Category Archives: Research

The Impact of Tuberculosis Preventive Therapy on Tuberculosis and Death in HIV-Infected Children

By Aleesha Ye

Tuberculosis (TB) is a contagious disease that is mainly an infection of the lungs. It is caused by a bacterial microorganism called the tubercle bacillus or Mycobacterium tuberculosis. The problem with this disease is that scientists have never come close to wiping it out, making it one of the most distressing disease as it continues to claim many lives. One big concern is that children with HIV are at a higher risk of acquiring TB. Tuberculosis can cause acute and chronic respiratory disease and death in HIV-infected children, especially ones who live in places with high TB prevalence. Scientists are looking to find solutions to prevent the infection and disease in HIV-infected children. One potential solution is an anti-tuberculosis medication called Isoniazid, so two scientists set out to test this solution.


Scientists Young Gray and Zar Cotton set out to determine the impact of TB preventive therapy on incidence and death in HIV-infected children. They studied a group of HIV-infected children. One group is randomly selected to receive the TB preventive therapy with the Isoniazid medication, and the other is to receive a placebo. After several trials, Gray and Cotton saw a marked reduction in TB incidence and death in the isoniazid group. However, they concluded that there is no long-term evidence on using this product on HIV-infected children, and they could not make conclusions on the impact this medication had on children receiving antiretroviral therapy, a treatment that suppresses or stops a retrovirus.

However, their research is important because Isoniazid has potential in reducing TB incidence and death in HIV-infected children, and this sets a precedent for future research into using this medication to prevent children living in low TB prevalence areas who have not had known contact with TB or children who are receiving antiretroviral therapy to contract the disease.

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Jet-Lag and Implications with Cancer

By Noah Beattie-Moss

The circadian rhythm, a 24-hour oscillation of physiological processes based on the day/night cycle, is vital for maintaining homeostasis of the body. Long-term disruption of this rhythm can have serious side-effects, as it has been implicated in tumorgenesis and cancer development. Women who work night shifts have been shown to have a moderate increase in breast cancer rates, and circadian disruption has been tied to liver carcinogenesis in mice models. The biological reasons for these connections have been largely unknown, but recent research published in the journal Cancer Cell may shed new light on the issue.

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Widespread Workplace Discrimination Against People with Major Depressive Disorder Puts Employees in a Double-Bind

By Alison Herman

In February 2016, the British Medical Journal released an expansive study of workplace discrimination against people with major depressive disorder (MDD) spanning 35 countries with a total of 834 participants. The analysis revealed anticipated and experienced discrimination against a majority of the study’s participants (62.5%). Both anticipated and experienced discrimination had a deterrence effect with respect to employment, discouraging people with MDD from applying for work.

The countries included in the analysis were separated into groups according to their scores on the Human Development Index (HDI), which are determined on the basis of average life expectancy, average number of years of schooling, and gross national income per capita (Brouwers et al. 3). The groups were very high development, high development, and middle and low development countries together. Employment deterrence was stronger and more prevalent among workers in very highly developed nations as compared to countries with low and middle development status. Although this distinction of workplace discrimination across different countries provides a valuable insight, the cross-cultural nature of the study also limits its generalizability because differences across cultures and countries make it difficult to draw concrete conclusions.

Participants were selected by their mental health specialists, who were instructed to choose a minimum of 25 people who experienced MDD in the past year and were deemed representative of the general population of patients across age, race, and gender. The study’s authors point out that this purpose-driven sampling further limits the generalizability of results because lack of randomization does not control for factors which may skew the results.

High rates of discrimination raises the question: Is disclosing your mental health status prudent?

CNN’s article “Depression in the workplace: don’t ask, don’t tell?” quotes Clare Miller, director of the American Psychiatric Foundation’s Partnership for Workplace Mental Health, as saying disclosure may be prudent in cases where your condition requires special accommodations or significantly affects your job performance. In the latter case, she advises, “Try to do it early in the game as opposed to waiting until you get a bad performance review.” The study’s authors recommend a decision aide to weigh the costs and benefits of disclosure as a possible means of addressing workplace discrimination.

