Lung Cancer Genome Surveys Find Many Potential Drug Targets.

Five new studies have identified genetic and epigenetic alterations in hundreds of lung tumors, including many changes that could be targeted by drugs that are already available or in clinical testing.

The reports, all published this month, included genomic information on more than 400 lung tumors. In addition to confirming genetic alterations previously tied to lung cancer, the studies identified other changes that may play a role in the disease. (Links to the study abstracts appear in the sidebar below.)

“These five papers are the first major salvo of genome-wide studies using all of the newest technologies to analyze a large number of lung cancers,” said Dr. John Minna, a clinician and lung cancer researcher at the University of Texas Southwestern Medical Center, who co-authored one of the studies.

Collectively, the studies covered the main forms of the disease—lung adenocarcinomas, squamous cell cancers of the lung, and small cell lung cancers.

Although preliminary, the findings could be used to develop molecular markers for identifying patients who are candidates for certain targeted drugs. At the same time, researchers in the lab can now evaluate the newly discovered changes to identify novel potential therapeutic targets.

“All of these studies say that lung cancers are genomically complex and genomically diverse,” said Dr. Matthew Meyerson of Harvard Medical School and the Dana-Farber Cancer Institute, who co-led several of the studies, including a large-scale analysis of squamous cell lung cancer by The Cancer Genome Atlas (TCGA) Research Network.

Some genes, Dr. Meyerson noted, were inactivated through different mechanisms in different tumors. He cautioned that little is known about alterations in DNA sequences that do not encode genes, which is most of the human genome.

Squamous Cell Tumors

The TCGA investigators sequenced the genomes or exomes (the protein-coding regions of DNA) of tumor samples from 178 patients with squamous cell lung cancer. In more than half of the tumors examined, the researchers found a change to a gene or a signaling pathway that is targeted by a drug that exists or is in development. The findings were reported in Nature on September 9.

“This gives us an enormous opportunity for progress in this disease,” said Dr. Meyerson.

The TCGA model integrates genomic data for squamous cell lung cancers with clinical information, when available, and with other tumor characteristics, such as gene expression, epigenetic changes to cells, and alterations in the number of gene copies.

“The framework for these five studies was built on a convergence of new technologies and the need to better understand the biology of lung cancers as it relates to new therapies for our patients,” said Dr. Paul Paik, who treats patients with lung cancer at Memorial Sloan-Kettering Cancer Center and was part of the clinical team involved in TCGA.

Small studies (for example, here and here) have provided hints that certain signaling pathways are important in squamous cell lung cancers, leading to new trials of targeted drugs. “Now, with the publication of the TCGA study, we know that squamous cell lung cancers have a myriad of potentially targetable changes,” Dr. Paik noted.

An unexpected finding was the presence of mutations in the EGFR gene in about 1 percent of squamous cell tumors. These tumors might respond to available drugs that block signals through the EGFR pathway.

The researchers also found evidence of genetic changes that may help lung cancer cells evade surveillance by the immune system.

The Five Studies

Testing Lung Tumors

Any therapeutic targets to emerge from the new reports would need to be incorporated into molecular tests that can identify candidates for certain drugs. A leader in this work is the Lung Cancer Mutation Consortium, which has been building knowledge of the mutations associated with the disease and testing for these changes.

Many patients with lung adenocarcinomas have benefited from targeted drugs. Crizotinib (Xalkori), for instance, has elicited some dramatic responses in patients whose tumors harbor a particular gene fusion. Some medical centers now routinely test tumors before selecting treatment for patients with lung adenocarcinomas.

“If you look at lung cancer as a whole, the big therapeutic targets were first identified in adenocarcinomas,” Dr. Minna explained. “Now there are new targeted therapies that could make an impact on squamous cell lung cancer.”

At Memorial Sloan-Kettering, all patients with squamous cell lung cancer have their tumors tested for drug targets using various techniques, including DNA sequencing. Among 28 of these patients evaluated recently, more than 60 percent had tumors that contained a potential target.

Dr. Paik noted that his group will use the TCGA results to expand their testing. “In a sense, the future potential of this new work is being realized now,” he said. “That’s pretty exciting.”

