European drugs regulators approve world's first malaria vaccine

European drugs regulators have voiced their approval for the world's first malaria vaccine, representing a major step toward prevention of a disease that kills more than half a million people worldwide every year - most of whom are children in Africa.
A syringe on an African map
The EMA recommend the RTS,S vaccine against malaria be given to children in Africa aged 6 weeks to 17 months.
After assessing the quality, safety and efficacy of the vaccine - called RTS,S (brand name Mosquirix) - the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) conclude it should be used for immunization of children in Africa aged 6 weeks to 17 months, alongside other protective measures against malaria - such as insecticides and bed nets.

The CHMP recommendation is the first step toward RTS,S becoming the first licensed vaccine for malaria. Later this year, independent advisory groups from the World Health Organization (WHO) will review evidence for the vaccine and decide whether to recommend its use.

Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted to humans through the bite of Anopheles mosquitoes.

The most deadly malaria parasite is Plasmodium falciparum, which the RTS,S vaccine targets. The vaccine works by inducing an immune response in the body when P. falciparum first enters the bloodstream, preventing the parasite from infecting and multiplying in the liver.

There were an estimated 198 million cases of malaria around the globe in 2013 and around 584,000 deaths from the disease. Around 90% of these deaths occurred in Africa, mostly among children under the age of 5 years.

At present, the only effective preventive measures against malaria in Africa are the use of artemisinin-based combination therapies (ACTs) - which need to be administered within 24 hours of fever onset - and insecticides and bed nets to prevent mosquito bites.

If licensed, however, the RTS,S vaccine - manufactured by British pharmaceutical company GlaxoSmithKline (GSK) - would be used alongside existing malaria-prevention strategies; in clinical trials, the vaccine has not proved effective enough to be used alone.

RTS,S would provide 'meaningful contribution' to controlling malaria burden
Earlier this year, Medical News Today reported on the results of a phase 3 clinical trial for RTS,S, which were published in The Lancet.

The trial involved 15,459 infants and 6-12 weeks and children aged 5-17 months from 11 sites across seven sub-Saharan countries, including Ghana, Kenya, Malawi and Mozambique.

Initial trial results revealed that among participants aged 5-17 months who received three doses of RTS,S, a 46% drop in malaria cases was observed in the 18 months following, while infants aged 6-12 weeks saw a 27% reduction in malaria cases.

The researchers then followed participants for a further 20-30 months after administering a booster vaccine 18 months after the third dose.

The 3-dose RTS,S regime plus the booster vaccine was found to reduce the number of malaria cases by 39% among children aged 5-17 months over a total of 4 years follow-up, while a 27% fall in malaria cases was found over 3 years of follow-up among infants aged 6-12 weeks.

Importantly, the trial results show that without a booster vaccine, the effect of RTS,S wanes over time. In addition, the absence of a booster jab impairs the vaccine's ability to reduce cases of severe malaria.

Because RTS,S does not offer complete protection against malaria, the CHMP say "It is important that established protective measures, for example, insecticide-treated bed nets, continue to be used in addition to the vaccine."

Still, it is estimated that in areas of sub-Saharan Africa with the highest malaria burden, RTS,S could prevent more than 6,000 malaria cases for every 1,000 children vaccinated.

Scientists discover first 'DNA ambulance'

U of T researchers have discovered how severely damaged DNA is transported within a cell and how it is repaired.

It's a discovery that could unlock secrets into how cancer operates -- a disease that two in five Canadians will develop in their lifetime.

"Scientists knew that severely injured DNA was taken to specialized 'hospitals' in the cell to be repaired, but the big mystery was how it got there," said Karim Mekhail, a Professor in the Faculty of Medicine's Department of Laboratory Medicine and Pathobiology. "We've now discovered the DNA 'ambulance' and the road it takes."

Mekhail discovered this DNA ambulance, which is a motor protein complex, by using yeast cells. His research was recently published in Nature Communications.