Additionally, the high rate of anticipated and experienced discrimination has troubling consequences. According to Brouwers et al., 30% of the participants “had stopped themselves from applying for work, education or training because of anticipated discrimination” (Brouwers et al. 1). This figure increases to 60% of participants for the very highly developed countries alone. These findings are consistent with labor statistics; Heather Stuart of the Department of Community Health and Epidemiology at Queen’s University reports that unemployment rates for people with MDD range estimate three to five times that of the general population. The effect of workplace discrimination on labor force participation places workers with MDD in a double bind: their absence from the workplace hinders normalization of depression in the workplace and this unaffected level of stigma further discourages seeking employment.

Furthermore, this employment effect presents an issue for effective management of depression since holding a job has been shown to promote feelings of self-efficacy and thereby benefit people with depression. Without the palliative effects of work on depression as a result of high levels of unemployment, patients have little opportunity to redress the root cause of their employment struggles.

Overall, in terms of intervention to remedy some of the ill effects of workplace discrimination, the authors suggest a balanced approach to both decrease stigma in the workplace and to increase confidence of people with MDD applying for jobs. One aspect of this approach that they suggest is implementation of legislation, such as the institution of disability quotas, in order to address the effects of discrimination. However, the authors are missing a crucial issue about the application of this legislation in practice. As Heather Stuart notes, “Employers are more likely to hire someone with a physical disability, thus raising doubts about the effectiveness of disability quotas as a method of affirmative action for people with mental disorders.”

Furthermore, the suggestion that we work toward increasing motivation for MDD as a solution has troubling implications. Placing the onus of resolution of the issue on people with depression places an additional burden on them and suggests that they are the root of the issue, when in fact the problem lies with prejudiced and discriminatory employers. Rather than a balanced approach to the problem, solutions should primarily seek to normalize depression and change negative and misinformed opinions of employers. Such an approach would help to address discrimination on a systematic level rather than relying on each individual person to find increased motivation to apply for work; further, improving the atmosphere of professional settings for people with MDD would preclude any need for a personal approach.


Battling Workplace Depression. August 11, 2015.

Brouwers, E. P M, J. Mathijssen, T. Van Bortel, L. Knifton, K. Wahlbeck, C. Van Audenhove, Kadri, Ch Chang, B. R. Goud, D. Ballester, Lf Tófoli, R. Bello, M. F. Jorge-Monteiro, H. Zäske, I. Milaćić, A. Uçok, C. Bonetto, A. Lasalvia, G. Thornicroft, and J. Van Weeghel. “Discrimination in the Workplace, Reported by People with Major Depressive Disorder: A Cross-sectional Study in 35 Countries.” BMJ Open 6, no. 2 (February 23, 2016). doi:10.1136/bmjopen-2015-009961.

Harding, Anne. “Depression in the Workplace: Don’t Ask, Don’t Tell?” CNN, September 20, 2010. Accessed December 3, 2016.

Stuart, Heather. “Mental Illness and Employment Discrimination.” Current Opinion in Psychiatry 19, no. 5 (2006): 522-26. doi:10.1097/01.yco.0000238482.27270.5d.

A mechanism of how alcohol consumption promotes human breast cancer


Alcohol has been shown to increase the risk of breast cancer development. However, the exact mechanism through which ethanol promotes breast cancer is not well characterized. This experiment aims to delve deeper in the specifics of the mechanism, which can be generally described as follows: ethanol is converted to acetaldehyde, a toxic intermediate, which is thought to promote tumor growth. Acetaldehyde induces oxidative stress, which generates reactive oxygen species (ROS) that directly interact with the DNA, contributing to DNA damage. Acetaldehyde is then converted to acetyl-CoA or synthesizes ketone bodies. But the question remains: how does ethanol interact with the tumor’s microenvironment?

