Meike and the Microbiome Bunch *New Book Release*

Did you know that we more bacteria on and in us than we have cells that make up our body? Estimates of bacteria to human cell ratio varies from 1:1 to 10:1.  Our bodies are a chimera of human and bacteria.  Just in the digestive system alone, or the “Big Colon” there are 100 trillion bacteria populating it.  One teaspoon of stool outnumbers the stars in the Milky Way Galaxy.

The microbiome helps our body in more ways than we realize.  Our bodies have adapted to this internal and external environment that abuts our cell lining.  The microbiome has earned a designation of “honorable organ,” with its weight of 2-6 lbs.  Other important organs weigh about the same (LIKE THE BRAIN!).

Synopsis:

Meike (MI-KAY) is a microbial journalist reporting the events that occur in and on our body.  She introduces children to a universe of bacteria on each and every one of us.  She explains what are factors that promote harmony and how bacteria can cause infection.  She introduces children to the microbiome in each of the systems of the body.

Children will familiarize themselves with the microbiome and some of the ways that bacteria grow.  The story will open their eyes to how our health affects our microbiome and how we can be stewards of it.  The book has a few fun features in it, that I am sure kids will love, including cute bacterial caricatures and artwork, a gallery of the microbiome bunch, and a sneak peak of the sequel, which I am sure will leave your child fascinated.

About the Authors:

The book was written by Christopher Cirino and Alicia Scheffer-Wong, a long-time frined and colleague.  Back in college, we were microbiology majors and lab-rates together.  I am grateful to have collaborated with her on this.  Already decades in our careers, I am an infectious diseases specialist and Founder of Your Health Forum and Alicia is an entrepreneur and microbiome expert (POOP!) with her company Floragraph Inc.

Please support our cause to make microbiology exciting (we already know that it is important!) and accessible to children and adults alike.

The book can be purchased on Amazon either in a Kindle Ebook ($6) or paperback ($9).

PICK UP YOUR COPY!!!

 

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Meike in her office preparing for her report

The post Meike and the Microbiome Bunch *New Book Release* appeared first on Your Health Forum.

Bathing Can Be Exhausting

As an OT I did not know how tiring a.m. care is because I never watched a stroke survivor do one task after.  Here is why bathing leaves me feeling refreshed instead of exhausted and frustrated.

Washing.  I do not struggle to soap up a washcloth one-handed or chase a bar of soap after I drop it.  I pour shower gel on a nylon poof and knead it a few times to get it soapy.  To wash my sound arm, I use a gross grasp in my affected hand to hold the nylon poof.  I do not struggle to wring out a washcloth one-handed.  I hang the nylon poof on a suction-cup hook, hose it down, and let it air dry.  I use shampoo suds to wash my face.

I press down on the nylon poof that is resting on my thighs to squeeze out suds so my sound hand can soap up my crotch.  Before I could hold the shower hose with my hemiplegic hand,
I used my forearm to press the shower hose against my stomach to rinse my crotch.  Water runs downhill.  This freed my sound hand to deal with the nooks and crannies.  If my husband was alive I would still want to bathe this private part of my body.

Drying.  My towel rack is next to the shower so I can reach it while sitting on my shower chair.  I drape the towel over one shoulder while I dry my arms and trunk.  When I get out of the shower I stand to dry my crotch with the towel draped over my shoulder.  My shoulder carries the weight of the towel so it is easy for my sound hand to manipulate the free end.  I never hold up my affected leg to dry it.  I don a terrycloth bathrobe which dries my buttocks and thighs and I let my calves air dry while I brush my teeth and comb my hair.

Dressing.  For the 1st year after my stroke, dressing was easier if I rested after bathing.  I laid on the bed in my bathrobe with a towel under my wet hair and listened to music on the radio.  homeafterstroke.blogspot.com

How I Escape from Covid-19

I have been reading e-books on Hoopla to pass the time while sitting at home during the covid-19 pandemic.  I recently reread My Antonia by Willa Cather.  This book brought back fond childhood memories of my father driving across Illinois and Iowa to visit my grandparents before there were interstate highways.  State highways built before World War II wove through miles of wheat fields that moved in the wind like ocean swells.  When we came to an intersection we could see cars for miles in all directions because the land is so flat.  One of Cather’s characters described the land this way – “I wanted to walk straight through the red grass and over the edge of the world which
could not be far away.”

When I moved east to New Jersey I freaked out for years when I drove on narrow state and county roads with sharp curves.  Not being able to see on-coming traffic around a bend was unnerving.  For years I also missed seeing the horizon at sunset.  I have gotten used to the closed-in landscape of the densely populated east coast, but the open vistas of the middle-west still thrill me.

I am grateful that a stunning writer who won a Pulitzer Prize helped me reconnect home and
happy memories.  homeafterstroke.blogspot.com

Covid-19 Made Me Smarter

Currently over 4,700 covid-19 deaths in New Jersey have occured in long-term-care facilities so
I am very motivated to do what it takes to stay in my home.  For example, my cleaning lady has not come for 6 weeks because of the pandemic.  When I smelled dust and started to sneeze I felt compelled to try vacuuming until it is safe for Isabel to be in my home for two hours.

I vacuumed years ago so I already knew 2 tricks.  (1) Vacuuming is exhausting because it requires stepping forwards and backwards abruptly a hundred times so I vacuum only one room a day.
(2)  I knew tripping on the cord was a huge fall hazard.  Thankfully I can hold the cord out of my way.  I rest the cord in my partially curled hemiplegic fingers and use shoulder abduction to hold the cord away from my body.

I discovered 2 new tricks to make vacuuming easier.  (3)  I do not step forwards and backwards.
I stand still and move the vacuum forward and backwards only one arm’s length.  Then I take two steps sideways to clean a two-vacuum wide path before moving forward.  Most of my falls have happened when I step backwards but I feel stable when I step sideways.  (4)  Instead of vacuuming in parallel rows the way people cut grass, I start by vacuuming around the perimeter of the room and gradually work towards the center.  Making 90 degree turns is easier than 180 degree turns.  homeafterstroke.blogspot.com

Nurturing the Resilient Spirit: Ways to support Mental Wellness During the COVID-19 Quarantine

Summary:    The COVID-19 Pandemic is an unprecedented event that requires a rift in the societal fabric in order to stop its spread.  This forced isolation, along with the threats on financial and health security, can create pressures on those already with a history of depression and anxiety and lead to challenges in those that don’t.