Mekhail's team also found that the DNA hospital, also known as the nuclear pore complex, repairs damaged DNA inaccurately.

This inaccurate fix is important because DNA contains the instructions for all our genetic information. While the repaired DNA can still replicate, it has irregular cell instructions -- a scenario that could cause cancer.

"This process allows cells to survive an injury, but at a great cost," said Mekhail. "The cell has a compromised genome, but it's stable and can be replicated, and that's usually a recipe for disaster."

Co-author Daniel Durocher, Senior Investigator at Mount Sinai's Lunenfeld-Tanenbaum Research Institute, helped the team track the damaged DNA in living cells by using advanced microscopy. The tracking showed that this DNA ambulance is necessary for damaged DNA to efficiently change location within the nucleus.

"Cancer often occurs when our chromosomes break and are misrepaired," said Durocher. "This work teaches us that the location of the break within the cell's nucleus has a big impact on the efficiency of repair."

The implications of the research could extend to a large number of developmental and disease settings.

"The processes we're studying are fundamental to the basic survival of a cell," said graduate student and first author Daniel Chung. "Almost every aspect of disease can be linked to problems with DNA."

Now Mekhail's team is searching for more DNA ambulances and roads while conducting a study to see what role they might play in causing cancer. "We expect that this may allow us to identify targets for a new class of anti-cancer drugs."

"Scientists have been searching for this DNA ambulance for a long time and now we suspect there may be more than one," said Mekhail. "It's exciting because it's a whole new area of research."

Source:UNIVERSITY OF TORONTO

TOPLESS plants provide clues to human molecular interactions

Scientists at Van Andel Research Institute (VARI) have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.-

In plants as in animals and humans, intricate molecular networks regulate key biological functions, such as development and stress responses. The system can be likened to a massive switchboard--when the wrong switches are flipped, genes can be inappropriately turned on or off, leading to the onset of diseases.

Now, VARI scientists have unraveled how an important plant protein, known as TOPLESS, interacts with other molecules responsible for turning genes off. The findings in plants provide a general model across species for this type of gene silencing, which is linked to several vital biological functions in humans. The discovery was published today in Science Advances.

"This is really a fundamental discovery--our structure shows the corepressor TOPLESS interacting with key repressor motifs, which constitutes a major component of gene silencing in plants," said Van Andel Research Institute's Karsten Melcher, Ph.D., one of the study's corresponding authors. "Understanding this interaction in plants gives us unique insight into similar pathways in humans that involve these proteins, which are notoriously tough to investigate."

Using a method called X-ray crystallography, the team determined the three- dimensional structure of TOPLESS, both on its own and when linked with other molecules responsible for turning genes off, thereby regulating gene expression. Although these interacting molecules were chosen from different signaling pathways in plants, they all linked up with TOPLESS in the same manner

"This structure will allow us to take a more targeted approach to investigating TOPLESS's counterparts in humans and significantly expands our knowledge base," said VARI's H. Eric Xu, Ph.D., who also is a corresponding author. "We're extremely excited to continue this work to better understand these proteins and how they interact with other molecules in health and disease states."

The new paper is the third in a trio of publications that unveil key components of fundamental molecular processes. Although the new study provides further insight into human molecular pathways, the work also directly describes how components of the molecular switchboard in plants interact to regulate responses to a multitude of stressors, including temperature fluctuations. The new findings follow an earlier Nature paper, which was included in the top ten list of scientific breakthroughs of 2009 by Science magazine, and an earlier Science paper, both of which describe how plants respond to drought and temperature stress. Taken together, the papers not only have implications for developing hardier plants but also for determining molecular structures for components of entire pathways.

Authors include Jiyuan Ke, Honglei Ma, and Xin Gu of VARI and VARI-Shanghai Institute of Materia Medica; Jiayang Li of the Chinese Academy of Sciences; Joseph S. Brunzelle of Northwestern University; and Adam Thelen, now at Michigan State University.