Alcohol is known to contribute to the development of fibrotic liver disease and advance the process of fibrosis. Liver fibrosis is caused by liver inflammation: collagen fiber deposits in the extracellular space of liver cells, causing liver cell hardening and loss of blood infusion. During fibrosis, myofibroblasts, which are employed in tissue repair during wound healing but can impair organ function during fibrosis, are generated in the liver, are thought to be related to cancer associated-fibroblasts, and are a key fibrotic component of breast cancer.

In order to study the effects of alcohol on breast cancer, Sanchez-Alvarez et al. performed a series of experiments to examine how ethanol treatment advances the generation of ROS in human fibroblasts, driving tumor growth and metastasis. Their main hypothesis was that ethanol induces metabolic changes in the tumor microenvironment, enhancing epithelial tumor growth.

To test this hypothesis, they used a co-culture system of fibroblasts with MCF7 human breast cancer cells, and human telomerase reverse transcriptase (hTERT)-immortalized fibroblasts, cells that give rise to connective tissue and proliferate indefinitely. They placed fibroblasts in two plates, one with just fibroblasts and another with MCF7 cells, controlling with a plate with untreated cells. Two days later, these cells were treated with ethanol for 72 hours.

They found that ethanol treatment increased ROS production and oxidative stress in cancer-associated fibroblasts. Specifically ROS production increased by 35% in the fibroblasts culture alone when compared with control cells, and 58% in the fibroblasts-cancer cells co-culture. Ethanol was also shown to convert cancer cells to a status associated with more aggressive behavior and a worse prognosis.

Their observations led them to formulate a “two-compartment” metabolic model, in which ethanol treatment induces ketone production in fibroblasts and ketone re-utilization in cancer cells, resulting in tumor cell growth through oxidative mitochondrial metabolism.

Their research is important because it illuminates the mechanism of alcohol consumption metabolically converting “low-risk” breast cancer patients to “high-risk.” This information could be used for breast cancer prevention and therapy, working to reduce the risk of breast cancer in women who consistently drink.

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Current Status of Zika: Human Trials and DNA Vaccines


The infamous Zika virus has been plaguing our lives and travel plans throughout the past year. Transferred widely by Aedes mosquitoes, the symptoms vary from nervous system disorders such as the Guillain-Barré syndrome, to even none at all. The true, insidious hazard of the virus lies in its ability to affect pregnancies in a way that produces microcephalic children, whose quality of life decreases dramatically with the onset of disabilities. The lack of vaccines or a cure keeps many of those who live in afflicted areas scramble for protection from mosquitoes.

With such high societal risks associated with the disease, researchers have been making assiduous efforts to develop a vaccine. Earlier this year in March, scientists at the National Institute of Allergy and Infectious Diseases had a goal of running tests later in the year, which is an incredibly accelerated test plan, according to BBC News (Mazumdar). Fast forward to the present, researchers have already started running trials on humans, which have been preceded by successful tests on mice and monkeys.

This accelerated progress has been due to DNA vaccine procedures, in which the vaccine itself is not able to cause disease, since it only utilizes the structure of the virus. In the case of Zika, vaccines have been made utilizing the “precursor transmembrane M (prM) and envelope (E) proteins” of the virus (National Library of Medicine). As a result, DNA vaccines are very safe and are administered directly into cells, which often means that there are no needles involved. This recently discovered methodology is in fact a much simpler process than the standard live or inactivated vaccines we are accustomed to. However, to this date, DNA vaccines have stumbled at the testing stage and were never approved to be widely distributed, although considering this line of extensive research and impressive progress thus far, positive test results against the Zika virus seem to not be a distant reality.

Currently the first series of clinical trials, dubbed “Phase 1”, is testing for immunity and possible side effects of the vaccine in participants ranging from 18 to 35 year olds.  The participants will have the vaccine injected more than once over the course of several weeks. The studies are still recruiting subjects in centers located in Georgia and Maryland. If all goes well, researchers have high hopes of a vaccine set for the public by the end of these clinical trials in 2018.


