March 23, 2017
Technical University of Munich (TUM)
Scientists have developed a new method that can be used to construct custom hybrid structures using DNA and proteins. The method opens new opportunities for fundamental research in cell biology and for applications in biotechnology and medicine.
Florian Praetorius and Prof. Hendrik Dietz of the Technical University of Munich (TUM) have developed a new method that can be used to construct custom hybrid structures using DNA and proteins. The method opens new opportunities for fundamental research in cell biology and for applications in biotechnology and medicine.
Desoxyribonucleic acid, better known by its abbreviation DNA, carries our genetic information. But to Prof. Hendrik Dietz and Florian Praetorius from TUM, DNA is also an excellent building material for nanostructures. Folding DNA to create three-dimensional shapes using a technique known as “DNA origami” is a long-established method in this context.
But there are limits to this approach, explains Dietz. The “construction work” always takes place outside of biological systems and many components must be chemically synthesized. “Creating user-defined structures in sizes on the order of 10 to 100 nanometers inside a cell remains a great challenge,” he adds. Their newly developed technique now allows the researchers to use proteins to fold double-stranded DNA into desired three-dimensional shapes. Here, both the DNA and the required proteins can be genetically encoded and produced inside cells.
Proteins act as staples
Designed “staple proteins” based on TAL effectors are the key to the method. TAL effectors are produced in nature by certain bacteria that infect plants and are able to bind to specific sequences in the plant DNA, thereby neutralizing the plant’s defense mechanisms. “We’ve constructed variants of the TAL proteins which simultaneously recognize two custom target sequences at different sites in the DNA and then basically staple them together,” says Dietz. “This was exactly the property we needed: proteins that can staple DNA together.”
The second component of the system is a DNA double strand containing multiple binding sequences that can be recognized and linked by a set of different staple proteins. “In the simplest case a loop can be created by binding two points to one another,” Praetorius explains. “When several of these binding sites exist in the DNA, it’s possible to build more complex shapes.” An essential aspect of the researcher’s work was therefore determining a set of rules for arranging the staple proteins themselves and how to distribute the binding sequences on the DNA double strand in order to create the desired form.
New tools for fundamental research
What’s more, the staple proteins serve as anchor points for additional proteins: A method referred to as genetic fusion can be used to attach any functional protein domain desired. The hybrid structures made of DNA and proteins then function as a three-dimensional framework which can put the other protein domains into a particular spatial position. All the building blocks for the DNA protein hybrid structures can be produced by the cell itself and then assemble themselves autonomously. The researchers were able to produce the hybrids in environments resembling cells starting from genetic information. “There is a fairly high probability that this will also work in actual cells,” says Dietz.
The new method paves the way for controlling the spatial arrangement of molecules in living systems, which allows probing fundamental processes. For example, it’s assumed that the spatial arrangement of the genome has a substantial influence on which genes can be read and how efficient the reading process is. The intentional creation of loops using TAL-DNA hybrid structures in genomic DNA may provide a tool for investigating such processes.
It would also be possible to geometrically position a series of proteins inside and outside the cell in custom ways in order to investigate the influence of spatial proximity for example on information processing in the cell. The spatial proximity of certain enzymes could also make processes in biotechnology more efficient. Lastly, it would also be conceivable to utilize protein-DNA hybrid structures for example to better stimulate the immune response of cells, which can depend on the precise geometrical arrangement of multiple antigens.
- F. Praetorius and H. Dietz. Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes. Science, 2017 DOI: 10.1126/science.aaf5488
Source: Technical University of Munich (TUM). “Designer proteins fold DNA: Biophysicists construct complex hybrid structures using DNA and proteins.” ScienceDaily. ScienceDaily, 23 March 2017. <www.sciencedaily.com/releases/2017/03/170323141326.htm>.
Cells in mouse lungs produce most blood platelets and can replenish blood-making cells in bone marrow, study shows
March 22, 2017
University of California – San Francisco
Using video microscopy in the living mouse lung, scientists have revealed that the lungs play a previously unrecognized role in blood production.
Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017 in Nature, the researchers found that the lungs produced more than half of the platelets — blood components required for the clotting that stanches bleeding — in the mouse circulation. In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.