Source:VAN ANDEL RESEARCH INSTITUTE

Protein Molecule That Accumulates in Blood Over the Years Linked to Cognitive Decline

Aging is associated with a progressive decline in cognitive function, and slower regeneration of message-relaying neurons in the brain. A protein molecule, called B2M, that accumulates in the blood with age may be linked to cognitive decline, revealed scientists who mooted hopes of a memory-restoring treatment. They observed that the protein was found in higher concentrations in the blood and cerebral spinal fluid of aging humans. Also in mice, inhibiting B2M improved learning and memory in laboratory experiments.

 Study co-author Saul Villeda of the University of California San Francisco said, "We are very excited about the findings because it indicates that there are two ways to potentially reverse age-related cognitive impairments. One is to introduce pro-youthful blood factors and the other is to therapeutically target pro-aging factors like B2M." 

The authors said, "Aging remains the most dominant risk factor for dementia-related neurodegenerative diseases, such as Alzheimer's disease. As such, it is imperative to gain mechanistic insight into what drives aging. In the brain in order to counteract vulnerability to cognitive dysfunction. B2M injections impaired the learning ability, memory, and neuron growth of lab mice. But the effect was reversible by stopping the injections." 

Villeda said, "In another experiment, the scientists eliminated B2M genetically in mice, and observed that the old mice lacking B2M did not develop memory loss. This all implied the molecule could be targeted to potentially restore cognitive ability in the elderly." 

The research is published in the Nature Medicine.

Source: AFP

 

Researchers identify plant cultivation in a 23,000-year-old site in the Galilee

The Middle East is called the "Cradle of Civilization" because it is where our hunter-gatherer ancestors first established sedentary farming communities. Recently, the traditional dating of humans' first agricultural attempt was shaken up by the discovery of the earliest-known example of plant cultivation in the Levant, 11,000 years earlier than previously accepted.

The team of archaeologists, botanists, and ecologists from Bar-Ilan University, Haifa University, Tel Aviv University, and Harvard University published their work in the scientific journal Plos One on July 22, 2015. The team's conclusions rest on three inter-connected findings, says the study's lead researcher, Prof. Ehud Weiss of Bar-Ilan University's Martin (Szusz) Department of Land of Israel Studies and Archaeology. First is the higher-than-usual presence at the site of domestic-type, rather than wild-type, wheat and barley dispersal units. Second, the researchers noted a high concentration of proto-weeds - plants of the type known to flourish in fields planted with domesticated crops. Finally, analysis of the tools found at the site revealed blades used for cutting and harvesting cereal plants.

First author is Dr. Ainit Snir, part of whose doctoral research - conducted in Prof. Weiss' lab - is included in the present study.

An Agricultural "Time Capsule" Hidden Under the Sea

The researchers' discovery was made at Ohalo II, a 23,000-year-old camp site of a community of hunter-gatherers that lived on the shore of the Sea of Galilee, Israel. The site is located 9 kilometers (5.5 miles) south of the modern city of Tiberias, and was discovered in 1989 when the level of the lake plummeted. The site was then excavated for six seasons by Prof. Dani Nadel from the Zinman Institute of Archaeology, the University of Haifa. Excavations at Ohalo II exposed six brush hut dwellings, a human grave, copious and well-preserved remains of both animal and plant foods, beads from the Mediterranean Sea, as well as evidence of flint tool manufacture and use.

According to Weiss, the study represents the earliest example of small-scale cultivation found anywhere in the world.

"The plant remains from the site were unusually well-preserved because of being charred and then covered by sediment and water which sealed them in low-oxygen conditions," Weiss explains. "Due to this, it was possible to recover an extensive amount of information on the site and its inhabitants - which made this a uniquely preserved site, and therefore one of the best archaeological examples worldwide of hunter-gatherers' way of life. Here we see evidence of repeated sowing and harvesting of later domesticated cereals."

