Pressure never sucks, pressure only pushes: a physiological exploration of the pushing power of pressure.

The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the resistance encountered by airways. In this process, the movement of air into and out of the lungs is driven by pressure gradients established by changes in lung volume and intra-alveolar pressure. However, pressure never sucks! The concept that pressure never sucks, pressure only pushes encapsulates a fundamental principle in the behavior of gases. This concept challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we explore the essence of this concept and its applications in pulmonary ventilation. Pressure is one of the most important concepts in physics and physiology. Atmospheric pressure at sea level is equal to 1 atmosphere or around 101,325 Pascal [Pa (1 Pa = 1 N/m2)]. This huge pressure is pushing down on everything all the time. However, this pressure is difficult to understand because we do not often observe the power of this incredible force. We used five readily available, simple, and inexpensive demonstrations to introduce the physics and power of pressure. This extraordinarily complex physics concept was approached in a straightforward and inexpensive manner while still providing an understanding of the fundamental concepts. These simple demonstrations introduced basic concepts and addressed common misconceptions about pressure.NEW & NOTEWORTHY The concept that pressure never sucks, pressure only pushes challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we will explore the essence of this concept and its applications in pulmonary ventilation. Specifically, we used five readily available, simple, inexpensive demonstrations to introduce the physics and power of pressure.

We used to get money to teach students, now we teach students to get money: medical education has become a market with credentials not knowledge the commodity!

Preclinical medical education has lost its way. In fact, it seems that preclinical medical education has forgotten its mission and has become focused on assembly line efficiency and profits. Administrators and students are increasingly considering preclinical medical education as a market with credentials (access to USMLE Step 1 or COMLEX Level 1) the commodity and students the consumers. Consider that, once banned, for-profit medical schools are on the rise in the United States. In response to these changes, medical schools are adopting corporate models, cutting costs, and seeking profit-making opportunities. One example is the broadcasting of content to multiple sites and satellite campuses. In addition, the customers need to feel satisfied with the educational experience bought for them at high tuition costs. However, providing students with what they want often happens at the expense of what they need, and administrators engage in subtle pandering to students. Furthermore, although the pursuit of credentials is understandable, a university is more than a factory that produces diplomas and careers. Universities exist to educate, discover, and impart knowledge while impacting our ways of living and thinking. In this context, universities exist for the greater good and betterment of societies. The "corporatization" of medical education and satisfying the customer creates an environment where a university is selling socioeconomic stability, professional status, and success, rather than a setting for the formation of character, intellect, and critical thinking. Our hope is that administrators, educators, and students will reconnect to the greater purpose and value of learning.NEW & NOTEWORTHY We should be preparing future physicians to deliver the care we want to receive as patients. This requires training in communication, collaboration, inquiry, discovery, and innovation while developing the habits of the mind and heart that advance the practice of medicine and the health of the public. However, the current "corporatization" of medical education is failing to accomplish this outcome. Specifically, medical schools are adopting corporate models, cutting costs, and seeking profit-making opportunities without improving what goes on in the classroom. Our hope is that we will reconnect to the greater purpose and value of learning.

Hypertension in Primary Aldosteronism Is Initiated by Salt-Induced Increases in Vascular Resistance With Reductions in Cardiac Output.

BACKGROUND: Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. METHODS: In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. RESULTS: In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. CONCLUSIONS: Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.

"Seeing red" reflects hemoglobin's saturation state: a discovery-based activity for understanding the science of pulse oximetry.

