Exertional Heat Stroke Survival at the Falmouth Road Race: 180 New Cases With Expanded Analysis.

CONTEXT: A high number of exertional heat stroke (EHS) cases occur during the Falmouth Road Race. OBJECTIVES: To extend previous analyses of EHS cases during the Falmouth Road Race by assessing or describing (1) EHS and heat exhaustion (HE) incidence rates, (2) EHS outcomes as they relate to survival, (3) the effect of the environment on these outcomes, and (4) how this influences medical provider planning and preparedness. DESIGN: Descriptive epidemiologic study. SETTING: Falmouth Road Race. PATIENTS OR OTHER PARTICIPANTS: Patients with EHS or HE admitted to the medical tent. MAIN OUTCOME MEASURE(S): We obtained 8 years (2012 to 2019) of Falmouth Road Race anonymous EHS and HE medical records. Meteorologic data were collected and analyzed to evaluate the effect of environmental conditions on the heat illness incidence (exertional heat illness [EHI] = EHS + HE). The EHS treatment and outcomes (ie, cooling time, survival, and discharge outcome), number of HE patients, and wet bulb globe temperature (WBGT) for each race were analyzed. RESULTS: A total of 180 EHS and 239 HE cases were identified. Overall incidence rates per 1000 participants were 2.07 for EHS and 2.76 for HE. The EHI incidence rate was 4.83 per 1000 participants. Of the 180 EHS cases, 100% survived, and 20% were transported to the emergency department. The WBGT was strongly correlated with the incidence of both EHS (r2 = 0.904, P = .026) and EHI (r2 = 0.912, P = .023). CONCLUSIONS: This is the second-largest civilian database of EHS cases reported. When combined with the previous dataset of EHS survivors from this race, it amounts to 454 EHS cases resulting in 100% survival. The WBGT remained a strong predictor of EHS and EHI cases. These findings support 100% survival from EHS when patients over a wide range of ages and sexes are treated with cold-water immersion.

Comparison between digital and paper urine color to assess hydration status.

PURPOSE: The purpose of this study was to investigate associations between digital urine color and paper urine color with other urine indices to assess hydration status. METHODS: Twelve male subjects (mean ± standard deviation; age, 26 ± 8 years; body mass, 57.8 ± 5.3 kg; height, 177.5 ± 8.9 cm; VO2max, 57.8 ± 5.8 ml·kg-1·min-1) performed four exercise trials in the heat. Before and following exercise trials, subjects provide urine samples. Urine samples were measured using a digital urine color chart on a portable device screen. Urine samples were also assessed with urine specific gravity (USG), urine osmolality (UOsmo), and a validated paper urine color chart. RESULTS: There were extremely large associations found between digital urine color and paper urine color (r = 0.926, p < 0.001). Correlation coefficients showing associations with USG and UOsmo were similar between digital urine color (USG, r = 0.695, p < 0.001; UOsmo, r = 0.555, p < 0.001) and paper urine color (USG, r = 0.713, p < 0.001; UOsmo, r = 0.570, p < 0.001). Bland-Altman analysis indicated that no proportional bias was observed between digital and paper urine colors (bias, - 0.148; SD of bias, 0.492; 95% LOA, - 1.11, 0.817; p = 0.094). CONCLUSIONS: Strong associations were found between digital and paper urine colors with no proportional bias. Furthermore, the degree of associations with USG and UOsmo was similar between digital and paper urine color. These results indicate that digital urine color is a useful tool to assess hydration status and this method could be used as an alternative method to using paper urine color.

The effect of heat mitigation strategies on thermoregulation and productivity during simulated occupational work in the heat in physically active young men.

Purpose: To investigate heat stress mitigation strategies on productivity and thermoregulatory responses during simulated occupational work in the heat. Methods: Thirteen physically active men (age, 25 ± 4 years; body mass,77.8 ± 14.7 kg; VO2peak, 44.5 ± 9.2 ml·kg-1·min-1) completed five randomized-controlled trials in a hot environment (40°C, 40% relative humidity). Each trial was 4.5 h in duration to simulate an outdoor occupational shift. Thermoregulatory responses (heart rate, HR; rectal temperature, Trec; mean skin temperature, Tsk), perceptual responses (rating of perceived exertion, RPE; thermal sensation; thermal comfort; fatigue) and productivity outcomes (box lifting repetitions, time to exhaustion) were examined in the following heat mitigation strategy interventions: (1) simulated solar radiation with limited fluid intake [SUN]; (2) simulated solar radiation with no fluid restrictions [SUN + H2O]; (3) shade (no simulated solar radiation during trial) with no fluid restrictions [SHADE + H2O]; (4) shade and cooling towels during rest breaks with no fluid restrictions [COOL + H2O]; and (5) shade with cooling towels, cooling vest during activity with no fluid restrictions [COOL + VEST + H2O]. Results: [COOL + VEST + H2O] had lower Trec compared to [SUN] [p = 0.004, effect size(ES) = 1.48], [SUN + H2O] (p < 0.001, ES = -1.87), and [SHADE + H2O] (p = 0.001, ES = 1.62). Average Tsk was lower during the treadmill and box lifting activities in the [COOL + VEST + H2O] compared to [SUN] (p < 0.001, ES = 7.92), [SUN + H2O] (p < 0.001,7.96), [SHADE + H2O] (p < 0.001), and [COOL + H2O] (p < 0.001, ES = 3.01). There were performance differences during the [COOL + VEST + H2O] (p = 0.033) and [COOL + H2O] (p = 0.023) conditions compared to [SUN] during phases of the experimental trial, however, there were no differences in total box lifting repetitions between trials (p > 0.05). Conclusion: Our results suggest that during a simulated occupational shift in a laboratory setting, additional heat mitigation strategies ([COOL + VEST + H2O] and [COOL + H2O]) reduced physiological strain and improved box lifting performance to a greater degree than [SUN]. These differences may have been attributed to a larger core to skin temperature gradient or reduction in fatigue, thermal sensation, and RPE during [COOL + H2O] and [COOL + VEST + H2O]. These data suggest that body cooling, hydration, and "shade" (removal of simulated radiant heat) as heat stress mitigation strategies should be considered as it reduces physiological strain while producing no additional harm.