Related Links/Sources:

News Report:

Zika overview:

DNA vaccines:

Current Zika progress:

Zika clinical trials (National Library of Medicine):

Combating Bacteria: A New Approach to Multi-Drug Resistance


Over the last decade, antibiotic-resistant bacteria have proliferated; according to the CDC, at least 90,000 deaths a year in the U.S. are due to bacterial infections, with a majority of these infections being resistant to some antibiotic. Alarmingly, hospitals and other health-care facilities have been the epicenter for the outbreak of drug-resistant bugs, simply because these places allow for bacteria to enter the bloodstream and open wounds most quickly. Bacterial infections caused by multidrug-resistant (MDR) bacteria are a serious threat to public health because of their virulence and resilience to many forms of treatment.

There are two major types of MDR bacteria — gram-positive and gram-negative, distinguished by how these bacteria stain on a Gram test. Although gram-positive MDR bacteria such as the well-known methicillin-resistant Staphylococcus aureus (MRSA) are still a major threat, there have been many developments of new antibiotics that should work effectively again them (at least for the time being). However, gram-negative MDR bacteria are much more concerning; these bacteria have an additional outer membrane that has effectively halted progress in drug development that can kill them. For this reason, there is currently a lack of drug candidates for this type of bacteria, posing a huge threat to global health.

Last month, though, in a study published in Nature Microbiology, researchers have described a new tool that has great potential in tackling these MDR gram-negative bacteria. They describe a new class of antimicrobial agents called structurally nanoengineered antimicrobial peptide polymers (SNAPPs); these so-called SNAPPs are engineered by a special type of peptide synthesis process. Two SNAPPs, S16 and S32, mimic naturally occurring anti-microbial peptides and have shown great results when tested against a range of MDR bacteria.

Specifically, researchers incubated SNAPPs with bacteria in a lab setting, and S16 and S32 were equally effective against strains of MDR gram-negative species, as drug resistance was not detected even after 600 generations of bacterial growth. They made sure that these peptides were not harmful to mammals by mixing the SNAPPs with human red blood cells and consequently observed no undesired interactions. The researchers also tested S16 and S32 in mouse models infected with MDR A. baumanii: treatment with S16 enabled survival of all mice for 24 hours, while 50% of the control mice died.

The scientists also ran experiments to determine what exactly in these SNAPPs can cause the death of MDR-resistant gram-negative bacteria. They found that the polymer peptide disrupts the outer membrane of these MDR bacteria because it can cross the membrane and the layers below that, leading to unregulated movement of ions across the membrane. SNAPPs can also cause the bacterial cell to spontaneously lyse (high concentrations) or cause the cell to follow programmed death (low concentrations).

This new research is crucial in facing this new global threat of multi-drug resistant gram-negative bacteria. For the first time, a suitable class of drug candidates that can not only destroy these bacteria but are also compatible with the mammalian body has been proposed. These SNAPPs may be the key to eliminating these unwanted pests that are resistant to any conventional method of antibiotic treatment. Hopefully, SNAPP-based drugs will be quickly developed and undergo clinical trials in the near future.



Immunotherapy’s Rise Among Cancer Treatments


Most cancer patients are treated with chemotherapy, radiation, and/or surgery, but recent promising research has given hope to another option: immunotherapy. This approach allows the immune system itself to fight the cancer. Tumorous cells often prevent the immune system from attacking, or even make themselves undetectable to the body’s white blood cells. Immunotherapy treatment types vary, solving all these sorts of issues. Treatments come in the form of drugs, vaccines, catheters, and even creams, sometimes combined with other cancer treatments. Researchers are currently studying various forms of immunotherapy, which have shown promising results. As studies are done and clinical trials run, the form of treatment is rapidly becoming more widely accepted. Just a few weeks ago, the FDA (U.S. Food and Drug Administration) approved Keytruda, a checkpoint inhibitor immunotherapy drug used to treat metastatic lung cancer, also known as the drug that cured former president Jimmy Carter from a deadly form of melanoma. Keytruda can now be used as a first step in treatment over chemotherapy, in certain cases. A number of other immunotherapy drugs have been approved in the past, including Provenge in 2010, a treatment for prostate cancer, and Imlygic in 2015, for metastatic melanoma. These recent advances indicate that immunotherapy will likely become more prevalent in treatments.

