Culture

Cognitive behavioral therapy reduces the impact of dissociative seizures

Scientists have found that adding cognitive behavioural therapy (CBT) to standardised medical care gives patients with dissociative seizures longer periods of seizure freedom, less bothersome seizures and a greater quality of life, in a study published in Lancet Psychiatry today and by the Cognitive behavioural therapy for adults with dissociative seizures (CODES) study group funded by National Institute for Health Research (NIHR).

Dissociative seizures, also called functional and non-epileptic seizures, look similar in appearance to epileptic seizures or fainting but are related to a different type of involuntary blackout that is typically distressing and disabling for patients and their carers. Up to 1 in 5 adults presenting in epilepsy clinics have this hidden condition which is one of several types of Functional Neurological Disorder (FND). Historically patients with dissociative seizures have often been ignored or disbelieved by doctors and research on treatment is limited. They are more likely to be found in women and usually have a poor outcome with a worse quality of life than people with epilepsy alone. People with dissociative seizures have a marked increase in health service use.

In the largest treatment trial to date for dissociative seizures, 368 patients from centres across England, Scotland, and Wales were followed up 6 months and 12 months after treatment courses began. Researchers found patients treated with dissociative seizure specific CBT alongside standardised medical care reported the highest number of consecutive dissociative seizure-free days in the previous 6 months, along with greater functional status, self-rated and doctor-rated change in global impression scores, and satisfaction with treatment when compared with standardised medical care alone.

Lead author Laura Goldstein, Professor of Clinical Neuropsychology at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London said, "We have delivered the first large-scale multi-centre and multi-professional trial investigating treatments for adults with dissociative seizures. This is especially important as the availability of treatment for people with this disorder has been so variable in the UK and elsewhere.

While overall there appeared to be a reduction in how often people in both groups of the study were having dissociative seizures at the end of the trial, with no clear difference between the groups, the group who had received our package of dissociative seizure-specific CBT were reporting better functioning across a range of everyday situations. They described their dissociative seizures as less bothersome, they were less distressed, reported better health and fewer symptoms, and were more satisfied with their treatment. It is important to consider providing dissociative seizure-specific CBT in addition to specialist care from neurologists and psychiatrists to treat people with dissociative seizures."

In the UK, there is currently no standardised care pathway for people with dissociative seizures. The researchers recommend the incorporation of seizure-specific CBT within specialist care from neurologists and psychiatrists. Furthermore, as participants received treatment in varied medical settings, this study suggests that the CBT combination intervention does not have to be limited to highly specialised centres and can be delivered by a range of clinical psychologists or cognitive behavioural psychotherapists. Researchers suggest future work is needed to identify which patients would benefit most from a dissociative seizure-specific CBT approach.

Neurologist, Professor Jon Stone, who was a co-investigator in the study said, "The CODES Trial is a landmark study for a condition which has, for too long, been ignored by health services. The trial has encouraged participating neurologists, psychiatrists and psychotherapists across the UK to raise their standard of care for these patients. The trial has set a new bar for evidence in this area, making it clear that there are thousands of new patients with this condition in the UK every year who we need to keep doing better for in terms of treatment and research in the future."

Credit: 
King's College London

Preclinical study offers hope for Hirschsprung's

image: Human intestine, engineered in the laboratory of Tracy Grikscheit, MD.

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Children's Hospital Los Angeles

Babies with Hirschsprung's disease are born with an incomplete or absent gut nervous system. Children's Hospital Los Angeles investigator Tracy Grikscheit, MD, runs a laboratory that investigates the therapeutic potential of tissue engineering - the induced growth of healthy tissue using stem cells. In a new study, Dr. Grikscheit successfully grew a fully functional gut nervous system - or ENS - in a pre-clinical model. While not yet available clinically, the finding brings surgeons like Dr. Grikscheit one step closer to helping babies in need.

Dr. Grikscheit, Chief of Pediatric Surgery at CHLA, published her findings this week in the Journal of Tissue Engineering. The growth of new, fully-functional nervous system tissue is an important milestone for research into a condition called Hirschsprung's disease. "The ENS forms when cells migrate down a major nerve throughout the digestive tract," explains Dr. Grikscheit. "In Hirschsprung's disease, the nerves don't make it all the way down the intestines." In the worst cases, she says, kids have no gut nervous system at all. This leaves intestinal tissue that cannot function. "When a baby has this disease, the situation is dire," she says. "And current medical therapies are not adequate." But the complex technique developed by Dr. Grikscheit could change this.

After years of searching for a model of Hirschsprung's disease, Dr. Grickscheit was unsatisfied with what was available to researchers. "The models weren't reliable," she explains, saying they didn't address growing the ENS from scratch. So, she made the model herself.

Growing a fully functional ENS is no simple feat. "The enteric nervous system is called the second brain because it is so beautifully diverse," says Dr. Grikscheit. The ENS coordinates intestinal muscle movement, hormone release and maintenance of stem cells, which are needed to maintain the intestinal lining.

"These cells are incredibly multi-faceted," she says. "The fact that we can implant them and they grow into this complex nervous system is a big step towards offering hope for these babies."

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Children's Hospital Los Angeles

When developing vaccines against COVID-19, 'fast is slow, and slow is fast'

Bypassing clinical trials for a potential SARS-CoV-2 vaccine would be "catastrophic," says Science Advances deputy editor Douglas Green in this Editorial. Instead, it's vital to take time to ensure any vaccine candidate's safety and investigate potential adverse effects, he says. A vaccine able to trigger strong neutralizing antibody responses in clinical tests will still not be ready for widespread implementation without comprehensive safety tests. For example, vaccines must be examined for causing an effect known as antibody-dependent enhancement (ADE), whereby vaccine-induced antibodies that bind to the virus also attach to the body's cells, facilitating infection of these cells - a concerning phenomenon that has been observed in vaccines against dengue, Ebola, HIV, and feline coronavirus. Ethical accelerated testing on humans should not be ruled out completely, but extreme risks must be weighed against potential benefits, Green says. There are currently 95 vaccines in development against SARS-CoV-2, with most expected to clear Phase I and two experimental vaccines already moving into Phase II trials.