Small Cell Lung Cancer

Two new reports describe genetic changes in small cell lung cancers, which tend to be aggressive and about which little has been known. The research teams conducted exome or whole-genome sequencing on a total of 82 samples of such tumors.

“This study gave us a host of new targets to explore,” said Dr. Charles Rudin of the Johns Hopkins Kimmel Cancer Center, who led one study. The next steps will be to validate which targets are driving the growth of tumors and are “druggable,” he added.

The researchers found that a gene called SOX2, which plays a role in normal development, may contribute to some small cell lung cancers, as well as other cancers, and could be targeted.

Small cell lung cancers have been challenging to study because most are not treated surgically, so tumor samples are rare. What’s more, these tumors have high rates of genetic mutations due to tobacco smoke, yet only some mutations are driving the disease, noted Dr. Roman Thomas of the University of Cologne in Germany, who led the other study.

Using statistical “filters,” his group found that genes involved in modifying histone proteins, which help package DNA within a cell, were frequently mutated in the disease.

“These cancers are extraordinarily complex, so as researchers our steps forward are incremental—but, still, they are steps,” Dr. Thomas noted. “No one would have imagined that lung cancer would be the prototypical disease for targeted medicine.”

Comparing Tumors in Smokers and Nonsmokers

Non-small cell lung cancers were the focus of two additional studies, which appeared in Cell. One group sequenced the exomes or genomes of 183 tumor samples, and the other conducted whole-genome sequencing of tumor tissues from 17 smokers and nonsmokers.

“We found a substantially lower number of mutations in the genomes of tumors from nonsmokers compared to the smokers,” said Dr. Ramaswamy Govindan of the Washington University School of Medicine in St. Louis, MO, who led the study. Five study participants who had never smoked had a mutation that could be targeted by an existing drug.

All these studies show how diverse and how complicated the cancer genome is. But we now have a panoramic view of the genomic landscape, and this is important for moving forward in this disease.

—Dr. Ramaswamy Govindan

In all, the study authors found 54 genes with potentially targetable alterations in the 17 patients.

“The days of large clinical trials for lung cancer are over,” Dr. Govindan said, noting that patients need to be selected for specific treatments based on the characteristics of their tumors. “We also need to develop clinical trials that move targeted therapies to earlier stages of lung cancer, where we have a better chance of a cure.”

Future clinical trials, he predicted, would look for relatively large effects of drugs in selected patients. Dr. Minna agreed, saying, “If the effects are not there, we will move on to the next target and the next drug.”

The new results are really a teaser for what’s coming. TCGA plans to sequence a total of 500 adenocarcinomas and 500 squamous cells tumors. These results could help shed light on issues such as epigenetic changes in lung cancer, mechanisms of drug resistance, and how tumors are influenced by the surrounding tumor microenvironment.

“All these studies published back to back show how diverse and how complicated the cancer genome is,” Dr. Govindan said. “But we now have a panoramic view of the genomic landscape, and this is important for moving forward in this disease.”

Dr. Minna added, “After treating thousands of patients with lung cancer and not doing too well, I am very excited about the new results.”

Source: NCI

Drug Targeting Tumor Suppressor Shows Promise in First Human Study.

An experimental drug that reactivates mutant forms of the tumor suppressor protein p53 is safe for humans, according to results from a phase I trial. The drug, APR-246, also stimulated signaling pathways that control p53 in tumor cells isolated from peripheral blood.

The study, published in the Journal of Clinical Oncology, was led by Dr. Sören Lehmann of Karolinska University Hospital in Stockholm.

The findings represent “a major step forward in targeting the most frequently altered pathway in cancer,” wrote Drs. Brian D. Lehmann and Jennifer A. Pietenpol of Vanderbilt University School of Medicine in an accompanying article.

The p53 protein suppresses tumor growth by increasing the expression of genes that slow the cell cycle, that prevent cells from dividing, or that cause programmed cell death (apoptosis). At least half of all tumors develop inactivating mutations in TP53, the gene that produces p53, allowing the tumor to evade this regulation. APR-246 counteracts TP53 mutations by restoring the gene-regulatory activity of mutant p53 protein and by inducing the death of cancer cells.