Here are seven tips to nurture your mental wellness and create resilience during this uncertain time of social distancing.  Not only will these strategies help you to maintain some normalcy through these times, they just might help you excel.

 

The COVID-19 pandemic has been responsible for widespread upheaval.  Literally overnight, we have been asked to change our behaviors, stay at home other than essential trips out, and wait for this pandemic to pass.  Trips, social events, religious gatherings, and restaurants have been canceled or closed.  We have been asked to work from home and hold teleconferences instead of physical meetings.  For many of us, these are the very ways that we define our social and support network.

Constant reporting of new case numbers and new virus-related deaths has been both emotionally distressing and overwhelming throughout the world. When paired with shelter-in-place orders and the inevitable time spent confined at home, this unprecedented global event has placed tremendous stress on some of the population’s most vulnerable. Current events are making it harder for everyone to protect and promote mental health. Absent of key resources and often unable to receive the same support and social engagement that’s typical of their daily lives, those with diagnosed and chronic mental health issues are finding themselves in an increasingly dangerous space. The good news is that even in times like these, there are still multiple ways to create the conditions for resilient mental health.

 

Who’s At Greatest Risk Of Experiencing Mental Health Issues During The COVID-19 Pandemic?

Right now and for the foreseeable future, everyone is at risk of experiencing deep depression, anxiety, and stress. So much of what’s going on in the world is impossible for people to control. This sense of helplessness invariably fosters feelings of hopelessness, even in many who have formerly enjoyed consistently good mental health, general mood balance, and overall high life qualities.

However, there is also a very large number of people who are especially prone to mental distress at this time. This includes people who by choice or by circumstance were already spending significant amounts of time alone and in virtual isolation such as: elderly adults with age-related mobility issues, those with agoraphobia or fear of leaving the home, and disabled individuals who largely live in confinement. Those at greater risk for mental and emotional distress at this time additionally include people who are presently battling drug or alcohol addiction, those who have dealt with substance abuse or addiction in the past, recent divorcees, widowers, those grieving close friends, and those with a history of trauma and who may also be living with post-traumatic stress disorder.

Stressors to Mental Health During Quarantine:

A recent review article from Lancet by Samantha Brooks et al. entitled The psychological impacts of quarantine and how to reduce it discussed several risk factors that provoked a greater risk of mental health issues.  It is with hopes that identifying the triggers to depression and anxiety can help us to construct ways to mitigate these risks.

  • Longer duration quarantine (>10 days) or duration uncertain:  Associated with poorer mental health, e.g. PTSD, avoidance behavior and anger.
  • Fears of Infection.  In one review, those who were concerned tended to be parents with young children or pregnant women.
  • Frustration and Boredom.  A change in usual behavior even routine things like shopping or social networking can create a sense of boredom and isolation.
  • Inadequate Supplies Concerns. This includes the ability to get regular medical care and prescriptions.
  • Inadequate Information.  In studies, participants raised the greatest concerns when there was unclear messaging from public health authorities or a concern for lack of transparency.  Some concern with adhering with quarantine protocols was a predictor of post-traumatic stress disorder in one study.
  • Financial Factors.  Many people have been asked to modify their work routines such as working from home and, in certain cases, have even lost their jobs.  Those with a lower financial safety net, such as those with high debt to income burden, are particularly at risk.

 

The seven simple strategies that follow can benefit anyone who’s feeling the pressure of world and economic events, and who’s struggling to maintain mental health in the face of prolonged and mandated social distancing and social isolation.

 

  1. Get Outside And Get Moving

 

Most shelter-in-place orders that are presently being enforced are not intended to prevent people from going outside entirely. Instead, these orders have been designed to limit gatherings and activities that bring large numbers of people together. Moreover, in addition to not restricting solitary outside activities, or outside activities involving two people or fewer, many of these orders have been issued by municipal bodies that are actively encouraging people to get outside and exercise. The general understanding is that too much time spent indoors and leading a highly sedentary lifestyle is not beneficial for anyone at any time.

Pick a time each day to get outside and get moving. This can be as simple as taking a short walk around your neighborhood or going for a ride on your bike during the early morning hours or late afternoon. Although there are fewer recreational areas still open for enjoyment, there is also far less traffic on the streets. You can use this as an opportunity to better appreciate your neighborhood without the hustle and bustle of moving vehicles and busy consumers.

A short walk or bike ride will lift your spirits and give you the opportunity to re-center your thoughts. It can also make you feel more connected to the world around you. Outside exercise can even be as simple as taking your yoga mat out into the yard or onto a patio or balcony.  It might be a good time to get outside to a local park and practice the calming art of Shinrin-yoku, or forest bathing.   In addition to benefiting from conscious and structured movement, you’ll have the benefit of fresh air, sunlight, and a restored sense of normalcy.

 

  1. Continue Interacting With Others Via Social Media And Other Online Platforms

 

Now is a great time to start making use of social networking platforms. If you haven’t leveraged them before, these are great spaces for reconnecting with distant family members, childhood friends that you’ve lost contact with, and loved ones that you normally communicate with in other ways. Video chat platforms such as Skype can give you the benefit of both speaking to and seeing the people who normally fill your life, and who provide you with the social stimulation and engagement that’s absolutely essential for maintaining good mental health.

 

  1. Brighten Each Day With Exploration, New Learning, And Other Enriching Activities

 

For many, the COVID-19 pandemic has provided a very bittersweet silver-lining; massive amounts of free time. For those who are no longer working or having to physically commute long distances to their jobs, as well as those who are no longer attending in-person classes at school, this event offers countless opportunities to engage in new forms of learning and exploration. If you’ve ever wanted to make your own sourdough starter, crochet a blanket for a brand new or aging family member, teach yourself a new language, or pick up the cello, piano, or guitar, now is a great time to do it. These activities are personally enriching. More importantly, efforts to promote personal growth often give people greater hope for the future.