Following the new FDA approval and general successes in immunotherapy testing, the media has displayed this exciting ray of hope for cancer patients. Dr. Crystal Mackall of Stanford’s School of Medicine, who specializes in this type of treatment, told FOX news that the recent immunotherapy findings are “turning the practice of oncology on its head.” New York times writer Denis Grady wrote: “All this has brought new optimism to cancer doctors — a sense that they have begun tapping into a force of nature, the medical equivalent of splitting the atom.”

Keytruda, the new drug, is a checkpoint inhibitor. These inhibitors are the most common form of immunotherapy drugs, and are relevant in treating different types of melanoma, lymphoma, lung, kidney, and bladder cancers. Normally, T-cells (white blood cells that have the ability to kill cancer cells) can detect which harmful cell to attack through reception of the antigen on the cell’s surface. Some cancer cells, however, can activate an immune checkpoint “switch” on the T-cell during the process, and prevent the T-cell from carrying out its function. Checkpoint inhibitor drugs block the checkpoints of T-cells so that the cancer cell cannot “switch off” T-cells. A recent study published in the June 2016 edition of the Cancer Immunology, Immunotherapy journal discusses the increase in the number of T-cells and their functionality in eighteen glioblastoma patients who were treated with the inhibitor Axitinib. Many other significant studies on the treatment have been published in recent years. In an article from last May, an approach similar to the checkpoint inhibitor method is described. Scientists designed specific molecules to remove sugars from the coatings of tumor cells, preventing the tumor cells from deactivating T-cells via these sugars.

CAR (chimeric antigen receptor) T-cells are another of the more prevalent types of immunotherapy methods, frequently used in clinical trials. T-cells are removed from the patient’s bloodstream and mutated in the lab to produce the chimeric antigen receptors, which enables the cell to attach to the cancer cell antigens. The mutated cells are given back to the patient through an infusion. CAR T-cells are used to treat leukemia and lymphoma and have had positive effects. In a trial that took place in Children’s Hospital in Philadelphia, in which T-cells were used, twenty-seven out of the thirty patients achieved remission.  Other types of monoclonal antibody treatments are also being tested. Researchers are working to create more of these antibodies that attach to antigens of cancer cells, essentially “flagging” the cancer cells so that the immune system can sense and attack. The antibodies are also sometimes made to target and destroy the cancer cells on their own.

While there are still many unanswered questions regarding the efficacy and side affects of immunotherapy, studies demonstrate potential for further improved treatments. In future work, researchers will begin to examine surrounding tissue of the cancer cells to gain a better understanding of the paths of the T-cells. Another step to be taken is looking for undiscovered checkpoints to be blocked, as well as combining this inhibitor method with other treatments. Implementing inhibitors with other methods could be particularly useful, as remnants of destroyed cancer cells from the other treatments could trigger immune system responses that would be refined via these inhibitors. Like all cancer treatments, immunotherapy has side effects and risks associated. If those obstacles can be eliminated, though, immunotherapy could be highly effective, as the immune system is the body’s natural tool and would typically only target unhealthy cells, unlike chemotherapy and radiation therapies, posing less collateral damage to the patient. Future studies are expected to be done in this growing branch of cancer research, with the Fred Hutchinson Cancer Researcher Center, a new immunotherapy research clinic that will focus on treatment with T-CELLS, scheduled to open in Seattle this December. All of us hoping for new forms of effective cancer treatment can expect to see more of this exciting, growing field of immunotherapy.