The 22 participants enrolled in the trial had various forms of leukemia, hormone-refractory metastatic prostate cancer, non-Hodgkin lymphoma, or multiple myeloma. These patients were included because prostate cancers have a high rate of TP53 mutations and because, in preclinical studies, leukemia cells were particularly sensitive to drugs that target p53.

The patients received intravenous infusions of APR-246 for 4 consecutive days. After a follow-up period of 17 days, the most common side effects were fatigue, dizziness, headache, and confusion.

While the trial was not designed to assess the drug’s antitumor effects, several patients showed clinical responses. To investigate the biologic activity of APR-246, Dr. Lehmann and his colleagues analyzed circulating tumor cells obtained before and after the 4-day treatment from the six patients who had these cells. Four of these patients had fewer proliferating cells after receiving APR-246. The investigators also observed signs of apoptosis and increased expression of several p53 target genes.

Microarray analysis of RNA isolated from the circulating tumor cells showed changes in genes responsible for regulating cell growth and death. The level of expression of genes that promote apoptosis appeared to correlate with the dose of APR-246.

Trials are being designed to investigate the effects of higher exposures to APR-246 through longer infusion times and of combining APR-246 with other chemotherapy drugs, most of which depend on a functional version of p53 to be effective.

Source: NCI

New Drug Improves Survival in Patients with Advanced Lung Cancer.

Patients with advanced lung cancer who received the drug bavituximab lived twice as long as trial participants who did not receive the drug. These results , from a phase II trial, were presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology. Peregrine Pharmaceuticals, Inc., the drug’s manufacturer, sponsored the trial.

Bavituximab is a monoclonal antibody that targets a molecule called phosphatidylserine (PS) that is found in the membranes of cells throughout the body, including those that line blood vessels. In normal cells, PS is restricted to the inside of cell membranes, where it is inaccessible to antibodies. Under certain conditions, like those found in the stressful tumor microenvironment, PS moves to the outer surface of the cell membrane, explained the study’s principal investigator, Dr. David Gerber of the University of Texas Southwestern Medical Center. In the case of tumor blood vessels, this means that PS is exposed and accessible to antibodies in the blood.

Laboratory studies have shown that bavituximab can trigger the destruction of tumor blood vessels. The drug may also work by harnessing the immune system. Tumors supplied by blood vessels with exposed PS can evade an immune response. That’s because exposed PS normally marks cells that are in the process of dying, so the immune system ignores them. The researchers hoped to learn whether bavituximab, by binding to PS, would signal to the immune system to attack tumor blood vessels with exposed PS, explained Dr. Gerber.

In the double-blind, placebo-controlled trial, the researchers randomly assigned 117 patients to one of three treatment groups: docetaxel (Taxotere) plus placebo, docetaxel plus a low dose of bavituximab, or docetaxel plus a higher dose of bavituximab. All patients had previously received initial chemotherapy. The trial was unblinded 18 months after the first patient was enrolled.

The results showed differences in tumor shrinkage (15 and 18 percent of patients in the low and high bavituximab groups had their tumors shrink, versus 8 percent of those receiving docetaxel plus placebo) and progression-free survival (about 4.5 months in the two bavituximab arms, versus 3 months with docetaxel plus placebo).

The greatest differences were for overall survival; patients receiving docetaxel plus placebo lived an average of 5.6 months from the start of treatment, whereas patients receiving docetaxel plus the low or high dose of bavituximab lived for an average of 11 and 13 months, respectively.

These survival differences are not likely due to differences in treatment received after the trial, Dr. Gerber noted. Seeing a larger improvement in overall survival than in progression-free survival is unusual for drugs that target cancer cells directly, he added. Because the improvement in survival with bavituximab “is persistent and most pronounced after a few months,” that suggests that the therapeutic benefit may be caused, at least in part, by an immune response, he said.

The researchers are planning a phase III trial of bavituximab in a larger group of lung cancer patients. Bavituximab is also being tested in combination with other treatments in patients with breast, rectal, liver, and prostate cancer.

Source: NCI



Changing Social Norms about Tobacco Use, One Campus at a Time

As the Assistant Secretary for Health, I have the honor of advancing a broad portfolio of public health issues on behalf of the Department of Health and Human Services (HHS). An overriding priority is reinvigorating our national commitment to tobacco control. The first-ever HHS Strategic Action Plan for Tobacco Control, entitled Ending the Tobacco Epidemic: A Tobacco Control Strategic Action Plan, commits the department to mobilizing leadership to encourage proven, pragmatic, and achievable interventions at the federal, state, and community levels.

