Does Covera-19 know 'when to hold 'em or 'when to fold 'em? A translational thought experiment.

The function of proteins depends on their structure. The structural integrity of proteins is dynamic and depends on interacting nearby neighboring moieties that influence their properties and induce folding and structural changes. The conformational changes induced by these nearby neighbors in the micro-environmental milieu at that moment are guided by chemical or electrical bonding attractions. There are few literature references that describe the potential for environmental milieu changes to disfavor SARS-CoV-2 attachment to a receptor for survival outside of a host. There are many studies on the effects of pH (acid and base balance) supporting its importance for protein structure and function, but few focus on pH role in extracellular or intracellular protein or actionable requirements of Covera-19. 'Fold 'em or Hold 'em' is seen by the various functions and effects of furin as it seeks an acidic milieu for action or compatible amino acid sequences which is currently aided by its histidine component and the structural changes of proteins as they enter or exit the host. Questions throughout the text are posed to focus on current thoughts as reviewing applicable COVID-19 translational research science in order to understand the complexities of Covid-19. The pH needs of COVID-19 players and its journey through the human host and environment as well as some efficacious readily available repurposed drugs and out-of-the box and easily available treatments are reviewed.

Autologous white blood cell infusion for trauma, brain trauma, stroke and select immune dysfunction co-morbidities: A promising and timely proposal?

All traumas suppress the immune system, resulting in higher morbidity and mortality. Infections, poor nutritional status, chronic illness, fatigue, therapies or procedures performed during and after transport also negatively affect the immune system. Large populations are impacted by trauma worldwide and suffer enormous costs in both direct and indirect expenditures from physical, psychological and functional losses. Most therapies and studies of trauma, brain trauma, stroke, immune suppression and their co-morbidities do not address nor discuss methods that promote immune system resuscitation or efficacy to support its role in post-trauma healing and rehabilitation. These omissions present an opportunity for using autologous stored naïve (unexposed to the current trauma and co-morbidities) white blood cell infusions (autologous white blood cell infusion) (AWBCI) to supplement treatment of most traumas, trauma-associated infections, other co-morbidities and immune suppression derived problems in order to improve the global standard of trauma care. We hypothesize to give the traumatized patients back their own immune system that has been 'stored' in some fashion, either cryogenically or just after or during the trauma event [surgery, etc for example]. We emphasize that other treatments should not be replaced - rather we suggest AWBCI as concurrent therapy. We present focused select animal and human studies as proofs of concept to arrive at and support our therapeutic suggestion and hypotheses, flowing historically from donor white blood cell therapy [DLI] to close cohort white blood cell therapy to autologous white blood cell infusion [AWBCI]. We integrate the concept of personalized medicine from an evidence-based framework while maintaining scientific rigor and statistical proof as a basis of our hypotheses.

Stroke, mTBI, infection, antibiotics and beta blockade: Connecting the dots.

Several themes supported by a robust literature are addressed in this clinical translational review and research paper: (1) the inadequate standard of care for minimal traumatic brain injury (mTBI)/concussion when compared to stroke because diagnosis and care for mTBI/concussion are based primarily on a symptom only framework; (2) the treatment of stroke (brain injury) infection with select antibiotics; (3) the use of beta blockade in stroke (brain injury). The various etiologies of brain injury appear to coalesce to common endpoints: potential neuronal demise, cognitive and functional losses, immune suppression and infection. The use of principles patterned after 'Koch's Postulates' (show/prove the presence of infection/illness/disease, treat until resolved, and prove objectively that the disease/illness is gone/healed/cured) appears to be marginalized in establishing a diagnosis and recovery from mTBI/TBI. The pathways of immune system interactions in stroke (brain injury) and infection are briefly discussed. The suggestion of combined specific antibiotic and beta blockade for ischemic stroke (brain injury) and mTBI is advanced for treatment and expeditious further study. Stroke is considered a brain injury in this paper. Stroke is also considered and recommended as a study model for mTBI therapy because of their common end points from brain damage. It is suggested that potential transfer or translation of therapy for stroke may be useful in mTBI.

The injured brain: TBI, mTBI, the immune system, and infection: connecting the dots.

Traumatic brain injury or stroke causes profound suppression of the cellular immune system and short- and long-term psychological sequelae. Infection is also a common result and is likely caused by bacterial translocation from the gut. Both the bacterial translocation from the gut and the ensuing pneumonia and sepsis are ameliorated by adoptive immune therapy. Huge health care costs are incurred by brain trauma and its sequelae in our soldiers, athletes, and general population. Diffusion tensor imaging and adoptive immune therapy should become standards of care to follow the injured brain serially as it heals and as the immune suppression and infections are overcome. Brain infrastructure healing is retarded by a suppressed immune system, and the blood-brain barrier's response to trauma offers opportunity for adoptive immune therapy to enhance microglial-directed neuronal repair and maintenance.