Fresh Fruit Dessert Plate with Stuffed Dates and Aril Garnish
Like many relatives, friends and colleagues, we’ve struggled with bouts of serious winter maladies. Weight loss has been the only redeeming feature. In our house, loss of appetite, lead to lethargy regarding creating any food combinations, resulting in new recipes. Luckily, during our down time, we craved fresh fruit. Above, is one of many fruit plates we feasted on, with a low desire for anything else. These ubiquitous plates appeared during breakfast, dinner, snacks and over the past three or four weekends, plus, ever-present at Scrabble. ©Joyce Hays, Target Health Inc.
Cara cara oranges
Red seedless grapes
Tofutti (soy cream cheese)
Basically, I went onto the fresh fruit page at FreshDirect, and bought a variety of peak oranges, tangerines, pink grapefruit, pomegranate arils, grapes, dates, Tofutti and a bottle of Grand Marnier. Just buy fresh fruit that you and your family like, and create a beautiful plate. ©Joyce Hays, Target Health Inc.
1. Start by peeling all the fruit. If you feel like marinating some of the fruit in Grand Marnier, do it now. I cut the Cara cara oranges in circles and covered them with this liqueur overnight. The strawberries are on the table, because I was planning to dip them in chocolate to serve with the fruit, but never had the energy to actually do it.
Cara cara oranges are at their peak now. Don’t miss this season’s a lovely range of citrus fruit in markets now. I bought these at FreshDirect. ©Joyce Hays, Target Health Inc.
Mangoes are very fine in markets right now and as healthy as can be. They can be addictive we found, as we slurped them down. Mmmm super delicious! ©Joyce Hays, Target Health Inc.
2. Cut your fruit in different shapes: I made some spear shaped mangoes; circles of Cara cara oranges; segments of tangerines; half circles of other oranges. I cut the dates almost in half, spread with Tofutti (soy cream cheese); distributed the grapes and sprinkled the entire plate with the pomegranate arils.
Many varieties of grapes are well rated, now. We’ve eaten a lot of these, often with plates of American and European cubed cheeses. ©Joyce Hays, Target Health Inc.
One of our favorite soft cheeses, to eat with grapes, is this Italian: Bra Tenero. If you haven’t tried it, you’re in for a treat. Sometimes, an evening meal of warm crusty bread, robust red wine, your favorite cheeses and lots of grapes, apples and pears, is all you need to feel happy …oh, and good conversation with plenty of laughs.
At one point, we tried some white wine with the fruit, which at any other time would have been just fine; but I found that it did not mix well with my illness and made me feel worse. I had not yet begun taking medication. Jules was okay with it. ©Joyce Hays, Target Health Inc.
May Your Days Be Merry and Bright (Irving Berlin)
From Our Table to Yours !
January 12, 2017
University of California – San Diego
Biologists have documented for the first time how very large viruses reprogram the cellular machinery of bacteria during infection to more closely resemble an animal or human cell — a process that allows these alien invaders to trick cells into producing hundreds of new viruses, which eventually explode from and kill the cells they infect.
Biologists at UC San Diego have documented for the first time how very large viruses reprogram the cellular machinery of bacteria during infection to more closely resemble an animal or human cell — a process that allows these alien invaders to trick cells into producing hundreds of new viruses, which eventually explode from and kill the cells they infect.
In a paper published in the January 13 issue of Science, the researchers conducted a series of experiments that allowed them to view in detail what happens inside bacterial cells as the invading viruses replicate.
“Scientists have been studying viruses for a hundred years, but we’ve never seen anything like this before,” said Joe Pogliano, a professor of molecular biology who headed the research team. “Every experiment produced something new and exciting about this system.”
Viruses that infect bacteria, also known as bacteriophages, are some of the most numerous entities on earth.
“We chose to study a family of unusually large bacteriophage and to apply cutting edge methods to watch their replication in unprecedented detail,” said Kit Pogliano, a professor of molecular biology who participated in the study.
Joe Pogliano and his colleagues found that shortly after bacteriophages infect bacteria, they destroy much of the existing architecture of the bacterial cells, including bacterial DNA, then hijack the remaining cellular machinery. The viruses then reorganize the entire cell into an efficient, centralized factory to produce the next generation of viruses.
“This factory and the surrounding arrangement of the infected cell are remarkably similar to the organization seen in plant and animal cells,” said Pogliano.
Bacteria lack many of the specialized structures that compartmentalize cellular processes in plant or animal cells, which biologists call “eukaryotic” cells. Bacteria, for example, lack an enclosed nucleus, which contains genetic information and acts as the control center of the cell.
But Vorrapon Chaikeeratisak, a postdoctoral fellow, and Katrina Nguyen, a graduate student in Pogliano’s laboratory, found that invading viruses organize the structures within bacteria to mimic those found in eukaryotic cells.
Using fluorescent microscopy, the two biologists discovered that as viruses replicate within bacterial cells, they build compartments to separate the different processes going on during infection.
“These compartments enclose all the viral DNA, just as a nucleus does in a plant or mammalian cell,” said Chaikeeratisak, the first author of the paper. “DNA processes, like replication or transcription, occur inside the compartment while proteins are produced outside the compartment.”