Kardar-Parisi-Zhang Physics and Phase Transition in a Classical Single Random Walker under Continuous Measurement.

We introduce and study a new model consisting of a single classical random walker undergoing continuous monitoring at rate γ on a discrete lattice. Although such a continuous measurement cannot affect physical observables, it has a nontrivial effect on the probability distribution of the random walker. At small γ, we show analytically that the time evolution of the latter can be mapped to the stochastic heat equation. In this limit, the width of the log-probability thus follows a Family-Vicsek scaling law, N^{α}f(t/N^{α/ß}), with roughness and growth exponents corresponding to the Kardar-Parisi-Zhang (KPZ) universality class, i.e., α_{KPZ}^{1D}=1/2 and ß_{KPZ}^{1D}=1/3, respectively. When γ is increased outside this regime, we find numerically in 1D a crossover from the KPZ class to a new universality class characterized by exponents α_{M}^{1D}≈1 and ß_{M}^{1D}≈1.4. In 3D, varying γ beyond a critical value γ_{M}^{c} leads to a phase transition from a smooth phase that we identify as the Edwards-Wilkinson class to a new universality class with α_{M}^{3D}≈1.

Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36.

The PHD finger motif is a signature chromatin-associated motif that is found throughout eukaryotic proteomes. Here we have determined the histone methyl-lysine binding activity of the PHD fingers present within the Saccharomyces cerevisiae proteome. We provide evidence on the genomic scale that PHD fingers constitute a general class of effector modules for histone H3 trimethylated at lysine 4 (H3K4me3) and histone H3 trimethylated at lysine 36 (H3K36me3). Structural modeling of PHD fingers demonstrates a conserved mechanism for recognizing the trimethyl moiety and provides insight into the molecular basis of affinity for the different methyl-histone ligands. Together, our study suggests that a common function for PHD fingers is to transduce methyl-lysine events and sheds light on how a single histone modification can be linked to multiple biological outcomes.

The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone H3.

The ING (inhibitor of growth) protein family includes a group of homologous nuclear proteins that share a highly conserved plant homeodomain (PHD) finger domain at their carboxyl termini. Members of this family are found in multiprotein complexes that posttranslationally modify histones, suggesting that these proteins serve a general role in permitting various enzymatic activities to interact with nucleosomes. There are three members of the ING family in Saccharomyces cerevisiae: Yng1p, Yng2p, and Pho23p. Yng1p is a component of the NuA3 histone acetyltransferase complex and is required for the interaction of NuA3 with chromatin. To gain insight into the function of the ING proteins, we made use of a genetic strategy to identify genes required for the binding of Yng1p to histones. Using the toxicity of YNG1 overexpression as a tool, we showed that Yng1p interacts with the amino-terminal tail of histone H3 and that this interaction can be disrupted by loss of lysine 4 methylation within this tail. Additionally, we mapped the region of Yng1p required for overexpression of toxicity to the PHD finger, showed that this region capable of binding lysine 4-methylated histone H3 in vitro, and demonstrated that mutations of the PHD finger that abolish binding in vitro are no longer toxic in vivo. These results identify a novel function for the Yng1p PHD finger in promoting stabilization of the NuA3 complex at chromatin through recognition of histone H3 lysine 4 methylation.

Methylation of histone H3 mediates the association of the NuA3 histone acetyltransferase with chromatin.

The SAS3-dependent NuA3 histone acetyltransferase complex was originally identified on the basis of its ability to acetylate histone H3 in vitro. Whether NuA3 is capable of acetylating histones in vivo, or how the complex is targeted to the nucleosomes that it modifies, was unknown. To address this question, we asked whether NuA3 is associated with chromatin in vivo and how this association is regulated. With a chromatin pulldown assay, we found that NuA3 interacts with the histone H3 amino-terminal tail, and loss of the H3 tail recapitulates phenotypes associated with loss of SAS3. Moreover, mutation of histone H3 lysine 14, the preferred site of acetylation by NuA3 in vitro, phenocopies a unique sas3Delta phenotype, suggesting that modification of this residue is important for NuA3 function. The interaction of NuA3 with chromatin is dependent on the Set1p and Set2p histone methyltransferases, as well as their substrates, histone H3 lysines 4 and 36, respectively. These results confirm that NuA3 is functioning as a histone acetyltransferase in vivo and that histone H3 methylation provides a mark for the recruitment of NuA3 to nucleosomes.

Marcfortine and paraherquamide class of anthelmintics: discovery of PNU-141962.

Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a different mode of action is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. This review describes the chemistry, efficacy and mode of action of PNU-141962.