Date:
December 13, 2017

Source:
University of Wisconsin-Madison

Summary:
In the wild, chimpanzees face any number of dire threats, ranging from poachers to predators to deforestation. That’s why scientists, investigating an outbreak of respiratory disease in a community of wild chimpanzees in Uganda’s Kibale National Park, were surprised and dismayed to discover that a human “common cold” virus known as rhinovirus C was killing healthy chimps.

 

A two-year-old chimp named Betty, who succumbed to the virus.
Credit: Richard Wrangham

 

 

In the wild, chimpanzees face any number of dire threats, ranging from poachers to predators to deforestation.

That’s why scientists, investigating an outbreak of respiratory disease in a community of wild chimpanzees in Uganda’s Kibale National Park, were surprised and dismayed to discover that a human “common cold” virus known as rhinovirus C was killing healthy chimps.

“This was an explosive outbreak of severe coughing and sneezing,” says Tony Goldberg, a professor in the University of Wisconsin-Madison’s School of Veterinary Medicine and one of the senior authors of a report documenting the event. The report was published online today (Dec. 13, 2017) in the journal Emerging Infectious Diseases.

“It was completely unknown that rhinovirus C could infect anything other than humans,” says Goldberg, referencing a two-year-old chimp named Betty, who succumbed to the virus and whose body was quickly recovered and autopsied after her death. “It was surprising to find it in chimpanzees, and it was equally surprising that it could kill healthy chimpanzees outright.”

The outbreak occurred in February of 2013 and affected most of the chimps in the community. During that time, five chimps out of a community of 56 died, including Betty; the other animals that died were adults up to 57 years old. The findings, says Goldberg, are a cautionary tale about human interactions with wild apes. In Africa, people encounter chimpanzees and other apes when human settlements expand into ape habitats, through activities like tourism and research, and when apes leave the forests to raid crops.

Rhinovirus C is one of three rhinovirus species, each causing respiratory disease in humans. But rhinovirus C is notably more severe than its relatives, rhinoviruses A and B. Although the virus had likely been infecting people for several thousand years, it was unknown to science until 2006, when it was discovered using new DNA sequencing technologies.

In people, rhinovirus C infection can be especially severe in children, notes James Gern, another senior author of the study and a professor of allergy and immunology in the UW School of Medicine and Public Health. Gern’s lab was the first to grow rhinovirus C in the laboratory where it could be studied. Gern’s lab also described the receptor that the virus uses to infect cells of the respiratory system.

“In general, this virus seems to affect young children the most,” says Gern, whose lab performs high-throughput viral diagnostics, processing thousands of human samples annually. Gern explains that the genetics of the receptor — which serves like a lock-and-key mechanism that allows the virus to enter and infect a host cell — influences who is likely to be most affected by the virus. Some people have a version of the receptor that makes them highly susceptible to the virus while others have a different version that makes them resistant. For some people (young children, in particular) rhinovirus C infection can be a precursor or complicating factor for asthma.

“Chimps seem to be genetically predisposed to have problems with this virus,” Gern says. “The virus found in Betty was one that looked like it came from a human, and the level of virus in the lung was comparable to what we see in children.”

The authors were also able to examine the DNA of the chimps in Uganda using fecal samples, and they looked at published chimp genomes from across Africa. Goldberg says it was sobering to see that every chimp had the receptor that makes cells exquisitely sensitive to rhinovirus C. “There’s a species-wide susceptibility of chimps to this virus,” says Goldberg.

Ann Palmenberg, a UW-Madison professor of biochemistry and an authority on cold viruses, says the genome of the virus obtained from Betty shows that the virus came from a human host. “We expected to see changes all over the genome, but it is not a chimp-adapted virus.”

Palmenberg, also a senior author of the study, says the virulence of the virus, with about a 9 percent mortality rate, was remarkable. “That’s why kids with the CDHR3 high-risk mutation are at increased risk for being hospitalized with severe respiratory illness.”

Goldberg, who has worked in Uganda for years tracking viruses in animals, says outbreaks of respiratory disease in wild chimpanzees are not uncommon, but for the most part they go undiagnosed. In the few cases where causes have been identified, other viruses unrelated to rhinovirus C have been in play.

“In most cases, we don’t find out what it is. We’re thinking that rhinovirus C might be a major, missed cause of disease outbreaks in chimps in the wild,” Goldberg notes.

Unlike other viruses known to cause respiratory disease in chimps, though, rhinovirus C is not typically found in feces and may have been overlooked in the past.

Finding rhinovirus C as the cause of the 2013 outbreak in Uganda was part good luck, says Goldberg. The opportunity to retrieve Betty’s body before it decomposed or scavengers set in was critical. So, too, were Goldberg’s colleagues at Harvard and the University of New Mexico, who run a long-term chimp study in Kibale and can identify all the chimps in the community. This, plus the fact that a Ugandan veterinarian was on hand with the proper tools to obtain and secure samples through a post mortem in the field, made the discovery possible, he says.