 

  1. Engage In Art Therapy

 

Now is also a time to break out your adult coloring books, or, better yet, start with a tabula rasa mentality and create your own work. Art is one of the most therapeutic activities that you can engage in. It’s immersive, cathartic, and relaxing. When you’re focused on drawing or coloring in the lines, choosing complementary colors, and achieving a very specific aesthetic, you cannot simultaneously dwell on all the outside problems that are beyond your realm of control. Creating art in any form can be both meditative and restorative. This is additionally a good time for art appreciation. Take advantage of online museum tours, free or discounted art or cooking classes, and other arts-related resources. Use online videos to start practicing and exploring martial arts, or start reading and writing poetry. Keeping a journal is also a great way to begin organizing your thoughts, analyzing your own emotions, and venting about your personal discomfort among other things. If you ever dreamed of writing your memoirs, the present moment is offering the perfect opportunity.

For those of you interested in using this form of expression and participating in an ongoing exhibition of art inspired by these current times, see the art that is posted on Instagram Hashtag #Cov19_art. I would like to compile the art, poetry, photography and writing into book that documents the psyche of these times and celebrates our perseverance.

 

  1. Unplug And Unwind

 

For all the resources, information, and assistance that the Internet is able to provide during this crisis, it can be just as harmful as it is beneficial. This is especially true when people spend too much time on the web, and when they spend too much time immersing themselves in activities and ideas that foster stress. While staying informed is vital, you must limit the amount of news that you’re reading. Nothing is currently so dire that it requires minute-by-minute updates. Set a special time for logging in and gathering essential information from trusted news sources. Then, set a special time for turning your phone off, logging off your computer, and turning off your TV. Whether you have diagnosed mental health issues or believe yourself to be in excellent mental health, too much information can lead to overload and can leave you feeling deflated, detached, depressed, or excessively anxious.

 

  1. Make Sure That You’re Getting Enough Quality Sleep

 

Getting poor-quality or insufficient sleep at this time is a bad idea. Not only will this undermine your efforts to maintain good mental health, but it can also lead to a flagging immune system. If you had a nighttime ritual before, try to stick to it. Moreover, don’t try to mute your emotions or lull yourself to sleep with increased indulgence in alcohol. Some areas under quarantine are reporting as much as a 40 percent increase in alcohol consumption since the institution of stay-at-home orders. Rather than promoting good sleep, alcohol actually reduces overall sleep quality, and shortens the amount of time that people are able to remain asleep.

Try reading a book or meditating before going to bed, taking a warm shower, and turning off all electronics and Internet-connected devices. If necessary, sip a warm cup of chamomile tea or a large mug of warm milk and honey. Making deep and restful sleep a top-priority is one the best things that you can do to promote physical and mental health at this time.

 

  1. Practice Mindfulness And Conscious Directing Of Your Thoughts

 

No other world event has highlighted the value and importance of mindfulness than the COVID-19 pandemic. With so much going on around you, it can be difficult to not let feelings of anxiety and panic set in. There is enough fear and stress in the present movement to exhaust anyone’s ability to mentally process current world circumstances. As such, there is no need, reason, or benefits in worrying about possible problems that might lie far ahead in the future. Practice focusing on the moment. Enjoy what you have you right now and work on fostering a mindset of gratitude. If you’re tired of being stuck alone at home, remind yourself that there are some people who have no homes to take shelter in. Give yourself permission to only worry about and deal with the problems that you’re immediately facing. Practicing mindfulness can help alleviate negative emotions about past events, while also limiting anxiety about what the future might hold.

 

The state of your mental health should be a key concern right now. Actively promoting good mental health and proactively protecting your general sense of well-being is critical. With greater mood balance, proper stress management techniques, and a focus on enriching and expanding yourself, you can successfully survive the mental and emotional ravages of this global pandemic, and any other unexpected life events.

 

 

COVID-19: From Zoonotic Spillover to Host and Pathogen Interaction in Human Disease

Key Points Answered in this Article

1. What constitutes a spillover?

2. What are the contributing factors?

3. How does SARS-CoV-2 cause infection in human pneumocytes

4. What are the contributing factors to more severe disease.

 

 

The United States prepares itself for the impact of COVID-19  that will likely be unprecedented.  Although we can say that most people who become infected will have a milder disease, we cannot always predict who is at greater risk for a severe outcome.  Particular attention goes to healthcare workers, lower-income communities, and people with advanced age and chronic health conditions.  To those unfortunate ones who develop severe disease and require hospitalization, the US health system faces shortages of ventilators, personal protective equipment (PPE), bedspace and the even the healthcare workers to attend to them.  Worst-case scenarios project hospitals to become flooded with those who have severe disease, particularly if cases were to occur with the same momentum as Italy or China.  The hope is that through the social distancing measures recently implemented, we may be able to blunt the outbreak peak and prevent overburdening our healthcare system.

The general audience has had access to many resources on COVID-19, such as the CDC, WHO, health blogs, video posts, and primary literature.  As we face this outbreak, never before has the nation’s working knowledge of viral infections been greater.  Since the outbreak was declared in December, we have had three months to learn more about this virus.

This post will go one step further into understanding the contributing factors to a viral emergence and how this likely is not the last outbreak we will have in the coming years.  What happens when a virus infects our bodies?  What occurs inside that leads to a certain presentation of a disease state?  Although COVID-19 is shrouded in mystery, it adheres to natural rules, many of which we still need to define.  The mechanism by which a pathogen causes an infection is a clue to how it can be defeated.

 

Viruses are Host and Cell-specific, until they cross species.

Viruses are intracellular pathogens that are species- and cell-specific. This means that they are usually only capable of infecting one animal.  Though there may be some fluidity to this concept.  A virus can reside in an animal, whether it is actively infecting the animal or not.  An animal virus is called a zoonotic virus, and the animal carrying it is a reservoir.  In viral zoonotic spread, mammals (e.g. bats, primates, etc) are the most common reservoir followed by birds.  When the conditions are right and several barriers are able to be breached, viruses can jump species, infecting other animals including humans. The process by which a virus jumps species and causes human infection is termed a spillover, an example of which is our current COVID-19 pandemic.

Over 75% of new or emerging diseases originate from animals.  From 1940 to 2004,Jones et al. (2008) determined that there were a total of 335 emerged diseases, 60% originating from animals.  In most outbreaks, human behaviors  shaped the conditions that made it possible.   The principal factor relates to human encroachment into animal habitats.  It is no coincidence that an acceleration of outbreak has occurred in the last sixty years (fourfold increase) in the setting of a massive population boom.  Eerily, a Times article  describing spillovers written in May 2017 was entitled The World is Not Ready for the Next Pandemic.