From Plant Gathering to Flour Production

In the Ohalo II dwellings was a particularly rich assemblage of some 150,000 plant remains, showing that the site's residents gathered over 140 different plant species from the surrounding environment. Among these, Weiss's team identified edible cereals - such as wild emmer, wild barley, and wild oats. These cereals were mixed with 13 species of "proto-weeds" - ancient ancestors of the current weeds known to flourish in cultivated, single-crop fields - indicating that they grew and were subsequently unintentionally gathered together.

A grinding slab set firmly on a brush hut floor, a stone tool from which microscopic cereal starch granules were extracted, as well as a unique distribution pattern of seeds around this tool, provided additional, unequivocal evidence that cereal grains were brought into the hut and processed into flour. This flour was probably used to make dough, maybe by baking it on an installation of flat stones, found just outside one of the shelters.

Plants' Statistics Show Genetic Change Linked with Cultivation

Examination of the cereals found at the site shows an unusual percentage of domesticated-type, rather than wild-type, ear morphology. As Weiss explains, this change in the plant population is characteristic of a genetic mutation triggered when wild-type plants are sown repeatedly in cultivated fields.

"The ears of cereals like wheat and barley - in their wild form - are built from separate units that break off and are easily dispersed, allowing the seeds to reach the ground, germinate, and grow into a new plant without any human intervention," he says. "When humans cultivate these grains over a number of successive seasons, however, a change occurs. They develop a rough scar that locks the seed dispersal units together. Such plants cannot sow themselves. This is the hallmark of domesticated, rather than wild-type plants."

As part of Snir's thesis, Weiss and Snir undertook field tests around Israel, establishing that stands of wild-type barley are characterized by a low level of this rough-scar appearance - about 10% of the total population. The study of Ohalo II's plant remains, however, revealed a greatly-increased incidence of 36% mutated domestic-type disarticulation units - proving that planned cereal sowing and harvesting in this ancient community had been underway for years.

Tools for Harvesting

Another intriguing finding relates to a number of sickle blades - harvesting tools composed of sharp flint implements inserted in wood or bone handles - found at the site; these are among the oldest of their kind ever found.

"We found several sickle blades at Ohalo II, and the study under the microscope of the gloss along their cutting edge indicates that they were used for harvesting cereals just before their complete ripening," says Prof. Dani Nadel. "Analysis showed the presence of silicon, transferred from the wheat and barley plants at the time of cutting. This is another indication that the presence of a high percentage of domestic-type cereals was not random, but rather is a sign of the long-term cultivation practices of the site's residents."

Weeds and Planted Fields

When studying the plants found at Ohalo II, the researchers were surprised to find a large number of plants similar to weeds previously seen only 11,000 years later than Ohalo II, at the traditional date for the beginning of agriculture. Does this indicate that agriculture indeed began much earlier than historians, archaeologists and botanists have traditionally believed? Weiss says that the isolated example on the shores of the Sea of Galilee is an insufficient basis for such a claim.

"From what we see at Ohalo II, it is clear that cultivation occurred at this surprisingly early point in time, but we have no evidence that it continued in the region," Weiss says. "This is why we term our findings to be evidence of trial cultivation only. Moreover, since weeds are defined by botanists as plants that developed in response to human agriculture, we call the plants that share characteristics with weeds 'proto-weeds'."

A Trial that Preceded Later-Adopted Practice

Prof. Marcelo Sternberg, a co-author of the paper who is an ecologist at the Department of Molecular Biology and Ecology of Plants at Tel Aviv University, claims that the findings are exceptional. "We are witnessing the earliest trial of cultivation combined with land-use changes that led to the appearance of the earliest weeds. The findings are a clear indication of early human disturbance of the natural ecosystem."

Weiss agrees, adding that the current study provides reason to rethink our ancestors' abilities. "Even prior to full-scale cultivation, humans clearly had some basic knowledge of agriculture and even more importantly, exhibited foresight and planning," Weiss says. "The current research results from this site, situated in the cradle of ancient civilizations, show our ancestors were cleverer and more skilled than we had assumed. Although full-scale agriculture did not develop until much later, the attempt had already begun."