“This finding definitely suggests a more sophisticated view of the lungs — that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said pulmonologist Mark R. Looney, MD, a professor of medicine and of laboratory medicine at UCSF and the new paper’s senior author. “What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”
The findings could have major implications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.
Mouse lungs produce more than 10 million platelets per hour, live imaging studies show
The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-author Matthew F. Krummel, PhD, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.
Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.
“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said Emma Lefrançais, PhD, a postdoctoral researcher in Looney’s lab and co-first author on the new paper.
More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature — estimated at 1 million per mouse lung.
Newly discovered blood stem cells in the lung can restore damaged bone marrow
The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:
First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.
“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, also a postdoctoral researcher in the Looney lab and the paper’s other co-first author. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”
In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation — much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.
Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.
“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” said Looney, who is also an attending physician on UCSF’s pulmonary consult service and intensive care units.
In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.
“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study for Nature. “The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”
The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. “We’re seeing more and more that the stem cells that produce the blood don’t just live in one place but travel around through the blood stream. Perhaps ‘studying abroad’ in different organs is a normal part of stem cell education.”
- Emma Lefrançais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier, Beñat Mallavia, Fengchun Liu, David M. Sayah, Emily E. Thornton, Mark B. Headley, Tovo David, Shaun R. Coughlin, Matthew F. Krummel, Andrew D. Leavitt, Emmanuelle Passegué, Mark R. Looney. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, 2017; DOI: 10.1038/nature21706
Source: University of California – San Francisco. “Surprising new role for lungs: Making blood: Cells in mouse lungs produce most blood platelets and can replenish blood-making cells in bone marrow, study shows.” ScienceDaily. ScienceDaily, 22 March 2017. <www.sciencedaily.com/releases/2017/03/170322143209.htm>.
Chicagoan receives stem cell transplant for CDA
March 20, 2017
University of Illinois at Chicago
Using a technique that avoids the use of high-dose chemotherapy and radiation in preparation for a stem cell transplant, physicians have documented the first cure of an adult patient with congenital dyserythropoietic anemia.
Using a technique that avoids the use of high-dose chemotherapy and radiation in preparation for a stem cell transplant, physicians at the University of Illinois Hospital & Health Sciences System have documented the first cure of an adult patient with congenital dyserythropoietic anemia. CDA is a rare blood disorder in which the body does not produce enough red blood cells, causing progressive organ damage and early death.
The transplant technique is unique, because it allows a donor’s cells to gradually take over a patient’s bone marrow without using toxic agents to eliminate a patient’s cells prior to the transplant.
Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the University of Illinois at Chicago, says the protocol can be used even in patients with a long history of disease and some organ damage because of the minimal use of chemotherapy.
“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant,” said Rondelli, who is also division chief of hematology and oncology and director of the stem cell transplant program at UI Health.
“This procedure gives some adults the option of a stem cell transplant which was not previously available.”
For more than 30 years, Northbrook, Illinois, resident David Levy’s only course of treatment for CDA was regular blood transfusions to ensure his organs and tissues received enough oxygen. Levy was 24 when the pain became so severe he had to withdraw from graduate school.
“I spent the following years doing nothing — no work, no school, no social contact — because all I could focus on was managing my pain and getting my health back on track,” Levy said.
By age 32, Levy required transfusions every two to three weeks; had lost his spleen; had an enlarged liver; and was suffering severely from fatigue, heart palpitations and iron poisoning, a side effect of regular blood transfusions.
“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr. Rondelli.”
Rondelli says that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a stem cell transplant. UI Health’s advances in curing sickle cell patients opened up a new possibility. Rondelli performed Levy’s transplant in 2014.
“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, now 35. “I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”
Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.
Rondelli says the potential of this approach to stem cell transplantation is very promising.
“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias — perhaps the only possible cure,” Rondelli said.
This case report is published in a letter to the editor in the journal Bone Marrow Transplantation.