Among other things, the action plan commits to reducing the initiation of tobacco use among young adults, a topic with special relevance to institutions of higher learning. Furthermore, the 31st Surgeon General’s Report on Tobacco, released in March, highlighted some startling statistics pertinent to this goal. Preventing Tobacco Use among Youth and Young Adults notes that 90 percent of all smokers start before age 18, and 99 percent start before age 26. Of concern, progression from occasional to daily smoking frequently occurs during the initial years following high school. Indeed, the number of smokers who initiated smoking after age 18 has increased substantially over the past decade—from 600,000 in 2002 to 1 million in 2010.

The report cites reasons for these disturbing trends. Tobacco industry expenditures related to marketing, promotion, and advertising of tobacco products exceed $1 million per hour—totaling more than $27 million a day. Targeted messages and images portray tobacco use as a desirable and appealing activity. As a result, smoking represents the current social norm in many movies, video games, websites, and communities, thereby promoting a culture that fosters tobacco dependence and disease.

Restoring the social norm to one that, instead, promotes wellness and health requires a commitment to smoke-free and tobacco-free environments.

The Affordable Care Act, the health care law of 2010, is also part of our comprehensive approach toward turning this goal into reality. Most health plans must now cover—without cost-sharing—tobacco-use screening and interventions for tobacco users. The law also makes it easier and more affordable for young adults to get health insurance coverage, by allowing them to stay on their parents’ employer-sponsored or individually purchased health plans.

Smokefree Teen, a website specifically developed to help teen smokers quit, offers several social media pages to connect teens with cessation tools.

In particular, colleges and universities can take the next step in protecting the health of their students and inspiring change through the adoption of smoke-free and tobacco-free campuses.

To launch a new chapter in ending the epidemic of smoking, I was honored to participate last week in the announcement of the Tobacco-Free College Campus Initiative(TFCCI). The University of Michigan School of Public Health in Ann Arbor hosted the September 12 event, which was webcast to nearly 500 attendees across the country. The TFCCI represents a public/private partnership involving key leaders from universities, colleges, and the public health community to promote the adoption of tobacco-free policies at institutions of higher learning. This landmark public health initiative will protect students, staff, and faculty against involuntary exposure to secondhand smoke while encouraging a change in social norms that can help reduce tobacco use.

To date, more than 700 colleges and universities, representing an estimated 17 percent of institutions of higher learning nationwide, have committed to smoke-free or tobacco-free campus policies.

HHS is pleased to recognize the leadership of institutions that promote public health in this way. Such actions exemplify a key pillar of the tobacco control action plan—“leading by example.” In fact, by adopting a tobacco-free campus policy on July 1, 2011, HHS has already joined the ranks of such institutions leading by example. This action now protects the health of our 80,000 employees who work in dozens of buildings, grounds, and facilities across the country.

It is my hope that the launch of the TFCCI will encourage all institutions of higher learning to take action. It is time for us to end the epidemic leading to the single most preventable cause of death in this nation.

Together we can make smoking history.

Dr. Howard K. Koh
Assistant Secretary for Health
U.S. Department of Health and Human Services

Source: NCI.

Study Reveals How Breast Cancer Spreads to Lymph Nodes.

A recent study offers new insights into how breast cancer may spread to nearby lymph nodes and also suggests that a drug commonly used to treat heart failure, digoxin, may be able to interrupt the process. The findings were reported September 10 in the Proceedings of the National Academies of Sciences (PNAS).

The lymphatic system is an important route through which cancer cells reach the circulatory system and travel to distant organs, where they develop into metastatic tumors. Metastasis—which is responsible for most cancer deaths—is not well understood, and few treatments actively target it. In breast cancer, nearly all women with metastatic disease have lymph node involvement.

Using mice, Dr. Gregg Semenza of Johns Hopkins University and his colleagues showed that hypoxia-inducible factor-1 alpha (HIF-1α) plays a direct role in the spread of breast cancer cells to the lymph nodes. HIF-1 α is a subunit of the HIF-1 protein, which promotes blood vessel formation under low-oxygen conditions, such as those in tumors. HIF-1α, the researchers found, activates the PDGF-B gene, which codes for platelet-derived growth factor (PDGF-B).