Paper co-author Prof. Ofer Bar-Yosef, a prehistorian from Harvard University's Department of Anthropology, notes that "the history of the evolution of technology is littered with new inventions that were either not accepted by their society or simply failed. An historical example is Leonardo da Vinci, who, in his notebooks, designed several flying machines during the early 15th century. Even though da Vinci was on the right track, we had to wait until the 19th century before the Wright brothers got their first plane off the ground."

Source:BAR-ILAN UNIVERSITY

Preventing knee pain in at-risk adults with diabetes

Knee pain in older adults, often caused by osteoarthritis, usually means more visits to the doctor and also can be a harbinger of disability.

A study led by Daniel White, assistant professor of physical therapy at the University of Delaware, found that an intensive regimen of regular exercise and a healthy diet might reduce the short-term onset of knee pain for overweight adults with Type 2 diabetes mellitus.

Published in Arthritis Care and Research, White's article "Can an Intensive Diet and Exercise Program Prevent Knee Pain Among Overweight Adults at High Risk'' was an editor's pick in the journal's July issue and was named as a key study for 2015 at the Osteoarthritis Society's international meeting.

Because old age and obesity are major risk factors for knee osteoarthritis, researchers asked whether an intensive program of weight loss combined with exercise could prevent the onset of knee pain among this cohort.

"Prior to this study, we did not have empirical data to support the claim that diet and exercise actually worked to prevent knee pain," White said. "Now we do have a study."

The study compared subjects receiving intensive lifestyle intervention (ILI) to a comparison group receiving standard diabetes mellitus support and education (DSE), measuring knee pain at the end of one year and four years.

White and his colleagues conducted a secondary analysis of the Action for Health in Diabetes (Look AHEAD) study, a randomized intervention of trial adults ages 45 to 76 years who were obese and had Type 2 diabetes mellitus that started in 2001.

"The analysis involved a subcohort of 2,889 subjects who reported no knee pain at baseline, but were at high risk due to obesity," White said.

The primary method of achieving weight loss was caloric intake restrictions, based on guidelines from the American Diabetes Association. The diet limits total calories from fat to 30 percent while mandating at least 10 percent of calories to be obtained from protein.

Intervention for exercise relied heavily on unsupervised exercise at home, with a gradual progression to 175 minutes per week of moderate to vigorous physical exercise.

For most participants, the study notes, this activity consisted of brisk walking, with moderate-intensity walking encouraged as a primary type of physical activity.

"We did not study people in the general population, but only adults who were diabetic and overweight," White said. "Among those we studied who were randomized to the diet and exercise intervention, it was found that they were 15 percent less likely to develop knee pain compared with their counterparts randomized to the control condition."

The study found that an intensive program of diet and exercise had a small but statistically significant protective effect against the development of knee pain in the short term among overweight adults with diabetes, White said.

At the four-year mark, this difference decreased to five percent and was no longer statistically significant. The study notes that this decrease might be a consequence of participants not being able to stay with the prescribed diet and exercise regimen over the four-year period.

"These findings are very important," White said. "They demonstrate that the recommendations to exercise and diet do make a difference for preventing the development of knee pain among those who are at high risk."

Knee pain is the most common type of chronic lower body pain among middle to older aged adults and is responsible for more disability than any other chronic condition in this age range, White said.

The University's Physical Therapy Clinics treat many individuals in this age group with recently developed knee pain, both with and without Type 2 diabetes mellitus, White said.

"I study physical activity among people with knee arthritis," White said. "I felt it was important to investigate whether exercise combined with diet did in fact protect against the development of knee pain."

Source:UNIVERSITY OF DELAWARE

Chemically Modified Nucleotides Could Be Used for Specific Killing of Cancer Cells

Recycled DNA building blocks are cancer's Achilles heel. Normal cells have highly selective mechanisms to ensure that nucleosides - the chemical blocks used to make new strands of DNA - don't carry extra, unwanted chemical changes, finds Ludwig Cancer Research scientists.
 