- A Oh, P R Patel, N Aardsma, S R Mehendale, R Chowdhery, K Sweiss, D Rondelli. Non-myeloablative allogeneic stem cell transplant with post-transplant cyclophosphamide cures the first adult patient with congenital dyserythropoietic anemia. Bone Marrow Transplantation, 2017; DOI: 10.1038/bmt.2017.17
Source: University of Illinois at Chicago. “First patient cured of rare blood disorder: Chicagoan receives stem cell transplant for CDA.” ScienceDaily. ScienceDaily, 20 March 2017. <www.sciencedaily.com/releases/2017/03/170320143831.htm>.
March 20, 2017
University of York
Researchers have developed a mathematical formula based on the rhythmic movement of a sperm’s head and tail, which significantly reduces the complexities of understanding and predicting how sperm make the difficult journey towards fertilizing an egg.
Researchers have developed a mathematical formula based on the rhythmic movement of a sperm’s head and tail, which significantly reduces the complexities of understanding and predicting how sperm make the difficult journey towards fertilizing an egg.
Researchers at the Universities of York, Birmingham, Oxford and Kyoto University, Japan, found that the sperm’s tail creates a characteristic rhythm that pushes the sperm forward, but also pulls the head backwards and sideways in a coordinated fashion.
Successful fertility relies on how a sperm moves through fluid, but capturing details of this movement is a complicated issue.
The team aim to use these new findings to understand how larger groups of sperm behave and interact, a task that would be impossible using modern observational techniques. The work could provide new insights into treating male infertility.
Dr Hermes Gadêlha, from the University of York’s Department of Mathematics, said: “In order to observe, at the microscale, how a sperm achieves forward propulsion through fluid, sophisticated microscopic high precision techniques are currently employed.
“Measurements of the beat of the sperm’s tail are fed into a computer model, which then helps to understand the fluid flow patterns that result from this movement.
“Numerical simulations are used to identify the flow around the sperm, but as the structures of the fluid are so complex, the data is particularly challenging to understand and use. Around 55 million spermatozoa are found in a given sample, so it is understandably very difficult to model how they move simultaneously.
“We wanted to create a mathematical formula that would simplify how we address this problem and make it easier to predict how large numbers of sperm swim. This would help us understand why some sperm succeed and others fail.”
By analysing the head and tail movements of the sperm, researchers have now shown that the sperm moves the fluid in a coordinated rhythmic way, which can be captured to form a relatively simple mathematical formula. This means complex and expensive computer simulations are no longer needed to understand how the fluid moves as the sperm swim.
The research demonstrated that the sperm has to make multiple contradictory movements, such as moving backwards, in order to propel it forward towards the egg.
The whip-like tail of the sperm has a particular rhythm that pulls the head backwards and sideways to create a jerky fluid flow, countering some of the intense friction that is created due to their diminutive sizes.
Dr Gadêlha said: “It is true when scientists say how miraculous it is that a sperm ever reaches an egg, but the human body has a very sophisticated system of making sure the right cells come together.
“You would assume that the jerky movements of the sperm would have a very random impact on the fluid flow around it, making it even more difficult for competing sperm cells to navigate through it, but in fact you see well defined patterns forming in the fluid around the sperm.
“This suggests that to achieve sperm stirs the fluid around in a very coordinated way locomotion, not too dissimilar to the way in which magnetic fields are formed around magnets. So although the fluid drag makes it very difficult for the sperm to make forward motion, it does coordinate with its rhythmic movements to ensure that only a few selected ones achieve forward propulsion.”
Now that the team has a mathematical formula that can predict the fluid movement of one sperm, the next step is to use the model for predictions on larger numbers of cells. They also believe that it will have implications for new innovations in infertility treatment.
- Kenta Ishimoto, Hermes Gadêlha, Eamonn A. Gaffney, David J. Smith, and Jackson Kirkman-Brown. Coarse-graining the fluid flow around a human sperm. Physical Review Letters, March 2017
Source: University of York. “Mystery of how sperm swim revealed in mathematical formula.” ScienceDaily. ScienceDaily, 20 March 2017. <www.sciencedaily.com/releases/2017/03/170320085505.htm>.