 

“We cut the trees; we kill the animals or cage them and send them to markets. We disrupt ecosystems, and we shake viruses loose from their natural hosts. When that happens, they need a new host. Often, we are it.”  David Quammen, author of Spillover: Animal Infections and the Next Pandemic writing in New York Times.

 

From the 1800’s, it took approximately 127 years for the population to increase by one billion, i.e. from one to two billion, an achievement that only took thirteen year intervals over the last several decades to achieve 7 billion.  The population growth may be a driving force for disputes over settlements, habitat invasion, the use of exotic animals as a food source in the setting of growing food insecurity,  or the trade and introduction of exotic animals to be used as products or pets.  Certain features directly related to the virus, including mutations, deletions and recombination, enable the virus to survive and then flourish within an introduced animal.

Ingredients of a Spillover Event.
Contributing Factors to a Spillover are related to human and animal behavior, as well as ability for the virus to persist in an introduced host.

Adapted form Nat Rev Microbiol. 2017; 15(8): 502–510.doi: 10.1038/nrmicro.2017.45

population growth chart

 

 

Ingredients for a Spillover Event. 

Although outbreaks are infrequent events, current conditions may allow for an increased risk.  For a virus to jump species from an animal reservoir to to human to human spread, usually several conditions would need to be met.  First, animals infected with a virus need to be stable and have persistent shedding of virus, while not succumbing to it.  Second, the animals would need to be in close proximity to humans.  Next, an exchange of infected fluids, such as saliva, mucus, feces or blood, or the ingestion of an animal allows for a sufficient amount of virus to be introduced into the new animal by its usual infection route.  While inside the human, some of the virus must possess a specific (enough) receptor mutation to allow for avidity (or connection) of the virus to a host receptor to gain entry into the specific cell.  Finally, it must be able to propagate and infect other cells, without being identified and neutralized by the host’s innate immunity.  Once it is able to survive and replicate within the human host, it must be able to be transmitted from one human to another.  If any of these conditions are not sustained, a spillover does not occur.

Street Light Diagram
Street Light Diagram of Components to A Spillover:  Adapted from RNA viruses: a case study of the biology of emerging infectious diseases.  Woolhouse M. et al. Oct 2013.  Microbiol Spectrum.

From the “Street Light Diagram,”  yellow (level 2) is intended to connote caution.   Red (level 3) indicates higher risk of pandemic potential, but certain viral and non-viral kinetics (e.g. population density, behaviors) prevent easy transmission.  These factors influence the basic reproductive number (Ro), with an Ro of greater than one to allow for risk  of exponential growth.  The black (level 4) designation is related to epidemic spread.  For a detailed list of RNA viruses that are recognized as causing infections in humans and their respective levels, refer to Woolhouse M. et al (list).

Of particular concern are the 180 and counting (2 newly identified per year) RNA viruses capable of infecting humans, the majority (89%) of which are zoonotic.  Examples of recent RNA viruses that have emerged include HIV, influenza virus, NIPAH virus and the Coronaviruses SARS, MERS and SARS-CoV-2.  RNA viruses may more easily jump species, because of their tendency to mutate and adapt more easily when introduced.  Not all RNA pathogens that cause infection in humans from animals are capable of being spread from human to humans.  The majority of zoonotic RNA viruses are restricted to level 2 (approx 107 out of 180 species).  An example of this would be avian influenza (H5, N2 or H9, N2), which does readily not cause human-to-human transmission.  It may be related to the cell type infected, the sialic acid receptor, which is in the upper respiratory tract of poultry and lower in humans. This is fortunate because it has an estimated case fatality rate of 14-30%.  Level 3 spread is seen only in about 73 species and spread is limited in 26 of these RNA viruses.  The remainder (47 Level 4 RNA viruses) can spread human to human, causing epidemics..

Very rarely, a virus may already be able to adapt to a human and lead to an outbreak, termed “off-the-shelf” virusesMore likely, viruses eventually adapt from repeated animal to human transmission and evolve to be more transmissable between humans (Level 3 to Level 4).  HIV probably crossed over from chimpanzees to humans in what is now the Democratic Republic of the Congo in the 1920’s, possibly from hunters who ate “bush meat” or had cuts and wounds contaminated with chimpanzee blood infected with Simian immunodeficiency virus (SIV), a milder disease which does not alter the lifespan of the infected animal.  The ability of HIV to cause a prolonged infection and be transmitted via various routes including bloodborne and sexually enabled it to become a level 4 pathogen and reach global transmission.

The SARS-CoV-2 emerged likely from bats with the possiblity of a secondary animal reservoir the pangolin.  Bats are known carriers of coronaviruses and have been determined to be the likely reservois for SARS and MERS.  Andersen et al.  published a recent correspondence entitled the proximal origin of SARS-CoV-2.   The authors discusss several possible and contributing scenarios.  On account of a 96% identical genome with a sampled bat coronavirus, bats were likely the original reservoir of SARS-CoV-2.  However, SARS-CoV-2 may have evolved the protein stucture of the S-spike to allow for better binding to human ACE2 receptors from pangolin through natural selection.  It is possible that a polybasic cleavage site (necessary for cell-cell fusion) may have evolved after being introduced into humans.

 

From Spillover to Infection and Disease

When COVID-19 emerged from an animal source and was capable of human to human transmission, humans had no prior memory of this virus.  The immune system was caught off-guard with minimal defense.  As a virus infects cells and increases its numbers in the host, the disease develops, a time when a person presents with signs and symptoms.  Even in the setting of a novel virus, most of the way a disease manifests is due to the host inflammatory response and not because of a distinct genetics, appearances (e.g. receptor sites) and other characteristics of a virus.

Cell infection

A virus is an obligatory intracellular pathogen, meaning it can only thrive within cells.  A specific virus infects a specific type of cell.  Hepatitis C virus infects hepatocytes; BK virus infects the transitional cells of the bladder;  influenza virus and coronaviruses infect type I and type II pneumocytes in the respiratory tract;  HIV infects CD4 lymphocytes and Langhans cells.  The specificity of cell-type is not accidental and relates to a lock-and-key mechanism that a virus has with the cell it infects.  Think of it as a parasite requiring the mechanics of the host to build more copies of itself.  It enters the lining of the respiratory tract and attaches onto cells by means of a receptor interaction.  Specifically, this is between an outer membrane receptor of the virus (Spike glycoprotein (S)) and a receptor(s) on the host cell.  The virus then enters the cell by a process known as endocytosis.