Pulse oximetry has become the standard of care in operating rooms, intensive care units, and hospitals worldwide. A pulse oximeter continuously and noninvasively monitors the functional oxygen saturation of hemoglobin in arterial blood ([Formula: see text]). [Formula: see text] is so important in medical care that it is often regarded as a fifth vital sign. Before pulse oximetry, arterial puncture for blood gas analysis was the only method available to determine [Formula: see text] and to identify the presence of hypoxemia. Pulse oximetry is based on the principle that oxygenated hemoglobin (O2Hb) absorbs more near-infrared light than deoxyhemoglobin (HHb) and HHb absorbs more red light than O2Hb. It is important to understand the principles of pulse oximetry, how the equipment works, and its limitations to interpret the information it provides. Accordingly, we used colored balloons to introduce the physics of how a pulse oximeter detects and measures oxyhemoglobin and deoxyhemoglobin in pulsatile (arterial) and nonpulsatile (venous and capillary) blood. The foundations of oximetry started in the 1700s with Johann Lambert (1728-1777). We approached this complex physics in a straightforward way while still providing an understanding of the fundamental concepts developed by Johann Lambert in 1760.NEW & NOTEWORTHY Educators must go beyond teaching the facts and encourage students to think, investigate, and appreciate the subject matter in a broader framework. To achieve these goals, we used a simple and inexpensive experimental approach to introduce the physics of how a pulse oximeter detects and measures oxyhemoglobin and deoxyhemoglobin in blood. We approached this complex physics in a straightforward way while still providing an understanding of the fundamental concepts developed by Johann Lambert in 1760.

Mechanism-based strategies to prevent salt sensitivity and salt-induced hypertension.

High-salt diets are a major cause of hypertension and cardiovascular (CV) disease. Many governments are interested in using food salt reduction programs to reduce the risk for salt-induced increases in blood pressure and CV events. It is assumed that reducing the salt concentration of processed foods will substantially reduce mean salt intake in the general population. However, contrary to expectations, reducing the sodium density of nearly all foods consumed in England by 21% had little or no effect on salt intake in the general population. This may be due to the fact that in England, as in other countries including the U.S.A., mean salt intake is already close to the lower normal physiologic limit for mean salt intake of free-living populations. Thus, mechanism-based strategies for preventing salt-induced increases in blood pressure that do not solely depend on reducing salt intake merit attention. It is now recognized that the initiation of salt-induced increases in blood pressure often involves a combination of normal increases in sodium balance, blood volume and cardiac output together with abnormal vascular resistance responses to increased salt intake. Therefore, preventing either the normal increases in sodium balance and cardiac output, or the abnormal vascular resistance responses to salt, can prevent salt-induced increases in blood pressure. Suboptimal nutrient intake is a common cause of the hemodynamic disturbances mediating salt-induced hypertension. Accordingly, efforts to identify and correct the nutrient deficiencies that promote salt sensitivity hold promise for decreasing population risk of salt-induced hypertension without requiring reductions in salt intake.

Remodeling of extracellular matrix in the urinary bladder of paraplegic rats results in increased compliance and delayed fiber recruitment 16 weeks after spinal cord injury.

The ability of the urinary bladder to maintain low intravesical pressures while storing urine is key in ensuring proper organ function and highlights the key role that tissue mechanics plays in the lower urinary tract. Loss of supraspinal neuronal connections to the bladder after spinal cord injury can lead to remodeling of the structure of the bladder wall, which may alter its mechanical characteristics. In this study, we investigate if the morphology and mechanical properties of the bladder extracellular matrix are altered in rats 16 weeks after spinal cord injury as compared to animals who underwent sham surgery. We measured and quantified the changes in bladder geometry and mechanical behavior using histological analysis, tensile testing, and constitutive modeling. Our results suggest bladder compliance is increased in paraplegic animals 16 weeks post-injury. Furthermore, constitutive modeling showed that increased distensibility was driven by an increase in collagen fiber waviness, which altered the distribution of fiber recruitment during loading. STATEMENT OF SIGNIFICANCE: The ability of the urinary bladder to store urine under low pressure is key in ensuring proper organ function. This highlights the important role that mechanics plays in the lower urinary tract. Loss of control of neurologic connection to the bladder from spinal cord injury can lead to changes of the structure of the bladder wall, resulting in altered mechanical characteristics. We found that the bladder wall's microstructure in rats 16 weeks after spinal cord injury is more compliant than in healthy animals. This is significant since it is the longest time post-injury analyzed, to date. Understanding the extreme remodeling capabilities of the bladder in pathological conditions is key to inform new possible therapies.