When mice with tumors formed from injected human breast cancer cells were treated with digoxin (which inhibits HIF-1α) or with imatinib (Gleevec; which inhibits PDGF-B), cancer cell spread was dramatically reduced.

In addition, mice with tumors formed from breast cancer cells that were genetically modified to block production of HIF-1α had 75 percent fewer lymph node metastases than mice with tumors formed from unmodified breast cancer cells.

In biopsy samples from human breast cancers, the authors also found that

  • PDGF-B was highly active in cells that were starved of oxygen,
  • HIF-1α directly activated transcription of PDGF-B,
  • the HIF-1α and PDGF-B proteins were found near each other in almost all of the biopsy samples they studied, and
  • levels of expression of these proteins in biopsy samples correlated with tumor grade.

Other studies have linked HIF-1α and PDGF-B to metastatic spread. “But this is the first time that anybody has connected all the dots in a single cancer,” Dr. Semenza explained.

Later this year, the Hopkins researchers plan to launch an early-phase clinical trial to test digoxin in women with operable breast cancer, Dr. Semenza said. Digoxin, an off-patent drug, will be given for about 2 weeks before surgery, and the researchers will analyze pre- and post-surgical tumor samples to determine whether the drug is inhibiting HIF-1 and its downstream target genes.

If the trial suggests that the drug is having the intended molecular effects, an early-phase trial combining digoxin with other standard treatments would likely be launched.

Source: NCI




Diagnostic Radiation Exposure May Raise Breast Cancer Risk in Some BRCA1/2 Mutation Carriers.

Radiation from conventional x-rays, mammograms, and other diagnostic tests before age 30 may increase the risk of breast cancer in women who carry BRCA1 or BRCA2 gene mutations. In a large, retrospective cohort study, this increased risk was seen at radiation doses considerably lower than those associated with increased risk of breast cancer in other cohorts exposed to radiation.

The findings, from an analysis of women in France, the Netherlands, and the United Kingdom who participated in the GENE-RAD-RISK study, were reported September 6 in the British Medical Journal.

Exposure to ionizing radiation is an established risk factor for breast cancer, particularly when the exposure occurs at an early age. Because the BRCA1 and BRCA2 proteins are important in repairing DNA damage, including damage caused by radiation, researchers have hypothesized that carriers of a mutation in one of these genes might be more sensitive than the general population to ionizing radiation. But previous studies designed to answer this question have yielded inconsistent results.

The new study, led by Dr. Flora van Leeuwen of the Netherlands Cancer Institute in Amsterdam, focused on 1,122 women aged 18 or older who were known to carry a BRCA1 or BRCA2 mutation. The women reported their histories of all diagnostic procedures involving radiation to the chest or shoulders. Researchers used this information to estimate the cumulative dose of radiation to the breast for each woman. They then used national registries or medical records to confirm breast cancer diagnoses among the participants.

When compared with no exposure, any exposure to diagnostic radiation before age 30 was associated with almost double the risk of breast cancer in BRCA1/2 mutation carriers. Women who received the highest doses of radiation before age 30 had an almost fourfold higher risk. By contrast, there was no evidence of an increased breast cancer risk associated with exposure at ages 30 to 39.

Because women with BRCA1 or BRCA2 mutations have a greatly increased risk of developing breast cancer, some guidelines recommend annual mammograms beginning at age 25 to 35 for these women.

These findings “support the recommendation to use non-ionising radiation imaging techniques (such as MRI) as the main tool for surveillance in young BRCA1 and BRCA2 mutation carriers,” the authors concluded.

Dr. Barry Kramer, director of NCI’s Division of Cancer Prevention, noted that the study “helps refine our knowledge” about the connection between radiation exposure and breast cancer risk in people who may be particularly sensitive to the effects of ionizing radiation. However, he cautioned, “the evidence in this study is not definitive.”

The authors acknowledge that their reliance on self report of prior radiation exposure could introduce statistical bias. “People who have cancer may be more likely than those without cancer to recall any radiation that they had,” Dr. Kramer explained.