Conference: eSource Data in Clinical Investigations – May 2-3, 2017 – Doubletree Center City, Philadelphia, Pa
Target Health Inc. is pleased to announce that Dr. Jules Mitchel will be presenting at CBI’s 4th Annual Bootcamp on eSource Data in Clinical Investigations. The conference aims to initiate meaningful dialogues, through collaborative sessions and investigative case studies, around early successes, challenges and failures, so that one can build an eSource adoption business case for senior leadership addressing balance of risk and cost.
Dr. Mitchel’s presentation is entitled: “The Future is Now: How to Obtain Stakeholder Buy-in and Initiate the Migration to eSource.” In this case study, you will learn how eSource reduced monitoring and increased overall data quality, as well as how to convince stakeholders to invest in eSource. You will also learn of the current challenges of interoperability between EHR and eSource and what the long-term strategy looks like in moving away from EDC as we know it today.
Please Mention Promo Code: NCE547 for a $500 discount when you register at the conference www.cbinet.com/esource.
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.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
The city of Jerusalem in Israel. Source: Avraham Graicer, copyright holder, hereby publish it under the Creative Commons license, Wikipedia
A bizarre mental illness that affects people visiting Israel is called Jerusalem Syndrome.
There are a lot of events, that can make a visitor feel dazed and confused, when traveling–delayed flights, missing luggage, clumps of tasteless airline food. But for some people who travel can actually induce a rare psychosis–especially if their destination is 1) ___. Tourists afflicted with the condition called Jerusalem Syndrome have been found wandering in the Judean desert wrapped in hotel bed sheets or camped in front of the Church of the Holy Sepulcher, convinced they will soon be birthing the infant Jesus.
Jerusalem Syndrome has been described by foreign visitors over the last few hundred years. Because he was the first to promote treatment and research for this disease, Dr. Bar-El who works at Kfar Shaul Hospital in Jerusalem is considered the father of Jerusalem 2) ___. Bar-El says that there are three categories of tourists who get Jerusalem fever. The first is individual visitors to Israel, who were already mentally ill in their countries of origin. They come to Jerusalem with psychotic ideas that they feel they must act upon in the Holy 3) ___. The second group–the largest one – consists of pilgrims who arrive with deep religious convictions. In some cases, they belong to fringe groups rather than regular churches. They believe they must do specific things to bring about major events like the coming of the Messiah, the appearance of the anti-Christ, the war of Armageddon, or the resurrection of Jesus Christ. The third group is the REAL Jerusalem Syndrome. It affects completely sane tourists without any psychiatric or drug abuse history. They arrive with normal tour groups and suddenly they develop what Bar-El called a specific imperative psychotic reaction. In all cases, the same clinical picture emerges. It begins with generalized 4) ___ and nervousness and then the tourist feels an imperative need to visit the holy places. First, he/she undertakes a series of purification rituals like shaving all body hair, cutting nails and washing over and over before donning white clothes. Most often, such a tourist, removes the white sheets from the hotel room. Then (s)he begins to cry or to sing Biblical or religious songs in a very loud voice. The next step is an actual visit to the holy places, most often from the life of Jesus. The afflicted tourist begins to deliver a sermon–which is frequently a confused oration, exhorting humanity to change their behavior by becoming calmer, purer, and less sophisticated or worldly.
Dr. Bar-El, said that from a 5) ___ point of view, the most interesting aspect is that in addition to this curious psychotic reaction, the patient doesn’t see strange things or hear voices, and recalls everything that happens. They know who they are; they don’t lose their own identity, and the illness passes completely in five to seven days. Sometimes, the afflicted visitor is on a package tour of the Mediterranean which includes Greece, Egypt and Israel. They may be completely sane in Greece, develop Jerusalem Syndrome in Israel, it passes in five days, and then they continues on with the group to Egypt. From a religious point of view, the Syndrome seems to favor Protestants, who account for 97% of all cases. Their current religious practices aren’t very important; the essential element seems to be an ultra-orthodox upbringing where the 6) ___ was the book of choice for family reading and problem solving. Several theologians who are fascinated by Jerusalem Syndrome speculate that Catholics have intermediaries like the Virgin Mary and saints. They also have other geographical locales that are important to them, like the Vatican, which is presided over by the 7) ___. But for Protestants, the only personification in the Bible is Jesus Christ, and the Holy Land is the only place where they can go to follow his life. Hence, they are very focused on Jesus and this sets the stage for the advent of the strange, temporary Holy Land aberration. Although the whole problem of Jerusalem Syndrome may seem like a benign curiosity, it is taken very seriously in Israel where everyone involved in security, tourism, or health and welfare is on the lookout for afflicted visitors. In an average year, about 40 tourists require hospitalization for psychiatric illness. Most are from the first two groups, who had severe problems before they arrived in Israel. A few–perhaps 3 or 4–develop true Jerusalem Syndrome.
