Complex regional pain syndrome (CRPS), once known as reflex sympathetic dystrophy, is a so-called “umbrella diagnosis” which encompasses a wide range of symptoms and conditions. It is used to describe prolonged pain and inflammation resulting from injury to the arm or leg [1]. Interestingly, the severity of CRPS is not correlated with the severity of the injury, but rather the overall robustness and nerve health of the affected individual. It is more common in women and people around the age of forty, and rarely seen in children or the elderly [1]. Complex regional pain syndrome can be chronic, debilitating, and difficult to manage, and scientists have begun researching whether stem cells may provide a viable treatment option. 

Individuals with CRPS are more sensitized to stimuli that would not normally be considered pain-inducing in the affected region: gentle touching, for example, or movement. The pain can be both intense and prolonged. The onset of these symptoms is caused by improper firing of the peripheral nerves which communicate pain signals to the brain and is thought to have an inflammatory/autoimmune component. Other common symptoms include changes in skin temperature or texture, abnormal nail or hair growth, abnormal sweating, joint stiffness, abnormal bone growth, and impairment of muscular strength [1]. Before the exact malfunctioning nerve has been identified, patients are diagnosed as having CRPS-I; once this specification has been made, they are given the diagnosis of CRPS-II. 

Though most patients recover from CRPS as their injury heals, some experience severe, chronic pain. For these patients, treatment involves long-term therapy, physical rehabilitation, or management of symptoms using low-grade analgesic drugs like acetaminophen [1]. Many of these treatments involve management of symptoms, and are not necessarily curative. Moreover, even acute CRPS can be debilitating and cause temporary disability, reduced quality of life, and absence from employment. 

To address the need for more reliable treatments for complex regional pain syndrome, scientists have turned towards a technology which has occupied the cutting edge of medical science throughout the past decade: stem cells. In recent years, the immunomodulatory capabilities of human mesenchymal stem cells, which are adult stem cells found in tissues like fat or bone marrow, have been of particular interest for treatment of CRPS. The relatively easy access to these stem cells makes them an ideal candidate for the treatment of a number of complex diseases. Scientists hypothesized that the introduction of human mesenchymal stem cells might help mitigate the autoimmune component of complex regional pain syndrome, reducing inflammation and allowing for restoration of the affected nerve. In 2020, a Chinese study showed that mesenchymal cells derived from bone marrow secreted neurotrophic factors in rats, which in turn promoted microglial polarization and helped to alleviate a common type of neuropathic pain [2]. Now, the Cleveland Clinic has just received a 5.5 million USD grant from the National Institute of Health to further the technology in humans [3]. If the project is successful, it could have a large implication for treating other types of neuropathic pain, according to Dr. Cheng, who is the director of the Cleveland Clinic’s Consortium for pain. He also noted that the approximately 50 million Americans living with chronic pain could certainly stand to benefit. 

References 

1. U.S. Department of Health and Human Services. (n.d.). Complex regional pain syndrome. National Institute of Neurological Disorders and Stroke. Retrieved from https://www.ninds.nih.gov/health-information/disorders/complex-regional-pain-syndrome 
2. Zhong, Z., Chen, A., Fa, Z., Ding, Z., Xiao, L., Wu, G., Wang, Q., & Zhang, R. (2020). Bone marrow mesenchymal stem cells upregulate PI3K/AKT pathway and down-regulate NF-κB pathway by secreting glial cell-derived neurotrophic factors to regulate microglial polarization and alleviate deafferentation pain in rats. Neurobiology of disease, 143, 104945. https://doi.org/10.1016/j.nbd.2020.104945
3. Stem cells could relieve CRPS pain and inflammation. Practical Pain Management. (2023, January 18). Retrieved from https://www.practicalpainmanagement.com/news/stem-cells-could-relieve-crps-pain-and-inflammation

As of the 2022 elections, there are fourteen doctors in the United States House of Representatives and four in the Senate [1, 2]. While these numbers represent a decline in the number of physicians in the federal legislative branch over the last few years, [3], the current makeup of Congress is reflective of the general rarity with which physicians have occupied this position. Consider, for instance, that, of the 2,196 people that held office in Congress between 1960 and 2004, there were only 25 physicians [4]. With such low numbers, it may appear that doctors have not made significant contributions to federal lawmaking; however, as this article will demonstrate, the impact of doctors in Congress has been quite pronounced. 