Story Source:

Materials provided by University of Wisconsin-Madison. Original written by Terry Devitt. Note: Content may be edited for style and length.


Journal Reference:

  1. E. J. Scully et al. Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013Emerging Infectious Diseases, 2017

 

Source: University of Wisconsin-Madison. “Chimpanzee deaths in Uganda pinned on human cold virus.” ScienceDaily. ScienceDaily, 13 December 2017. <www.sciencedaily.com/releases/2017/12/171213130223.htm>.

Date:
December 13, 2017

Source:
University of Zurich

Summary:
Biochemists have used cryo-electron microscopy to determine the detailed architecture of the chloride channel TMEM16A. This protein is a promising target for the development of effective drugs to treat cystic fibrosis.

 

Structure of the calcium-activated chloride channel TMEM16A. The channel, which consists of two identical subunits, is shown in the center. The position of the membrane is indicated by lines. The ion conduction pore is highlighted (grey rectangle) and shown in detail on the right. The picture on the left shows the movement of an ?-helix (*) leading to channel opening. Bound calcium ions are depicted as blue spheres.
Credit: Raimund Dutzler, UZH

Cystic fibrosis is a severe hereditary disease of the lung, for which there is currently no cure. The underlying cause of the disease is a malfunction of the chloride channel CFTR, which prevents the secretion of chloride in certain body cells. This leads to dehydration of the mucus layer in the lung. A promising approach for treating cystic fibrosis is the activation of the calcium-activated chloride channel TMEM16A as an alternative route for chloride efflux. Since TMEM16A is expressed in the same epithelium as CFTR, its activation could restore hydration of the mucus layer. TMEM16A is part of a protein family whose members facilitate the flow of negatively charged chloride ions or lipids across the cell membrane.

Structure of a chloride channel determined

The structure of a TMEM16 scramblase, which functions as a lipid transporter and plays an important role in blood coagulation, was already known from previous work. Researchers of the Department of Biochemistry at the University of Zurich have now also succeeded in decrypting the structure of the chloride channel TMEM16A. To do so, the team led by Professor Raimund Dutzler used cryo-electron microscopy (cryo-EM), a technique whose pioneers were recently awarded the Nobel Prize in Chemistry. “The molecular architecture of this membrane protein is crucial for the targeted development of drugs for treating cystic fibrosis,” emphasizes Dutzler.

Discovery of a novel activation mechanism

The chloride channel TMEM16A can be found in different organs of the body and plays a key role in the secretion of chloride in the lung, the contraction of smooth muscles, and the perception of pain. How its structure differs from closely related scramblases of the same family and how the protein is activated by calcium was now revealed through a combination of cryo-EM and electrophysiology. While its general architecture resembles scramblases of the same family, there are distinct differences in the pore region located in each subunit of the dimeric protein. Scramblases contain a membrane-exposed polar furrow, which allows for the diffusion of lipid headgroups across the lipid bilayer. In contrast, at the same location, TMEM16A forms an hourglass-shaped protein-enclosed channel, which is closed in the absence of calcium. The binding of positively charged calcium ions in its vicinity opens the channel and allows negatively charged chloride ions to permeate across the membrane. “This activation mechanism is unique, since the bound calcium ions directly change the structure and electrostatics of the ion permeation pore,” explains Cristina Paulino, lead author of the study.

Paving the way for novel therapies

The findings that describe the structure and function of TMEM16A pave the way for a mechanistic understanding of this important family of membrane proteins, and they provide a promising template for developing drugs for the treatment of cystic fibrosis. “Substances leading to the activation of the TMEM16A would compensate the defect in the secretion of chloride ions in the lung,” states Raimund Dutzler.

Story Source:

Materials provided by University of ZurichNote: Content may be edited for style and length.


Journal Reference:

  1. Cristina Paulino, Valeria Kalienkova, Andy K. M. Lam, Yvonne Neldner, Raimund Dutzler. Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EMNature, 2017; DOI: 10.1038/nature24652

Source: University of Zurich. “Protein structure could unlock new treatments for cystic fibrosis.” ScienceDaily. ScienceDaily, 13 December 2017. .

Date:
December 8, 2017

Source:
University of Cologne

Summary:
Scientists show for the first time that fast insects can change their gait — like a mammal’s transition from trot to gallop. These new insights could contribute to making the locomotion of robots more energy efficient.

 

Cockroach on a slippery tile. (stock image)
Credit: © vitali_chesnokov / Fotolia

 

 

Using the example of cockroaches, the Cologne-based zoologist Dr Tom Weihmann and his team were able to show that quickly running insects change their gait at mid-speed. This behaviour has previously only been observed in fast mammals. This change in gait is similar to the way horses change from trop to gallop. The results of the study have now been published in the journal Frontiers in Zoology.

