CAR T-Cells and Cancer Treatment

In the past, cancer treatment has consisted of surgery, chemotherapy, and radiation therapy. However, over the past ten years, immunotherapy has become a popular method of treatment. According to the National Cancer Institute, immunotherapy is a therapy that utilizes the strength of a patient’s own immune system to attack the cancer tumors. Immunotherapy typically takes the form of drugs that have proven their ability to decrease the size of tumors, and even eradicate some. An example of an immunotherapy drug class is immune checkpoint inhibitors. 

Another form of immunotherapy is called CAR T-cell therapy. In CAR T-cell therapy, T cells are taken from the patient’s blood and altered in a lab. Scientists are able to add a gene that causes T cells to have the receptor which binds to the cancer cell antigen. These receptors are called chimeric antigen receptors, or CAR. Each receptor is made specifically for the type of cancer that the patient has. So far, CAR T-cell therapy is being used to treat the blood cancer, leukemia, which has the antigen CD19.

There are currently six CAR T-cell therapies that are FDA approved to treat leukemia, lymphoma, and multiple myeloma. In this Nature article, scientists examine the long-lasting effects of CAR T-cell therapy by studying two patients that received the treatment in 2010. Upon examination, scientists noticed even 10 years after receiving treatment, there is a detectable presence of CAR T-cells in the patients’ blood. Additionally, there is an absence of leukemia cells in both patients indicating the long-lasting impact of this treatment. The presence of the CAR T-cells was determined using PCR and flow cytometry. These results show the promising future for immunotherapy as a treatment option for cancer. 

Malaria in the Time of Covid

In the past two years, the Covid-19 Pandemic has, understandably, taken over the global health world. However, the emergence of Covid-19 has not caused other major diseases, such as malaria to simply cease to exist. I was interested in looking into the relationship between the Covid-19 pandemic and malaria cases, particularly in India. Malaria is a parasitic disease spread by Anopheles mosquitos. Its symptoms can range from mild to life-threatening. In more harmful cases, malaria can cause kidney failure, epilepsy, coma, and even death. 

According to this article, Malaria has been a major problem in India for many years and is particularly present in its urban areas where population density is high. Many prevention and treatment programs for malaria have been created in India and proven to have great results. However, due to the dire need for resources to aid in the prevention of Covid-19, many malaria-prevention resources have been re-allocated. This has consequently caused an increase in the number of malaria cases. According to the World Health Organization, there were 14 million more cases of malaria in 2020, than in 2019. This increase in cases is directly linked to the re-allocation of malaria prevention resources. 

Another problem with the presence of Covid-19 is that it is made the diagnosis of malaria more difficult. Covid-19 and malaria have similar symptoms including difficulty breathing, fever, and exhaustion. Early diagnosis can be pivotal in preventing the long-term effects of malaria, however, due to the similar symptoms diagnosis is stalled. Doctors can not longer rely simply on symptoms to make a diagnosis and would require further testing which can be hard to obtain in such a populous country. While there have clearly been some setbacks in the fight against malaria due to Covid, healthcare and humanitarian workers have worked hard to continue fighting. About 75% of the predicted amount of insecticide-treated mosquito nets were distributed in 2020. While this is clearly not the ideal amount, it is still a significant one and is a step in the right direction. In conclusion, the Covid-19 has clearly had a negative impact on the attempts to eradicate malaria in India. However, as cases of Covid-19 are beginning to decrease, there is hope that we can turn our focus back toward malaria prevention.

The Mediterranean Diet is Easing my Basketball Stress

In light of the game which will be occurring this Saturday, I thought it would be the perfect time to post one of my favorite healthy game day recipes. Here is a great recipe for vegetable skewers. I think this is a great snack for game day because it is easy to eat on the go. As an added bonus, this recipe is quite healthy because consists of a variety of vegetables. Additionally, this is a great recipe because it is easy to adjust and customize based on personal preferences. 

Yummy Vegetable Skewers from The Forked Spoon

According to a study conducted on the Mediterranean diet, there seems to be a clear link between eating foods in the Mediterranean diet and improved heart health. The Mediterranean diet (MD) is able to increase the diversity of the gut microbiota. The microbiota of an individual that follows the MD is much different than the gut microbiota of an individual that follows a Western diet. Individuals that follow the Western diet have increased gut permeability. This causes metabolic endotoxemia which refers to an increase in blood LPS levels. In addition to cardiovascular disease prevention, adopting an MD has shown a reduction in Alzheimer’s disease and an increase in life expectancy.  