Credit: 
American Association for the Advancement of Science (AAAS)

Mississippi Delta marshes in a state of irreversible collapse, Tulane study shows

image: Salt marshes about 30 miles (50 km) southeast of New Orleans are vulnerable to drowning.

Image: 
Photo by Torbjörn Törnqvist

Given the present-day rate of global sea-level rise, remaining marshes in the Mississippi Delta are likely to drown, according to a new Tulane University study.

A key finding of the study, published in Science Advances, is that coastal marshes experience tipping points, where a small increase in the rate of sea-level rise leads to widespread submergence.

The loss of 2,000 square miles (5,000 km2) of wetlands in coastal Louisiana over the past century is well documented, but it has been more challenging to predict the fate of the remaining 6,000 square miles (15,000 km2) of marshland.

The study used hundreds of sediment cores collected since the early 1990s to examine how marshes responded to a range of rates of sea-level rise during the past 8,500 years.

"Previous investigations have suggested that marshes can keep up with rates of sea-level rise as high as half an inch per year (10 mm/yr), but those studies were based on observations over very short time windows, typically a few decades or less," said Torbjörn Törnqvist, lead author and Vokes Geology Professor in the Tulane Department of Earth and Environmental Sciences.

"We have taken a much longer view by examining marsh response more than 7,000 years ago, when global rates of sea-level rise were very rapid but within the range of what is expected later this century."

The researchers found that in the Mississippi Delta most marshes drown in a few centuries once the rate of sea-level rise exceeds about one-tenth of an inch per year (3 mm/yr). When the rate exceeds a quarter of an inch per year (7.5 mm/yr), drowning occurs in about half a century.

"The scary thing is that the present-day rate of global sea-level rise, due to climate change, has already exceeded the initial tipping point for marsh drowning," Törnqvist said. "And as things stand right now, the rate of sea-level rise will continue to accelerate and put us on track for marshes to disappear even faster in the future."

While these findings indicate that the loss of remaining marshes in coastal Louisiana is probably inevitable, there are still meaningful actions that can be taken to prevent the worst possible outcomes. The most important one, Törnqvist said, is to drastically curb greenhouse gas emissions to prevent sea-level rise from ramping up to rates where marshes will drown within a matter of decades.

The other one is to implement major river diversions as quickly as possible, so at least small portions of the Mississippi Delta can survive for a longer time. However, the window of opportunity for these actions to be effective is rapidly closing, he said.

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Tulane University

A clue as to why it's so hard to wake up on a cold winter's morning

EVANSTON, Ill. --- Winter may be behind us, but do you remember the challenge of waking up on those cold, dark days? Temperature affects the behavior of nearly all living creatures, but there is still much to learn about the link between sensory neurons and neurons controlling the sleep-wake cycle.

Northwestern University neurobiologists have uncovered a clue to what's behind this behavior. In a study of the fruit fly, the researchers have identified a "thermometer" circuit that relays information about external cold temperature from the fly antenna to the higher brain. They show how, through this circuit, seasonally cold and dark conditions can inhibit neurons within the fly brain that promote activity and wakefulness, particularly in the morning.

"This helps explains why -- for both flies and humans -- it is so hard to wake up in the morning in winter," said Marco Gallio, associate professor of neurobiology in the Weinberg College of Arts and Sciences. "By studying behaviors in a fruit fly, we can better understand how and why temperature is so critical to regulating sleep."

The study, led by Gallio and conducted in Drosophila melanogaster, was published today (May 21) in the journal Current Biology.

The paper describes for the first time "absolute cold" receptors residing in the fly antenna, which respond to temperature only below the fly's "comfort zone" of approximately 77 degrees Fahrenheit. Having identified those neurons, the researchers followed them all the way to their targets within the brain. They found the main recipients of this information are a small group of brain neurons that are part of a larger network that controls rhythms of activity and sleep. When the cold circuit they discovered is active, the target cells, which normally are activated by morning light, are shut down.

Drosophila is a classic model system for circadian biology, the area in which researchers study the mechanisms controlling our 24-hour cycle of rest and activity. The focus of much current work is on how changes in external cues such as light and temperature impact rhythms of activity and sleep and how the cues reach the specific brain circuits that control these responses.

While detection of environmental temperature is critical for small "cold-blooded" fruit flies, humans are still creatures of comfort and are continually seeking ideal temperatures. Part of the reason humans seek optimal temperatures is that core and brain temperatures are intimately tied to the induction and maintenance of sleep. Seasonal changes in daylight and temperature are also tied to changes in sleep.

"Temperature sensing is one of the most fundamental sensory modalities," said Gallio, whose group is one of only a few in the world that is systematically studying temperature sensing in fruit flies. "The principles we are finding in the fly brain -- the logic and organization -- may be the same all the way to humans. Whether fly or human, the sensory systems have to solve the same problems, so they often do it in the same ways."

Gallio is the corresponding author of the paper. Michael H. Alpert, a postdoctoral fellow in Gallio's lab, and Dominic D. Frank, a former Ph.D. student in Gallio's lab, are the paper's co-first authors.

"The ramifications of impaired sleep are numerous -- fatigue, reduced concentration, poor learning and alteration of a myriad of health parameters -- yet we still do not fully understand how sleep is produced and regulated within the brain and how changes in external conditions may impact sleep drive and quality," Alpert said.