Until more definitive evidence is available, he continued, “Women who carry BRCA1 or BRCA2 mutations ought to know what we do and don’t know.” Physicians should review the screening and prevention options with each woman and help her consider the potential benefits and downsides of each, he concluded.

Source: NCI




Measuring Aerosol Production from Patients with Active TB.

Twenty-eight of 101 patients with culture-confirmed pulmonary tuberculosis had culture-positive cough aerosols, suggesting infectiousness; likelihood of a culture-positive aerosol was directly correlated with degree of sputum-smear positivity.

Although tuberculosis (TB) is transmitted by aerosols of droplet nuclei <5 µm in diameter, determination of infectiousness has been based on microscopic examination of sputum for the presence of organisms (smear assessment) — a method that may be neither sensitive nor specific. The magnitude and particle-size distributions of the aerosols generated by patients with active TB are unknown.

In a study conducted in Uganda, researchers attempted to collect, quantify, and size the aerosols produced by voluntary coughing in patients with active pulmonary TB and to compare these findings with results from sputum smears and aerosol cultures. Patients with culture-confirmed TB were asked to cough in two 5-minute sessions into a custom-built chamber that analyzed and collected their cough aerosol. Plates within the chamber contained 7H11 agar for mycobacterial culture.

Among the 101 patients, 28 produced aerosols that grew Mycobacterium tuberculosis. The proportion of patients who generated culture-positive aerosols increased significantly as the sputum smear microscopy grade increased (P=0.03). All patients with a culture-positive aerosol were smear positive; none of those with a negative smear produced a culture-positive aerosol. More than 96% of the culturable particles collected were between 0.7 and 4.7 µm in diameter.

Comment: Although the authors conclude that cough aerosols might provide a better determination of infectiousness than smear assessment, the data indicate that smear results correlate well with aerosol culture results.

Source: Journal Watch Infectious Diseases

Pharma’s Image Problem.

Practicing internists accurately assess the methodological rigor of clinical trials but discount the findings of those that are industry-funded.

As clinicians peruse published clinical research, what factors affect the likelihood that they will believe the results? To address this question, investigators enlisted 269 board-certified internists (among 503 who were approached) to read abstracts of hypothetical clinical drug trials and to provide their assessment of the trial methods, their confidence in the results, and their willingness to prescribe the drugs. Each participant evaluated three scenarios — involving imaginary drugs for the treatment of hyperlipidemia, diabetes, and angina — with randomly selected combinations of two variables: methodological rigor (low, medium, or high) and disclosure of funding status (none, funding by NIH, or funding by a pharmaceutical company with financial involvement of the lead author).

A strong, direct association was found between methodological rigor and physician perception of study quality. The physicians also had more confidence in — and were more willing to prescribe the study medications from — the studies with stronger methods. By contrast, participants were less likely to consider studies to be rigorous, to have confidence in them, and to prescribe a medication based on their results if pharmaceutical companies funded them. Of the three types of disclosure, NIH funding elicited the greatest confidence and was the most likely to change practice.

Comment: These internists demonstrated a keen understanding of study methods, aptly discriminating among different studies based on design. They were also alert to funding, tending to give more credit to NIH-funded studies than to industry-funded ones. The author of an accompanying editorial decries this tendency, but events of the past have apparently given rise to skepticism among doctors. Pharmaceutical companies might instill more trust by more-systematic efforts to share data and methods.

Source:Journal Watch Cardiology


10 More Amazing Things About Our Bodies.

Your body truly is amazing, and we’ve only scratched the surface as far as discovering all of the mysteries of its extremely complex capabilities and inner workings.

The featured article highlighted 10 particularly noteworthy facts you may not be aware of, but which are utterly fascinating about your body.

10 Amazing Human Body Facts

10. You Can’t Swallow and Breathe at the Same Time

Virtually every other mammal can; however, human babies can only until they’re about 9 months old. Around this time the voice box drops quite low in the neck compared to other animals, which allows us to have a wide range of sounds for speech – but takes our ability to breathe and eat or drink at the same time.