Dr. Bar-El said that a woman was picked up by the police for kicking and hitting people at the Church of the Holy Sepulcher, proclaiming, I am the Prophetess of the Olive Tree, and I am very powerful, and I will announce the coming of Christ. She was in a very anxious state, and she insisted she had to remain outdoors, under the influence of the sun and the moon so that her branches could grow green, which was a sign of the immediate return of Jesus. If she was moved inside, under a roof, her branches would grow black, and that would be a sign of the anti-Christ. Besides these claims and her aggressive behavior, everything else about the Olive Tree Prophetess was completely normal. Another seemingly normal man was a teacher from Denmark. Apparently, every year he comes to Jerusalem because only there can he dialogue with the Virgin Mary. Lourdes and other miraculous sites have not had the same effect on him. Bar-El talked about a memorable case which actually led to one of the first instances of collaboration between Palestinian and Israeli police. The Palestinians found a man without clothes, money or ID, and, after interrogation, they figured out he wasn’t a security risk. They had no idea what to do with him, so they contacted an Israeli officer. The Israeli asked only one question: Is the guy really completely nude? No, answered the Palestinian, he is wearing an animal skin. Oh, said the Israeli, you’ve got another John the Baptist. It was the sixth John the Baptist the Israelis had run into. As in the Bible, John the Baptist conducted days of purification between Jerusalem and Galilee before ending up at the Jordan River to baptize Jesus and/or the first Christians. Part of the trek was through 8) ___ territory. John the Baptist heads the Jerusalem Syndrome list for Christian men. Christian women prefer the Virgin Mary. For Jews of both genders, the identification is generally with the Messiah.
At one point, Dr. Bar-El decided to perform a classical experiment. He put two would-be Messiahs in a room together to see if one would prevail. The experiment was a dismal failure because after the meeting each said, I am the real Messiah. He’s an impostor. Dr. Gregory Katz, a Russian psychiatrist, works in the units where Jerusalem Syndrome patients are brought and treated. According to Dr. Katz, who works with Jerusalem Syndrome patients, they are basically unremarkable. Their treatment can include anything from melatonin for jet-lag to minor tranquilizers to anti-psychotic drugs. Dr. Katz says that his Jerusalem hospital is equipped to treat tourists in many different languages, although no one in the unit has mastered Norwegian. He explained that the age of the afflicted, ranges from l8 to 70, and the mean age is 35. Most of the patients have higher education and not all of them are connected to religious institutions, although many are. A very timely medical health issue is that Jerusalem Syndrome poses an economic problem for Israel. Some people who fall ill, come from countries where medical insurance is provided for all citizens and they are covered for their treatment. However, tourists from the U.S.A., often don’t have any 9) ___ coverage. The Israeli government must pay for their treatment, their hospital stay and then, if they are long-term patients who were ill before they arrived in Israel, the government must also provide a psychiatric escort to return them home. This has placed a drain on Israeli resources.
No one is certain about exactly what causes Jerusalem Syndrome. It has been posited that it can be very jarring for a serious Bible student to arrive in modern-day Israel where, instead of prophets in sandals, he hears businessmen discussing profits on cell phones. Another theory is that Jerusalem has always been a huge backdrop for delivering messianic messages and visitors can get temporarily carried away by the dramatic historic setting. For the moment, there are no clear 10) ___ and the emphasis is on rapid and effective diagnosis and treatment. Source: Psychology Today (Judith Fein)
ANSWERS: 1) Jerusalem; 2) Syndrome; 3) Land; 4) anxiety; 5) psychiatric; 6) Bible; 7) Pope; 8) Palestinian; 9) medical; 10) answers
Kfar Shaul Mental Health Center in Jerusalem
Psychiatric hospital Kfar Shaul In Jerusalem – Source: Wikipedia, Public Domain, Creative Commons
Kfar Shaul Mental Health Center, established in 1951, is an Israeli public psychiatric hospital located between Givat Shaul and Har Nof, Jerusalem. It is affiliated with the Hadassah Medical Center and the Hebrew University of Jerusalem. The hospital is Jerusalem’s designated psychiatric hospital for tourists who display mental health disturbances, and is widely known for its research on Jerusalem Syndrome.