‘I was particularly surprised that a change in mechanisms stabilizing the animal’s movement goes hand in hand with a change in leg coordination’, Weihmann notes. An insect’s slow run is very stable because its centre of gravity is low and three legs are always moving in a coordinated manner. The research showed that the change in gait at high speed and on a slippery surface was accompanied by a change from static to dynamic stabilization. This minimizes the need of the central nervous system to control the motion while attaining high energy efficiency.

‘This discovery not only has far-reaching implications regarding the behaviour and ecology of insects and other arthropodes’, says Weihmann. ‘Our results can also contribute to solving some problems we still have with the movement of robots.’

Robots with legs generally have better cross-country mobility than robots with wheels. Particularly at high running speeds, however, robots use up a lot of energy — in contrast to many animals. Thus, the cockroaches’ locomotion pattern could contribute to finding a solution that would let robots run at a high speed with an acceptable expenditure of energy. ‘Robots with legs that can be used here on Earth after disasters, or on Mars or other planets, are often modelled on insects’, Weihmann explains. ‘Adapting the coordination patterns of robot legs to those of fast-running cockroaches can help the robot use energy more efficiently and hence increase its endurance in an inhospitable environment.’

The scientists used the organism Nauphoeta cinerea to study its locomotion on slippery and non-slippery surfaces. The results showed that at high speed, the animals reduce the degree to which their legs move in a synchronized manner. This allowed them to avoid disruptions in their coordination or falls even on slippery surfaces.

Story Source:

Materials provided by University of CologneNote: Content may be edited for style and length.


Journal Reference:

  1. Tom Weihmann, Pierre-Guillaume Brun, Emily Pycroft. Speed dependent phase shifts and gait changes in cockroaches running on substrates of different slipperinessFrontiers in Zoology, 2017; 14 (1) DOI: 10.1186/s12983-017-0232-y

 

Source: University of Cologne. “Insights on fast cockroaches can help teach robots to walk.” ScienceDaily. ScienceDaily, 8 December 2017. <www.sciencedaily.com/releases/2017/12/171208095536.htm>.

Wow!! Celebrating 23 Years of ON TARGET

 

We were rummaging through some papers the other days and found our first ON TARGET Newsletter from 1994. While the company was founded in 1993 by Joyce Hays, our CEO, as a marketing company, the pharmaceutical drug and device development services began in 1994.

 

We are thrilled that over 6,200 people have subscribed to one of the oldest published newsletter in the pharmaceutical industry. Readers include colleagues, friends, regulators and just regular folks from all over the world, no matter what ethnicity, religion, or political viewpoint. We try to bring people together as only together, can we beat diseases, poverty and inequality throughout the world.

 

We want to thank our loyal readers and followers who still come up to us and say, wow! That recipe last week was really special.

 

Please send any Holiday wishes to us and we will share them.

 

Snowy weekend in NYC. ©Target Health Inc.

 

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. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

QUIZ

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Holding Infants — or Not — Can Leave Traces on Their Genes

Newborn Examination. Photo credit: Nevit Dilmen – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1428959

 

Pediatrics is the branch of medicine that involves the medical care of infants, children, and adolescents. The American Academy of Pediatrics recommends people be under pediatric care up to the age of 21. A medical doctor who specializes in this area is known as a 1) ___. The word pediatrics and its cognates mean “healer of children“; they derive from two Greek words: pais (“child“) and iatros (“doctor, healer“). Pediatricians work both in hospitals, particularly those working in its subspecialties such as neonatology, and as primary care physicians.

 

The body size differences are paralleled by maturation changes. The smaller body of an infant or neonate is substantially different physiologically from that of an 2) ___. Congenital defects, genetic variance, and developmental issues are of greater concern to pediatricians than they often are to adult physicians. A common adage is that children are not simply “little adults“. The clinician must take into account the immature physiology of the infant or child when considering symptoms, prescribing medications, and diagnosing illnesses. A major difference between the practice of pediatric and adult medicine is that children, in most jurisdictions and with certain exceptions, cannot make decisions for themselves. The issues of guardianship, privacy, legal responsibility and informed 3) ___ must always be considered in every pediatric procedure. Pediatricians often have to treat the parents and sometimes, the family, rather than just the child. Adolescents are in their own legal class, having rights to their own health care decisions in certain circumstances. The concept of 4) ___ consent combined with the non-legal consent (assent) of the child when considering treatment options, especially in the face of conditions with poor prognosis or complicated and painful procedures/surgeries, means the pediatrician must take in to account the desires of many people, in addition to those of the patient.