The study, a collaborative effort many years in the making, was performed in the Gallio lab by a range of scientists at different stages of their careers, ranging from undergraduate students to the principal investigator.

"It is crucial to study the brain in action," Frank said. "Our findings demonstrate the importance of functional studies for understanding how the brain governs behavior."

Overall, the study heavily relied on the ability to study both the activity of neurons and the role of these neurons on behavior. To do this, the researchers developed new tools and used a combination of functional and anatomical studies, neurogenetic and behavioral monitoring approaches to conduct these experiments in both wild type and transgenic flies.

Credit: 
Northwestern University

COVID-19 news from Annals of Internal Medicine

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach

As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors from McMaster University and St. Joseph's hospital suggest that there is convincing evidence to support this recommendation. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2567.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Catherine M. Clase, MB BChir, MSc can be reached through Veronica McGuire at vmcguir@mcmaster.ca.

2. Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence

Researchers from McMaster University reviewed evidence about the benefits and harms of alternative noninvasive and invasive ventilation strategies in acute hypoxic respiratory failure in patients infected with COVID-19. Indirect evidence related to other coronaviruses and evidence related to virus transmission to health care workers was also examined. Based on the evidence, they conclude that use of noninvasive ventilation, similar to invasive mechanical ventilation, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2306.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Holger J. Schünemann, MD, PhD, MSc, can be reached at schuneh@mcmaster.ca or through Veronica McGuire at vmcguir@mcmaster.ca.

Credit: 
American College of Physicians

Women quotas in politics have unintended consequences

Aside from Indira Gandhi, Margaret Thatcher, and more recently Angela Merkel and Jacinda Ardern, women continue to be scarce in the halls of power.

To rectify this inequality, a majority of countries (or at least one political party in most) have imposed female electoral quota systems, or rules designed to increase the representation of women. The catch? Boosting gender may well curtail representation in other respects.

An unintended consequence of such quotas is the reduction of other underrepresented minorities, finds a recent University of Rochester study in the American Journal of Political Science.

The Rochester study looked at India's caste system and female representation in local government, where female-reserved seats have been enshrined in the 73rd and 74th Amendments of the Indian Constitution since the early 1990s.

"The effect of electoral quotas for women in India was to reduce the representation of lower caste groups," says lead author Alexander Lee, an associate professor in the Department of Political Science at the University of Rochester, who looked specifically at what happened in Delhi in local elections once gender quotas were introduced.

"In many poorer or developing countries electoral quotas can reduce the representation of marginalized groups."

For their study, Lee and his coauthor, Varun Karekurve-Ramachandra, a PhD graduate student in the same department, examined the consequences of women quotas on the electoral representation of caste groups in local government bodies in Delhi. They found that constituencies reserved for women were less likely--compared to unreserved constituencies--to elect members of groups where the status of women was low.

In practice, this meant that those reserved constituencies were less likely to elect members of several traditionally underprivileged groups--especially of the so called "Other Backward Class" or OBC castes--a collective term used by the Indian Government to classify castes, which are educationally or socially disadvantaged. Instead, the scientists discovered, voters in women-reserved constituencies tended to elect candidates from the Hindu upper castes.

"In India if you have a policy that lets you choose only women, a disproportionate number of these women will be upper caste," says Lee.

The author of From Hierarchy to Ethnicity: The Politics of Caste in Twentieth-Century India (Cambridge University Press, 2020), Lee is interested in the factors governing the success or failure of political institutions in South Asia and other areas of the developing world. In particular, his work focuses on the historical evolution of state capacity, the causes and consequences of identity politics, and bureaucratic politics.

Key findings

In countries where women have a higher social standing among elite groups, women quotas and/or rules to improve female representation will lead to increases in the representation of the elite and simultaneously lead to a reduction in the representation of people from historically marginalized groups.

When trying to increase the representation of one identity (such as female) through quotas--the representation of the second identity (such as social class, race, or religion) depends on the number of potential candidates who possess both traits.

If the number of candidates with both traits is disproportionately low, quotas will reduce the representation of the second identity even further.

A society's attitudes toward gender are important when it comes to candidate pools: female candidates are less common among groups, societies, and in countries where the social involvement of women outside the home is discouraged.

So-called "proxy candidates" are especially common among marginalized (here lower caste groups) groups--women who are running for office in name only and are really stand-ins for their husbands.

When women quotas were introduced in India the proportion of proxy candidates (identifiable because they don't give an occupation and have never paid income taxes in their lives, which means they have never worked outside their homes) increased.

In women-reserved constituencies in India the number of candidates decreased and fewer people ran for public office.

Among the small number of women in India who run for office a disproportionately large number come from the upper castes.

While the gender quotas imposed for local government elections in Delhi specifically achieved their narrow aim of upping the representation of women to just above 50 percent, the change had clear implications for caste groups. The proportion of winning candidates from castes with traditional gender norms (i.e., lower caste groups) decreased by 7.7 percentage points for a seat reserved for women. The team notes that the number may still understate the effect for active female politicians, because it counts also so-called proxy candidates. "Without the ability to run proxies, the effects would probably be larger," says Lee.

In practice, this meant that the representation of members of the OBC category declined, while the numbers for members of the Hindu upper castes increased, in particular among the Brahmins and Banias.

"Gender quotas tend to politically strengthen groups at the top of traditional caste hierarchies and favor empowered groups over disempowered ones," says Karekurve-Ramachandra. "These unintended consequences are plausible because we think that women from marginalized groups--at the intersection of two disadvantaged identities--tend be especially disadvantaged."

The results highlight the difficulties of balancing descriptive representation on multiple, crosscutting dimensions, and the possible unintended consequences of the type of single-dimension quotas currently proposed for inclusion in the Indian constitution.

Do the findings from India translate to other parts of the world, to the US?