Elizabeth Villa, a professor of chemistry and biochemistry at UC San Diego, and David Agard, a professor of biochemistry and biophysics at UC San Francisco, used a specialized technique, called “cryo-electron tomography,” to produce images of the processes that Chaikeeratisak and Nguyen initially discovered at extremely high magnification.
Those pictures showed viral offspring being assembled around the nucleus-like compartment in the bacterium. Eventually, these new viruses burst the cell open and spread out to infect neighboring cells.
“These observations of viral manipulation of a cell are completely unexpected, as no bacterial virus has been seen to reorganize a cell in so drastic a manner,” said Pogliano. “The restructuring of a simple cell to resemble an existing, more complicated system blurs the line between simple bacterial cells and those of ‘higher’ organisms, such as plants and animals.”
Could this be how multicellular organisms evolved? One existing theory, called “viral eukaryogenesis,” suggests that the first eukaryotic cell was created when a large virus took over a bacterium. Eventually, the bacterium and virus formed a compound cell, in which the virus evolved into the nucleus.
“It may be too early to know if this particular virus is an intermediate step in the transition from bacteria and viruses to multicellular eukaryotes, but this discovery could broaden knowledge about the origins of life as we know it,” said Pogliano.
The study was supported by grants from the National Institutes of Health (GM031627, GM104556, GM57045, 1DP2GM123494-01) and the Howard Hughes Medical Institute.
- Vorrapon Chaikeeratisak, Katrina Nguyen, Kanika Khanna, Axel F. Brilot, Marcella L. Erb, Joanna K. C. Coker, Anastasia Vavilina, Gerald L. Newton, Robert Buschauer, Kit Pogliano, Elizabeth Villa, David A. Agard, Joe Pogliano. Assembly of a nucleus-like structure during viral replication in bacteria. Science, 2017; 355 (6321): 194 DOI: 10.1126/science.aal2130
Source: University of California – San Diego. “Biologists discover how viruses hijack cell’s machinery.” ScienceDaily. ScienceDaily, 12 January 2017. <www.sciencedaily.com/releases/2017/01/170112141203.htm>.
January 11, 2017
Washington University in St. Louis
A team of seismologists analyzing the data from 671 earthquakes that occurred between 30 and 280 miles beneath the Earth’s surface in the Pacific Plate as it descended into the Tonga Trench were surprised to find a zone of intense earthquake activity in the downgoing slab. The pattern of the activity along the slab provided strong evidence that the earthquakes are sparked by the release of water at depth.
Tonga is a seismologists’ paradise, and not just because of the white-sand beaches. The subduction zone off the east coast of the archipelago racks up more intermediate-depth and deep earthquakes than any other subduction zone, where one plate of Earth’s lithosphere dives under another, on the planet.
“Tonga is such an extreme place, and that makes it very revealing,” said S. Shawn Wei, a seismologist who earned his doctorate at Washington University in St. Louis and now is a postdoctoral fellow at the Scripps Institution of Oceanography in San Diego.
That swarm of earthquakes is catnip for seismologists because they still don’t understand what causes earthquakes to pop off at such great depths.
Below about 40 miles, the enormous heat and pressure in Earth’s interior should keep rock soft and pliable, more inclined to ooze than to snap. So triggering an earthquake at depth should be like getting molasses to shatter.
In the Jan. 11 issue of Science Advances, a team of seismologists from Washington University, Scripps Institution of Oceanography and Carnegie Institution for Science analyze the data from 671 earthquakes that occurred between 30 and 280 miles beneath Earth’s surface in the Pacific Plate as it descended into the Tonga Trench.
Analyzing data from several seismic surveys with both ocean bottom seismometers and island-based seismic stations, they were surprised to find a zone of intense earthquake activity in the downgoing slab, which they call a seismic belt.
The pattern of the activity along the slab provided strong evidence that the earthquakes are sparked by the release of water at depth.
“It looks like the seismic belt is produced by the sudden flushing of water when the slab warms up enough that the hydrated minerals can decompose and give off their water,” said Doug Wiens, the Robert S. Brookings Distinguished Professor of earth and planetary sciences in Arts & Sciences at Washington University.
“The pressure of the fluid causes earthquakes in the same way that wastewater injected into deep wells causes them in Oklahoma,” Wiens said. “Although the details are very different when it’s many miles down, it’s the same physical process. ”
A champion subduction zone
The Tonga Trench holds a place of honor in the annals of seismology because this is where American scientists, invited to investigate the grumbling earth by the King of Tonga, got their first clear glimpse of a subduction zone in action.
The classic paper that scientists Bryan Isacks, Jack Oliver and Lynn Sykes published in 1968 led to the acceptance of the then speculative theory of plate tectonics.
In 1985, the Japanese seismologist Hitoshi Kawakatsu discovered something else interesting in Tonga: the descending slab has a double seismic zone. “There are two zones of earthquakes in the slab,” Wiens said. “One is in the top part of the slab and the other is toward the middle of the slab.”
Wiens, who has been studying the Tonga subduction zone since the early 1990s, says it is a great natural laboratory because its characteristics are so extreme. The ocean floor taking the dive there is older and colder than most other subducting slabs. It is also moving very fast.