The racist "one drop rule" influencing science: it is time to stop teaching "race corrections" in medicine.

Glomerular filtration rate (GFR) is a key index of renal function. The classic method for assessing GFR is the clearance of inulin. Several current methods using isotopic (125I-iothalamate, 51Cr-EDTA, or 99Tc-DTPA) or nonisotopic (iohexol or iothalamate) markers are available. Clinically, GFR is estimated (eGFR) from serum creatinine or cystatin C levels. Estimated GFR based on creatinine and/or cystatin are less accurate than measured GFR. The creatinine-based equations calculate higher eGFR values (suggesting better kidney function) for black individuals. This upward adjustment for all black individuals is embedded in eGFR calculations on the belief of higher serum creatinine concentrations among black individuals than among white individuals. Thus "race-corrected" eGFR has become a widely accepted and scientifically valid procedure. However, race is not a genetic or biological category. Rather, race is a social construction defined by region-specific cultural and historical ideas. Furthermore, there is no accepted scientific method for classifying people as black or white individuals. Studies typically rely on self-identification of race. However, any person in the United States with any known black ancestry is considered to be a black individual. This is known as the "one-drop rule," meaning that a single drop of "black blood" makes anyone a black individual. It does not matter if an individual has 50%, 25%, 5%, or 0.5% African ancestry. The limited accuracy and reliability of this approach would not be allowed for any other scientific variable. Admixture and migration have produced such broad variations that race categories should not be used as experimental variables.

No evidence of racial disparities in blood pressure salt sensitivity when potassium intake exceeds levels recommended in the US dietary guidelines.

On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension.

Critical skill of teaching: learning the cognitive and emotional states of our students during class.

There has been an increased reliance on prerecorded lectures as a source of learning in place of live lectures in higher education. However, we must appreciate that our students send countless intended and unintended messages during class that relate to their cognitive and emotional states. Shaping productive learning experiences requires understanding their cognitive and emotional states by interpreting their statements, actions, and body language in real time. This can only occur with face-to-face instruction and makes it possible to tailor the class to the students' needs. Becoming aware of the students' cognitive and emotional state by listening and learning their body language is fundamental to teaching, as it will alert educators to cognitive effort and attention, surprise, or uncertainty, as well as a range of emotions, including confusion. Without an understanding of the students cognitive and emotional states, we lose our ability to structure conversations or to reinforce difficult concepts and important ideas in real time. We also lose our ability to adjust on the fly and modify instruction on the basis of the needs of our students. Thus, learning the cognitive and emotional states of our students during class is an essential skill of teaching and the critical means that a teacher uses to promote understanding and positive attitudes about education.

Electrify your class with a simple battery: battery demonstration of electrocardiogram vectors.

William Arthur Ward stated, "The mediocre teacher tells. The good teacher explains. The superior teacher demonstrates. The great teacher inspires." Discovery experimentation is an inductive method that demonstrates and inspires by creating an interest in determining the underlining basis of a phenomenon. This experiential approach also fosters motivation and enhances learning. Starting with what the student knows augments this approach. By starting with what the student already knows, the student can consciously and explicitly link the subsequent new information with previous knowledge. Accordingly, we used a simple battery as an analogy for electrocardiogram vectors to introduce the theoretical physics of how the heart produces voltages that are detectable at the body surface. This extraordinarily complex physics was approached in a straightforward and inexpensive way while still providing an understanding of the fundamental concepts developed by Willem Einthoven in 1895.

Direct comparison of cervical and high thoracic spinal cord injury reveals distinct autonomic and cardiovascular consequences.