Not directly, say the researchers. In many rich countries the opposite actually holds true. For starters, the United States does not have legislative gender quotas, although the Democratic Party added language to its charter in 2018 that the party's National Committee, the Executive Committee, and other similar bodies "shall be as equally divided as practicable according to gender" in an attempt to address the prevailing gender gap.

The Rochester team theorizes that the effects of women quotas depend on the relative social standing of women in the pool of political candidates for the underrepresented group. In a situation with many qualified female candidates, Lee says, the quotas will raise the proportion of minorities in politics. However, if there are disproportionately low numbers of qualified female candidates in the minority pool, it'll result in fewer minority politicians.

In the United States, for instance, the proportion of women among African American members the US House of Representatives is higher than the proportion of women among white House members. Also, the proportion of Muslim women in legislative bodies in many European countries is higher than that of Muslim men.

"Why this happens is debated a lot," says Lee, who ascribes part of the effect to stereotyping. "If you have a minority that is seen by some as potentially threatening, women of that minority may be perceived as less threatening by members of the majority group and are therefore more likely to be elected."

The relative status of women within minority groups may also play a central role when it comes to being perceived as a qualified candidate. Generally, the level of educational attainment among African American women is higher than among African American men for a variety of reasons, Lee notes.

The team believes that their findings in India can be generalized to a broad set of countries where the status of women is lower within underprivileged groups, including many developing nations. The exact effects, the researchers caution, depend on the exact natures of the imposed quotas, the role of partisanship, and social attitudes.

One thing, however, is clear: quotas for women can have consequences that go well beyond gender. And that effect, they caution, should be carefully considered in the design of any gender and ethnic electoral quota system.

Credit: 
University of Rochester

Exploring the origins of genetic divergence within the Italian population

Genetic adaptations of early Italian ancestors to environmental changes, such as those that occurred soon after the Last Glacial Maximum, may explain some of the genetic differences between northern and southern Italian populations today, according to a study published in BMC Biology. The research suggests that northern and southern Italian populations may have begun to diverge genetically as early as 19,000-12,000 years ago and constitutes the earliest known evidence of genetic divergence in Italy so far.

A team of researchers at the University of Bologna sequenced the genomes of 38 unrelated participants from different regions in Italy, each the third generation of their family native to each region. The genomes were selected as representative of known genetic differences across the Italian population and over 17 million distinct genetic variants were found between individuals. The authors compared these variations with existing genetic data from 35 populations across Europe and the Mediterranean and with variants previously observed in 559 ancient human remains, dating from the Upper Palaeolithic (approx. 40,000 years ago) to the Bronze Age (approx. 4,000 years ago).

Prof. Marco Sazzini, lead author of the study said: "When comparing sequences between modern and ancient genome samples, we found early genetic divergence between the ancestors of northern and southern Italian groups dating back to the Late Glacial, around 19,000-12,000 years ago. Migrations during the Neolithic and Bronze Age periods, thousands of years later, then further differentiated their gene pools. Divergence between these ancestral populations may have occurred as a result of temperature rises and subsequent shrinking of glaciers across Northern Italy during this time, allowing ancestors who survived the glaciation period to move north, separating from groups who remained in the south."

Further analyses also revealed signatures ascribable to specific biological adaptations in northern and southern Italian genomes suggestive of habitation in differing climates. The genetic history of northern Italians showed changes in the genes responsible for regulating insulin, body-heat production and fat metabolism, whilst southern Italians showed adaptations in genes regulating the production of melanin and responses to pathogens.

Prof. Sazzini said: "Our findings suggest that the ancestors of northern Italians adapted to lower environmental temperatures and the related high-calorie diets by optimising their energy metabolism. This adaptation may play a role in the lower prevalence of Type 2 Diabetes recorded in Northern Italy today. Conversely, southern Italian ancestors adapted to a warmer climate with higher UV levels by increasing melanin production, which may explain the lower incidence rates of skin cancers recorded across Southern regions. The genomes of southern Italians also showed changes in the genes encoding mucins, which play a role in protection against pathogens, and genetic variants linked to a longer lifespan. Further research in this area may help us understand how the observed genetic differences can impact population health or predisposition to a number of diseases."

The authors caution that although correlations may be drawn between evolutionary adaptations and current disease prevalence among populations, they are unable to prove causation, or rule out the possibility that more recent gene flow from populations exposed to diverse environmental conditions outside of Italy may have also contributed to the different genetic signatures seen between northern and southern Italians today.

Credit: 
BMC (BioMed Central)

Earliest evidence of Italians' genetic diversity dates back to end of last glacial period

In Europe, Italians are the richest population in terms of genetic wealth. This is now common knowledge. The gradient of their genetic variability, scattered all over the peninsula, encloses on a small scale the whole genetic variance between southern and continental Europeans. This amazing diversity started to accumulate soon after the Late Glacial Maximum, which ended approximately 19,000 years ago.

This is what some researchers of the University of Bologna report in a paper published in the BMC Biology journal. It is the first time that a group of scientists is able to go so back in time in retracing Italians' genetic history. Results also show that there are some genetic peculiarities characterising people living in the north and south of Italy, that evolved in response to different environments. These peculiarities contribute to reducing, on the one hand, the risk of kidney inflammation and skin cancers, and, on the other hand, the risk of diabetes and obesity, favouring sometimes a longer lifespan.

"Gaining an understanding of the evolutionary history of the ancestors of Italians allows us to better grasp the demographic processes and those of environmental interactions that shaped the complex mosaic of ancestry components of today's European populations", explains Marco Sazzini, one of the principal investigators of this study and professor of Molecular Anthropology at the University of Bologna. "This investigation provides valuable information in order to fully appreciate the biological characteristics of the current Italian population. Moreover, it let us understand the deep causes that can impact on this population's health or on its predisposition to a number of diseases".