“In the northern part of the Tonga Trench, the slab is moving 9 inches a year,” said Wiens. “The San Andreas Fault, by comparison, moves 2 inches a year.”
And the subducting slab has another useful quirk. It isn’t descending into the trench at uniform speed but instead going down much faster at the northern end of the trench than at the southern end.
This means that the slab warms up at different rates along its length. “It’s like pushing a cold bar of chocolate into a bubbling pan of pudding,” said Wiens. “If you push slowly, the chocolate has a chance to warm up and melt, but if you push fast, the chocolate stays cold longer.”
This is a perfect setup for studying temperature-dependent phenomenon.
When Wei analyzed the data from Tonga, he saw the double seismic zone the Japanese scientist had discovered. “We’re pretty much to follow up on that 1985 paper,” he said.
“Where the double seismic zone started to break down in Tonga, however, we saw this really active area of earthquakes that we named the seismic belt,” Wiens said. “That was a surprise; we weren’t expecting it.”
Why the sudden burst of earthquakes as the slab descended? The telling clue was that the burst angled upward from north to south along the slab. The faster the slab was moving, the deeper the earthquakes, and the slower the slab, the shallower the earthquakes.
The angled seismic belt told the scientists that the mechanism triggering earthquakes was temperature sensitive. “We think the earthquakes occur when the mantle in the downgoing slab gets hot enough to release its water,” Wiens said.
“People have proposed this mechanism before, but this is the smoking gun, ” Wiens continued. “The seismicity is changing depth in a way that’s correlated with the subduction rate and the slab temperature. ”
The deep water cycle
But where does the water come from, and why is it released suddenly?
The interior of the Pacific plate is exposed to seawater as the plate is pulled under the Tonga Plate and faults open on its upper surface, Wei said. Seawater reacts with the rock to form hydrous minerals (minerals that include water in their crystal structure) in the serpentine family. The most abundant of these serpentine minerals is a green stone called antigorite.
But as the slab descends and the temperature and pressure increases, these hydrous minerals become unstable and break down through dehydration reactions, Wei said.
This sudden release of large amounts of water is what triggers the earthquakes.
“The temperature we predict in the earthquake locations strongly suggests that minerals dehydrate very deep in the Tonga subduction zone, said Peter van Keken, a staff scientist at the Carnegie Institution for Science and a co-author on the paper.
The “phase diagrams” for antigorite dehydration reactions overlap neatly with the pressure and temperature of the slab at the seismic belt.
But the phase diagrams aren’t that reliable at these extreme temperatures and depths. So Wei, for one, would like to see more laboratory data on the behavior of antigorite and other hydrous minerals at high temperature and pressure to nail down the mechanism.
For him, the most exciting part of the research is the evidence of water 180 miles beneath the surface. ” We currently don’t know how much water gets to the deep Earth or how deep the water can finally reach,” Wei said. “In other words, we don’t know how much water is stored in the mantle, which is a key factor for Earth’s water budget.”
The water down there may be as important to us as the water up here. It is beginning to look like water is the lubricant that oils the machine that recycles Earth’s crust.
“The Tonga dataset is such a great treasure chest that we’ll be exploiting for many years to come,” said Wei. “Tonga has many more stories to tell us about Earth’s interior.”
- S. Shawn Wei et al. Slab temperature controls on the Tonga double seismic zone and slab mantle dehydration. Science Advances, January 2017 DOI: 10.1126/sciadv.1601755
Source: Washington University in St. Louis. “Release of water shakes Pacific plate at depth.” ScienceDaily. ScienceDaily, 11 January 2017. <www.sciencedaily.com/releases/2017/01/170111151428.htm>.
January 10, 2017
University of California – San Francisco
Signatures of ethnicity in the genome appear to reflect an ethnic group’s shared culture and environment, rather than their common genetic ancestry, report scientists. Epigenetic signatures distinguishing Mexican and Puerto Rican children in this study cannot be explained by genetic ancestry alone, the researchers say.
A UC San Francisco-led study has identified signatures of ethnicity in the genome that appear to reflect an ethnic group’s shared culture and environment, rather than their common genetic ancestry.
The study examined DNA methylation — an “annotation” of DNA that alters gene expression without changing the genomic sequence itself — in a group of diverse Latino children. Methylation is one type of “epigenetic mark” that previous research has shown can be either inherited or altered by life experience. The researchers identified several hundred differences in methylation associated with either Mexican or Puerto Rican ethnicity, but discovered that only three-quarters of the epigenetic difference between the two ethnic subgroups could be accounted for by differences in the children’s genetic ancestry. The rest of the epigenetic differences, the authors suggest, may reflect a biological stamp made by the different experiences, practices, and environmental exposures distinct to the two ethnic subgroups.
The discovery could help scientists understand how social, cultural, and environmental factors interact with genetics to create differences in health outcomes between different ethnic populations, the authors say, and provides a counterpoint to long-standing efforts in the biomedical research community to replace imprecise racial and ethnic categorization with genetic tests to determine ancestry.