9. You Have Two Brains

Just as you have neurons in your brain, you also have neurons in your gut – including neurons that produce neurotransmitters like serotonin, which is also found in your brain and is linked to mood. Your gut literally serves as your second brain, and even produces more of the neurotransmitter serotonin – known to have a beneficial influence on your mood – than your brain does.

In other words, you have two nervous systems: the central nervous system, composed of your brain and spinal cord, and the enteric nervous system, which is the intrinsic nervous system of your gastrointestinal tract. Both are actually created out of the same type of embryonic tissue. During fetal development, one part turns into your central nervous system while the other develops into your enteric nervous system.

To put this into more concrete terms, you’ve probably experienced the visceral sensation of butterflies in your stomach when you’re nervous, or had an upset stomach when you were very angry or stressed. The flip side is also true, in that problems in your gut can directly impact your mental health, leading to issues like anxiety, depression, and perhaps even more serious neurodevelopmental disorders such as autism.

8. Loneliness is Physically Painful

Loneliness is emotionally painful for sure, but it’s physically painful as well. In fact, both loneliness and physical pain are processed in the same region of your brain, the anterior cingulate cortex. So just as you have a powerful drive to avoid causing physical pain to your body, you have a similarly powerful drive to connect with others and seek companionship – in order to avoid painful feelings of loneliness.

7. You Salivate More Before You Vomit

…And there’s a very good reason for this. Because stomach acid can be harsh on your throat and mouth, the extra saliva helps dilute the acid and rinse it away to minimize any damage caused by vomiting.

6. Sugar Can Help Your Wounds Heal

Not by eating it, of course, but rather by sprinkling it directly on the wound. Sugar is hygroscopic, which means it absorbs water that bacteria need to survive. This method has been popular among healers in Africa for generations, and it is reportedly useful for bed sores, leg ulcers, amputations and more.

A twist on this idea is to use honey, which will help draw fluid away from your wound and suppress the growth of microorganisms. Part of what gives honey its antibacterial properties is an enzyme called glucose oxidase, which the worker bees excrete into the nectar (this is found only in raw honey). Another part is the presence of beneficial Lactobacillus bacteria, found only in raw honey, which fight infection.

5. Memories Work in Mysterious Ways

Have you ever walked into a room and then forgotten why you went there in the first place? This is because your brain perceives the doorway as an “event boundary,” and memories from the room you just left are “stored” there for when you need them. This is why when you go back through the doorway into the prior room you can often remember what it is that you forgot!

4. Some Women See More Colors

Most people have three types of color receptors that allow them to see color vision. Some women have four, however, which allows them to see a wider range of colors than the average person (a small percentage of women even have five color receptors). Why women? The red and green color receptors, which can be shifted to allow for a greater range of color vision, are located on the X chromosome; blue is on the Y.

3. It Might be Healthy to Eat Boogers

Your nasal mucus might be host to small amounts of contaminants (acting as antigens) that may actually “educate” and boost your immune system when they’re consumed. So contrary to the belief that eating boogers could make you sick, it might actually help your body to fight off illnesses.

2. Most People Only Breathe Through One Nostril at a Time

Though you’ve got two nostrils, about 85 percent of people only use one at a time. But, erectile tissue in your nose slowly swells the tissue in one nostril while shrinking it in the other, so you automatically switch breathing between nostrils about every four hours.

Interestingly, body position, illness and other factors can influence which nostril you breathe from when, and, in turn, the nostril you’re breathing from can impact your health. For instance, breathing through the right nostril causes you to use more oxygen and raises your blood sugar levels.

1. Seven Miles of New Blood Vessels for Every Pound of Fat Gained

When you gain a pound of fat, your body makes seven new miles of blood vessels. This means your body must work harder to pump blood through all of these extra new vessels, which may put a strain on your heart, and may reduce oxygenation and nutrient replenishment in other tissues. Fortunately, if you lose a pound, your body will break down and re-absorb the now unnecessary vessels.

Source: By Dr. Mercola

Effect of restricted pacifier use in breastfeeding term infants for increasing duration of breastfeeding.