Antibody therapy offers promising lead for sustained HIV control


HIV/AIDS is a global pandemic, and has remained at the forefront of American consciousness since the 1980s, when hundreds of thousands of people, predominantly young gay men, passed away from the disease. Today, over 36 million people live with the disease worldwide, with over 1.2 million patients in the United States alone. It can be managed with continuous antiretroviral therapy, but there is still no known cure or vaccine. Recent research published in the journal Science, however, suggests the potential for a new combination therapy that may act as a functional cure.

Human immunodeficiency virus is categorized as a retrovirus, meaning it has an RNA genome enclosed by a protein capsid and a lipid envelope derived from the cell membrane of the host. Molecules on the HIV particle bind to receptors on the surface of T helper cells, especially CD4+ T cells, which play an essential role in the proper functioning of the immune system. Once inside a host cell, the viral RNA is converted into DNA, transported into the nucleus, and integrated into the cellular genome. This viral DNA is called a provirus, and is transcribed by the cell to produce new virus particles.

HIV-infected T cell, captured by a scanning electron microscope.

Antiretroviral therapy (ART) can target several different steps in this viral life cycle, such as blocking membrane fusion of HIV with the cell, or inhibiting reverse transcriptase, the enzyme which transcribes the viral RNA into DNA. But it has downsides: ART requires continuous daily medication, and viral loads regenerate if therapy is stopped, so it is not a cure. Long-term ART also has side effects such as toxicity, inflammation, and an elevated risk of aging-related diseases such as liver dysfunction and osteoporosis. In addition, access to medication poses a problem: in 2010, the average lifetime cost of treating HIV in the US was approximately $380,000, and distribution of ART medication in developing countries is extremely limited.

Research led by Dr. Aftab Ansari of the Emory University School of Medicine, published on October 14, 2016, investigated the effect of ART alongside an antibody targeting α4β7, a receptor on the surface of CD4+ cells which enables them to traffic into gastrointestinal tissues. During a typical infection, depletion of CD4+ cells in these tissues causes gut epithelial damage and allows the formation of persistent viral reservoirs, leading to general immune dysfunction. It was hypothesized that by blocking entry of CD4+ cells into this area, the immune system would remain strong enough to control the infection.

The investigation was conducted on macaques, using SIV, the simian analogue of HIV. Eighteen monkeys were infected with the virus and were started on a daily ART regimen after five weeks. Starting at week nine, eleven of the animals were treated with the α4β7 antibody, while the other seven received a nonspecific antibody as a control. ART was terminated for both groups at 18 weeks, and antibody treatment was terminated at 32 weeks.

The results were dramatic: macaques which received the α4β7 antibody had an absent or minimal viral load after ART was ceased, while the control group rebounded to high viral levels. Control over viral levels persisted through the end of the study, at week 90.

This indicates that α4β7-directed therapy not only stopped temporary entrance of HIV-infected T cells into gastrointestinal tissue, reducing tissue damage, but also allowed the immune system to subsequently control infection after therapy was discontinued.

The precise mechanism by which this operates is yet unknown, but the combination of α4β7-directed antibodies with ART seems to have functionally cured SIV infection in the macaques, granted this is not a complete cure, because the viral genome is still present in the host. The human equivalent for the α4β7 antibody is already an FDA-approved drug called vedolizumab, currently used to treat Chron’s disease and ulcerative colitis. A clinical trial was begun in May 2016 to see if vedolizumab is safe for AIDS patients, and whether it allows the immune system to control HIV infection after ART is discontinued. The study is expected to be completed in 2020.

A great deal of work remains to be done to understand the molecular implications of this treatment, but the results of the clinical trial are eagerly awaited. Long-term immune control over infection promises to be a groundbreaking step forward in our ability to treat AIDS and could effectively eliminate the need for recurring medication. This would solve a major distribution challenge for developing countries, and could herald a new era in humanity’s relationship with this virus.

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