AN UNEXPECTED OUTCOME

To carry out this study, researchers sequenced the entire genome of forty participants, who were selected as representatives of the biological variability of the Italian population with a good approximation. The analysis brought to the fore more than 17 million genetic variants. Scientists then made a twofold comparison. First, they compared these data against the genetic variants observed in other 35 populations from Europe and from the Mediterranean. Second, they compared the same data against the genetic variants found in studies on almost 600 human remains dating from the Upper Palaeolithic (approx. 40,000 years ago) to the Bronze Age (approx. 4,000 years ago).

These comparisons reached such high levels of precision that it was possible, for the first time, to go way back in time in Italians' genetic history, extending the investigation to very remote time periods with respect to what achieved by previous studies. Eventually, this led to the identification of traces left in Italians' gene pool by events that just followed the last glaciation, which ended more or less 19,000 years ago.

The bulk of the scholarship in this field has so far suggested that the oldest events leaving a trace in Italians' DNA were the migrations that had taken place in the Neolithic and the Bronze Ages, between 7,000 and 4,000 years ago. The results of this study show, on the contrary, that the earliest biological adaptations to the environment and migrations underlying Italians' extraordinary genetic diversity are much older than previously thought.

CLIMATE CHANGES AND POST-GLACIAL MIGRATIONS

Researchers traced the evolutionary history of the two groups at the opposite ends of Italians' gradient of genetic variability. This means that they evaluated and measured differences between the gene pools of participants from southern and northern Italy and observed when these differences became evident.

"We observe some partially overlapping demographic trends among the ancestors of these two groups from 30,000 years ago and for the remaining years of the Upper Palaeolithic", illustrates Stefania Sarno, a researcher at the University of Bologna and one of the co-first authors of the paper. "However, we witness to a significant variation between their gene pools from the Late Glacial period, thus some thousands of years before those great migrations that happened in Italy from the Neolithic onwards".

Here, the main hypothesis is that with temperatures rising and, as a consequence, glaciers shrinking, some groups of people who made it through the glaciation period thanks to "glacial refugia" in central Italy, moved north and drifted away, and thus progressively isolating themselves, from the inhabitants of southern Italy.

The DNA of people living in northern Italy shows traces of these post-glacial migrations. If compared to individuals from southern Italy, Italians from the north present a close genetic relation to human remains attributed to ancient European cultures such as the Magdalenian and the Epigravettian cultures and dated respectively between 19,000 and 14,000 years ago and between 14,000 and 9,000 years ago. Moreover, in northern Italians' gene pool ancestry components even more ancient were observed, such as those proper of Eastearn European hunter-gatherers, which are thought to characterize all European populations between 36,000 and 26,000 years ago and that later on spread again to western Europe with migratory movements from "glacial refugia" during the Late Glacial period.

Conversely, in southern Italians, these post-glacial migrations traces seem to vanish, as more recent events significantly reshaped their gene pool. This is confirmed by their closer genetic relation with Neolithic human remains from Anatolia and the Middle East, and with Bronze-Age remains from the South Caucasus. Differently from the north of Italy, the south was the main hub for migratory movements, which firstly spread agriculture to the Mediterranean area during the Neolithic transition, and then, during Bronze Age, fostered a new ancestry component. The latter differs from the ancestry component associated with populations of the Eurasian steppe that spread during the same time across continental Europe and northern Italy.

GENETIC ADAPTATIONS: DIFFERENCES AND PECULIARITIES ACROSS ITALY

19,000 years ago, after the end of the Last Glacial Maximum, ancestors of northern and southern Italians started living in increasingly different environmental and ecological contexts, which gradually led to the emergence of differences and peculiarities in their gene pools.

For millennia, the populations resettling in northern Italy endured abrupt climate changes and environmental pressures similar to those of the Last Glacial Maximum. These circumstances brought to the evolution of specific biological adaptations. For instance, populations in northern Italy developed a metabolism optimized for a diet rich in calories and animal fat, which are essential to survive in cold climates. "In the subjects from northern Italy, we observed changes in the gene networks regulating insulin and body-heat production as well as in those responsible for fat tissue metabolism", says Paolo Garagnani, professor of Experimental Medicine and Pathophysiology at the University of Bologna. "These changes could have developed, today, in key factors reducing the susceptibility to diseases like diabetes and obesity".

While this was happening in northern Italy, in the south, a warmer climate exposed its populations to a different kind of environmental pressures. The genomes of people from southern Italy show changes in the genes encoding for mucins, which are proteins to be found in the mucous membranes of the respiratory and gastro-intestinal systems and that prevent pathogens to attack the tissues. "These genetic adaptations may have evolved in response to ancient micro-organisms", says Paolo Abondio, Ph.D. student at the University of Bologna and another co-first author of this study. "Some scholars have linked some of these genetic variants with a reduced susceptibility to Berger's disease, which is a common inflammation affecting the kidneys and is indeed less frequent in the south than in the north of Italy".

Researchers identified also other peculiarities in the genome of southern Italians. For example, there are some modifications in the genes regulating the production of melanin, the pigment that provides colour to the skin. Most probably, these alterations developed in response to more intense sun-light and to a higher number of sunny days that characterise the Mediterranean regions. In turn, these alterations may also have contributed to a lower incidence of skin cancers among southern Italians. "We observed that some of these genetic variants have been also linked to a longer lifespan. This is also true for other genetic modifications which are characteristic of southern Italians. These are found on genes involved in the arachidonic acid metabolism and on those encoding for FoxO transcription factors", according to Claudio Franceschi, Emeritus Professor of the University of Bologna.

THE AUTHORS OF THE STUDY

The study was led by professors of the University of Bologna, Marco Sazzini, Claudio Franceschi and Paolo Garagnani, in collaboration with Patrick Descombes (Nestlé Research Center, Lausanne, Switzerland) and Massimo Delledonne (University of Verona). A paper entitled "Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans" was then published in the BMC Biology journal.

