Pandemic Pricing Policies: Professional Prerogative or Political Plaything

Pricing a product is considered an important component of the marketing mix that induces consumer behavior. During the 2020 Covid-19 pandemic, price gouging emerged from obscure rarely litigated business law to sensational above the fold headlines. $79.99 hand sanitizer went from a ridiculous pricing decision to an abuse of power and a criminal offense. This paper will begin with an overview of common pricing strategies and then examine the limits placed on pricing in the form of laws which prohibit price gouging. While many of the jurisdictions which make short term increases in the price of certain goods and services illegal, the laws vary as to the definitions and requirements of the necessary elements of a price gouging violation. The political reasons for price gouging laws albeit seemingly obvious, will be examined. The safety and consumer protection arguments will be discussed in the context of almost universal opposition by economists of price gouging regulation. Finally, if price gouging does not protect consumers and if artificial legal parameters of prices actually intrude on healthy appropriate market forces, why do price gouging laws exist in 34 states and in the federal law? What alternatives to price gouging laws would yield a more efficient marketplace and concurrently meet the government’s duty to protect consumers and citizens’ health and safety during a state of emergency

Effects of Endocannabinoid System Modulation on Cognitive and Emotional Behavior

Cannabis has long been known to produce cognitive and emotional effects. Research has shown that cannabinoid drugs produce these effects by driving the brain’s endogenous cannabinoid system and that this system plays a modulatory role in many cognitive and emotional processes. This review focuses on the effects of endocannabinoid system modulation in animal models of cognition (learning and memory) and emotion (anxiety and depression). We review studies in which natural or synthetic cannabinoid agonists were administered to directly stimulate cannabinoid receptors or, conversely, where cannabinoid antagonists were administered to inhibit the activity of cannabinoid receptors. In addition, studies are reviewed that involved genetic disruption of cannabinoid receptors or genetic or pharmacological manipulation of the endocannabinoid-degrading enzyme, fatty acid amide hydrolase (FAAH). Endocannabinoids affect the function of many neurotransmitter systems, some of which play opposing roles. The diversity of cannabinoid roles and the complexity of task-dependent activation of neuronal circuits may lead to the effects of endocannabinoid system modulation being strongly dependent on environmental conditions. Recent findings are reviewed that raise the possibility that endocannabinoid signaling may change the impact of environmental influences on emotional and cognitive behavior rather than selectively affecting any specific behavior

The effects of vasopressin deficiency on aggression and impulsiveness in male and female rats

The role of vasopressin in aggression received much attention in recent years. However, vasopressin has complex roles on social behavior, which are affected by social experience, motivation and hormonal background, suggesting that its effects depend on the condition of subjects. This hypothesis was tested here by studying the impact of vasopressin deficiency on aggressiveness in reproductively naive and reproductively experienced males, as well as in lactating females, with special reference to the patterns and contexts of attack behavior. We also studied effects on impulsiveness, a behavioral feature strongly related to aggression. Vasopressin deficiency did not affect aggressiveness in reproductively experienced males, decreased the share of violent attacks in reproductively inexperienced males without affecting total attack counts, and suppressed maternal aggression in both early and late phases of lactation; violent forms of attack were decreased in the latter but not the former phase. Changes in aggression appeared unrelated to general changes in maternal behaviors. Impulsivity in the delay discounting task was markedly decreased by vasopressin deficiency in lactating females but not males. Taken together, our findings confirm that vasopressin has an impact on aggressiveness, but show that this impact depends on the condition of subjects, and suggest that the effects of vasopressin on maternal aggression develop in conjunction with impulsivity. Interestingly, overall effects on aggression and specific effects on violent attacks dissociated in both males and females, which hints to the possibility that vasopressin has distinct roles in the development of escalated forms of aggression

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

Cardiac progenitor cells including c-kit(+) cells and cardiosphere-derived cells (CDCs) play important roles in cardiac repair and regeneration. CDCs were reported to contain only small subpopulations of c-kit(+) cells and recent publications suggested that depletion of the c-kit(+) subpopulation of cells has no effect on regenerative properties of CDCs. However, our current study showed that the vast majority of CDCs from murine heart actually express c-kit, albeit, in an intracellular and non-glycosylated form. Immunostaining and flow cytometry showed that the fluorescent signal indicative of c-kit immunostaining significantly increased when cell membranes were permeabilized. Western blots further demonstrated that glycosylation of c-kit was increased during endothelial differentiation in a time dependent manner. Glycosylation inhibition by 1-deoxymannojirimycin hydrochloride (1-DMM) blocked c-kit glycosylation and reduced expression of endothelial cell markers such as Flk-1 and CD31 during differentiation. Pretreatment of these cells with a c-kit kinase inhibitor (imatinib mesylate) also attenuated Flk-1 and CD31 expression. These results suggest that c-kit glycosylation and its kinase activity are likely needed for these cells to differentiate into an endothelial lineage. In vivo, we found that intracellular c-kit expressing cells are located in the wall of cardiac blood vessels in mice subjected to myocardial infarction. In summary, our work demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage

The Compassion Balance: Understanding the Interrelation of Self- and Other-Compassion for Optimal Well-being

Objectives: This study examined the role of self-other harmony in the relations between self-compassion, other-compassion, and well-being. Past research has shown self- and other-compassion to be positively related. But we hypothesised that self-compassion can be perceived as incompatible with other-compassion, and that self-compassion and other-compassion might be uncorrelated or negatively correlated in daily life for some individuals. We termed this pattern lack of self-other harmony in compassion and hypothesised that it would undermine the benefits of compassion. Method: Using an experience sampling method in patients (n=154) with a variety of diagnoses, we measured self-compassion, other-compassion, life-satisfaction, mood, and contextual variables six times per day for 42 time points. Results: For most participants, self-compassion was positively associated with other-compassion. However, there was substantial heterogeneity in this effect. The degree of self-other harmony moderated the link between compassion directed towards self or other and well-being. Higher levels of compassion were associated with higher levels of well-being, but only for those who experienced the harmony. When the two forms of compassion were not in harmony, levels of self/other-compassion were largely unrelated to well-being. Conclusions: The findings emphasise the importance of personalised compassion interventions rather than a one-size-fits-all approach. Increasing self-compassion or other-compassion is likely to improve well-being for most people. However, for a minority lacking the self-other harmony, it may be necessary to assess their interpretation of self- and other-compassion, then work with them to promote the compassion balance optimal for their well-being

Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed competitive inhibition of cardiotonic steroid binding to Na/K-ATPase and partially inhibited collagen synthesis induced by marinobufagenin in cultured cardiac fibroblasts. Therefore, we sought to examine whether female rats displayed less uremic cardiomyopathy than male rats when subjected to partial nephrectomy. Although partial nephrectomy caused the induction of smaller increases in blood pressure of female rats, they appeared to be similarly susceptible to cardiac remodeling induced by partial nephrectomy in terms of hypertrophy and fibrosis as age-matched male rats. The possible explanations for our findings are therefore discussed

Involvement of Reactive Oxygen Species in a Feed-Forward Mechanism of Na/K-ATPase Mediated Signaling

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial 22Na+ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, ouabain stimulated direct carbonylation of two amino acid residues in the actuator domain of the Na/K-ATPase α1 subunit. Taken together, the data indicate that carbonylation modification of the Na/K-ATPase α1 subunit is involved in a feed-forward mechanism of regulation of ouabain-mediated renal proximal tubule Na/K-ATPase signal transduction and subsequent sodium transport

The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats.

RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. OBJECTIVES: Here, we investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter, we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration was ~30 mug/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol. High levels of illumination halved the time spent by controls in the open arms of the plus-maze. No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30 % in controls, but not in rats with prelimbic URB597 implants. Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety. URB597 implants targeting the BLA did not affect stimulus responsiveness. CONCLUSIONS: Our findings show that elevated prelimbic anandamide signaling leads to less environment-dependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping.

Protein Carbonylation of an Amino Acid Residue of the Na/K‐ATPase α1 Subunit Determines Na/K‐ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells

Background We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K‐ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K‐ATPase α1 subunit, reactive oxygen species are required for ouabain‐stimulated Na/K‐ATPase/c‐Src signaling and subsequent regulation of active transepithelial 22Na+ transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K‐ATPase signaling and sodium handling. Methods and Results Stable pig α1 knockdown LLC‐PK1‐originated PY‐17 cells were rescued by expressing wild‐type rat α1 and rat α1 with a single mutation of Pro224 (corresponding to pig Pro222) to Ala. This mutation does not affect ouabain‐induced inhibition of Na/K‐ATPase activity, but abolishes the effects of ouabain on Na/K‐ATPase/c‐Src signaling, protein carbonylation, Na/K‐ATPase endocytosis, and active transepithelial 22Na+ transport. Conclusions Direct carbonylation modification of Pro224 in the rat α1 subunit determines ouabain‐mediated Na/K‐ATPase signal transduction and subsequent regulation of renal proximal tubule sodium transport