Upon entry, the virus hijacks the cell’s ability to read nucleic acids and produce proteins.  COVID-19 is a positive strand RNA virus,  with the viral RNA serving as a messenger RNA, leading to the production of hundreds of copies of virus RNA and proteins in a single cell (known as replication). These copies self-assemble and form multiple viruses, or progeny.  This results in stress on the cell and cause changes in the cell membrane (membrane rearrangements), damages the infected cell, and go on to infect other cells.

The extent to which a virus can infect cells in known as its pathogenicity.  The speed at which a virus can spread through the body and infect other cells is known as the virus lifecycle.  In the case of viruses, typically thousands of copies can be generated in a period of a day and lead to significant inflammatory changes in the body as a response to infection.

+RNA-replication

 

ACE2 as a SARS-CoV-2 receptor

The S receptor on the SARS-CoV-2 binds to a specific receptor that lines the cells of the lung tissue, as well as heart kidney, endothelium (the inner lining of blood vessels) and the intestines, known as the Angiotensin-converting enzyme 2 (ACE2) receptor.  This interaction is a required step for viral entry into the cell.  Using a mouse model, an increased expression of the ACE2 receptor allowed for more viral entry into the cells and resulted in greater disease severity.  Further studies will have to sort out the speculation that medications such as ACE inhibitors, Angiotensin receptor blockers (ARBs), ibuprofen, or thiazolidinediones,  all of which upregulate ACE2 receptors would potentially worsen COVID-19 disease.  As for now, it does not appear to be the case.  In the realm of vaccine and therapy options, it remains to be seen if blocking these receptors, for instance through antibody therapies, or providing a vaccine that triggers antibodies to the S receptor would alter pathogenesis of the virus.

coronavirus_structure_large

 

How does our immune system recognize these invaders?

The evolution of the immune system occurred in the face of the continuous onslaught of microbes from the environment.The human immune system consists of innate and adaptive immunity.

Innate Immune System

The innate immune system is the first branch to respond to a viral assault.  The components of the innate immune system include cells, such as natural killer cells, dendritic cells, monocytes and neutrophils, and complement proteins.  The innate system senses changes that occur to the cell from viral products and cell damage (Pattern Recognition Receptors).  This triggers the release of interferons (IFN), which promote inflammation (activate molecules known as cytokines) and reduce virus replication.  The cytokines signal special cells, known as natural killer and dendritic cells, which destroy infected host cells to reduce the spread of the viral infection.  The PRRs also trigger a process known as autophagy, in which an infected cell degrades itself to reduce (or the intent to reduce) further infection.

The complement system consists of several proteins that form a complex, leading to cell breakdown (lysis).  They can also signal certain cells such as activated macrophages to engulf infected cells, a process known as opsonization.

Adaptive Immune System

Adaptive immunity requires antibody production and cell-mediated mechanisms.  Some natural antibodies may already be circulating for a given virus that can provide some initial immunity (known as IgM class antibodies).  These are generated by antibody-producing white blood cells known as B cells.  Otherwise specific cells known as Activated macrophages can engulf cells to produce antigen that express more pathogen-specific antibodies by B cells.  The dominant antibody types in humans are IgM, IgD, IgG, IgA, and IgE, each of which has specific roles in the immune response.  The IgG is involved in the memory responses and form to neutralize a virus.

Another white blood cell line, known as T lymphocytes (T cells), are produced in a small gland known as the thymus, which is inside the front part of the chest (behind the sternum and in between the lungs).   These T cells provide cell-mediated immunity. Specific cells are produced that have receptors for a given pathogen and can neutralize them.

From Infection to Disease

When a person becomes infected with a virus or bacteria, there is a period of time at  which s/he is symptomatic.  The term that is used from onset of the infection and expression of the disease is known as incubation period.  Various viral infections have different incubation periods.  For instance, influenza’s incubation period is one to four days; COVID-19 may take one to fourteen days (average of 6) to show symptoms.  During the prodromal phase, the person develops early symptoms of a viral disease.  This could be the beginning of nasal congestion, sore throat, cough and tiredness.  After a threshold is reached and enough cells become infected, a more sizable inflammatory response is generated.  It is at this time, the person becomes symptomatic.

During the invasive phase, the number of circulating virus intensifies, while the body responds to the infection with a maelstrom of inflammatory markers.  The severity of the presentation correlates to the intensity of infection and the inflammatory response.  Eventually, the inflammation subsides as neutralization of the virus as a result of the immune system.  It is at this point that a person’s symptoms gradually resolve.  stages of an infection

 

Viral Disease: It’s all about inflammation

In approximately 80-85% of those infected with SARS-CoV-2, only a mild disease is seen.  In the remaining, a severe infection can lead to hypoxia (low oxygen levels) and need for mechanical ventilation. Owing to increased cellular damage, the subsequent inflammatory response may pose a threat on life.

Risk Factors: In a study of clinical course and risk factors for mortality in COVID-19, risk factors were identified in almost half of the patients, with hypertension, diabetes and coronary heart disease.  Smoking likely leads to a two-fold risk of more severe disease than a non-smoker.  Advanced age is also a significant mortality risk.  From the Wuhan epicenter data:  80+ years, 14.8%; 70-79 years, 8%; 60-69 years, 3.6%; 50-59 years 1.3%.  This is likely on account of dysfunctional innate immunity, IL-2 signaling (not down-regulating) and T-cell mediated immune system with aging.  What still remains unknown for COVID-19 infection is whether there exist genetic determinants (as seen in other viral diseases) that lead to a greater risk of a more severe infections.  This could explain why we are hearing reports of severe disease in the “otherwise healthy” youth.

Pathogenecity and Inflammation Contribute to Disease Manifestations.  The extent to which someone presents with more severe disease relates to an interaction of amount of cell destruction from viral burden and host response.  Below is a depiction of the contributing effects of Viral Pathogenicity and Host Inflammatory Response in disease.  Increased viral infection burden is likely an important contributor to a greater immune response.   It may be that type 2 pneumocyte infection in the lower respiratory tract may cause a greater cytokine release than infection in upper respiratory cells.

disease manifestations
Disease:  A “dance” between viral infection and immune response

 

Disease Presentation

The most common symptoms on admission were fever and cough, sometimes with sputum production and fatigue.  Interestingly, the average time of presentation of respiratory complaints, such as shortness of breath, is approximately 7 days and need for invasive ventilation is 14.5 days (range 12-19 days), suggesting that the latter part of infection may be when greater inflammation develops “cytokine storm”.  The most frequently observed complication was sepsis, followed by respiratory failure, ARDS, heart failure and septic shock.

