons of carbon - greater than 10 times the amount emitted each year from the use of fossil fuels.

Over the last four decades, more than 18 percent of the Brazilian Amazon -- picture an area roughly the size of California -- has been lost to illegal logging, soy plantations and cattle ranches, though at a decelerating pace; the rate of deforestation went down 76 percent from 2004 to 2017.

However, research by scientists at Oregon State University and in Brazil suggests another, possibly widespread threat: the practice of falsifying timber inventory data to provide legal cover to transport and market illegally harvested trees.

"If a company receives permits to extract and transport more timber than exists on the property covered by the permits, wood harvested illegally from other areas can be sold as if it came from the permitted property," said study co-author Mark Schulze, faculty member in OSU's College of Forestry and director of the H.J. Andrews Experimental Forest.

Schulze, corresponding author Pedro Brancalion of the University of Sao Paulo and Brazilian colleagues analyzed discrepancies between estimated timber volumes in a national forest inventory and volumes of logging permits. They found a strong and deliberate "overestimation bias" of high-value species - that means there weren't as many of those trees as had been estimated, or they weren't as large, opening the door for those permits to become attached to trees harvested illegally from other locations.

"Illegal logging is a huge barrier for using timber markets to promote sustainable use and conservation of forests," Schulze said, noting that almost half of the harvest in 2015 and 2016 in the Brazilian Amazon's top timber-production area was illegal.

The analysis found a relatively small subset of those in charge of logging permits was responsible for the pattern of egregiously overestimating the volume of high-value trees - at rates that would suggest corruption as opposed to simple identification mistakes.

"Field assessments of some of the most implausible timber inventories confirmed they did overestimate actual volumes of high-value timber species like ipe?," Schulze said. "We found 13 commercial species 'erroneously' identified as ipe?, with low-value tanimbuca, jarana and timborana being the most frequent."

Most of the non-ipe? trees were of species not included in the logging permit - not considered valuable enough to harvest - which means they wouldn't be harvested and the extra ipe? volume picked up through "misidentification" could be easily used as cover for illegal ipe?s.

"Until timber inventories submitted to Brazilian regulatory agencies are scrutinized for plausibility and substantial resources are dedicated to field audits, this form of fraud will not be detected," Schulze said.

Ipe? species, he noted, are easy to identify and distinguish from jarana, tanimbuca and timborana. The diameter of the real ipe? trees was also frequently exaggerated.

"Only companies wishing to generate a surplus of permitted timber volume would benefit from producing inaccurate forest inventory data," Schulze said. "Inaccuracies could also result from rushed or incompetent field work, but such mistakes would be expected to produce both underestimates and overestimates of timber volume. Consistent overestimates of the stocks of the highest-value timber species are unlikely to result from random errors."

The scientists say changes to the logging control system that governs the Brazilian Amazon are needed to protect key species and prevent widespread forest degradation.

"Well-regulated forest management in the Amazon can contribute to local livelihoods and conservation goals, but without effective enforcement of existing laws and regulations illegal logging will continue to lead directly to forest degradation and indirectly to deforestation," Schulze said. "If consumers of tropical hardwoods are concerned about inadvertently supporting illegal harvests, they can look for third-party certification labels that ensure the wood was harvested legally and did not mix with wood of unknown origin en route from the forest to the lumberyard."

A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method may help change this.

Researchers at the Georgia Institute of Technology engineered a molecular matrix, a hydrogel, to deliver muscle stem cells called muscle satellite cells (MuSCs) directly to injured muscle tissue in patients whose muscles don't regenerate well. In lab experiments on mice, the hydrogel successfully delivered MuSCs to injured, aged muscle tissue and boosted the healing process while protecting the stem cells from harsh immune reactions.

The method was also successful in mice with a muscle tissue deficiency that emulated Duchene muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease.

Inflammation war zone

Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient, in part because the stem cells encounter an immune system on the warpath.

"Any muscle injury is going to attract immune cells. Typically, this would help muscle stem cells repair damage. But in aged or dystrophic muscles, immune cells lead to the release a lot of toxic chemicals like cytokines and free radicals that kill the new stem cells," said Young Jang, an assistant professor in Georgia Tech's School of Biological Sciences and one of the study's principal investigators.

Only between 1 and 20 percent of injected MuSCs make it to damaged tissue, and those that do, arrive there weakened. Also, some tissue damage makes any injection unfeasible, thus the need for new delivery strategies.

"Our new hydrogel protects the stem cells, which multiply and thrive inside the matrix. The gel is applied to injured muscle, and the cells engraft onto the tissues and help them heal," said Woojin Han, a postdoctoral researcher in Georgia Tech's School of Mechanical Engineering and the paper's first author.

Han, Jang and Andres Garcia, the study's other principal investigator, published their results on August 15, 2018, in the journal Science Advances. The National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health funded the research.

Hydrogel: watery nets

Hydrogels often start out as water-based solutions of molecular components that resemble crosses, and other components that make the ends of the crosses attach to each other. When the components come together, they fuse into molecular nets suspended in water, resulting in a material with the consistency of a gel.

If stem cells or a drug are mixed into the solution, when the net, or matrix, forms, it ensnares the treatment for delivery and protects the payload from death or dissipation in the body. Researchers can easily and reliably synthesize hydrogels and also custom-engineer them by tweaking their components, as the Georgia Tech researchers did in this hydrogel.

"It physically traps the muscle satellite cells in a net, but the cells also grab onto chemical latches we engineered into the net," Han said.

This hydrogel's added latches, which bond with proteins protruding from stem cells' membranes, not only increase the cells' adhesion to the net but also hinder them from committing suicide. Stem cells tend to kill themselves when they're detached and free-floating.

The chemical components and the cells are mixed in solution then applied to the injured muscle, where the mixture sets to a matrix-gel patch that glues the stem cells in place. The gel is biocompatible and biodegradable.

"The stem cells keep multiplying and thriving in the gel after it is applied," Jang said. "Then the hydrogel degrades and leaves behind the cells engrafted onto muscle tissue the way natural stem cells usually would be."

Stem cell breakdown

In younger, healthier patients, muscle satellite cells are part of the natural healing mechanism.

"Muscle satellite cells are resident stem cells in your skeletal muscles. They live on muscle strands like specks, and they're key players in making new muscle tissue," Han said.

"As we age, we lose muscle mass, and the number of satellite cells also decreases. The ones that are left get weaker. It's a double whammy," Jang said. "At a very advanced age, a patient stops regenerating muscle altogether."

"With this system we engineered, we think we can introduce donor cells to enhance the repair mechanism in injured older patients," Han said. "We also want to get this to work in patients with Duchene muscular dystrophy."

"Duchene muscular dystrophy is surprisingly frequent," Jang said. "About 1 in 3,500 boys get it. They eventually get respiratory defects that lead to death, so we hope to be able to use this to rebuild their diaphragm muscles."

If the method goes to clinical trials, researchers will likely have to work around the potential for donor cell rejection in human patients.