The Givat Shaul mental health center opened in 1951, utilizing the houses and school building of Deir Yassin, which had been left untouched. It was originally a therapeutic community of 300 patients who spent most of the day working outdoors. It was called the Kfar Shaul Government Work Village for Mental Patients. In its early years, the majority of the patients were Holocaust survivors.
The hospital is equipped with Snoezelen rooms, a Dutch therapy technique which uses controlled stimulation of the five senses to benefit the mentally and physically disabled. The hospital is known in particular for its association with Jerusalem Syndrome, a condition in which the sufferer is gripped by religious delusions. The hospital sees some 50 patients a year who are diagnosed with the condition Israel psychologist Gregory Katz has said many of the patients are Pentecostals from rural parts of the United States and Scandinavia. The syndrome was first diagnosed in 1993 by Yair Bar-El, a former director of the hospital. In 2000, archaeologists unearthed the remains of a winepress dated to the Byzantine or Roman era on the grounds of the hospital.
The Shaare Zedek Medical Center, which means: “Gates of Justice,” is a major hospital in Jerusalem, Israel established in 1902. Source: Wikipedia, Public Domain, Creative Commons
Original, 1902 Shaare Zedek hospital building on Jaffa Road, now headquarters of the Israel Broadcasting Authority. Source: Wikipedia, Creative Commons
Shaare Zedek was the first large hospital to be located in the Western portion of Jerusalem and is today the city’s fastest growing hospital and the only major medical facility in the city’s center. After the Ottoman Turks gave permission in the 1890s, and with funding from European donors, the hospital was built on Jaffa Road, two miles (3 km) outside the Old City. Its opening ceremony took place on January 27, 1902. Dr. Moshe Wallach was the director from then until 1947. Schwester Selma lived in the hospital and cared for abandoned children. The building in Bayit Vegan was inaugurated in 1980. In December 2012, Shaare Zedek assumed operational control over Bikur Cholim Hospital and merged many of its activities. The hospital treats over 600,000 patients per year in more than 30 inpatient departments and over 70 outpatient units and maintains a very active academic service as a leading research and teaching institution. Shaare Zedek is classified as a public/private hospital, serving as a non-profit institution and dependent on donor support for capital development, while committed to offering advanced medical care for the wider Jerusalem-area community.
African-Specific Genomic Variant Associated With Obesity
Obesity is a global health problem, contributing to premature death and morbidity by increasing a person’s risk of developing diabetes, hypertension, heart disease and some cancers. While obesity mostly results from lifestyle and cultural factors, including excess calorie intake and inadequate levels of physical activity, it has a strong genomic component. The burden of obesity is, however, not the same across U.S. ethnic groups, with African-Americans having the highest age-adjusted rates of obesity. Interestingly, most of the genomic studies conducted on obesity to date have been in people of European ancestry, despite an increased risk of obesity in people of African ancestry.
According to an article published online the journal Obesity (13 March 2017), an international team of researchers has conducted the first study of its kind to look at the genomic underpinnings of obesity in continental Africans and African-Americans. The study discovered that approximately 1% of West Africans, African-Americans and others of African ancestry carry a genomic variant that increases their risk of obesity, a finding that provides insight into why obesity clusters in families. Results from the study showed that people with genomic differences in the semaphorin-4D (SEMA4D) gene were about six pounds heavier than those without the genomic variant.
This is the first study to use a Genome-Wide Association Study (GWAS) to investigate the genomic basis of obesity in continental Africans. A GWAS compares the genomes of people with and without a health condition – in this case, people who are obese and those who are not — to search for regions of the genome that contain genomic variants associated with the condition. Most previous studies on obesity using a GWAS have been conducted with populations of European ancestry; these studies wouldn’t have found the SEMA4D genomic variant, which is absent in both Europeans and Asians.