“These data suggest that the interplay between race and ethnicity as social constructs and genetic ancestry as a biological construct is more complex than we had realized,” said Noah Zaitlen, PhD, a UCSF assistant professor of medicine and co-senior author on the new study. “In a medical context both elements may provide valuable information.”
The research — published January 3, 2017 in the online journal eLife — was led by Joshua Galanter, MD, MAS, formerly an assistant professor of medicine, of bioengineering and therapeutic sciences, and of epidemiology and biostatistics at UCSF, who is now a scientist at Genentech. The research was jointly supervised by Zaitlen and co-senior author Esteban Burchard, MD, MPH, a professor of bioengineering and therapeutic sciences and of medicine in UCSF’s schools of Pharmacy and Medicine and the Harry Wm. and Diana V. Hind Distinguished Professorship in Pharmaceutical Sciences II at UCSF.
“This is a big advancement of our understanding of race and ethnicity,” Burchard said. “There’s this whole debate about whether race is fundamentally genetic or is just a social construct. To our knowledge this is the first time anyone has attempted to quantify the molecular signature of the non-genetic components of race and ethnicity. It demonstrates in a whole new way that race combines both genetics and environment.”
Teasing apart roles of genetics, environment in ethnic differences in disease
Researchers and clinicians have known for many years that different racial and ethnic populations get diseases at different rates, respond differently to medications, and show very different results on standard clinical tests: “For a whole range of medical tests, whether your physician is told that your lab result is normal or abnormal depends entirely on the race/ethnicity box that you tick on an intake form,” Zaitlen said.
It’s tempting to assume that such health disparities between races and ethnicities all stem from inherited genetic differences, but that’s not necessarily the case. Different racial and ethnic groups also eat different diets, live in neighborhoods with more or less pollution, experience different levels of poverty, and are more or less likely to smoke tobacco, all of which could also impact their health outcomes.
“A lot of our research involves trying to tease apart how much of health differences between populations are genetic and how much are environmental,” Zaitlen said.
The researchers turned to epigenetics to search for answers to these questions because these molecular annotations of the genetic code have a unique position between genetic ancestry and environmental influence. Unlike the rest of the genome, which is only inherited from an individual’s parents (with random mutations here and there), methylation and other epigenetic annotations can be modified based on experience. These modifications influence when and where particular genes are expressed and appear to have significant impacts on disease risk, suggesting explanations for how environmental factors such as maternal smoking during pregnancy can influence a child’s risk of later health problems.
Epigenetic signatures of ethnicity could be biomarkers for shared cultural experiences
In the new study, the team examined methylation signatures in 573 children of self-identified Mexican or Puerto-Rican identity drawn from the GALA II study, a cohort previously developed by Burchard to study environmental and genetic components of asthma risk in Latino children. They identified 916 methylation sites that varied with ethnic identity, but found that only 520 of these differences could be completely explained by genetic ancestry — 109 could be partially explained by ancestry, while 205 could not be explained by ancestry at all.
Overall, the researchers found that about 76 percent of the effect of ethnicity on DNA methylation could be accounted for by controlling for genetic ancestry, suggesting that nearly a quarter of the effect must be due to other, unknown factors. The researchers found that many of these additional methylation sites corresponded to sites that previous studies had shown to be sensitive to environmental and social factors such as maternal smoking, exposure to diesel exhaust, and psychosocial stress. This led the team to hypothesize that a large fraction of their newly disovered epigenetic markers of ethnicity likely reflect biological signatures of environmental, social, or cultural differences between ethnic subgroups.
“This suggests that using epigenetics as a biomarker could give you a lot of information about environmental exposures within particular populations that’s not captured by genetics,” Zaitlen said. “Our next step will be to understand how specific epigenetic signatures are linked to particular environmental exposures, and use those signals to understand patient risk.”
Scientists and clinicians have increasingly tried to move away from simplistic racial and ethnic categories in disease research, the authors say, and — with the rise of precision medicine — in clinical diagnosis and treatment as well. Studies by the Burchard group and others have found that using genetic ancestry rather than ethnic self-identification significantly improves diagnostic accuracy for certain diseases.
But the new data showing that a large fraction of epigenetic signatures of ethnicity reflect something other than ancestry suggests that abandoning the idea of race and ethnicity altogether could sacrifice a lot of valuable information about the drivers of differences in health and disease between different communities.
“Like a standard family history, ethnicity is association with disease for both genetic and environmental reasons,” Zaitlen said. “If your dad or mom had a heart attack, that tells doctors a lot about your risk for a heart attack. Part of that is genetic, but part of it is that your lifestyle is influenced heavily by your parents’ lifestyle. Your ethnic group is like a much bigger family — it’s partly a matter of genetics, but it also reflects the environment of your broader community.”
Materials provided by University of California – San Francisco. Note: Content may be edited for style and length.
- Joshua M Galanter, Christopher R Gignoux, Sam S Oh, Dara Torgerson, Maria Pino-Yanes, Neeta Thakur, Celeste Eng, Donglei Hu, Scott Huntsman, Harold J Farber, Pedro C Avila, Emerita Brigino-Buenaventura, Michael A LeNoir, Kelly Meade, Denise Serebrisky, William Rodríguez-Cintrón, Rajesh Kumar, Jose R Rodríguez-Santana, Max A Seibold, Luisa N Borrell, Esteban G Burchard, Noah Zaitlen. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. eLife, 2017; 6 DOI: 10.7554/eLife.20532
Source: University of California – San Francisco. “Cultural differences may leave their mark on DNA.” ScienceDaily. ScienceDaily, 10 January 2017. <www.sciencedaily.com/releases/2017/01/170110120638.htm>.
