Topical Menthol, Ice, Peripheral Blood Flow, and Perceived Discomfort

Context : Injury management commonly includes decreasing arterial blood flow to the affected site in an attempt to reduce microvascular blood flow and edema and limit the induction of inflammation. Applied separately, ice and menthol gel decrease arterial blood flow, but the combined effects of ice and menthol gel on arterial blood flow are unknown. Objectives : To compare radial artery blood flow, arterial diameter, and perceived discomfort before and after the application of 1 of 4 treatment conditions. Design : Experimental crossover design. Setting : Clinical laboratory. Participants or Other Participants : Ten healthy men, 9 healthy women (mean age = 25.68 years, mean height = 1.73 m, mean weight = 76.73 kg). Intervention(s) : Four treatment conditions were randomly applied for 20 minutes to the right forearm of participants on 4 different days separated by at least 24 hours: (1) 3.5 mL menthol gel, (2) 0.5 kg of crushed ice, (3) 3.5 mL of menthol gel and 0.5 kg of crushed ice, or (4) no treatment (control). Main Outcome Measure(s) : Using high-resolution ultrasound, we measured right radial artery diameter (cm) and blood flow (mL/min) every 5 minutes for 20 minutes after the treatment was applied. Discomfort with the treatment was documented using a 1-to-10 intensity scale. Results : Radial artery blood flow decreased (P \u3c .05) from baseline in the ice (−20% to −24%), menthol (−17% to −24%), and ice and menthol (−36% to −39%) treatments but not in the control (3% to 9%) at 5, 10, and 15 minutes. At 20 minutes after baseline, only the ice (−27%) and combined ice and menthol (−38%) treatments exhibited reductions in blood flow (P \u3c .05). Discomfort was less with menthol than with the ice treatment at 5, 10, and 20 minutes after application (P \u3c .05). Arterial diameter and heart rate did not change. Conclusions : The application of 3.5 mL of menthol was similar to the application of 0.5 kg of crushed ice in reducing peripheral blood flood. Combining crushed ice with menthol appeared to have an additive effect on reducing blood flow

Prediction of VO\u3csub\u3e2\u3c/sub\u3e Peak Using Sub-Maximum Bench Step Test in Children

The purpose of this study was to develop a valid prediction of maximal oxygen uptake from data collected during a submaximum bench stepping test among children ages 8-12 years. Twentyseven active subjects (16 male and 11 female), weight 36.1 kg, height 144.4 cm and VO2 47.4 ± 7.9 ml/kg/min participated. Subjects completed a maximal oxygen consumption test with analysis of expired air and a submaximal bench stepping test. A formula to predict VO2max was developed from height, resting heart rate and heart rate response during the submaximum bench stepping test. This formula accounted for 71% of the variability in maximal oxygen consumption and is the first step in verifying the validity of the submaximum bench stepping test to predict VO2max. VO2max = -2.354 + (Height in cm * 0.065) + (Resting Heart Rate * 0.008) + (Step Test Average Heart Rate as a Percentage of Resting Heart Rate * -0.870

Stuck on Gold: Real Exchange Rate Volatility and the Rise and Fall of the Gold Standard

Did adoption of the gold standard exacerbate or diminish macroeconomic volatility? Supporters thought so, critics thought not, and theory offers ambiguous messages. A hard exchange-rate regime such as the gold standard might limit monetary shocks if it ties the hands of policy makers. But any decision to forsake exchange-rate flexibility might compromise shock absorption in a world of real shocks and nominal stickiness. A simple model shows how a lack of flexibility can be discerned in the transmission of terms of trade shocks. Evidence on the relationship between real exchange rate volatility and terms of trade volatility from the late nineteenth and early twentieth century exposes a dramatic change. The classical gold standard did absorb shocks, but the interwar gold standard did not, and this historical pattern suggests that the interwar gold standard was a poor regime choice.

Trade costs, 1870–2000

What has driven trade booms and trade busts in the past century and a half? Was it changes in global output or in the costs of international trade? To address this question, we derive a micro-founded measure of aggregate bilateral trade costs based on a standard model of trade in differentiated goods. These trade costs gauge the difference between observed bilateral trade and frictionless trade in terms of an implied markup on retail prices of foreign goods. Thus, we are able to estimate the combined magnitude of tariffs, transportation costs, and all other macroeconomic frictions that impede international trade but that are inherently difficult to observe. We use this measure to examine the growth of global trade between 1870 and 1913, its retreat from 1921 to 1939, and its subsequent rise from 1950 to 2000. We find that trade cost declines explain roughly 55 percent of the pre–World War I trade boom and 33 percent of the post–World War II trade boom, while a precipitous rise in trade costs explains the entire interwar trade bust

Real inequality in Europe since 1500

Introducing a concept of real, as opposed to nominal, inequality of income or wealth suggests some historical reinterpretations, buttressed by a closer look at consumption by the rich. The purchasing powers of different income classes depend on how relative prices move. Relative prices affected real inequality more strongly in earlier centuries than in the twentieth. Between 1500 and about 1800, staple food and fuels became dearer, while luxury goods, especially servants, became cheaper, greatly widening the inequality of lifestyles. Peace, industrialization, and globalization reversed this inegalitarian price effect in the nineteenth century, at least for England

Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. Neurofibromatosis type 2 (NF2)1 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial nerve. Mutations and loss of heterozygosity of theNF2 gene have been detected in NF2 patients and in various sporadic tumors, including schwannomas, meningiomas, and ependymomas (1). In further support of a role for NF2 in tumor suppression, mice heterozygous for an Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential (2). In a separate model in which Nf2 is inactivated specifically in Schwann cells, mice develop schwannomas and Schwann cell hyperplasia (3). The longest and predominant splice form of the Nf2gene codes for a 595-amino acid protein highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins,moesin, ezrin, and radixin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia (4, 5). Likewise, merlin is localized to cortical actin structures, in patterns that partially overlap with the ERMs (1). It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homodimers and heterodimers, among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins (6). The recently solved crystal structure of the moesin N/C-terminal complex strengthens this model of conformational regulation (7). Given the sequence and, most likely, structural similarities of merlin to the ERM proteins, it is possible that merlin itself could be regulated in a similar fashion. Recent studies (8, 9) have implicated additional factors in the regulation of the ERMs, including phospholipids and phosphorylation. Previous work from our group and others (10, 11) has shown that merlin is differentially phosphorylated as well and that merlin protein levels are affected by growth conditions such as cell confluency, loss of adhesion, or serum deprivation. Merlin is found in an hypophosphorylated form when the combination of cellular and environmental conditions are growth-inhibitory (10). ERMs can be phosphorylated by Rho kinase, and this phosphorylation can affect intramolecular association and cellular localization. Phosphorylation and/or phospholipids may promote the transition of the proteins to an active form by “opening” intra- and intermolecular associations. These active monomers can then bind to other interacting proteins and the actin cytoskeleton and induce actin-rich membrane projections (5,8, 12, 13). The induction of merlin phosphorylation by activated alleles of the Rho family GTPases has also been examined. Interestingly, although activated Rho did not induce noticeable phosphorylation of merlin, activated forms of Rac and cdc42 did. The site of Rac-induced phosphorylation was determined to be a serine at position 518; mutation of serine 518 results in reduced basal phosphorylation and eliminated Rac-induced phosphorylation (11). Although Rac and cdc42 are implicated in the regulation of many pathways, they are most associated with regulation of cytoskeleton reorganization and gene expression (for recent reviews see Refs.14-16). In light of the data demonstrating that activated Rac/cdc42 leads to phosphorylation and possible inactivation of merlin, the elucidation of the responsible effector pathways and their effects on merlin function are of major importance. Understanding this regulation of merlin could lead to a more complete appreciation of the effects of merlin loss in tumors

Trade booms, trade busts and trade costs

What has driven trade booms and trade busts in the past and present? We derive a micro-founded measure of trade frictions from leading trade theories and use it to gauge the importance of bilateral trade costs in determining international trade flows. We construct a new balanced sample of bilateral trade flows for 130 country pairs across the Americas, Asia, Europe, and Oceania for the period from 1870 to 2000 and demonstrate an overriding role for declining trade costs in the pre-World War I trade boom. In contrast, for the post-World War II trade boom we identify changes in output as the dominant force. Finally, the entirety of the interwar trade bust is explained by increases in trade costs

Comparison of the Effects of Ice and 3.5% Menthol Gel on Blood Flow and Muscle Strength of the Lower Arm

Context: Soft-tissue injuries are commonly treated with ice or menthol gels. Few studies have compared the effects of these treatments on blood flow and muscle strength. Objective: To compare blood flow and muscle strength in the forearm after an application of ice or menthol gel or no treatment. Design: Repeated measures design in which blood-flow and muscle-strength data were collected from subjects under 3 treatment conditions. Setting: Exercise physiology laboratory. Participants: 17 healthy adults with no impediment to the blood flow or strength in their right arm, recruited through word of mouth. Intervention: Three separate treatment conditions were randomly applied topically to the right forearm: no treatment, 0.5 kg of ice, or 3.5 mL of 3.5% menthol gel. To avoid injury ice was only applied for 20 min. Main Outcome Measures: At each data-collection session blood flow (mL/min) of the right radial artery was determined at baseline before any treatment and then at 5, 10, 15, and 20 min after treatment using Doppler ultrasound. Muscle strength was assessed as maximum isokinetic flexion and extension of the wrist at 30°/s 20, 25, and 30 min after treatment. Results: The menthol gel reduced (–42%, P \u3c .05) blood flow in the radial artery 5 min after application but not at 10, 15, or 20 min after application. Ice reduced (–48%, P \u3c .05) blood flow in the radial artery only after 20 min of application. After 15 min of the control condition blood flow increased (83%, P \u3c .05) from baseline measures. After the removal of ice, wrist-extension strength did not increase per repeated strength assessment as it did during the control condition (9–11%, P \u3c .05) and menthol-gel intervention (8%, P \u3c .05). Conclusions: Menthol has a fast-acting, short-lived effect of reducing blood flow. Ice reduces blood flow after a prolonged duration. Muscle strength appears to be inhibited after ice application