10.1016-S0140-6736(20)30566-3Figure1

**The shortness of breath (“Dyspnea” in blue) started around day 7 in both groups**

 

Laboratory Findings for Hospital Management

There is a significant inflammatory response in more severe infections of COVID-19.  Patients may develop ARDS, which is the leading cause of mortality.  Several findings of the disease support a hypercytokine, hyperinflammatory response that contribute to a more severe presentation.  These patients have a persistent fever, low white blood cell count, elevated cytokines (IL-2, IL-7, IL-6, GM-CSF, Interferon gamma and others), an elevated ferritin, and an elevated D-dimer.

Future Therapy

In an unprecedented move, the FDA has granted emergency authorization for the use of hydroxychloroquine along with azithromycin based on early clinical data that there may be a benefit of hydroxychloroquine in reducing viral load and inflammatory state.   We await further progress in other therapeutics and vaccine trials, many of which are now underway.

Summary

The COVID-19 outbreak was a spillover event of a novel coronavirus from an animal reservoir that led human to human transmission.  Further research is required to understanding the way the infection can lead to various disease manifestations, including who may be susceptible to more severe presentations.  Hydroxychloroquine along with azithromycin may provide some benefit in treating those with severe disease.  As for now, we await for the results on the treatment and vaccination fronts.

 

Resources:

References are embedded in the Text

Simon A, Hollander G, McMichael A.  Evolution of the immune systen in humans from infancy to old age.  Proceedings of the Royal Society B.  22 Dec 2015.

Zhou F, Yu T, Du R, Fan, G, Liu Y, Liu Z et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.  The Lancet.  Vol 395, issue 10229, p 1054-1062.  28 Mar 2020.

My Stroke Strategies for the Corona Virus

These strategies are related to my daily routine.  They are examples of what stroke survivors can do to protect themselves.  Your risk of catching the corona virus is probably different from mine but I think we can agree that a stroke creates enough drama for a lifetime.

Washing hands with the backwards rule:   With the soap dispenser facing away from me, I push down on the nozzle with my palm and catch soap with my fingers.  After I scrub my hands, I run my soapy thumb over the top of the handle before I rinse.  I started washing my hands this way years ago when I handled raw chicken.  I did not want to leave chicken fluids on the bar of soap and soap dish.

Paying:  Many infected people do not cough so the rapid spread of the corona virus cannot be explained by lots of people spraying germs in the air.  We do not know how long the corona virus lives on environmental surfaces.  For now I pay with a credit card instead of handling coins that hundreds of people have touched.  It is cold enough to wear a coat so I put this credit card in my coat pocket rather than dig through my purse to find it.

Shopping cart:  It is easier to push and steer a shopping cart with both hands.  However, physical exertion makes my hemiplegic thumb bend fully so I don a piece of foam to stop my thumb nail from cutting into my skin.  I use a Kleenex tissue to take the foam off when I get in the car and then I isolate it in a special location.

Handles and keys:  Some people wipe the handle of a cart before they start shopping.  This does not protect them when they touch cans and boxes touched by employees who stock the shelves.
We do not know how long the corona virus lives on environmental surfaces.  I currently have 2 cuts on my sound fingers so before I get out of the car I don a thin vinyl glove used by beauticians.  It is one size too large so it is easier to don.  I remove the glove after I get the cart to my car.  My sound hand is clean when I open the car door, pull my car key out of my purse (green wrist band), and put my hand on the gear shift handle and steering wheel.  I throw the glove in a bag in my car.  My sound hand is clean when I pull out my house key (purple band) and open my front door.  I wash both hands when I get inside.

Touch screens:  Before the corona virus I refused to use a filthy touch screen to order a meal and then pick up food with my sound hand.  Ordering in person is slower but safer as long as I use a napkin to handle the menu which is never washed.  If a transaction forces me to use a touch screen, I use the back of a knuckle which I never stick in my ear, nose, or mouth.

Touching my face:  On the news a reporter touched her face 13 times in one hour while using a computer even though she was trying not to.  Transferring germs from our hand to our eyes, nose, or mouth is a common way to get sick.  The news story concluded that it is really hard to stop this unconscious behavior.  Any suggestions would be welcome.            homeafterstroke.blogspot.com

High Cholesterol is a Bad Thing, and Now Low Cholesterol Is Not Much Better

Since I was a little girl and able to understand scary stuff, my mother said that her body “manufactured” too much cholesterol. Never mind the fatty foods she ate like red meat and extra buttery toast and cheesecake, her favorite dessert. She stood by her story to the end. I was scared I would inherit the same “manufactured” condition. But I was spared even though I had a hemorrhagic stroke that was from Protein S deficiency. (Don’t get me started on a lousy gene pool).

My mother probably familial hypercholesterolemia, this news  brought you by US National Library of Medicine, a disorder that is passed down through families. It causes LDL (bad or think of loathsome) cholesterol level to be very high. The condition begins at birth and can cause heart attacks at an early age. My mother didn’t have a heart attack, but she could have had one.

Familial hypercholesterolemia is a genetic disorder. It is caused by a defect on chromosome 19. The defect makes the body unable to remove low density lipoprotein (LDL, or bad) cholesterol from the blood. This results in a high level of LDL in the blood.

This condition makes you more likely to have narrowing of the arteries from atherosclerosis at an early age. The condition is typically passed down through families in an autosomal dominant manner (that is, inheriting a disease, condition, or trait depending on which type of chromosome was affected).

And that’s probably what she meant by manufacturing high cholesterol. So I thought to myself, I’m lucky that I escaped the high-cholesterol syndrome, and now that I am a pescatarian or, as I like to say, a vegan with fish. That got me thinking: Can your cholesterol be too low? The answer scared me more.

In April of 2019, a study by the American Academy of Neurology said that low cholesterol was linked to a higher risk of “bleeding [hemorrhagic] stroke” in women.