January 9, 2017
Even before they are born, premature babies may display alterations in the circuitry of their developing brains, according to a first-of-its kind research study.
Even before they are born, premature babies may display alterations in the circuitry of their developing brains, according to a first-of-its kind research study by Yale School of Medicine researchers and their colleagues at the National Institutes of Health (NIH) and Wayne State University.
The findings are published in the journal Scientific Reports, a Nature Publishing Group Journal.
According to the authors, 10% to 11% percent of American babies are born prematurely. This new study suggest that factors contributing to early birth might also impact the brain’s development in the womb, leading to significant neurodevelopmental disorders, such as autism, attention deficit hyperactivity disorder, and cerebral palsy.
In the study, Yale School of Medicine researchers Laura Ment, M.D., Dustin Scheinost, and R. Todd Constable collaborated closely with principal investigator Moriah Thomason of Wayne State University, and Roberto Romero, M.D., chief of the Perinatology Research Branch and Program Director for Obstetrics and Maternal-Fetal Medicine of NICHD/NIH.
The research team used fetal resting-state functional magnetic resonance imaging to measure brain connectivity in utero in 32 human fetuses with normal brain anatomy, 14 of which were subsequently delivered preterm (between 24 and 35 weeks).
Patients were studied at Wayne State and Scheinost, assistant professor in the Magnetic Resonance Research Center at Yale School of Medicine, spearheaded the analysis using novel functional magnetic resonance imaging strategies to detect differences in neural networks between study groups.
The team found that systems-level neural connectivity was weaker in fetuses that would subsequently be born preterm. The findings were localized in left-hemisphere, pre-language regions of the brain.
“It was striking to see brain differences associated with preterm birth many weeks before the infants were prematurely-born,” said Scheinost. “Preterm infants are known to have brain changes in language regions, and we were particularly surprised that the fetal differences we detected were in these same language regions.”
Co-author Ment said these findings suggest that some prematurely born infants show changes in neural systems prior to birth. “Impaired connectivity in language regions in infants born long before their due dates needs further study, but is important for future research into both the causes and outcomes of preterm birth,” said Ment, professor of pediatrics and neurology at Yale School of Medicine.
The team’s future research will focus on potential causes of prematurity, such as infection and inflammation, to determine whether and how those conditions influence brain development in utero. They also will follow the study participants’ children to establish long-term outcomes.
- Moriah E. Thomason, Dustin Scheinost, Janessa H. Manning, Lauren E. Grove, Jasmine Hect, Narcis Marshall, Edgar Hernandez-Andrade, Susan Berman, Athina Pappas, Lami Yeo, Sonia S. Hassan, R. Todd Constable, Laura R. Ment, Roberto Romero. Weak functional connectivity in the human fetal brain prior to preterm birth. Scientific Reports, 2017; 7: 39286 DOI: 10.1038/srep39286
Source: Yale University. “Brain impairments in premature infants may begin in the womb.” ScienceDaily. ScienceDaily, 9 January 2017. <www.sciencedaily.com/releases/2017/01/170109133958.htm>.
Dave Luke, PharmD, FACA, FCCP, Joins Target Health as Sr. Director of Clinical and Scientific Affairs
As part of the continuing growth of Target Health Inc. we welcome Dave Luke, PharmD, FACA, FCCP, as Sr. Director of Clinical and Scientific Affairs. Dave will work closely with all departments at Target Health to provide both clinical, scientific and leadership support for all of our programs.
Prior to joining Target Health, Dave spent 20 years at Pfizer where he was Senior Medical Director, MSL in the areas of Infectious Diseases, Oncology, Immunology, Cardiology, Neurology, Pain; National Medical Council Coordinator, MSL; Faculty Member, Pfizer Research University; and Senior Associate Director, Clinical Research – Phase 3 Development. Prior to joining Pfizer, Dave was Director of the HIV Clinical Research, Clinical Pharmacology Unit at Hoffmann-La Roche Inc., and held academic positions at Rutgers, State University of New Jersey, University of Houston, and University of Texas M.D. Anderson Cancer Center, Houston, TX. Dave has a Doctor of Pharmacy degree from the University of the Sciences in Philadelphia (formerly known as the Philadelphia College of Pharmacy and Sciences). Between 1997 and 2004 Dave was also a Member of the NASA/Johnson Space Center Steering Committee.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Homosexuality May Have Evolved in Humans Because It Helps Us Bond
Source: Public Domain, Wikipedia Commons
Homosexuality, or being gay is romantic attraction between members of the same gender. As such, being gay is an enduring pattern of emotional, romantic, and/or attractions to people of the same 1) ___. It also refers to a person’s sense of identity based on those attractions, related behaviors, and membership in a community of others who share those attractions. Along with bisexuality and heterosexuality, being gay is one of the three main categories within the heterosexual-homosexual continuum. The exact cause of being gay is not known, but it is believed to be caused by a complex interplay of genetic, hormonal, and environmental influences, and do not view it as a 2) ___. The favored biologically-based theories point to genetic factors, the early uterine environment, both, or the inclusion of genetic and social factors. There is no substantive evidence which suggests parenting or early 3) ___ experiences play a role when it comes to being gay. While some people believe that gay activity is unnatural, scientific research has shown that being gay could be a normal and natural variation in human 4) ___ and is not in and of itself a source of negative psychological effects.