But they also found that some types of cancer cells aren't so selective. These cells incorporate chemically modified nucleosides into their DNA, which is toxic to them. The findings indicate that it might be possible to use modified nucleotides for specific killing of cancer cells. Lead author Skirmantas Kriaucionis said that they sought to find out what happens to these modified bases when DNA is recycled, and were excited that their biochemical analysis uncovered "loopholes," which could hopefully be exploited for intervention in cancer. 

Exploiting the unexpected killing of cancer cells by epigenetically modified nucleotides demonstrated in a model system that modified nucleotides can be used as a specific anti-cancer agent. Kriaucionis said that it has been suggested that CDA inactivates cytidine analogues that were already used in the clinic to treat some blood and pancreatic cancers. In a strikingly reverse scenario, the nucleosides that they used in their study were relatively harmless until they encountered CDA, which converted them into hostile cytotoxic agents. 

The researchers will likely continue to investigate this new avenue for "epigenetic" drugs as cancer therapies. The study is published in the journal Nature.

Source: ANI
 

Indian Health Ministry Proposes Health Schemes for the Welfare of Rural Children

In an official release under the Rural Health Mission, the Ministry of Health and Family Welfare gave details of the provision of health care to children particularly in rural areas.
 The release disclosed that under Janani Shishu Suraksha Karyakaram (JSSK) all pregnant women who deliver in public health institutions will be absolutely free and no charges to be levied even for Caesareans.

Facility Based Newborn Care (FBNC) at different levels to reduce newborn morbidity and mortality by setting up of facilities for care of sick and small newborn such as Special New Born Care Units (SNCUs), Newborn Stabilization Units (NBSUs) and Newborn Care Corners (NBCCs) at different levels is a thrust area under NHM. Home Based New Born Care (HBNC) through ASHAs has been initiated to improve newborn practices at the community level and early detection and referral of sick newborn babies. 

Newer interventions to reduce newborn mortality- Vitamin K injection at birth, Antenatal corticosteroids for preterm labor, Kangaroo Mother Care and injection Gentamicin to young infants in cases of suspected sepsis have been rolled out. Management of severe acute malnutrition in children is being done at Nutritional Rehabilitation Centers (NRCs) which have been established across the country. Village Health and Nutrition Days (VHNDs) are organized for imparting nutritional counseling to mothers and to improve child care practices. 

Mother and Child Tracking System (MCTS) a name based Mother and Child Tracking System has been put in place which is web based to ensure registration and tracking of all pregnant women and newborn babies so that provision of regular and complete services to them can be ensured. Rashtriya Bal Swasthya Karyakram (RBSK) for health screening and early intervention services has been launched to provide comprehensive care to all the children in the age group of 0-18 years in the community. The purpose of these services is to improve the overall quality of life of children through early detection of birth defects, diseases, deficiencies, development delays including disability. 

Capacity building of health care providers through various training is being conducted under NHM to train doctors, nurses and ANMs for essential newborn care, early diagnosis and case management of common ailments of children. Universal Immunization Program (UIP) covers about 13.5 crore children for vaccination against seven vaccine preventable diseases, through 90 lakh immunization sessions each year. Mission Indradhanush, launched on 25th December, 2014, seeks to achieve 90% full immunization coverage of India by year 2020. 

The objective of Mission Indradhanush is to ensure high coverage of children with all vaccines in the entire country with a high focus on the 201 identified districts. It is proposed to conduct four special vaccination campaigns between March and June 2015 with intensive planning and monitoring of these campaigns covering all children up to two years of age and pregnant women for tetanus toxoid vaccine. 

To sharpen the focus on vulnerable and marginalized populations in underserved areas, 184 High Priority Districts have been identified across the country for accelerating implementation of Reproductive Maternal Newborn Child Health+ Adolescent (RMNCH+A) interventions for achieving improved maternal and child health outcomes.

Source: ANI

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