 

New research shows that the amount of physical contact between infants and their caregivers can affect children at the molecular level. The study of DNA methylation patterns showed that children who had been more distressed as 5) ___ and had received less physical contact had a molecular profile that was underdeveloped for their age. This is the first study to show in humans that the simple act of touching, early in life, has deeply-rooted and potentially lifelong consequences on genetic expression. The amount of close and comforting contact between infants and their 6) ___ can affect children at the molecular level, an effect detectable four years later, according to new research from the University of British Columbia and BC Children’s Hospital Research Institute. The study showed that children who had been more distressed as infants and had received less 7) ___ contact had a molecular profile in their cells that was underdeveloped for their age — pointing to the possibility that they were lagging biologically. “In children, we think slower epigenetic aging might indicate an inability to thrive,“ said Michael Kobor, a Professor in the UBC Department of Medical Genetics who leads the “Healthy Starts“ theme at BC Children’s Hospital Research Institute.

 

Although the implications for childhood development and adult health have yet to be understood, this finding builds on similar work in rodents. This is the first study to show in humans that the simple act of touching, early in life, has deeply-rooted and potentially lifelong consequences on genetic expression. The study, published last month (November 2017) in Development and Psychopathology, involved 94 healthy children in British Columbia. Researchers from UBC and BC Children’s Hospital asked parents of 5-week-old babies to keep a diary of their infants’ behavior (such as sleeping, fussing, crying or feeding) as well as the duration of caregiving that involved bodily contact. When the children were about 4 1/2 years old, their DNA was sampled by swabbing the inside of their 8) ___. The team examined a biochemical modification called DNA methylation, in which some parts of the chromosome are tagged with small molecules made of carbon and hydrogen. These molecules act as “dimmer switches“ that help to control how active each gene is, and thus affect how cells function. The extent of methylation, and where on the DNA it specifically happens, can be influenced by external conditions, especially in childhood. These epigenetic patterns also change in predictable ways as we age. The authors found consistent methylation differences between high-contact and low-contact children at five specific DNA sites. Two of these sites fall within genes: one plays a role in the immune system, and the other is involved in metabolism. However, the downstream effects of these epigenetic changes on child development and health aren’t known yet. The children who experienced higher distress and received relatively little contact had an “epigenetic age“ that was lower than would be expected, given their actual age. Such a discrepancy has been linked to poor 9) ___ in several recent studies. The authors plan on following up to see whether the ?biological immaturity’ they saw in these children carries broad implications for their health, especially their psychological development. The authors added that if further research confirms this initial finding, it will underscore the importance of providing physical 10) ___, especially for distressed infants.

 

Sources: University of British Columbia: Sarah R. Moore, Lisa M. McEwen, Jill Quirt, Alex Morin, Sarah M. Mah, Ronald G. Barr, W. Thomas Boyce, Michael S. Kobor. Epigenetic correlates of neonatal contact in humans. Development and Psychopathology, 2017; 29 (05): 1517 DOI: 10.1017/S0954579417001213; ScienceDaily; Wikipedia

 

ANSWERS: 1) pediatrician; 2) adult; 3) consent; 4) legal; 5) infants; 6) caregivers; 7) physical; 8) cheeks; 9) health; 10) contact

 

Great Ormond Street Hospital (London) for Children

The above photo shows part of Great Ormond Street Hospital in London, United Kingdom, which was the first pediatric hospital in the English-speaking world.

Photo credit: Nigel Cox, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=5364709

 

Great Ormond Street Hospital (informally GOSH or Great Ormond Street, formerly the Hospital for Sick Children) is a children’s hospital located in the Bloomsbury area of the London Borough of Camden, and a part of Great Ormond Street Hospital for Children NHS Foundation Trust. The hospital, founded in 1852, is the largest center for child heart surgery in the UK and one of the largest centers for heart transplantation in the world. In 1962, almost one hundred years after its founding, they developed the first heart and lung bypass machine for children. With children’s book author Roald Dahl, they developed an improved shunt valve for children with water on the brain (hydrocephalus), and non-invasive (percutaneous) heart valve replacements. They did the first UK clinical trials of the rubella vaccine, and the first bone marrow transplant and gene therapy for severe combined immunodeficiency. This children’s hospital is closely associated with University College London (UCL) and in partnership with the UCL Great Ormond Street Institute of Child Health, which is adjacent to it, is the largest center for research and postgraduate teaching in children’s health in Europe.

 

After a long campaign by Dr. Charles West, the Hospital for Sick Children was founded on 14 February 1852 and was the first hospital providing in-patient beds specifically for children in England. Despite opening with just 10 beds, it grew into one of the world’s leading children’s hospitals through the patronage of Queen Victoria, counting Charles Dickens, a personal friend of Dr. West, the Chief Physician, as one of its first fundraisers.