The number of people who identify as gay or lesbian is difficult to estimate reliably for a variety of reasons, including many gay or lesbian people not openly identifying as such due. Homosexual behavior has also been documented and is observed in many non-human 5) ___ species. Many gay and lesbian people are in committed same-gender relationships, though only recently have census forms and political conditions facilitated their visibility and enumeration. These relationships are equivalent to heterosexual relationships in essential psychological respects.
Gay relationships and acts have been admired, as well as condemned, throughout recorded 6) ___, depending on the form they took and the culture in which they occurred. Since the end of the 19th century, there has been a global movement towards increased visibility, recognition, and legal rights for gay people, including the rights to marriage and civil unions, adoption and parenting, employment, military service, equal access to health care, and the introduction of anti-bullying legislation to protect gay minors.
Scientists have long been puzzled by homosexuality, as it seems to be at odds with the basic human drive to 7) ___. Various theories have been offered, from the notion that gay men make more diligent uncles than their heterosexual counterparts (and thus are better at ensuring the survival of their relatives) to the notion that the same gene that codes for homosexuality in men makes women more fertile. Now researchers from the University of Portsmouth in England have put forth a controversial new theory. They say homosexuality evolved in humans and other primates because it helps us form 8) ___ with one another. From an evolutionary perspective, we tend to think of sexual behavior as a means to an end for reproduction, Dr. Diana Fleischman, an evolutionary psychologist at the university and one of the researchers, said in a written statement. However, because sexual behavior is intimate and pleasurable, it is also used in many species, including non-human primates, to help form and maintain social bonds. We can all see this in romantic couples who bond by engaging in sexual behavior even when reproduction is not possible. For the study, 92 women were asked to indicate the extent to which they agreed or disagreed with various hypothetical statements about homosexual behavior, such as: The idea of kissing a person of the same gender is sexually arousing to me and If someone of the same gender made a pass at me I would be disgusted. Then the researchers measured levels of the hormone 9) ___ in the women’s saliva. Progesterone is linked to social bonding. What did the researchers find? Women with high progesterone levels were more open to engaging in homosexual activity. The researchers theorize that progesterone may make people want to bond with others, and since sexual activity is one form of bonding, homosexual as well as heterosexual behavior is encouraged. In another experiment, 59 men did word completion puzzles, filling in the blanks of words from one of the following three categories: friendship (for instance, fr ds becomes friends), or neutral (sq.ar. becomes square). The researchers found that the men who completed the friendship puzzles were 26% more likely to be open to the idea of having relationships with other men compared to the men in the other two groups. In other words, when men were led to think about forming bonds with others, they were more open to homosexual as well as heterosexual behavior, Fleischman told The Huffington Post in an email. It’s very complex, but it’s clear there’s a continuum between 10) ___ and sexuality, and the ability to engage sexually with those of the same gender or the opposite gender is common, Fleischman said in the statement. In humans, much, if not most of same-gender behavior occurs in those who don’t identify as homosexual. An intriguing theory, for sure. But not everyone is buying the new research. It is a plausible theory that there is a societal benefit from homosexual behavior, but the link to progesterone is probably spurious, Dr. Gerard Conway, professor of reproductive endocrinology at University College, London, who was not involved in the study, told reporters. It’s a long way from proving cause and effect. The study was published November 25, 2016 in the journal Archives of Sexual Behavior. TED lecture: Homosexuality: It’s about survival| James O’Keefe MD
ANSWERS: 1) gender; 2) choice; 3) childhood; 4) behavior; 5) animal; 6) history; 7) reproduce; 8) bonds; 9) progesterone; 10) affection
Burning of two homosexuals at the stake outside Z?rich, 1482 (Spiezer Schilling).
Source: Public Domain, Wikipedia Commons
Classical period: Europe
The earliest Western documents (in the form of literary works, art objects, and mythographic materials) concerning same-gender relationships are derived from ancient Greece. With regard to male homosexuality such documents depict a world in which relationships with women and relationships with youths were the essential foundation of a normal man’s love life. Same-gender relationships were a social institution variously constructed over time and from one city to another. The formal practice, an erotic yet often restrained relationship between a free adult male and a free adolescent, was valued for its pedagogic benefits and as a means of population control, though occasionally blamed for causing disorder. Plato praised its benefits in his early writings but in his late works proposed its prohibition. Aristotle, in the Politics, dismissed Plato’s ideas about abolishing homosexuality; he explains that barbarians like the Celts accorded it a special honor, while the Cretans used it to regulate the population.