What equips doctors with the ability to make such a strong impact in Congress? For one, physicians can use their expertise in medical issues to make contributions, particularly on health issues, that other congresspeople who have been trained in distinct fields may not be well-equipped to make [4]. For instance, former Senate majority leader and academic transplant surgeon William Frist drew on his experience working on organ transplants to introduce the Organ Donation and Recovery Improvement Act in 2002 [4]. The Act, which directed $25 million towards “efforts to promote organ donation,” was signed into law in 2004 [4]. 

Not only do doctors have the skills necessary to analyze scientific data and understand complex medical problems, but they also have the lived experience of working alongside other healthcare practitioners, treating patients, and interacting with medical administration [4]. As a result, they are in a unique position to raise notable issues before Congress and thereby fortifying the country’s national healthcare landscape [5]. In an analysis of physician involvement in parliamentary bodies around the world, Rees and colleagues found that the presence of physician-legislators contributes to a wide range of healthcare topics being debated in such bodies [5]. By having physician voices in Congress, issues such as funding for biomedical research and healthcare systems are more likely to receive their due consideration [5]. 

Furthermore, doctors can have a significant impact on Congress due to their credibility. Especially when it comes to healthcare lawmaking, Americans have historically lent great credence to physicians’ perspectives [4]. This is evident from a 2012 poll, in which 90% of the people surveyed accorded physicians with a “fair amount” or even a “great deal” of respect, compared to 48% for business executives and 45% for lawyers [4]. As a result, physicians may play an important role in garnering public support for medical legislation. That being said, public trust in US healthcare and healthcare workers has dropped since the start of the Covid-19 pandemic. 

And, lastly, doctors may have an impact on Congress in line with their other demographic characteristics. Currently, the physicians in Congress tend to be “male, White, older than 55 years, and Republican” [6]. Asian doctors account for only 6% of federal physician-legislators, while there are no African Americans in such a position [6]. Because physician-legislators tend to come from such a narrow subset of the United States population, their activity in Congress may be reflective of their demographic characteristics. Though doctors can bring important perspectives to lawmaking, it is also necessary to have input that is reflective of the population’s voices and interests. 

To bolster physician involvement in Congress, organizations such as the American Medical Association and the American College of Obstetricians and Gynecologists run programs meant to help prospective candidates [3]. If doctors enjoyed a more pronounced role in Congress, they could help pass more informed healthcare laws. And, if doctors from a more diverse set of backgrounds were elected, healthcare policy could reflect a broader set of needs and interests. Clearly, physician involvement in Congress has historically been impactful and, in the future, may continue to expand. How this will impact medical legislation in the U.S. is to be seen. 

References 

[1] R. Southwick, “There will be doctors in the House, and a few in the Senate: Election 2022,” Chief Healthcare Executive, Updated November 10, 2022. [Online]. Available: https://www.chiefhealthcareexecutive.com/view/there-will-be-doctors-in-the-house-and-a-few-in-the-senate-election-2022.  

[2] United States Senate, “Physicians in the Senate.” [Online]. Available: https://www.senate.gov/senators/PhysiciansintheSenate.htm.  

[3] D. Pittman, “Wanted: Doctors in Congress,” Politico, Updated June 14, 2018. [Online]. Available: https://www.politico.com/story/2018/06/14/wanted-doctors-in-congress-594972/.  

[4] B. Powers and S. H. Jain, “Physicians In Congress: A Prescription For Better Health Policy?,” Health Affairs, Updated March 5, 2014. [Online]. Available: https://www.healthaffairs.org/do/10.1377/forefront.20140305.037591/.  

[5] C. A. Rees, “The ‘Physician-Legislator’: a Comparative Analysis of Physician Membership in National Parliamentary Bodies,” Journal of General Internal Medicine, vol. 37, no. 8, p. 2096-2099, June 2021. [Online]. Available: https://doi.org/10.1007/s11606-021-06972-6. 

[6] R. Payerchin, “Physicians among the lawmakers as House struggles over leadership for next Congress,” Medical Economics, Updated January 6, 2023. [Online]. Available: https://www.medicaleconomics.com/view/physicians-among-the-lawmakers-as-house-struggles-over-leadership-for-next-congress.

Oxygen is essential for the survival and proper functioning of most eukaryotic organisms, including humans [3].  It plays a vital role in cellular respiration, the process by which cells generate energy by breaking down glucose and other nutrients. Cells have highly evolved systems for sensing and responding to having too little oxygen [3]. At the cell membrane, specialized ion channels on the cell membrane, particularly K+ channels, are responsible for the detection of oxygen, while several oxygen-responsive transcription factors inside the cell drive the molecular responses to hypoxia [9]. Lack of oxygen or excessive oxygen consumption could result in inadequate oxygen supply at the tissue or cellular level to sustain appropriate homeostasis, a condition defined as hypoxia [2,3]. Several factors can contribute to hypoxia, including various conditions, such as respiratory disorders, cardiovascular diseases, anemia, and high altitudes [6,9]. If hypoxic conditions are sustained, it can lead to a metabolic crisis that is ultimately lethal to cells and results in several detrimental outcomes if left untreated. 