A study found out that women who have levels of LDL cholesterol 70 mg/dL or lower may be more than twice as likely to have a hemorrhagic stroke than women with LDL cholesterol levels from 100 to 130 mg/dL.

The study also discovered that women with the lowest triglyceride levels, that is, fat found in the blood, had an increased risk of hemorrhagic stroke compared to those with the highest triglyceride levels.

“Strategies to lower cholesterol and triglyceride levels, like modifying diet or taking statins, are widely used to prevent cardiovascular disease,” said Pamela Rist, ScD, study author of Brigham and Women’s Hospital in Boston and a member of the American Academy of Neurology.

“But our large study shows that in women, very low levels may also carry some risks. [I’ll say]. Women already have a higher risk of stroke than men, in part because they live longer, so clearly defining ways to reduce their risk is important. Women with very low LDL cholesterol or low triglycerides should be monitored by their doctors for other stroke risk factors that can be modified, like high blood pressure and smoking, in order to reduce their risk of hemorrhagic stroke.

“Also, additional research is needed to determine how to lower the risk of hemorrhagic stroke in women with very low LDL and low triglycerides,” Rist said.

My head was spinning. Low cholesterol and low triglyceride are considered bad now? I wanted to find out more.

The study of 27,937 women age 45 and older participated  in the Women’s Health Study (supported by the National Institutes of Health) who had total cholesterol, LDL cholesterol, high density lipoprotein (HDL or good cholesterol), and triglycerides measured at the beginning of the study. Researchers reviewed tons of medical records to determine how many women had a hemorrhagic stroke.

With an average follow up at 19 years, researchers identified 137 women who had a bleeding stroke. Nine out of 1,069 women with cholesterol 70 mg/dL or lower, or 0.8 percent, had a bleeding stroke, compared to 40 out of 10,067 women with cholesterol 100 mg/dL up to 130 mg/dL, or 0.4 percent.

Some other factors were weighed in that could affect risk of stroke, such as age, smoking status, high blood pressure and treatment with cholesterol-lowering medications, and researchers discovered that those with extremely low LDL cholesterol were 2.2 times more likely to have a bleeding stroke.

Researchers divided the women into four groups for triglyceride levels. Women in the group with the lowest levels had fasting levels 74 mg/dL or lower, or non-fasting levels of 85 mg/dL or lower. Women in the group with the highest levels had fasting levels that were higher than 156 mg/dL, or non-fasting levels that were higher than 188  mg/dl. Researchers found that 34 women of the 5,714 women with the lowest levels of triglycerides, or 0.6 percent, had a bleeding stroke, compared to 29 women of the 7,989 with the highest triglycerides, or 0.4 percent.

The study’s key limitation was that cholesterol and triglyceride levels were only measured once at the beginning of the study. In addition, menopause was evident in a large number of the women, which prevented researchers from examining whether menopause status may be the missing link between cholesterol and triglyceride levels and bleeding stroke. More study is needed.

WELCOME TO CHECK. CHANGE. CONTROL. CALCULATOR, compliments of the American Heart association (AHA).

Through blood tests, CBC and Lipid Panel, and vitals like blood pressure, you can fill in the blanks on the form to see if you’re susceptible to a heart attack or stroke. Shouldn’t you know rather than guess?

Statins are effective at lowering cholesterol and protecting against a heart attack and stroke, although they may lead to side effects for some people.

The Mayo Clinic says that doctors “often prescribe statins for people with high cholesterol to lower their total cholesterol and reduce their risk of a heart attack or stroke.” But they have been associated with the onslaught of muscle pain, digestive problems, and mental confusion in some people who take them and may cause liver damage, albeit rare.

Statins include:
  • atorvastatin (Lipitor)
  • fluvastatin (Lescol XL)
  • lovastatin (Altoprev)
  • pitavastatin (Livalo)
  • pravastatin (Pravachol)
  • rosuvastatin (Crestor, Ezallor)
  • simvastatin (Zocor, FloLipid)

 

The reason that doctors prescribe statins is that that block a substance your liver needs to make cholesterol, and causes your liver to remove cholesterol from your blood.
If you’re already on statins, talk to your doctor before stopping them. My doctor told me to stop reading articles on the Internet. Hoo, boy. Like that’s gonna happen.
If you have muscle pain, the statin you’re on may be producing  rhabdomyolysis which can cause severe pain, liver damage, kidney failure, and death. The risk is very low, and numbers are equal to a few cases per million people taking statins. Rhabdomyolysis can happen when you take statins in combination with certain drugs so ask your pharmacist.

Or statin use could cause an increase in liver inflammation. But if the increase is severe, you may need to try a different statin because all statins are not alike. Again, talk to your doctor, if you also have unusual and increased fatigue or weakness, loss of appetite, pain in your upper abdomen, dark-colored urine, or yellowing of your skin or eyes.

It also possible your blood sugar level may increase when you take a statin, which may lead to developing type 2 diabetes.
The risk is barely significant but important enough that the Food and Drug Administration (FDA) has issued a change on warning labels regarding blood glucose levels and diabetes with statin use prevalent.

Also, the FDA issues a warning on statin labels that some people have memory loss or confusion while using statins.

Everyone who takes a statin may not experience side effects.

Risk factors include:

  • Being female
  • Being age 80 or older
  • Having kidney or liver disease
  • Drinking too much alcohol
  • Having certain conditions such as hypothyroidism or neuromuscular disorders including amyotrophic lateral sclerosis (ALS)
  • Having a small body frame
  • Taking multiple medications to lower your cholesterol

If your doctor says it’s fine, take a small break from statin and see whether the muscle aches or other problems you’re having are statin side effects. It may be just part of the aging process.

Or switch to another statin drug if that’s ok with your doctor.
Or change your dose with the doctor’s permission. Another option is to take the medication every other day, especially if you take a statin that stays in the blood for several days. Again, talk to your doctor.
More than usual exercise may increase the risk of muscle injury. And it’s difficult to know if your muscle pain comes exercise or a statin.
One more thing. Is your diet healthy enough not to produce high cholesterol and, by the way, high triglycerides? My mother, again, probably had Familial hypercholesterolemia, the inherited gene that you could help by eating healthy, exercising, and not smoking, all of which my mother did not do.