The MD consists of an abundance of fruits and vegetables, as well as legumes, whole grains, and nuts. Extra virgin olive oil is the main source of fat in most Mediterranean cuisine. There is less of an emphasis on meat consumption, and when it is eaten, individuals typically use leaner meats such as chicken and turkey. Therefore, my vegetable skewers recipe is a perfect recipe for individuals that are hoping to adopt a more Mediterranean diet. The skewers include fresh vegetables such as zucchini, red onion, bell peppers, and a delicious garlic herb sauce. Considering the various heart palpitations I will be experiencing during the Saturday basketball game, I think it will be good to eat something that will help ease my heart. Go Heels!!

The Struggles with Vaccine Development

The development of new vaccines is a long and painstaking process. According to the CDC, the process of vaccine discovery involves research, preclinical trials, clinical trials, FDA review, and ACIP review. When a vaccine is developed it is first tested utilizing computers that simulate how a body would respond to the drug. The researchers then test vaccines on animals including mice, rabbits, and monkeys. An application called an investigational new drug application, IND, is sent to the FDA. The IND includes a thorough description of the drug as well as possible trial methods. If the IND is approved scientists may begin clinical trials. 

Clinical trials generally have three stages. This youtube video, created by scientists at Johns Hopkins explains the three phases of clinical trials. In phase 1, the primary focus of the trial is testing vaccine safety. This trial consists of around 20-100 individuals. This phase of the trial typically lasts 1-2 years and if it is successful, scientists are able to progress to phase 2. In phase 2, hundreds of individuals who are given the vaccine are monitored to observe the safety of the vaccine as well as begin to look at efficacy. If this phase is also successful, scientists will continue onto phase 3 which is the largest one. Phase 3 consists of thousands of individuals getting the vaccine and scientists observe the efficacy of the vaccine. This phase typically lasts over 5 years as it is important to observe the efficacy over time. If phase 3 is also successful then the researchers proceed to receive FDA approval.

Researchers at United Neurosciences are currently in Phase 2a trials for the development of an Alzheimer’s vaccine. In the phase 2a trial, there is a group of 42 patients that have mild cognitive impairment and are likely in the early stages of Alzheimer’s disease. The group is broken up into three subgroups: one is given a placebo, and two are given the vaccine. For those receiving the vaccine, it is given in three parts and then followed up with a booster, three to six months after the initial vaccine. Trial 2a exhibited extraordinary results. Nearly all of the patients, specifically 96%, showed improved cognition and lower levels of amyloid-beta. This is a very positive response and scientists are hopeful as they progress towards trial 2b. This study should further determine the efficacy of the vaccine.

The vaccine in this trial is aiming to attack amyloid-beta levels in the body via an amyloid-beta According to Dr. Reiss’s research on amyloid toxicity in Alzheimer’s disease, Beta-amyloid is a protein that can clump together and form a plaque in individuals with Alzheimer’s disease. The formation of these plaques is the main virulence factor of Alzheimer’s disease. The amyloid-beta peptide is toxic to neurons and promotes apoptosis as well as synaptic loss. Many scientists hoping to develop treatments for Alzheimer’s disease are working on the reduction of amyloid-beta production. The hope is that reducing the production or levels of amyloid-beta peptides will slow the development of Alzheimer’s.  

Vaccine Hesitancy and the Corrupt Study That Caused It.

In 1998, Dr. Andrew Wakefield presented a research study that claimed to link the MMR vaccine to the development of autism in children. In this research study, there were 12 boys, ages 3-10 that were involved and examined by a pediatric gastroenterology unit. This research study has now been retracted and there has been much evidence that proves the study was biased. In an article written by Brian Deer, Deer investigates the many ways Wakefield’s study does not comply with the proper scientific procedures of a typical research study. First, Wakefield did not use random selection to pick the subjects of the trial, many of the subjects had already begun demonstrating developmental issues prior to receiving the MMR vaccine. Furthermore, Wakefield lied about the number of patients that demonstrated signs of regressive autism. He claimed that nine of the subjects exhibited signs, but upon further evaluation, only six did. Wakefield had a specific result that he wanted to occur, rather than running an experiment in order to determine a relationship. In a research funding proposal Wakefield submitted, he wrote 