According to the authors, by studying people of West Africa, the ancestral home of most African-Americans, and replicating our results in a large group of African-Americans, new insights are now available into biological pathways for obesity that have not been previously explored. The authors added that these findings may also help inform how the African environments have shaped individual genomes in the context of obesity risk.
The authors plan to replicate these findings in more populations and conduct experiments using cell lines and model organisms such as zebrafish to identify the role of genomic variants in SEMA4D in obesity and obesity-related traits. (The SEMA4D gene plays a role in cell signaling, the immune response and bone formation.) Available data show that the newly identified genomic variant overlaps a region of DNA called an “enhancer“ that can be activated to increase the work of a particular gene. The authors plan to conduct larger studies of DNA sequencing of this gene in different human populations with the hope of identifying other genomic factors that may be associated with obesity. The overall goal of the program is to learn how to better prevent or treat obesity.
Impaired Glucose Homeostasis in First-Episode Schizophrenia
Schizophrenia is associated with an increased risk of type 2 diabetes. However, it is not clear whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term treatment. As a result, a study published in JAMA Psychiatry (2017;74:261-269) conducted a meta-analysis examining whether individuals with first-episode schizophrenia already exhibit alterations in glucose homeostasis compared with controls.
For the study, the EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining measures of glucose homeostasis in antipsychotic-naive individuals with first-episode schizophrenia compared with individuals serving as controls. Study selection included case-control studies reporting on fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in first-episode antipsychotic-naive individuals with first-episode schizophrenia compared with healthy individuals serving as controls. Two independent investigators selected the studies. Two independent investigators extracted study-level data for a random-effects meta-analysis. Standardized mean differences in fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and HbA1c levels were calculated. Sensitivity analyses examining the effect of body mass index, diet and exercise, race/ethnicity, and minimal (<2 weeks) antipsychotic exposure were performed.
Results showed that of the 3,660 citations retrieved, 16 case-control studies comprising 15 samples met inclusion criteria. The overall sample included 731 patients and 614 controls. Fasting plasma glucose levels (P=0.03), plasma glucose levels after an oral glucose tolerance test (P=0.007), fasting plasma insulin levels (P=0.01), and insulin resistance (homeostatic model assessment of insulin resistance) (P=0.001) were all significantly elevated in patients compared with controls. However, HbA1c levels (P=0.55) were not altered in patients compared with controls.
According to the authors, the findings show that glucose homeostasis is altered from illness onset in schizophrenia, indicating that patients are at increased risk of diabetes as a result. The authors added that this finding has implications for the monitoring and treatment choice for patients with schizophrenia.
Helping to Speed Cures and Treatments to Patients
The FDA is committed to helping deliver innovative, safe, and effective treatments and cures to the patients who need them as quickly as possible. To achieve this goal, FDA has implemented a variety of expedited review programs and are working to help shorten the development time before a product is even submitted for FDA review.
As a result of these efforts, in 2014 alone, FDA approved 51 new molecular entities and biological products (41 by the Center for Drug Evaluation and Research and 10 by the Center for Biological Evaluation and Research). These approvals included major therapeutic advances in the treatment of cancer, hepatitis C and type-2 diabetes. They also included vaccines for meningococcus type B, and more new orphan drugs for rare diseases than any previous year.
FDA has also made strides with medical devices. As a result of activities coordinated by CDRH Innovation, and programmatic improvements and innovative use of our existing approval and clearance pathways, many devices investigated in the United States now reach the market a full year sooner than they did at the beginning of this decade. Products recently approved or cleared by FDA include the BrainPort V100, a first-of-its-kind wearable device that can help orient profoundly blind individuals to their physical surroundings; Watchman LAA Closure Technology, a permanently implanted device that prevents certain clots from entering the bloodstream and potentially causing a stroke; and the Maestro Rechargeable System to treat obesity in certain adult patients (it targets the nerve pathway between the brain and the stomach that controls feelings of hunger and fullness).