The study featured researchers of the Molecular Anthropology Lab and the Centre for Genome Biology of the Department of Biological, Geological and Environmental Sciences at the University of Bologna: Marco Sazzini, Paolo Abondio, Stefania Sarno, co-first authors of the paper, and also Sara De Fanti, Claudia Ojeda-Granados, Cristina Giuliani, Alessio Boattini and Davide Pettener. Moreover, researchers at the Department of Experimental, Diagnostic and Specialty Medicine also took part in the study: Chiara Pirazzini, Elena Marasco, Gastone Castellani, Claudio Franceschi and Paolo Garagnani. Researchers of these two departments worked together within the framework of the activities of the Interdepartmental Center "Alma Mater Research Institute on Global Challenges and Climate Change".

Donata Luiselli from the Department of Cultural Heritage of the University of Bologna also participated in this study. Finally, Guido Alberto Gnecchi Ruscone (Max Planck Institute for the Science of Human History in Jena, Germany), Massimo Delledonne (University of Verona), Luciano Xumerle (University of Verona), Alberto Ferrarini (University of Verona) and researchers of the Nestlé Research Center in Lausanne (Switzerland), of the Policlinico of Milan, of the University of Florence and of the University of Calabria took part in the study.

Credit: 
Università di Bologna

Researchers discover biomarkers of ALS in teeth

New York, NY (May 21, 2020)--Mount Sinai scientists have identified biological markers present in childhood that relate to the degenerative and often fatal neurological disease called amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, according to a study published in the Annals of Clinical and Translational Neurology in May. (https://www.youtube.com/watch?v=Bw-_XUZssMM&feature=youtu.be)

The researchers found the markers in the teeth of patients who went on to develop ALS as adults. They used lasers to map growth rings that form daily in the teeth and discovered evidence in the growth rings formed at birth and within the first 10 years of life that patients with ALS metabolized metals differently than patients without the disease.

ALS is a condition that usually manifests when someone is in their 50s or 60s. The cause is not known, and there is no test to predict its onset. Genetic studies have not revealed a great deal yet, and while experts believe environmental factors play a significant role in the development of the disease, there have been no clear indications of which ones.

"This is the first study to show a clear signature at birth and within the first decade of life, well before any clinical signs or symptoms of the disease," said senior author Manish Arora, BDS, MPH, PhD, Edith J. Baerwald Professor and Vice Chair of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. "We hope in the long term, after validation of this work in larger studies, that this will lead to preventive strategies. What's exciting about this work is that we are looking at biological pathways that we could potentially modify with drug development."

The study showed dysregulated uptake of a mixture of essential elements, including zinc and copper, as well as toxins like lead and tin, in 36 ALS patients compared to 31 controls. The markers of metal uptake dysregulation were also observed in teeth from an ALS mouse model that also showed differences in the distribution of metals in the brain compared to controls.

"Our previous work showed that the dysregulation of elemental metabolism in early life was associated with the onset of neurological disease such as autism and ADHD," said Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, a major contributor to this work. "This study shows that metabolic dysregulation is also associated with neurological conditions with a much greater lag to symptom onset".

Researchers at the University of Michigan played an important role in this study, and their clinics provided samples and data from ALS patients and patients in the control group.

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

Social isolation increases the risk of heart attacks, strokes, and death from all causes

(Vienna, Friday, 22 May, 2020) Those who are socially isolated are over 40% more likely to have a cardiovascular event, such as a heart attack or stroke, than those who were socially integrated, new research has shown.

The German study, due to presented tomorrow at the European Academy of Neurology (EAN) Virtual Congress, found that those who are socially isolated are almost 50% more likely to die from any cause. The research also showed that a lack of financial support independently increased the risk of cardiovascular events.

Performed within the Heinz Nixdorf Recall study (HNR) and led by Dr Janine Gronewold and Prof Dirk M. Hermann from the University Hospital in Essen, Germany, the research analysed data from 4,316 individuals (average age 59.1 years) who were recruited into the large community-based study between 2000 and 2003.

The study participants entered the study with no known cardiovascular disease and they were followed for an average of 13 years. At the start of the study, information was collected on different types of social support, with social integration assessed based on marital status and cohabitation, contact with close friends and family, and membership of political, religious, community, sports or professional organisations.

"We have known for some time that feeling lonely or lacking contact with close friends and family can have an impact on your physical health", commented Dr Gronewold. "What this study tells us is that having strong social relationships is of high importance for your heart health and similar to the role of classical protective factors such as having a healthy blood pressure, acceptable cholesterol levels, and a normal weight."

Professor Jöckel, one of the PI's of the HNR added, "This observation is of particular interest in the present discussion on the COVID-19 pandemia, where social contacts are or have been relevantly restricted in most societies."

During the 13.4 years of follow-up, 339 cardiovascular events such as heart attacks or strokes occurred, and there were 530 deaths among the study participants. After adjusting for (removing the influence of) other factors that might have contributed to these events and deaths (for example, standard cardiovascular risk factors), a lack of social integration was found to increase the future risk of cardiovascular events by 44% and to increase the risk of death from all causes by 47%, A lack of financial support was associated with a 30% increased risk of cardiovascular events.

"We don't understand yet why people who are socially isolated have such poor health outcomes, but this is obviously a worrying finding, particularly during these times of prolonged social distancing," said Dr Gronewold. "What we do know is that we need to take this seriously, work out how social relationships affect our health, and find effective ways of tackling the problems associated with social isolation to improve our overall health and longevity," said Prof Hermann.

