One Small Step for a Patient, One Giant Leap for Orthostatic Hypotension.

A 52-year-old man with ischemic cardiomyopathy presented with progressive, severe orthostatic hypotension refractory to medical therapy. Standard abdominal and leg compression devices were used without success. A novel, inflatable abdominal compression device was created that alleviated the patient's symptoms and maintained his blood pressure.

Incorporation of omics analyses into artificial gravity research for space exploration countermeasure development.

The next major steps in human spaceflight include flyby, orbital, and landing missions to the Moon, Mars, and near earth asteroids. The first crewed deep space mission is expected to launch in 2022, which affords less than 7 years to address the complex question of whether and how to apply artificial gravity to counter the effects of prolonged weightlessness. Various phenotypic changes are demonstrated during artificial gravity experiments. However, the molecular dynamics (genotype and molecular phenotypes) that underlie these morphological, physiological, and behavioral phenotypes are far more complex than previously understood. Thus, targeted molecular assessment of subjects under various G conditions can be expected to miss important patterns of molecular variance that inform the more general phenotypes typically being measured. Use of omics methods can help detect changes across broad molecular networks, as various G-loading paradigms are applied. This will be useful in detecting off-target, or unanticipated effects of the different gravity paradigms applied to humans or animals. Insights gained from these approaches may eventually be used to inform countermeasure development or refine the deployment of existing countermeasures. This convergence of the omics and artificial gravity research communities may be critical if we are to develop the proper artificial gravity solutions under the severely compressed timelines currently established. Thus, the omics community may offer a unique ability to accelerate discovery, provide new insights, and benefit deep space missions in ways that have not been previously considered.

A reassessment of the SIDS Back to Sleep Campaign.

The Back to Sleep Campaign was initiated in 1994 to implement the American Academy of Pediatrics' (AAP) recommendation that infants be placed in the nonprone sleeping position to reduce the risk of the Sudden Infant Death Syndrome (SIDS). This paper offers a challenge to the Back to Sleep Campaign (BTSC) from two perspectives: (1) the questionable validity of SIDS mortality and risk statistics, and (2) the BTSC as human experimentation rather than as confirmed preventive therapy. The principal argument that initiated the BTSC and that continues to justify its existence is the observed parallel declines in the number of infants placed in the prone sleeping position and the number of reported SIDS deaths. We are compelled to challenge both the implied causal relationship between these observations and the SIDS mortality statistics themselves.

A unifying concept of seizure onset and termination.

Recent discoveries in molecular biology and human genetics have contributed greatly to an understanding of the nature of seizure (ictal) activity. However, two questions of fundamental clinical importance continue to resist scientific inquiry: when and why does a seizure begin; and when and why does a seizure end? This paper cites evidence from the medical literature in support of two counterintuitive concepts that address this issue. First, that despite the diversity of conditions that are associated with seizures, the ictal response results from disturbances of a mitochondrial metabolic pathway that is common to them all. Second, that the seizure is not inherently harmful but is, instead, associated with massive intracerebral circulatory changes that are intended to restore impaired mitochondrial function. We hypothesize that the protogenic pathophysiological condition leading to neuronal hyperexitability and seizures results from inadequate mitochondrial energy production due to hypoxia or a hypoxia-equivalent state. Failure to generate sufficient adenosine triphosphate compromises ionic pump function and the ability to maintain neuronal homeostasis and stability. The seizure cascade is a heroic effort to perfuse the brain when local mechanisms fail to restore energy production and ionic equilibrium. In summary, a seizure starts when the neuron's aerobic machinery fails to maintain effective ionic pump function and terminates when increased cerebral perfusion, associated with the seizure response, restores adequate supplies of metabolic nutrients required for mitochondrial respiration. This unorthodox unifying concept that views ictogenesis as part of a restorative process rather than as a life threatening event may provide the basis for a much needed paradigm shift in the management of seizures. Current antiepileptic drugs are associated with many serious side effects, including death, and fail to control seizures in 20% of patients with primary generalized epilepsy and 35% of patients with partial epilepsy. We propose that efforts to prevent and control seizures should be directed away from pharma-chemical suppression towards removing the causes of disturbed neuronal energy production and developing methods and bioactive agents that promote an optimized physiological milieu within the brain.

Ictogenesis: the origin of seizures in humans. A new look at an old theory.

Seizure (ictal) behavior in humans has been observed and recorded since ancient times. A satisfactory solution to this vexing problem continues to elude medical science. Antiepileptic drug (AED) therapy fails to control seizures in 20% of patients with primary generalized epilepsy and 35% of patients with partial epilepsy and has many side effects, including death. This paper cites evidence from the current literature that supports a plausible hypothesis of seizure genesis that was published in 1942, but somehow escaped recognition. It presents a concept that challenges contemporary thinking and may provide the basis for a much needed paradigm shift in the understanding of the nature of seizures and an approach to their management. The theory views a seizure as a natural reflex defense response to a lethal threat to the brain. Although capable of inflicting bodily injury due to falls, drowning, etc., the seizure is not considered inherently harmful to the brain and may be associated with beneficial circulatory changes. Efforts to control and prevent seizures should be directed away from pharma-chemical suppression towards developing methods and bioactive agents that promote neuroplasticity, neurogenesis, and an optimized physiological milieu within the brain.