 

Audrey Callaghan, wife of James Callaghan (prime minister of the United Kingdom from 1976 to 1979), served the hospital as Chairman of the Board of Governors from 1968 to 1972 and then as Chairman of the Special Trustees from 1983 until her final retirement in 1990. Diana, Princess of Wales, served as president of the Hospital from 1989 until her death. A plaque at the entrance of the hospital commemorates her services, as well as a bust in the lobby of the hospital chapel. The Charles West School of Nursing transferred from Great Ormond Street to London South Bank University in 1995. In 2002 Great Ormond Street Hospital commenced a redevelopment program which is budgeted at ?343 million and the next phase of which was scheduled to be complete by the end of 2016. The redevelopment was needed to expand capacity, deliver treatment in a more comfortable and modern way, and to reduce unnecessary inpatient admissions. In July 2012, Great Ormond Street Hospital was featured in the opening ceremony of the London Summer Olympics and in 2017 Great Ormond Street Hospital was subject to international attention regarding the Charlie Gard treatment controversy. The hospital’s archives are available for research under the terms of the Public Records Act 1958 and a catalogue is available on request. Admission records from 1852 to 1914 have been made available online on the Historic Hospital Admission Records Project.

 

St Christopher’s Chapel, in Great Ormond Street Hospital, is a chapel decorated in the Byzantine style and a Grade II listed building located in the Variety Club Building of the hospital. Designed by Edward Middleton Barry (son of the architect Sir Charles Barry who designed the Houses of Parliament) and built in 1875, it is dedicated to the memory of Caroline Barry, wife of William Henry Barry (eldest son of Sir Charles Barry) who provided the money required to build the Chapel and a stipend for the chaplain. It was built in “elaborate Franco-Italianate style.“ As the chapel exists to provide pastoral care to ill children and their families, many of its details refer to childhood. The stained glass depicts the Nativity, the childhood of Christ and biblical scenes related to children. The dome depicts a pelican pecking at her breast in order to feed her young with drops of her own blood, a traditional symbol of Christ’s sacrifice for humanity. When the old hospital was being demolished in the late 1980s, the chapel was moved to its present location via a ‘concrete raft’ to prevent any damage. The stained glass and furniture were temporarily removed for restoration and repair. It was reopened along with the new Variety Club Building on 14 February 1994 by Diana, Princess of Wales, then president of the hospital.

 

In April 1929 the hospital was the recipient of playwright J. M. Barrie’s copyright to the Peter Pan works, with the provision that the income from this source not be disclosed. This gave the institution control of the rights to these works, and entitled it to royalties from any performance or publication of the play and derivative works. Four theatrical feature films were produced, innumerable performances of the play have been presented, and numerous editions of the novel were published under license from the hospital. Its trustees commissioned a sequel novel, Peter Pan in Scarlet, which was published in 2006 and received mixed reviews, with a film adaptation planned. When the copyright first expired at the end of 1987 in the UK, 50 years after Barrie’s death, the UK government’s Copyright, Designs and Patents Act of 1988 granted the hospital a perpetual right to collect royalties for public performances, commercial publication, or other communications to the public, of the work, but this does not constitute a true copyright. When copyright term itself was subsequently extended to the author’s life plus 70 years by a European Union directive in 1996 standardizing terms throughout the EU, GOSH revived its copyright of Peter Pan which then expired in 2007. The terms of the Copyright, Designs and Patents Act now prevail in the UK.

 

GOSH has been in legal disputes in the United States, where the copyright term is based on date of publication, putting the 1911 novel in the public domain, although the Hospital asserts that the 1928 version of the play is still under copyright in the US. Legal opinion as to whether or not permission is required for new works based on the story and characters is divided and open to interpretation and so far, there has been no legal precedent to prove one view or the other.

 

The hospital has relied on charitable support since it first opened. One of the main sources for this support is Great Ormond Street Hospital Children’s Charity. While the NHS meets the day-to-day running costs of the hospital, the fundraising income allows Great Ormond Street Hospital to remain at the forefront of child healthcare. The charity aims to raise over 50 million pounds every year to complete the next two phases of redevelopment, as well as provide substantially more fundraising directly for research. The charity also purchases up-to-date equipment, and provides accommodation for families and staff. The charity’s teardrop logo was designed for the Wishing Well Appeal in 1987 by the firm Collett Dickenson Pearce. Great Ormond Street Hospital Children’s Charity was one of the charities that benefited from the national Jeans for Genes campaign, which encourages people across the UK to wear their jeans and make a donation to help children affected by genetic disorders. All Great Ormond Street Hospital Charity’s proceeds from the campaign went to its research partner, the UCL Institute of Child Health.

 

On 6 August 2009, Arsenal F.C. confirmed that Great Ormond Street Hospital Children’s Charity was to be their ‘charity of the season’ for the 2009-10 season. They raised over 800,000 pounds for a new lung function unit at the hospital, having raised 532,816 pounds for Teenage Cancer Trust in the previous season. Two charity singles have been released in aid of the hospital. In 1987, “The Wishing Well”, recorded by an ensemble line-up including Boy George, Peter Cox and Dollar among others, and became a top 30 hit. In 2009, The X Factor finalists covered Michael Jackson’s “You Are Not Alone” in aid of the charity, reaching No.1 in the UK Charts. Also, the winner’s singles of James Arthur and Sam Bailey have been released in aid of the charity. On 30 March 2010, Channel 4 staged the first Channel 4’s Comedy Gala at the O2 Arena in London, in aid of the charity. The event has been repeated every year since, raising money for Great Ormond Street Hospital Children’s Charity each time. In 2011, Daniel Boys recorded a charity single called ‘The World is Something You Can Imagine’. It was also released as with proceeds going to the Disney Appeal at Great Ormond Street Hospital. Source: Wikipedia

 

HIV/AIDS

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Combination HIV Prevention Reduces New Infections by 42%

 

Combination HIV Prevention Reduces New Infections by 42%% In Ugandan District NIH-supported study provides evidence for implementing approach broadly.