Credit: 
Spink Health

When plant pollen scarce, bumblebees biting leaves causes flowers to bloom early

Facing a scarcity of pollen, bumblebees will nibble on the leaves of flowerless plants, causing intentional damage in such a way that accelerates the production of flowers, according to a new study, which reports on a previously unknown behavior of bumblebees. The leaf-damaging bumblebee bites have a drastic effect on plant flowering, compelling some to bloom two weeks to a full month earlier. Although the mechanisms by which deliberate bee damage accelerate flowering remain unclear, the results reveal bumblebees as powerful agents in influencing the local availability of floral resources. "An encouraging interpretation of the new findings is that behavioral adaptations of flower-visitors can provide pollination systems with more plasticity and resilience to cope with climate change than hitherto suspected," writes Lars Chittka in a related Perspective. Plants and pollinators rely on one another for survival. Just as pollinators, like bumblebees, depend on flowers for crucial nutrition, plants need pollinators to reproduce. This symbiotic relationship is kept in balance by the synchronous timing of the emergence of hibernating insects and spring blossoms as spring temperatures rise and the days get longer. But this fragile arrangement is threatened by climate change. For instance, warming early season temperatures could cause pollinators to wake up too soon, before the springtime bloom and without a source of food. Foteini Pashalidou and colleagues discovered an adaptive strategy used by food-deprived bumblebees to manipulate the timing of a plant's flowering. Pashalidou et al. observed bumblebee workers from pollen-starved colonies use their mouthparts to cut distinctively shaped holes in the leaves of flowering plants, which resulted in them flowering significantly earlier. The authors were not able to reproduce the flower-stimulating effects by mimicking the damage on their own, however, suggesting a yet-unknown feature distinct to the bees' approach. "Understanding the molecular pathways by which one could accelerate flowering by a full month, as reported [by Pashalidou et al.], would be a horticulturalist's dream," Chittka writes.

Credit: 
American Association for the Advancement of Science (AAAS)

How to identify which interventions work best in a pandemic

In lieu of a vaccine or reliable preventative medications, the only approaches currently available to help prevent the spread of COVID-19 are behavioral - handwashing, mask-wearing and social distancing, for example. In a Policy Forum, Johannes Haushofer and Jessica Metcalf argue that it is crucial to identify the "nonpharmaceutical interventions" (NPIs) that most effectively reduce virus transmission at the lowest economic and psychological costs. While handwashing initiatives are relatively inexpensive, sanctioned school and business closures are extremely costly. However, many NPIs are often applied without rigorous evaluation and the approaches to implementing and regulating them are varied, thus making their impact relative to their cost difficult to know. Haushofer and Metcalf discuss how randomized controlled trials (RCTs), compartmental models and spillovers can each be harnessed to evaluate and identify the interventions that work best during a pandemic situation. The authors demonstrate how RCTs can be practically and ethically conducted during a pandemic and used to systematically evaluate the impact of specific intervention strategies, as well as how the effects of NPIs on disease transmission can be estimated using epidemiological compartmental models. What's more, Haushofer and Metcalf suggest that "spillover" effects - or the spread of intervention strategies into non-targeted groups - can be leveraged to increase the overall impact and coverage of NPIs. "If policymakers and scientists combine insights from infection disease epidemiology with carefully and ethically designed impact evaluation, alongside other... methods for studying impact, they will have a powerful tool for reducing the human health, societal and economic costs in the SARS-CoV-2 pandemic," write the authors.

Credit: 
American Association for the Advancement of Science (AAAS)

Tropical forests can handle the heat, up to a point

image: A view from the canopy at Gunung Mulu's heath forest, dominated by Shorea albida. Sarawak, Borneo.

Image: 
Dr Lindsay F. Banin

Tropical forests face an uncertain future under climate change, but new research published in Science suggests they can continue to store large amounts of carbon in a warmer world, if countries limit greenhouse gas emissions.

The world's tropical forests store a quarter-century worth of fossil fuel emissions in their trees alone. There are fears that global heating can reduce this store if tree growth reduces or tree death increases, accelerating climate change.

An international research team measured over half a million trees in 813 forests across the tropics to assess how much carbon is stored by forests growing under different climatic conditions today.

The team reveal that tropical forests continue to store high levels of carbon under high temperatures, showing that in the long run these forests can handle heat up to an estimated threshold of 32 degrees Celsius in daytime temperature.

Yet this positive finding is only possible if forests have time to adapt, they remain intact, and if global heating is strictly limited to avoid pushing global temperatures into conditions beyond the critical threshold.

Lead author Dr Martin Sullivan, from the University of Leeds and Manchester Metropolitan University, said: "Our analysis reveals that up to a certain point of heating tropical forests are surprisingly resistant to small temperature differences. If we limit climate change they can continue to store a large amount of carbon in a warmer world.

"The 32 degree threshold highlights the critical importance of urgently cutting our emissions to avoid pushing too many forests beyond the safety zone.

"For example, if we limit global average temperatures to a 2°C increase above pre-industrial levels this pushes nearly three-quarters of tropical forests above the heat threshold we identified. Any further increases in temperature will lead to rapid losses of forest carbon."

Forests release carbon dioxide into the atmosphere when the amount of carbon gained by tree growth is less than that lost through tree mortality and decay.

The study is the first to analyse long-term climate sensitivity based on direct observation of whole forests across the topics. The research suggests that over the long-term, temperature has the greatest effect on forest carbon stocks by reducing growth, with drought killing trees the second key factor.

The researchers conclude that tropical forests have long-term capacity to adapt to some climate change, in part because of their high biodiversity as tree species better able to tolerate new climatic conditions grow well and replace less well-adapted species over the long-term.

But maximizing this potential climate resilience depends on keeping forests intact.