“The objective … is to seek evidence which will be acceptable in a court of law of the causative connection between either the mumps, measles, and rubella vaccine or the measles/rubella vaccine and certain conditions which have been reported with considerable frequency by families of children who are seeking compensation”

Cambridge Center for Behavioral Studies

This quotation proves a clear bias from the researcher. Deer also discovered another bias against vaccines in that Wakefield was employed by the attorneys that were building a lawsuit against a vaccine manufacturer. This essentially means that Wakefield was being paid — a rather large sum — to prove the link between vaccines and autism. Deer also stated that Wakefield and his researchers mistreated the subjects in the trial. They were subjected to numerous invasive tests which were later proved to be not justified. The General Medical Council of England charged Wakefield with 30 serious ethical charges, including 4 charges of dishonesty. Additional problems include the inability to replicate results, and the lack of clearly defined dependent variables. 

In 2002, The New England Journal of Medicine published the results of a cohort study that observed all the children born in Denmark from 1991 to 1998. This means that 537,303 children’s information was studied. The information regarding vaccination status and autism status was obtained for each subject. When analyzing the data obtained for the study it was found that the relative risk (RR) of autistic disorder in the group of vaccinated children as opposed to unvaccinated children in 0.92. Furthermore, the RR of other autistic-spectrum disorders is 0.83. If the RR of a study is less than 1, this means that the exposed group, in this case, the vaccinated group, has a decreased risk than the unexposed group. This data directly disproves the concept that the MMR vaccine causes autism.

I, personally, am a big advocate of vaccines. I have all of my childhood vaccines, as well as three doses of the Moderna Covid Vaccine. While I have always supported vaccines, I was not particularly passionate about them until the Covid Pandemic. During the pandemic, I began working as a pharmacy technician in a chain grocery store. While working I have been able to see our pharmacist give hundreds of vaccines as well as, talk with many patients that are opposed to vaccines. It is a really heartbreaking feeling that there is so much fear and distrust of scientists all due to this one initial report. I am hopeful that in the future, we can work on increased vaccine education as a way of combatting these problems.

Recent outbreaks of Salmonella

Salmonella enterica is a Gram-negative bacterium that is part of the Enterobacteriaceae family. This family consists of a large group of Gram-negative bacillus-shaped bacteria. S. enterica has many serotypes, however, they all cause salmonellosis. Common symptoms of salmonellosis include abdominal cramps, nausea, vomiting, and most prominently, watery diarrhea. Animals are the reservoir for S. enterica, specifically turtles, frogs, ducks, and chickens. Transmission of S. enterica can be either direct through animal handling, or indirect via salmonella-contaminated food.

According to Consumer Reports, contaminated salad greens caused a salmonella outbreak in June and July 2021. The produce company, Bright Farms, conducted a recall of eight varieties of their packaged salad greens after discovering they were linked to a salmonella outbreak. The outbreak impacted four states: Indiana, Illinois, Iowa, and Wisconsin. Luckily the outbreak was relatively minimal, with only 31 reported cases and 4 hospitalizations. However, according to the CDC, for every case which gets reported, there are likely 30 cases that arise but do not get reported. It is generally advised to grow produce inside a greenhouse, in order to ensure a clean and controlled environment. Since the greens for the salad kits were grown indoors, the greens were most likely contaminated by coming in contact with fecally contaminated water from a nearby farm, or by coming in contact with previously contaminated greens that were grown in outdoor facilities.

Later that year, there was an extensive outbreak of Salmonella infections due to backyard poultry flocks. According to Food Safety News, this outbreak stretched across 48 states and infected 1,135 people. Of the infected, there were 273 hospitalizations and 2 deaths. This was clearly a larger outbreak than the salad kits outbreak as it involved far more states and people. Unlike the previous outbreak, which was spread via contaminated food, this outbreak was caused via direct transmission by coming in contact with poultry. It seems that children under five years old were the most impacted by this outbreak and accounted for 25% of the cases. These two outbreaks shared many similarities which are shared amongst all S. enterica infections including symptoms and reservoir. However, the notable differences were the type of transmission and the severity of the two outbreaks.