Little is known of female homosexuality in antiquity. Sappho, born on the island of Lesbos, was included by later Greeks in the canonical list of nine lyric poets. The adjectives deriving from her name and place of birth (Sapphic and Lesbian) came to be applied to female homosexuality beginning in the 19th century. Sappho’s poetry centers on passion and love for various personages and both genders. The narrators of many of her poems speak of infatuations and love (sometimes requited, sometimes not) for various females, but descriptions of physical acts between women are few and subject to debate.
Sappho reading to her companions on an Attic vase of c. 435 BCE.
Source: Public Domain, Wikipedia Commons
In Ancient Rome the young male body remained a focus, but relationships were between older free men and slaves or freed youths who took the receptive role. The Hellenophile emperor Hadrian is renowned for his relationship with Antinous, but the Christian emperor Theodosius I decreed a law on 6 August 390, condemning passive males to be burned at the stake. Justinian, towards the end of his reign, expanded the proscription to the active partner as well (in 558), warning that such conduct can lead to the destruction of cities through the wrath of God. Notwithstanding these regulations, taxes on brothels of boys available for homosexual relationships continued to be collected until the end of the reign of Anastasius I in 518.
During the Renaissance, wealthy cities in northern Italy – Florence and Venice in particular – were renowned for their widespread practice of same-gender love, engaged in by a considerable part of the male population and constructed along the classical pattern of Greece and Rome. But even as many of the male population were engaging in same-gender relationships, the authorities, under the aegis of the Officers of the Night court, were prosecuting, fining, and imprisoning a good portion of that population. From the second half of the 13th century, death was the punishment for male homosexuality in most of Europe. The relationships of socially prominent figures, such as King James I and the Duke of Buckingham, served to highlight the issue, including in anonymously authored street pamphlets: The world is chang’d I know not how, For men Kiss Men, not Women now;.Of J. the First and Buckingham: He, true it is, his Wives Embraces fled, To slabber his lov’d Ganimede (Mundus Foppensis, or The Fop Display’d, 1691).
18th and 19th Centuries
Love Letters Between a Certain Late Nobleman and the Famous Mr. Wilson was published in 1723 in England and was presumed by some modern scholars to be a novel. The 1749 edition of John Cleland’s popular novel Fanny Hill includes a homosexual scene, but this was removed in its 1750 edition. Also in 1749, the earliest extended and serious defense of homosexuality in English, Ancient and Modern Pederasty Investigated and Exemplified, written by Thomas Cannon, was published, but was suppressed almost immediately. It includes the passage, Unnatural Desire is a Contradiction in Terms; downright Nonsense. Desire is an amatory Impulse of the inmost human Parts. Around 1785 Jeremy Bentham wrote another defense, but this was not published until 1978. Executions for certain activities continued in the Netherlands until 1803, and in England until 1835. Between 1864 and 1880 Karl Heinrich Ulrichs published a series of twelve tracts, which he collectively titled Research on the Riddle of Man-Manly Love. In 1867, he became the first self-proclaimed gay person to speak out publicly in defense of gayness when he pleaded at the Congress of German Jurists in Munich for a resolution urging the repeal of discriminatory laws. A book by Havelock Ellis, published in 1896, challenged theories that homosexuality was abnormal, as well as stereotypes, and insisted on the ubiquity of homosexuality and its association with intellectual and artistic achievement. Although medical texts like these (written partly in Latin to obscure the graphic details) were not widely read by the general public, they did lead to the rise of Magnus Hirschfeld’s Scientific-Humanitarian Committee, which campaigned from 1897 to 1933 against discriminatory laws in Germany, as well as a much more informal, unpublicized movement among British intellectuals and writers, led by such figures as Edward Carpenter and John Addington Symonds. Beginning in 1894 with Homogenic Love, Socialist activist and poet Edward Carpenter wrote a string of pro-gay articles and pamphlets, and came out in 1916 in his book My Days and Dreams. In 1900, Elisar von Kupffer published an anthology of homosexual literature from antiquity to his own time, Lieblingminne und Freundesliebe in der Weltliteratur.
Hearing Loss Prevalence Declining in Adults Aged 20-69
According to an article published in JAMA Otolaryngology – Head & Neck Surgery, (15 December 2016), hearing loss among U.S. adults aged 20 to 69 has declined over the last decade, even as the number of older Americans continues to grow. These findings, also confirm that hearing loss is strongly associated with age and other demographic factors such as gender, race/ethnicity, and education. Noise exposure, which is potentially preventable, was also significant but less strongly associated after adjustment for other factors..
For the study, hearing loss trends over time were examined in adults aged 20 to 69, by comparing hearing health data collected as part of the National Health and Nutrition Examination Survey (NHANES) over two time periods: 2011-2012 and 1999-2004. NHANES is a nationally representative health interview and examination survey of U.S. adults. NHANES participants listened to tones of various frequencies that were presented at different loudness levels. The study defined hearing loss as an average hearing threshold in at least one ear that was greater than 25 decibels in loudness (about as loud as rustling leaves). Data were also age- and gender-adjusted to reduce the effects of demographic differences across the two time periods.