Reduced energy generation is one of the most direct repercussions of cells receiving too little oxygen. Cellular respiration needs oxygen to make ATP, the cell’s energy currency.4 However, during hypoxic conditions, ATP-consuming processes are inhibited, and metabolism is disrupted until oxygen homeostasis is restored [4]. When cells cannot create energy through cellular respiration, they may turn to alternate metabolic pathways that are often less effective and generate toxic byproducts [13]. These byproducts can accumulate in the cell and cause damage, leading to cell death [13].  

Too little oxygen in cells can also cause inflammation and oxidative stress [8]. Oxygen acts as the last electron acceptor in oxidative phosphorylation [8]. Reactive oxygen species (ROS) are normal byproduct of oxidative phosphorylation, but during cellular hypoxia, ROS production may become unbalanced, leading to an overabundance of these molecules [8]. ROS accumulation may increase the susceptibility of cells to degeneration, resulting in inflammation, oxidative stress, and other forms of cellular damage [8]. This damage can inhibit the cell’s ability to self-repair, which may result in cell dysfunction or death [8].  

Oxygen is also essential for the proper functioning of the immune system, including neutrophils and monocytes [7,12].  Without enough oxygen, the immune system may not function optimally, resulting in a compromised immune system and potentially leading to an increased susceptibility to infection and other disorders [5]. Hypoxia can also affect the production of cytokines, which are proteins that help to regulate the immune response [9]. When the body is hypoxic, the production of specific cytokines may be reduced, leading to an impaired immune response [9].

The effects of too little oxygen on cells and the body can vary depending on the severity and duration of the condition. In mild instances, symptoms include shortness of breath, tiredness, and headache [2]. However, severe or prolonged hypoxia requires immediate medical attention and may result in organ damage and failure, coma, and even death [2]. It is important to address and treat hypoxia as quickly as possible to minimize the potential for cellular damage and the associated negative consequences. Treatment may involve oxygen therapy, medications, or addressing any underlying conditions contributing to the hypoxia. Early diagnosis and treatment can help to prevent further complications and improve the chances of a full recovery. 

References 

1. Abe, H., Semba, H., & Takeda, N. (2017). The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases. Journal of atherosclerosis and thrombosis, 24(9), 884–894. https://doi.org/10.5551/jat.RV17009 
2. Bhutta BS, Alghoula F, Berim I. Hypoxia. [Updated 2022 Aug 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482316/ 
3. Chen, P. S., Chiu, W. T., Hsu, P. L., Lin, S. C., Peng, I. C., Wang, C. Y., & Tsai, S. J. (2020). Pathophysiological implications of hypoxia in human diseases. Journal of biomedical science, 27(1), 63. https://doi.org/10.1186/s12929-020-00658-7 
4. Lee, P., Chandel, N. S., & Simon, M. C. (2020). Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nature reviews. Molecular cell biology, 21(5), 268–283. https://doi.org/10.1038/s41580-020-0227-y 
5. Maggini, S., Pierre, A., & Calder, P. C. (2018). Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients, 10(10), 1531. https://doi.org/10.3390/nu10101531 
6. Mozos I. (2015). Mechanisms linking red blood cell disorders and cardiovascular diseases. BioMed research international, 2015, 682054. https://doi.org/10.1155/2015/682054 
7. Palazon, A., Goldrath, A. W., Nizet, V., & Johnson, R. S. (2014). HIF transcription factors, inflammation, and immunity. Immunity, 41(4), 518–528. https://doi.org/10.1016/j.immuni.2014.09.008 
8. Semenza G. L. (2012). Hypoxia-inducible factors in physiology and medicine. Cell, 148(3), 399–408. https://doi.org/10.1016/j.cell.2012.01.021 
9. Taylor A. T. (2011). High-altitude illnesses: physiology, risk factors, prevention, and treatment. Rambam Maimonides medical journal, 2(1), e0022. https://doi.org/10.5041/RMMJ.10022 
10. Taylor, C. T., & Colgan, S. P. (2017). Regulation of immunity and inflammation by hypoxia in immunological niches. Nature reviews. Immunology, 17(12), 774–785. https://doi.org/10.1038/nri.2017.103 
11. Trayhurn P. (2019). Oxygen-A Critical, but Overlooked, Nutrient. Frontiers in nutrition, 6, 10. https://doi.org/10.3389/fnut.2019.00010 
12. Zenewicz L. A. (2017). Oxygen Levels and Immunological Studies. Frontiers in immunology, 8, 324. https://doi.org/10.3389/fimmu.2017.00324 
13. Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiological reviews, 94(3), 909–950. https://doi.org/10.1152/physrev.00026.2013 