The dangers of antibiotic resistance

Antibiotic resistance has become a serious health concern and a large contributor to health-related deaths in the world. As explained by the Mayo Clinic, antibiotic resistance is provoked by the presence of antibiotics which cause bacteria to adapt. These adaptations may not cause a real impact, or could even be harmful to the bacteria, however, they generally make them stronger, and develop resistance mechanisms. While it is very important to take antibiotics if an individual has a bacterial infection, the misuse or overuse of antibiotics has caused an increase in antibiotic resistance. In order to prevent further developments of antibiotic resistance, scientists urge individuals to only take antibiotics when they are prescribed and to get vaccinated against bacterial infections such as whooping cough and diphtheria. It is important to reduce antibiotic resistance as much as possible because resistance can lead to longer recovery times, worse infections, and longer hospitalizations.

According to the Lancet report, over 1.2 million individuals died in 2019 due to antibiotic resistance. This is more deaths than those caused by HIV or malaria. It seems that the African continent, particularly West sub-Saharan Africa, has been the most impacted by antibiotic resistance. In West Africa, 27 deaths per every 100,000 are caused by these bacterial infections. The majority of the diseases which are caused by antibiotic resistance are lower respiratory infections. The six main bacteria which are causing resistance-related death and Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Streptococcus pneumoniae.

The CDC lists numerous resistance mechanisms which bacteria can employ to evade anti-bacterial medication. These mechanisms include restricting access to antibiotics, destroying them, or bypassing their effects. Pseudomonas aeruginosa has developed a pump which can get rid of many anti-bacterial drugs including beta-lactams and chloramphenicols. Klebsiella pneumoniae is able to produce carbapenemases which can break down carbapenem drugs, as well as other beta-lactams. Certain Escherichia coli can add a compound to their cell wall which prevents drugs from latching on to them. Staphylococcus aureus has gone through numerous waves of resistance, as outlined in this paper. Originally, penicillin was introduced to treat S. aureus infections, but then a penicillin-resistant strain of S. aureus arose. This strain “produced a plasmid that encoded penicillinase” which essentially makes the beta-lactam ring in penicillin break apart. Eventually, a new drug therapy, methicillin, was created, and then quickly afterward, a new strain of Methicillin-resistant S. aureus (MRSA) arose. The resistance mechanism in MRSA was different than the penicillin-resistant strains because, in MRSA strains, there is a very low affinity for penicillin-binding protein. This gives MRSA a much broader resistance as it is resistant to penicillins, cephalosporins, and carbapenems.

How clean are our household cleaning products?

Classic household cleaning products including Lysol or Clorox are staples in nearly every household in America. We often buy these products based on packaging, or reviews, without ever really investigating their impact or significance. In my house, we use Mrs. Meyers Multi-Surface Everyday Cleaner. The standard bottle size, 16 fluid ounces, is priced at $4.29. Mrs. Meyers advertises their cleaner with the tagline “Removes Dirt” and “Freshens Surfaces”, and it is lemon verbena scented. 

Mrs. Meyer’s Clean Day Multi-Surface Everyday Cleaner

Meyer’s is not a disinfectant and refers to itself as a cleaner. According to Mrs. Meyer’s website, the ingredients in Meyer’s cleaner are as follows: 

Water, Decyl Glucoside,Polysorbate 20, Betula Alba (Birch) Bark Extract, Citrus Limon (Lemon) Peel Oil, Abies Alba (Fir) Leaf Oil, Cymbopogon Schoenanthus (Lemongrass) Oil, Fragrance, Sodium Citrate, Glycerin, Sodium Methyl 2-Sulfolaurate, Citric Acid, Tetrasodium Glutamate Diacetate, Sodium Sulfate, PEG-5 Cocoate, Methylisothiazolinone, Benzisothiazolinone.”

mrsmeyers.com

The main ingredient in the Meyer’s cleaning spray is decyl glucoside. Decyl glucoside is a sugar-derived surfactant that keeps ingredients blended while cleaning. The next ingredient, polysorbate, is an emulsifier that has the primary purpose of ensuring even dispersion of fragrance. Of the sixteen ingredients in the Meyer’s cleanser, there is only one product that is meant as the cleaning agent. Sodium Methyl 2-Sulfolaurate provides cleaning and foaming qualities to the cleanser. I find this very concerning and certainly do not want to use my Meyers cleanser in the future. 

Now that I need a new household cleaning product, I considered making my own from household items. According to the blog, Old House to New Home, an easy three-ingredient homemade antibacterial cleanser involves combining water, white vinegar, and essential oil. More specifically, I should add three cups of water, 1/2 cup of white vinegar, and 15 drops of scented essential oil. The essential oil adds a scent to mask the strong scent of vinegar, water acts as a diluent, and vinegar acts as a cleaning product. White vinegar is comprised of acetic acid and water. Acetic acid, along with other acidic cleaners are used to remove rust stains, get rid of the film caused by soap, remove tarnish, and dissolve hard water deposits. In the future, perhaps I will try to make my own household cleaner using this simple recipe, and feel better knowing that my counters will be clean. 