A wide range of spinal cord levels (cervical 8-thoracic 6) project to the stellate ganglia (which provides >90% of sympathetic supply to the heart), with a peak at the thoracic 2 (T2) level. We hypothesize that despite the proximity of the lesions, high thoracic spinal cord injuries (i.e., T2-3 SCI) do not closely mimic the hemodynamic responses recorded with cervical SCI (i.e., C6-7 SCI). To test this hypothesis, rats were instrumented with an intra-arterial telemetry device (Data Sciences International PA-C40) for recording arterial pressure, heart rate, and locomotor activity as well as a catheter within the intraperitoneal space. After recovery, rats were subjected to complete C6-7 spinal cord transection (n = 8), sham transection (n = 4), or T2-3 spinal cord transection (n = 7). After the spinal cord transection or sham transection, arterial pressure, heart rate, and activity counts were recorded in conscious animals, in a thermoneutral environment, for 20 s every minute, 24 h/day for 12 consecutive weeks. After 12 wk, chronic reflex- and stress-induced cardiovascular and hormonal responses were compared in all groups. C6-7 rats had hypotension, bradycardia, and reduced physical activity. In contrast, T2-3 rats were tachycardic. C6-7 rats compared with T2-3 and spinal intact rats also had reduced cardiac sympathetic tonus, reduced reflex- and stress induced cardiovascular responses, and reduced sympathetic support of blood pressure as well as enhanced reliance on angiotensin to maintain arterial blood pressure. Thus injuries above and below the peak level (T2) of spinal cord projections to the stellate ganglia have remarkably different outcomes.NEW & NOTEWORTHY Twelve consecutive weeks of resting hemodynamic data as well as chronic reflex- and stress-induced cardiovascular, autonomic, and hormonal responses were compared in spinal intact and C6-7 and T2-3 spinal cord-transected rats. C6-7 rats compared with T2-3 and spinal intact rats had reduced cardiac sympathetic tonus, reduced reflex- and stress-induced cardiovascular responses, and reduced sympathetic support of blood pressure as well as enhanced reliance on angiotensin to maintain arterial blood pressure. Thus injuries above and below the peak level (T2) of spinal cord projections to the stellate ganglia have remarkably different outcomes.

Spinal cord injury alters purinergic neurotransmission to mesenteric arteries in rats.

Complications associated with spinal cord injury (SCI) result from unregulated reflexes below the lesion level. Understanding neurotransmission distal to the SCI could improve quality of life by mitigating complications. The long-term impact of SCI on neurovascular transmission is poorly understood, but reduced sympathetic activity below the site of SCI enhances arterial neurotransmission (1). We studied sympathetic neurovascular transmission using a rat model of long-term paraplegia (T2-3) and tetraplegia (C6-7). Sixteen weeks after SCI, T2-3 and C6-7 rats had lower blood pressure (BP) than sham rats (103 ± 2 and 97 ± 4 vs. 117 ± 6 mmHg, P < 0.05). T2-3 rats had tachycardia (410 ± 6 beats/min), and C6-7 rats had bradycardia (299 ± 10 beats/min) compared with intact rats (321 ± 4 beats/min, P < 0.05). Purinergic excitatory junction potentials (EJPs) were measured in mesenteric arteries (MA) using microlectrodes, and norepinephrine (NE) release was measured using amperometry. NE release was similar in all groups, while EJP frequency-response curves from T2-3 and C6-7 rats were left-shifted vs. sham rats. EJPs in T2-3 and C6-7 rats showed facilitation followed by run-down during stimulation trains (10 Hz, 50 stimuli). MA reactivity to exogenous NE and ATP was similar in all rats. In T2-3 and C6-7 rats, NE content was increased in left cardiac ventricles compared with intact rats, but was not changed in MA, kidney, or spleen. Our data indicate that peripheral purinergic, but not adrenergic, neurotransmission increases following SCI via enhanced ATP release from periarterial nerves. Sympathetic BP support is reduced after SCI, but improving neurotransmitter release might maintain cardiovascular stability in individuals living with SCI.NEW & NOTEWORTHY This study revealed increased purinergic, but not noradrenergic, neurotransmission to mesenteric arteries in rats with spinal cord injury (SCI). An increased releasable pool of ATP in periarterial sympathetic nerves may contribute to autonomic dysreflexia following SCI, suggesting that purinergic neurotransmission may be a therapeutic target for maintaining stable blood pressure in individuals living with SCI. The selective increase in ATP release suggests that ATP and norepinephrine may be stored in separate synaptic vesicles in periarterial sympathetic varicosities.