Most people who contract COVID-19 recover fully within a couple of weeks. However, a minority experience long-term symptoms for weeks or even months after the acute infection. Known as “long Covid,” these patients may suffer from debilitating fatigue, headaches, muscle pain, brain fog, and depression and anxiety (5). As many as ten percent of those who are infected by SARS-CoV-2 will experience lingering symptoms by some estimates (5). However, the phenomenon of long-term, systemic illness following viral infections is not new. High incidences of similar illnesses have been recorded following infectious outbreaks throughout the twentieth century (5). These conditions can collectively be studied as post-viral fatigue syndrome. 

For instance, after the 2003 outbreak of SARS-CoV-1, 60% of patients were still experiencing fatigue at twelve months (5). And during the 1918 H1N1 influenza pandemic, many of those affected experienced long-term, neurological disorders (3). For some, post-viral fatigue syndrome progressed to a debilitating neuroinflammatory illness known as Chronic Fatigue Syndrome (2). Patients’ calls for increased research and support around these chronic conditions have often been dismissed or discredited by medical professionals. Now, new findings surrounding long Covid may offer evidence to bolster research and treatment for post-viral fatigue syndrome. 

Post-viral fatigue syndrome is defined as a multi-systemic, complex condition that is caused by an acute or chronic viral infection (4). Patients experience various physical, cognitive, and neurological disabilities that may severely impact their ability to function in daily life. Viruses that can trigger post-viral fatigue syndrome include Epstein-Barr virus, influenza, Zika virus, Ebola, and Lyme disease (3). These viruses may also be responsible for other chronic diseases. For instance, strong evidence suggests that Epstein-Barr virus can cause Multiple Sclerosis (M.S.), an autoimmune disorder in which the immune system attacks the myelin sheath around nerves (7). 

In some cases, the severity and duration of symptoms may evolve into a condition called Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS). ME/CFS patients suffer from severe fatigue that does not improve with sleep, worsening of symptoms after physical or mental exertion, insomnia, exercise intolerance, and digestive, immune, and cognitive issues (2). Despite the severity of the condition, ME/CFS remains one of the illnesses that is most underfunded for research compared to disease burden (2). In part, this may be because 75 to 85 percent of ME/CFS patients are women, and illnesses that primarily impact women have been historically overlooked (2).  

Researchers at the Yale School of Medicine recently launched the Yale LISTEN Study in response to growing public interest in long Covid. The study aims to “learn more about long COVID, post-vaccine adverse events, and the corresponding immune responses” to illuminate some of the causes, symptoms, and effective treatments for poorly understood, chronic illnesses (2). Professors Akiko Iwasaki and Harlan Krumholz, who are leading the study, hypothesize several different causes that could be responsible for long Covid and other types of post-viral fatigue syndrome. For instance, the acute infection may trigger an autoimmune response or create an imbalance of bacteria in the gut microbiome (2). Another possibility is that irreparable tissue damage occurs during the acute infection, leading to long-term symptoms (2). 

Nevertheless, in order to better understand post-viral fatigue syndrome, a more holistic approach for management and treatment needs to be developed. Collaboration between multidisciplinary teams of doctors is necessary to treat this complex condition, and treatment should strive to improve quality of life for patients through both pharmacological and non-pharmacological methods (5). Moreover, increased funding for studying ME/CFS and other related conditions is necessary to develop treatments for these long-standing yet still poorly understood illnesses that cause great human suffering. 