Kobe Bryant and Me: Thoughts on Life and Death

I never knew Kobe Bryant even though we each lived in Pennsylvania at some point in our lives, less than 30 minutes and years apart –me for 60 years and Kobe for 18 years when, upon graduation, he went to his only team, the Los Angeles Lakers where he had a 20-year career. He was scouted as #1 in the country and played in the National Basketball Association (NBA). Among his many accomplishments, as a shooting guard, he won five NBA championships, was an 18-time All-Star, and got to be the best shooter ever after Wilt Chamberlain.

Unless you’ve been sequestered with jury duty or living under a rock, Kobe died Sunday along with his daughter and 7 others in a foggy and then fiery helicopter crash which killed them all.

I watched the news reports Sunday and, after a while, stopped watching because the reporters occasionally brought up that incident where in 2003, Bryant was accused of sexual assault by a 19-year-old hotel employee. Shortly after, Bryant issued a public apology, with his wife by his side, but that action resulted in several endorsements which were cut off immediately including McDonalds and Nutella.

Then the devil sat on one shoulder and said, “Was that really necessary to bring that up considering all the good things he did, like the Kobe and Vanessa Bryant Family Foundation whose goals were helping young people in need of support, encouraging the development of physical, emotional, and social skills through sports, and assisting the homeless? Didn’t the good things eventually overpower the bad? Can’t we just move on?”

But the angel who sat on the opposite shoulder said, “Can you really get over sexual assault?” The angel won.

It was 1 in the morning now on Monday. But I was really into it–the thinking, I mean. I sat on my comfortable sofa, for 3 hours, just hammering out what had happened. The Grammys were on Sunday as well in the Staples Center where the Lakers played. I started feeling overwhelmed.

I said to myself, if Kobe was so famous, and people tend to forget even the famous over time, little by little, what chance do I, a regular person, have to be remembered? I fell asleep somewhere in the middle but didn’t lose direction one bit, returning to the internal discussion at hand.

Then around 2 on Monday, I thought of my father who was killed in his North Philadelphia store in 1971, and I didn’t even think of him every day after awhile, except right around the holidays which were important to him because, other than working seven days a week to support his family, he liked fun.

It was about 3:30 on Monday. The only thing was the country by Randy Travis called Three Wooden Crosses that pulled me out of whatever had taken over my mind. The song is  about four people–a farmer, a teacher, a preacher, and a hooker–going down to Mexico in search of various things. He was awarded the Academy of Country Music Award for Song of the Year. Listen to it for a moment.

https://www.youtube.com/watch?v=LT1sNrgnJZc

It’s the refrain.
I guess it’s not what you take when the you leave this world behind you.

 

It’s what you leave behind you when you go. 

And then I also knew. My father left his incredible work ethic, Kobe left his iconic basketball fame, and I guess people will remember me, too, albeit I don’t know for what.

I asked one of my sons the next day, “Will you miss me when I’m gone?”

He took a long time to answer and then he said, “You have your moments.”

That’s good enough for me, wiseass.

Patient Education: Making Sleep a Health Priority

Get the best out of your sleep

Good sleep is a necessity for the healthy functioning of the mind and body.  It is also one of the things that we can forcibly deprive ourselves.  Ideally, we spend one-third of our lives asleep.  Improving your sleep quality can be the first step toward stress resilience and  healthy decisions.

Could you imagine sleeping for 4 hours, then waking up to go to the gym to exercise, then going to work, and taking an extra cup of coffee to stay up?! If this happens to you, wouldn’t you skip the gym and maybe skip preparing a healthy meal? Without sleep, the brain has a lower threshold to develop stress, anger and impatience.  Driving a car after not sleeping well the night before is equivalent to driving under the influence of alcohol.  The system doesn’t just recalibrate the sleep deficit by sleeping in on a Saturday morning.

Sleep affects more than just the neurologic system.  Many first-time parents probably remember getting up at night because of a crying baby.  Most people recognize that sleep reduces memory and concentration and impairs judgement, but sleep also reduces the immune system, leads to weight gain and increases the risk of high blood pressure and stroke.  The endocrine, immunologic and vascular systems are regulated by sleep.

Here is a list of tips to ensure ideal sleep:

  1. Tone down technology: Silence your cellphones and other technology and put them in a different room at a set time each evening, preferably at least 2 hours before bedtime.  The screen lights can inhibit the production of melatonin, which would otherwise prepare you for sleep.
  2. Preparation: Provide yourself a 30-60 minute of winding down before lights out. Limit reading time to 20-30 minutes.
  3. Make sleep a routine: Go to bed and wake up at consistent times.  Most of the time, you will sleep for 6-8 hours naturally.  With a natural routine, you will very likely not need an alarm clock.  If you do use it, stop it and get up – don’t hit snooze 5 times.
  4. Your bed, the slumber throne. Limit activities to sex and sleep.  Watching TV, eating, working on the computer may affect your body’s ability to rest in bed.
  5. Avoid medicating to sleep: Medications to sleep should be avoided or limited to a low dose of melatonin (2-4mg nightly).  Although the medications may sometimes “work”, they come with side effects and, moreover, are not addressing the source of the problem.  The last thing you want to do is develop dependence on alcohol, benzodiazepines or ambien, etc.  and then can’t sleep without it.  As for the other side of things, avoid any intake of caffeine after noon hours.  Avoid any stimulant medications, e.g. albuterol inhalers, immediately prior to sleeping.  One interesting association of sleep apnea is the patient who drinks high levels of caffeine during the day and then takes a sleeping medication at night.
  6. Environment: Keep sleeping area dimly lit or dark.  Ambient noise should be at a minute, though white noise is acceptable.  Temperature should be on the lower side, between 60-67 degrees F.
  7. Trouble-shoot for the future: If you are having problems sleeping at night and find yourself tossing and turning, thinking too much or waiting until that magic click to start, limit time in bed to about 15-20 minutes. There is usually a reason that this has happened and it is up to you to brainstorm it.  You can sit in your chair to begin to rest, meditate and then return to your bed to sleep.  The next day, think why this happened:  It could have been that maybe you exercised too close to bedtime, took too warm of a shower before sleeping, saw a stimulating program on TV, or tried to squeeze some work on the computer too close to bedtime.

If you still have trouble sleeping after following this checklist, you should consider being evaluated for sleep apnea or other conditions (parasomnias) associated with sleeping, such as restless legs, etc.

sleep man on desk

sleep man on desk