SARS-CoV-2 and its variants

The Covid-19 Virus has been rampaging throughout the United States, as well as the rest of the world for nearly two years and it doesn’t seem to be slowing down. A large factor that has contributed to the continued presence of the Covid-19 virus in our society is the numerous variants that have arisen. The introduction of new Covid-19 variants has led many scientists, including Dr. Bollinger at Johns Hopkins Medicine, to investigate the driving force and rate of these mutations. It is typical of RNA viruses to have new strains and change over time due to random mutation during replication. These mutations are the reason a new flu vaccine gets created every year, and SARS-CoV-2 is no exception to this. While some mutations do not have a greater impact upon the population, the delta and omicron variants have both proven to be more contagious, and transmissible than the original strain. 

Mutations of SARS-CoV-2 seem to have impacted pathogenicity, transmissibility, and infectivity. According to Harvey, et al., multiple mutations that have caused variants to be more infectious are mutations regarding the spike proteins. Spike proteins are present on the outer lipid bilayer of SARS-CoV-2 and are the part of the virus which binds to human cell receptors. Researchers have found that an amino acid on the spike protein was mutated, and this mutation is called D614G. It appears that D614G is now being created at quicker rates. This mutation causes the variant to be more transmissible and infectious. 

Additionally, researchers in Shanghai have been looking specifically at the mutations present in the omicron variant. It appears that the omicron variant of SARS-CoV-2 has 32 mutations in the spike proteins. This is the most seen in any variant, and twice that which was seen in the delta variant. One of the mutations in the omicron variant increases the spike protein’s affinity to its binding site which results in more viral attachment to human cells. It is apparent that the spike protein is the key to the virulence of SARS-CoV-2, and it should therefore be the focus of future treatments.

Obesity and the Microbiome

If taking pills that contained stool samples from other individuals could cause you to lose weight, would you do it? This is a question that was posed to a group of volunteers who participated in a trial, discussed in a New York Times Article, that examined the relationship between obesity and the microbiome. (O’Connor, 2019) The microbiome refers to the collection of microorganisms in a given environment. In recent years, there has been an increased focus on examining the microbiome and its relationship with a variety of diseases. Scientists have discovered that the microbiome of the gut is a cause and possibly an avenue of treatment for obesity. (O’Conner, 2019)

In “Gut microbiota: A new path to treat obesity”, Muscogiuri examines the impact of the gut microbiome on individuals with obesity and considers possible treatment options. According to Muscogiuri, 

“The gut microbiota has an important role in the regulation of fat storage, increasing energy harvesting, and in modulating the formation of substrates for storable fat synthesis.” 

Muscogiuri, 2019

Certain gut microbiota increases the permeability of the intestine which can result in insulin resistance and inflammation. (Muscogiuri, 2019) These are both indicators of obesity and type 2 diabetes. Additionally, while the gut microbiome is normally very diverse, individuals that are obese have less diversity in their microbiota. (Muscogiuri, 2019) This causes those individuals to have reduced “metabolic energy consumption in comparison with that of the microbiota of lean people”. (Muscogiuri, 2019) An example of this can be seen with the microorganism, Bacteriodes, which appears to be present in higher volumes in lean people, as opposed to obese people. (Muscogiuri, 2019) Bacteriodes are responsible for digesting dietary sugars, and therefore when there are more present in the stomach, more sugars are able to be digested, resulting in a leaner body. (Muscogiuri, 2019)

These discoveries have prompted scientists to believe that the microbiome of the gut does impact if an individual will become obese. Furthermore, it has led researchers to investigate the possibility that changing one’s gut microbiome could target obesity. There are many skeptics of this theory that recognize the complexities of obesity and claim that diet and exercise are still the best treatment for obesity. (O’Connor, 2019) However, Muscogiuri argues that current treatments, including diet changes and surgery, may already change the microbiome and therefore prove the significance of considering it when treating the disease. (Muscogiuri, 2019) There is still further research that must be done to gain more information regarding possible treatments, however, it seems clear that the microbiome is the key to fighting obesity.