 

According to a study published in the New England Journal of Medicine (29 November 2017), a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections in a population. The study found that HIV incidence dropped by 42% among nearly 18,000 people in Rakai District, Uganda, during a seven-year period in which the rates of HIV treatment and voluntary medical male circumcision increased significantly.

 

The HIV prevention strategy whose impact was observed in the study is based on earlier findings by the National Institutes of Health and others demonstrating the protective effect of voluntary medical male circumcision for HIV-uninfected men, and of HIV-suppressing antiretroviral therapy (ART), for halting sexual transmission of the virus to uninfected partners. The strategy is also based on studies showing that changes in sexual behavior, such as having only one sexual partner, can help prevent HIV infection.

 

The study involved nearly 34,000 people ages 15 to 49 years residing in 30 communities that participate in the Rakai Community Cohort Study (RCCS) conducted by the Rakai Health Sciences Program in Uganda. This program promoted HIV testing, ART and voluntary medical male circumcision to study participants. Every one or two years from April 1999 until September 2016, participants were tested for HIV and surveyed about their sexual behavior, use of HIV treatment, and male circumcision status. Results showed that the proportion of study participants living with HIV who reported taking ART climbed from zero in 2003 to 69% in 2016. The proportion of male study participants who were voluntarily circumcised grew from 15% in 1999 to 59% in 2016. While levels of condom use with casual partners and the proportion of people reporting multiple sexual partners remained largely unchanged, the proportion of adolescents ages 15 to 19 who reported never having sex rose from 30% in 1999 to 55% in 2016.

 

As an apparent consequence of these increases, particularly in ART use and voluntary male circumcision, the annual number of new HIV infections in the cohort fell from 1.17 per 100 person-years in 2009 to 0.66 per 100 person-years in 2016, a 42% decrease. Person-years are the sum of the number of years that each cohort member participated in the study. The researchers calculated the annual number of new HIV infections using data from nearly 18,000 of the almost 34,000 total participants. In addition, the proportion of cohort members living with HIV whose treatment suppressed the virus increased from 42% in 2009 to 75% in 2016, showing the feasibility of meeting the goal of the UNAIDS 90-90-90 initiative  to achieve 73% viral suppression.

 

According to the authors, these findings are extremely encouraging and suggest that with sustained commitment to increase the number of people who use combination HIV prevention, it may be possible to achieve epidemic control and eventual elimination of HIV.

 

HIV incidence dropped the most  among circumcised men (57%), likely because both their own circumcision and ART taken by their female sexual partners living with HIV protected these men from the virus. HIV incidence declined by 54% among all men but by only 32% among all women. According to the authors, this difference probably occurred because a greater percentage of women living with HIV than men living with HIV took ART, and because nearly two-thirds of men chose the extra preventive benefit of circumcision. The authors also suggest addressing this gender imbalance by influencing more men living with HIV to take ART and by giving HIV-uninfected women HIV prevention tools that they can control unilaterally, such as pre-exposure prophylaxis (PrEP). The authors anticipate that the RCCS will add PrEP to its combination HIV prevention package as the study continues.

 

The Rakai Health Sciences Program is an independent research organization whose collaborators include the Uganda Virus Research Institute of the Ministry of Health in Kampala, the NIAID Division of Intramural Research-supported International Center for Excellence in Research in Rakai, the U.S. Centers for Disease Control and Prevention partnership with Uganda (CDC-Uganda), Makerere University and the Johns Hopkins University Bloomberg School of Public Health.

 

Unexplained Anaphylaxis Linked to Red Meat Allergy

 

While rare, some people experience recurrent episodes of anaphylaxis, a life-threatening allergic reaction that causes symptoms such as the constriction of airways and a dangerous drop in blood pressure, for which the triggers are never identified. Recently, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, found that some patients’ seemingly inexplicable anaphylaxis was actually caused by an uncommon allergy to a molecule found naturally in red meat. They note that the allergy, which is linked to a history of a specific type of tick bite, may be difficult for patients and health care teams to identify.