It is well recognized that breast milk is superior to formula feeding in providing balanced nutrition, protection against allergy and infection in newborns; and several Cochrane Reviews have investigated ways to promote and prolong breastfeeding. As a consequence, it is widely recommended that babies should be exclusively breastfed for up to the first six months of their lives and there are concerns that the use of a pacifier (a non-nutritive sucking device to calm an infant) might be a barrier to this. For example, the World Health Organization’s Ten Steps to Successful Breastfeeding recommends that pacifiers should not be given to breastfeeding infants. However, their use is relatively widespread and they have become a cultural norm in many parts of the world with a belief that they are harmless or, potentially, necessary and beneficial for an infant’s development.

This updated Cochrane Review, published in July 2012, sets out to identify and present the evidence that might resolve this uncertainty, by assessing the effect of unrestricted versus restricted pacifier use in healthy full-term newborn babies whose mothers initiated breastfeeding with the intention of exclusively breastfeeding. The outcomes of primary interest for the review relate to the duration of breastfeeding, with secondary outcomes including breastfeeding difficulties experienced by the mother, maternal satisfaction and level of confidence in parenting, infant crying and fussing, and infants’ health. However, the included studies did not provide data for analyses of these secondary outcomes.


The authors relied mainly on the Cochrane Pregnancy and Childbirth Group’s Trials Register to identify studies for the review. This comprehensive register has been compiled over two decades and includes regular searches of the Cochrane Central Register of Controlled Trials, the MEDLINE bibliographic database and dozens of journals relating to maternity care. The eligibility criteria for the review sought randomised and quasi-randomised trials in which an intervention with unrestricted use of pacifiers was compared with one in which there were restrictions on the use of pacifiers, in healthy full-term babies, for whom breastfeeding had been started. However, because of the potential for bias, if more than one in five of the randomized participants had been excluded from the final analyses, the trial was deemed ineligible. This was the case with one of the three potentially eligible studies identified. This had randomized 602 babies to either a group in which bottles, teats and pacifiers were to be avoided (with any medically indicated supplements to be administered by cup or spoon) or a group in which pacifiers were offered to all babies without restriction and supplements were conventionally offered by bottle after breastfeeding. In this trial, which was conducted in Switzerland, nearly 40% of the babies in the first group were excluded due to protocol violation in the first week, most of which related to the used of bottles or pacifiers, and further babies were lost from the other group and from the overall follow-up, leading to its exclusion from the review on the grounds of high attrition.

The other two eligible trials that were identified could be included in the meta-analyses of some of the primary outcomes, contributing data from a total of 1302 babies. The larger of these studies recruited just over 1000 women from five centres in Argentina, who were highly motivated to breastfeed. They were randomly assigned to a group given a pack of silicone pacifiers, a written guide and advice to use other pacifiers if they wished (528 babies) or to a group that were given a guide with alternative strategies for a crying baby. The other trial, from a single hospital in Canada, recruited a total of 281 healthy breastfeeding women who had given birth to a healthy singleton baby at term. They were randomly allocated to one of two counselling interventions, provided by a trained research nurse. In one group (140 babies), the mother was asked to avoid pacifier use when the infant cried or fussed and to offer her breast first and then to try carrying or rocking the infant if this proved unsuccessful. The other 141 mothers and babies were in a group where all options for calming the infant were discussed, including pacified use, along with breastfeeding, carrying and rocking.

The results of these two studies could be combined in a meta-analysis of the proportion of babies who were exclusively breastfed at three months of age. This showed no significant difference between the babies in the pacifier-use and the pacifier-avoidance groups, with a risk ratio (RR) of 0.99, and a 95% confidence interval (CI) running from 0.93 to 1.05. The larger study also provided data on exclusive breastfeeding at four months, and the result was similar (RR: 0.99; 95% CI 0.92-1.06).

The authors of the Cochrane Review conclude that pacifier use in healthy term breastfeeding infants with motivated mothers, did not significantly affect the prevalence or duration of exclusive and partial breastfeeding up to four months of age. They recommend that until further information becomes available on the effects of pacifiers on the infant, mothers who are well motivated to breastfeed be enabled to make a decision on the use of a pacifier based on personal preference. The authors suggest that further research should explore additional outcomes, such as the rate of breastfeeding difficulties experienced by mothers associated with pacifier use and the long-term effect of pacifier use on mother and infant health; as well as examining the effects on breastfeeding when the parents are less motivated than those in the trials included in the review.

Sourece: Cochrane Library