Co-author Professor Beatriz Marimon from the State University of Mato Grosso in Brazil studies some of the world's hottest tropical forests in central Brazil. She noted: "Our results suggest that intact forests are able to withstand some climate change. Yet these heat-tolerant trees also face immediate threats from fire and fragmentation.

"Achieving climate adaptation means first of all protecting and connecting the forests that remain."

Professor Marimon notes the clear limits to adaptation. "The study indicates a heat threshold of 32 degrees Celsius in daytime temperature. Above this point tropical forest carbon declines more quickly with higher temperatures, regardless of which species are present.

"Each degree increase above this 32 degree threshold releases four-times as much carbon dioxide as would have been released below the threshold."

The insights into how the world's tropical forests respond to climate were only possible with decades of careful fieldwork, often in remote locations. The global team of 225 researchers combined forests observations across South America (RAINFOR), Africa (AfriTRON) and Asia (T-FORCES). In each monitoring plot the diameter of each tree and its height was used to calculate how much carbon they stored. Plots were revisited every few years to see how much carbon was being taken in, and how long it was stored before trees died.

To calculate changes in carbon storage required identifying nearly 10,000 tree species and over two million measurements of tree diameter, across 24 tropical countries. According to Professor Simon Lewis of the University of Leeds and University College London: "The amount of carbon absorbed and stored by forests is a crucial element in how the Earth responds to climate change."

"The study underlines why long-term research collaboration is essential for understanding the effects of environmental change. Scientists need to work together more than ever, as monitoring the health of our planet's great tropical forests is vital for all of us."

Cutting carbon emissions enough to keep forests within the safety zone will be very challenging. Study author Professor Oliver Phillips of the University of Leeds said: "Keeping our planet and ourselves healthy has never been more important. Right now, humanity has a unique opportunity to make the transition toward a stable climate.

"By not simply returning to 'business as usual' after the current crisis we can ensure tropical forests remain huge stores of carbon. Protecting them from climate change, deforestation and wildlife exploitation needs to be front and centre of our global push for biosecurity.

"Imagine if we take this chance to reset how we treat our Earth. We can keep our home cool enough to protect these magnificent forests - and keep all of us safer."

Credit: 
University of Leeds

Researchers: As Ohio abortion regulations increased, disparities in care emerged

COLUMBUS, Ohio - Ohio has seen a growing disparity between abortion rates in rural and urban communities, later abortions, and less use of medication abortion care as the state has heavily regulated abortion and clinics have closed, a new study has found.

Researchers say their study raises concerns about inadequate and inconsistent access to a full spectrum of reproductive health care.

The researchers looked at abortion services performed in Ohio from 2010 to 2018, a time when more than 15 new abortion regulations were instituted and when the number of surgical abortion clinics in the state dropped from 15 to eight. The study, led by Alison Norris of The Ohio State University, appears today (May 21, 2020) in the American Journal of Public Health.

In this study, researchers examined a variety of characteristics of those who received abortions during the eight-year study period, including how far along they were in their pregnancies, county of residence and what methods of abortion were used.

Nationally and in Ohio, abortion rates declined significantly during this time period. But a decrease in early first-trimester abortions and simultaneous increase in later first-trimester abortions was unique to Ohio, and may signal delays in women and teens receiving prompt care because of the burdens they have to overcome to get that care, said Norris, an associate professor of epidemiology in Ohio State's College of Public Health.

"Abortion care is one of the safest procedures that we have. Because it becomes more complex later in pregnancy, women benefit from quick access to abortion services when they choose to end a pregnancy," Norris said.

The research is part of a multidisciplinary reproductive health research consortium called the Ohio Policy Evaluation Network, or OPEN, which includes scientists from Ohio State, the University of Cincinnati, Cincinnati Children's Hospital and Case Western Reserve University.

Ohio's abortion laws include mandatory in-person counseling 24 hours before the procedure and limitations about how abortion can be funded, which can create significant obstacles to early care for some women, Norris said.

From 2010 to 2018, abortion ratios decreased sharply, and disproportionately, in most rural Ohio counties, the study found. In rural counties, the number of abortions per 1,000 live births dropped more than 32 percent compared to the 24 percent reduction seen in urban counties.

And in areas where clinics closed, use of abortion dropped off among women and teens living both within the county and in surrounding counties.

"This geographic inequity in abortion access is concerning, because it likely means that some people who have unintended pregnancies and want to end those pregnancies are not getting the care they want and deserve," Norris said, adding that regulations passed in Ohio during the study period, including requirements that clinics have a written patient transfer agreement with a private hospital, have created administrative hurdles for abortion providers.

Norris said there's no evidence that she's aware of to support the idea that abortions are happening less frequently in rural Ohio because there are fewer unintended pregnancies or less demand for services. In fact, she said, it's possible that unintended pregnancies are more common in some rural areas where access to contraceptive options could also be limited.

"It could actually be the case that there are higher rates of unintended pregnancy in some rural areas, because people who live in those areas have reduced access to all kinds of health care, including high-quality reproductive care," said Norris, adding that the OPEN research team hopes to explore that possibility in future work.

Medication abortion care also decreased significantly in Ohio during this time, likely largely due to the state's narrow interpretation of how the medications had to be dispensed, Norris said.

Nationally, annual abortion rates overall dropped from about 12 per 1,000 women of childbearing age to fewer than 10 per 1,000 during the study period.

"This national trend, one that has also been seen in Ohio, aligns with increased access to contraception and highly effective modes of contraception, particularly long-acting reversible contraceptives," Norris said.

"But declines in the use of abortion are being experienced differently by different groups of people, and that's what we found is happening in Ohio."

While this study focuses on Ohio, it likely has broader implications, Norris said.

"I think we can expect similar experiences for people who live in states with a high regulatory burden around abortion care. It's reasonable to imagine that the things that we see in Ohio are playing out in other places."

Credit: 
Ohio State University