 

The study, published in Allergy (28 November 2017), showed that 6 of the 70 study participants evaluated for unexplained frequent anaphylaxis tested positive for an allergy to galactose-a-1,3-galactose, or alpha-gal, a sugar molecule found in beef, pork, lamb and other red meats. The six adult male participants all had IgE antibodies — immune proteins associated with allergy — to alpha-gal in their blood. After implementing diets free of red meat, none of them experienced anaphylaxis in the 18 months to 3 years during which they were followed. While the prevalence of allergy to alpha-gal, or “alpha-gal syndrome” is not known, the authors observed that it occurs mostly in people living in the Southeast region of the United States and certain areas of New York, New Jersey and New England. This distribution may occur because most people with an allergy to alpha-gal, including all six participants evaluated at NIH, have a history of bites from juvenile Ambylomma americanum, or Lone Star ticks.

 

The authors noted that physicians may have mistakenly diagnosed these patients as having unexplained anaphylaxis because alpha-gal allergy presents differently from more common food allergies and routine allergy tests do not typically scan for antibodies to alpha-gal. Furthermore, most allergic reactions to common food allergens, such as peanuts or crustacean shellfish, begin about 5 to 30 minutes after a person is exposed. For unknown reasons, allergic reactions to alpha-gal may occur between 3 to 6 hours after red meat consumption, making it difficult to identify what substance caused the reaction. Some episodes may even begin overnight when a person is sleeping, which is a particularly uncommon presentation for anaphylaxis.

 

According to the authors, the unusually long time gap between a meal and an allergic reaction is probably a big reason that alpha-gal allergies are often initially misdiagnosed. The authors added that “If you start to have trouble breathing in the middle of the night, you probably are not going to blame the hamburger you had for dinner.”

 

The connections between the alpha-gal syndrome and exposure to Lone Star tick bites was first discovered in 2002. At that point it was recognized that patients who had unusual allergic reactions to the cancer drug cetuximab, which contains alpha-gal molecules, also shared a history of Lone Star tick bites. At present, the as to how Lone Star tick bites lead to alpha-gal allergies, is not known.

 

Among the study participants with alpha-gal allergy evaluated at NIH, two also had a rare condition called indolent systemic mastocytosis, or ISM. People with ISM have an abnormally elevated number of mast cells, an immune cell type which contributes to anaphylaxis and other allergic symptoms by releasing histamine and other chemicals that cause inflammation. The participants with ISM experienced more severe reactions than those without ISM, even though they had lower levels of antibodies to alpha-gal. This finding builds on evidence that mast cell abnormalities may increase the likelihood of people developing allergies and experiencing severe reactions, including allergies and reactions to alpha-gal.

 

Once-Monthly Buprenorphine Injection for Opioid Use Disorder

 

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis. Opioid use disorder (OUD) is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress. OUD includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition. MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.

 

Buprenorphine for the treatment of moderate-to-severe OUD is currently approved as a tablet, as an implant, or a sublingual film (absorbed under the tongue) that dissolves in the mouth. The FDA has recently approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment OUD in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade.

 

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

 

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film. Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group. The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

 

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose). Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

 

The FDA granted approval of Sublocade to Indivior Inc. and the application had Priority Review and Fast Trackdesignations.

 

Spinach Salad with Arugula, Clementines and Croutons

It’s fun to be aware of which fruit and veggies are in season and build a recipe around it. Here, the Clementines, at their peak now, are the star attraction. Not only do they add the perfect color, but their sweet tang is the perfect foil for the dressing and slight edginess of the greens. ©Joyce Hays, Target Health Inc.

 

This salad was so-o good, it became my whole dinner with wine and a light dessert. ©Joyce Hays, Target Health Inc.

 

Get all of the ingredients together in one place. Use fresh! Fresh garlic is better than garlic powder. Fresh lemon is better than bottled. Freshly grated parmesan is better than bought and freshly baked croutons taste much better than store bought. I forgot to include the Clementines in this photo. ©Joyce Hays, Target Health Inc.

 

Ingredients 

The Dressing

3 anchovy fillets packed in oil, drained

4 fresh garlic cloves

Pinch Kosher salt

1 large egg yolk (boil egg for 1 minute and not longer)

Zest of 1/2 fresh lemon

2 Tablespoons fresh lemon juice, plus more (to your taste)

3/4 teaspoon Dijon mustard

2 Tablespoons excellent extra virgin olive oil

2 Tablespoons canola oil

6 Tablespoons finely grated FRESH Parmesan

Pinch black pepper

Worchester sauce (one drop)

 

The Croutons

1 cup torn 1“ (bite-size) pieces old bread, with crusts

1 Garlic clove, squeezed

2 teaspoons olive oil

 

The Greens

3 or 4 (packed in tightly) cups of fresh spinach and 3 or 4 cups of (packed in tightly) fresh arugula all leaves separated, washed three times, dried with paper towel. Then leaves torn by hand, put into a bowl and set aside. Both of these green veggies are grown in sandy soil. This is why you really need to wash all the leaves three times, draining each time. Even though the packaging makes the leaves look clean, there’s always a certain amount of sand and/or grit left on the leaves, that’s not visible. It ruins a good salad to feel your teeth crunch down on grains of sand or grit. Also, you have no idea who handled the leaves before or during packaging. It means 5 extra minutes of work, to do this washing routine, but it’s worth the time.