The hypertension advantage and natural selection: Since type 2 diabetes associates with co-morbidities and premature death, why have the genetic variants remained in the human genome?

Type 2 diabetes is a major public health crisis around the world. It is estimated that more than 300 million people worldwide have type 2 diabetes. Furthermore, the World Health Organization estimates that deaths from the complications of diabetes will increase by two thirds between 2008 and 2030. Since type 2 diabetes is a major public health crisis, why have the genetic variants for diabetes not been removed from the genome by natural selection? We hypothesize that insulin resistance, a predisposition to type 2 diabetes, and the associated elevation in sympathetic nervous system activity and arterial blood pressure provided an advantage to humans who lived as hunter-gatherers. Specifically, sympathetic hyperactivity stimulates the renin-angiotensin aldosterone system, promotes sodium reabsorption, and increases blood volume, heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension. The hypertension in turn provides a hemodynamic advantage for hunter-gatherers. Specifically, sympathetic hyperactivity and increased blood pressure increases blood flow delivery to working muscles by increasing cardiac output and shunting blood from non-active tissue. This natural selection for hypertension occurred during the time in human evolutionary history when the lifespan of most individuals was probably 30-40 years, and morbidity and mortality from cardiovascular disorders was limited. Thus, the selection pressure for elevation in sympathetic nervous system activity and blood pressure provided an advantage for hunting and gathering that would be greater than the selection pressure exerted by the manifestations of cardiovascular disease in aged individuals.

Development of In-Browser Simulators for Medical Education: Introduction of a Novel Software Toolchain.

BACKGROUND: Simulators used in teaching are interactive applications comprising a mathematical model of the system under study and a graphical user interface (GUI) that allows the user to control the model inputs and visualize the model results in an intuitive and educational way. Well-designed simulators promote active learning, enhance problem-solving skills, and encourage collaboration and small group discussion. However, creating simulators for teaching purposes is a challenging process that requires many contributors including educators, modelers, graphic designers, and programmers. The availability of a toolchain of user-friendly software tools for building simulators can facilitate this complex task. OBJECTIVE: This paper aimed to describe an open-source software toolchain termed Bodylight.js that facilitates the creation of browser-based client-side simulators for teaching purposes, which are platform independent, do not require any installation, and can work offline. The toolchain interconnects state-of-the-art modeling tools with current Web technologies and is designed to be resilient to future changes in the software ecosystem. METHODS: We used several open-source Web technologies, namely, WebAssembly and JavaScript, combined with the power of the Modelica modeling language and deployed them on the internet with interactive animations built using Adobe Animate. RESULTS: Models are implemented in the Modelica language using either OpenModelica or Dassault Systèmes Dymola and exported to a standardized Functional Mock-up Unit (FMU) to ensure future compatibility. The C code from the FMU is further compiled to WebAssembly using Emscripten. Industry-standard Adobe Animate is used to create interactive animations. A new tool called Bodylight.js Composer was developed for the toolchain that enables one to create the final simulator by composing the GUI using animations, plots, and control elements in a drag-and-drop style and binding them to the model variables. The resulting simulators are stand-alone HyperText Markup Language files including JavaScript and WebAssembly. Several simulators for physiology education were created using the Bodylight.js toolchain and have been received with general acclaim by teachers and students alike, thus validating our approach. The Nephron, Circulation, and Pressure-Volume Loop simulators are presented in this paper. Bodylight.js is licensed under General Public License 3.0 and is free for anyone to use. CONCLUSIONS: Bodylight.js enables us to effectively develop teaching simulators. Armed with this technology, we intend to focus on the development of new simulators and interactive textbooks for medical education. Bodylight.js usage is not limited to developing simulators for medical education and can facilitate the development of simulators for teaching complex topics in a variety of different fields.