References  

1. Astin, Rónan et al. “Long COVID: mechanisms, risk factors and recovery.” Experimental Physiology, 2022, pp. 1-16, doi:10.1113/EP090802 
2. Backman, Isabella. “Will Long COVID Research Provide Answers for Poorly Understood Diseases Like ME/CFS?” Yale School of Medicine, 01 Nov 2022, medicine.yale.edu/news-article/will-long-covid-research-provide-answers-for-poorly-understood-ailments-like-chronic-fatigue/ 
3. Balfour, Hank and William Hoffman. “It’s Not Just Long COVID.” The Atlantic, 12 Aug 2022., www.theatlantic.com/ideas/archive/2022/08/long-covid-monovirus-ebv/671080/ 
4. Kopf, Michael. “Post-viral Fatigue Syndrome: Symptoms & Treatment.” K Health, 11 April 2022, khealth.com/learn/fatigue/post-viral-fatigue-syndrome/ 
5. Pintos-Pascual, Ilduara, et al. “Is SARS-CoV-2 the only cause of long-COVID?” Aids reviews, 25 Nov 2022, doi:10.24875/AIDSRev.22000025 
6. “Post-viral fatigue: a guide to management.” North Bristol NHS Trust, The British Associations of Clinicians in ME/CFS, n.d., www.nbt.nhs.uk/our-services/a-z-services/bristol-me-service/post-viral-fatigue-a-guide-management/ 
7. Tingley, Kim. “The Strange Connection Between Mono and M.S.” The New York Times Magazine, 7 March 2022, www.nytimes.com/2022/02/23/magazine/epstein-barr-virus-multiple-sclerosis.html 

The United States experienced its largest outbreak of polio in 1952, with about 20,000 cases. Shortly after, in 1955, the availability of the inactivated poliovirus vaccine eradicated the disease in the United States 1. However, in July 2022, the New York State Department of Health reported that a person in Rockland County tested positive for polio—shortly after which it was identified in New York City’s wastewater samples. How did polio re-emerge, why, what can be done to curb the spread of new cases? 

The Centers for Disease Control (CDC) in September 2022 announced that polioviruses identified in New York met the World Health Organization (WHO)’s criteria for circulating vaccine-derived poliovirus. Indeed, the viral sequences from the polio patient and from three different wastewater specimens harbored sufficient genetic changes to meet the definition of a vaccine-derived poliovirus 2. Globally, the virus’ genetic sequences have been linked to wastewater samples from Jerusalem, Israel, and London, UK—pointing to substantial community transmission 3. Today, the United States now joins a list of approximately 30 other countries to date within which new circulating vaccine-derived poliovirus cases have been identified 4.  

Circulating vaccine-derived poliovirus occurs when local immunity to poliovirus is low enough to allow for the prolonged transmission of the original weakened virus from an oral polio vaccine in a vulnerable individual 5. As the virus circulates and accumulates genetic changes, the virus can regain its ability to infect the central nervous system and cause paralysis. Contrary to common misconceptions, circulating vaccine-derived poliovirus cases are not caused by children receiving the polio vaccine.  

The treatment of polio remains sparse and minimal. Treatment specifically addresses symptoms and signs of polio, such as fever, but also ensures a certain amount of physical therapy to improve any weakness or paralysis. To date, there remain no Food and Drug Administration (FDA) or internationally-approved antivirals against polio 6. Therefore, it is very important to prevent the emergence of polio in the first place. 

The CDC is working closely with the WHO, the Pan American Health Organization (PAHO), and other international public health partner organizations on developing polio prevention measures. In parallel, the CDC continues to support New York State Department of Health’s investigation through ongoing wastewater testing in order to better understand the virus’ spreading dynamics and in order to support vaccination efforts across affected communities 7.  

Improving vaccination coverage is the key to preventing additional cases of paralytic polio in the United States, and although no additional new polio cases have been recently identified, New York State will expand its polio vaccination and surveillance efforts. In addition, frequent hand washing, access to clean water, modern sewage systems, and efficient wastewater management further help to prevent the spread of germs, including viruses like poliovirus, and minimize its medical toll.  

Meanwhile, proactive public education efforts on the nature and spreading dynamics of the disease, as well as further clinical research on preventive and/or treatment measures for polio and related diseases will remain of the utmost importance now and into the future.  

References 

1. United States confirmed as country with circulating vaccine-derived poliovirus | CDC Online Newsroom | CDC. Available at: https://www.cdc.gov/media/releases/2022/s0913-polio.html. (Accessed: 17th October 2022)
2. Updated statement on report of polio detection in United States – GPEI. Available at: https://polioeradication.org/news-post/report-of-polio-detection-in-united-states/. (Accessed: 17th October 2022)
3. Outbreak Countries – GPEI. Available at: https://polioeradication.org/where-we-work/polio-outbreak-countries/. (Accessed: 17th October 2022)
4. Polio Investigation | CDC. Available at: https://www.cdc.gov/ncird/investigation/polio/index.html. (Accessed: 17th October 2022)