 

Even fresh looking greens need to be washed three times and drained in between the washing. Last, dry the leaves with paper towel. ©Joyce Hays, Target Health Inc.

  

Clementines

 

1, 2 or 3, depending on your taste

 

They’re in season now and couldn’t be more sweet and juicy. Simply peel and separate the segments. Use whole segments or cut them in half. Pick out any seeds that’re sticking out, but don’t bother digging into a segment to get them out, unless you feel like doing it.

 

Directions

The Croutons, certainly, can be made the day before and so can the dressing. Otherwise, make croutons first, before you make the dressing. Can you buy packaged croutons? Of course, but try to make them yourself. The flavor is so much better. If you’re going to make a really great salad, you might as well make great tasting croutons. There is simply no comparison! Once you taste the richness of your own croutons, you’ll never buy them again. They’re not a peripheral ingredient, they make the salad better. That’s why they’re in the recipe.

 

1. Preheat oven to 375 degrees.

2. In a medium bowl, add the 2 teaspoons olive oil and the squeezed juice of one fresh garlic clove. Stir

3. Tear or cut any left-over bread, you have, into (1 inch) bite size pieces, enough for 1 cup (press the bread down a bit, in the measuring cup). Then put the pieces of bread, into the bowl with oil/garlic. My favorite bread for croutons is day old (or older) sour dough bread.

4. Now, toss the bread pieces or cubes and be sure that the bread cubes are all covered (as much as possible) with the oil mixture. Let them sit for a while to absorb the oil, like 30 to 60 minutes. Stir them around every once in a while

5. Arrange croutons on a baking sheet or large pan and bake, tossing occasionally, until golden, 10-15 minutes. Watch them carefully. Just a little too long in the oven, and they will burn and won’t be useable for the salad. When golden, remove from oven and set aside to cool.

 

Croutons are about to go into the oven. You can see that some pieces have more oil than others. Doesn’t matter. Once added to the salad, dressing will rub onto the croutons and they’ll be delicious. ©Joyce Hays, Target Health Inc.

 

Out of the oven, crisp, crunchy and delicious; ready to be added to the salad. These are a hundred times better than store-bought. ©Joyce Hays, Target Health Inc.

 

The Dressing

1. Use a medium bowl to make the dressing in.

2. Boil one large egg for one minute and remove from heat after 1 minute. Immediately run the egg under cold water. Then carefully crack it open, so as not to break the yolk. You have to separate the yolk from the egg white and use only the yolk in this recipe. Separate and put the yolk into a small container, ready to use in the dressing. This is a precaution worth taking, to prevent salmonella. Never use a completely raw egg.

 

You’ve got to boil the one egg (for the dressing), for 1 minute and not longer. This is a short cautionary step, so as not to get salmonella. ©Joyce Hays, Target Health Inc.

 

Freshly grated parmesan means doing it yourself. There’s no substitute. Buying a container that reads “freshly grated“ simply is NOT. After a while, you’ll see, there’s something satisfying about doing it yourself. However, if you’re working and raising kids, everyone understands that, so do what you have to do. If kids are old enough, let them share the various steps of a recipe. ©Joyce Hays, Target Health Inc.

 

3. In bottom of salad serving bowl put the garlic and the anchovies. With a fork, mash these two ingredients into a paste

4. Next, with a small whisk, add the egg yolk and whisk it into the garlic/anchovy paste; or continue to use the fork.

5. Now, add the lemon zest, 2 Tablespoons of fresh lemon juice and whisk; then add the mustard and 1 drop of Worchester sauce, whisk again

 

This type of lemon squeezer catches the seeds while letting the juice flow through. ©Joyce Hays, Target Health Inc.

 

6. Next, add the extra virgin olive oil and whisk it into the dressing.

7. Add the canola oil drop by drop, while you whisk it into the dressing.

8. Finally, add the freshly grated parmesan and black pepper (to your taste). Taste to see if the dressing needs more of anything (to your taste). With the anchovies, you may decide not to use any salt. You might want more lemon juice. This is the time to taste and decide. I don’t think you need salt, since the anchovies are salty enough.

9. Whisk the dressing so it’s thick and glossy.

10. When you’re ready to serve, add the greens to the dressing in bottom of salad bowl and toss many times to get each leaf covered with the delicious dressing.

11. Finally, add the croutons and the Clementine segments and toss a few more times, to combine everything.

 

Enjoy!

 

Such a delicious way to get your daily dose of magnesium. ©Joyce Hays, Target Health Inc.

 

Experimenting recently, with Chateauneuf du Pape. So far, not living up to expectations, but will keep you posted as we move forward into this new taste adventure. ©Joyce Hays, Target Health Inc.

 

Have a great week everyone!

 

From Our Table to Yours

Bon Appetit!

 

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