Results showed that the overall annual prevalence of hearing loss dropped slightly, from 16% to 14%, or 28 million adults, in the 1999-2004 period versus 27.7 million in the 2011-2012 period. This decline in absolute numbers was observed despite an increase in the population generally, and in the relative number of adults aged 50 to 69 in the more recent time period. The new results are consistent with previous findings showing improvements in hearing over time, when researchers compared NHANES data from 1999 to 2004 with data from 1959 to 1962.
The authors were not able explain the reason why hearing loss prevalence is declining but speculate possible factors could include fewer manufacturing jobs, increased use of hearing protectors, less smoking, and advances in health including better medical care to manage risk factors associated with hearing loss. The study found that age was the strongest predictor of hearing loss, with the greatest amount of hearing loss in the oldest age group surveyed (aged 60 to 69). Across all ages, men were about twice as likely as women to have hearing loss. In addition, lower education level and heavy use of firearms were associated with hearing loss. Non-Hispanic white adults were more likely to have hearing loss than adults in other ethnic groups, with non-Hispanic black adults having the lowest risk. The study also found that age- and gender-adjusted hearing loss declined over the years for the averaged high frequencies (3-6 kilohertz) in both ears, and for speech frequencies (0.5-4 kilohertz) in one ear. People aged 70 and above, although not studied in this report, have the highest prevalence of hearing loss of any age group.
Clinical Trial Demonstrates Shrinkage in Pediatric Neural Tumors
Neurofibromatosis type 1 (NF1), also called von Recklinghausen’s disease, is a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormally decreased or increased coloration (hypo- or hyperpigmentation) of the skin. Areas of abnormal pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots) on the skin of the trunk and other regions as well as freckling, particularly under the arms (axillary) and in the groin (inguinal) area. Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time. At birth or early childhood, affected individuals may have relatively large benign tumors that consist of bundles of nerves (plexiform neurofibromas). Individuals with NF1 may also develop benign tumor-like nodules of the colored regions of the eyes (Lisch nodules) or tumors of the optic nerves (second cranial nerves), which transmit nerve impulses from the innermost, nerve-rich membrane of the eyes (retinas) to the brain. More rarely, affected individuals may develop certain malignant (cancerous) tumors. NF1 may also be characterized by unusual largeness of the head (macrocephaly) and relatively short stature. Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs, and improper development of certain bones. Plexiform neurofibromas develop in up to 50% of people with NF1. Complete surgical removal of the tumors is rarely feasible, and incompletely resected tumors tend to grow back.
The disease-causing gene for NF1 was first identified in 1990 by two independent teams, one of them led by NIH Director Francis S. Collins, Ph.D., M.D., who at the time was chief of Medical Genetics at the University of Michigan. The other team was led by Ray White at the University of Utah. Research to understand the gene’s function revealed that deregulation of the RAS signaling pathway was the most likely cause of tumor development. Numerous drugs that target RAS-related signaling pathways have been tested in patients with NF1 in phase I and phase II clinical trials, with disappointing results.
According to an article published online in the New England Journal of Medicine (29 Dec. 2016), in an early-phase clinical trial of a new oral drug, selumetinib, children with NF1 and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage. NF1 affects 1 in 3,000 people.
The multicenter phase I clinical trial, which included 24 patients, and was conducted at the NIH Clinical Center and three participating sites. The primary aim of the clinical trial was to evaluate the toxicity and safety of selumetinib in patients with NF1 and inoperable plexiform neurofibromas, and, encouragingly, most of the selumetinib-related toxic effects were mild. At present, no therapies are considered effective for NF1-related large plexiform neurofibromas, but, in this trial, partial responses, meaning 20% or more reduction in tumor volume, were observed in over 70% of the patients. Responses were observed in tumors that were previously growing at a rate of greater than 20% per year, as well as in non-progressing lesions. Tumor shrinkage was maintained long term, for approximately two years, and, as of early 2016, no disease progression had been observed in any trial participant. Additionally, anecdotal evidence of clinical improvement, such as a decrease in tumor-related pain, improvement in motor function, and decreased disfigurement, was reported.
Selumetinib, provided for the study by AstraZeneca, is a selective inhibitor of the MEK protein, a part of the complex network of RAS signaling pathways. The drug has demonstrated activity in some advanced cancers, but it is not yet approved by the FDA. It is manufactured in capsule form to be taken orally.
Trial enrollment began in September 2011 and 24 children (11 girls, 13 boys) participated. Twice daily doses of the medicine were taken continuously, over a median of 30 month-long treatment cycles. The majority of patients are still continuing with therapy, some for as long as five years, and the long-term treatment has had no observed adverse effect on their development or overall health. In some patients, a loss of response to selumetinib with slow regrowth of tumors was observed, particularly after dose reductions. The authors believe that additional studies are warranted to characterize tumors that no longer respond to selumetinib. NCI is currently sponsoring an ongoing phase II trial of the drug for adults with NF1, in which serial tissue samples are being obtained. This study should provide information about possible mechanisms of resistance to selumetinib. In addition, a larger phase II pediatric trial is enrolling patients and should help establish the efficacy of selumetinib treatment in children. In this trial, in addition to tumor volume measurements, evaluations are being performed to assess the effect of selumetinib on plexiform neurofibroma related disfigurement, pain, quality of life, and function.