Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review.

Heat acclimation/acclimatisation (HA) mitigates heat-related decrements in physical capacity and heat-illness risk and is a widely advocated countermeasure for individuals operating in hot environments. The efficacy of HA is typically quantified by assessing the thermo-physiological responses to a standard heat acclimation state test (i.e. physiological biomarkers), but this can be logistically challenging, time consuming, and expensive. A valid molecular biomarker of HA would enable evaluation of the heat-adapted state through the sampling and assessment of a biological medium. This narrative review examines candidate molecular biomarkers of HA, highlighting the poor sensitivity and specificity of these candidates and identifying the current lack of a single 'standout' biomarker. It concludes by considering the potential of multivariable approaches that provide information about a range of physiological systems, identifying a number of challenges that must be overcome to develop a valid molecular biomarker of the heat-adapted state, and highlighting future research opportunities.

First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

T cell-extrinsic IL-1 signaling controls long-term gammaherpesvirus infection by suppressing viral reactivation.

Gammaherpesviruses establish life-long infection in over 95% of adults and are associated with several cancers, including B cell lymphomas. Using the murine gammaherpesvirus 68 (MHV68) animal model, we previously showed a pro-viral role of Interleukin-1 (IL-1) signaling that supported viral reactivation during the establishment of chronic infection. Unexpectedly, in this study we found that the proviral effects of IL-1 signaling originally observed during the establishment of chronic gammaherpesvirus infection convert to antiviral effects during the long-term stage of infection. Specifically, IL-1 signaling promoted expansion of antiviral CD8+ T cells and control of viral reactivation in the peritoneal cavity of a long-term infected host. Using a novel mouse model of T cell-specific IL-1 signaling deficiency, we found that the antiviral effects of IL-1 signaling were T cell extrinsic. Our study highlights a dynamic nature of host factors that shape the parameters of chronic gammaherpesvirus infection.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

In pursuit of the unicorn.

This short review was prompted by The Physiological Society's recent online symposium on variability. It does not deal with a specific methodology, but rather with the myth that certain environmentally-induced clinical conditions can be identified, quantified, simplified and monitored with a single methodology. Although this might be possible with some clinical conditions, others resist the prevailing reductionist approach of minimizing rather than exploring variation in pathogenesis and pathology, and will not be understood fully until the variation in cause and effect are embraced. This is likely to require comprehensive methodologies and collaboration.

Estimated health impacts from maritime transport in the Mediterranean region and benefits from the use of cleaner fuels.

Ship traffic emissions degrade air quality in coastal areas and contribute to climate impacts globally. The estimated health burden of exposure to shipping emissions in coastal areas may inform policy makers as they seek to reduce exposure and associated potential health impacts. This work estimates the PM2.5-attributable impacts in the form of premature mortality and cardiovascular and respiratory hospital admissions, from long-term exposure to shipping emissions. Health impact assessment (HIA) was performed in 8 Mediterranean coastal cities, using a baseline conditions from the literature and a policy case accounting for the MARPOL Annex VI rules requiring cleaner fuels in 2020. Input data were (a) shipping contributions to ambient PM2.5 concentrations based on receptor modelling studies found in the literature, (b) population and health incidence data from national statistical registries, and (c) geographically-relevant concentration-response functions from the literature. Long-term exposure to ship-sourced PM2.5 accounted for 430 (95% CI: 220-650) premature deaths per year, in the 8 cities, distributed between groups of cities: Barcelona and Athens, with >100 premature deaths/year, and Nicosia, Brindisi, Genoa, Venice, Msida and Melilla, with tens of premature deaths/year. The more stringent standards in 2020 would reduce the number of PM2.5-attributable premature deaths by 15% on average. HIA provided a comparative assessment of the health burden of shipping emissions across Mediterranean coastal cities, which may provide decision support for urban planning with a special focus on harbour areas, and in view of the reduction in sulphur content of marine fuels due to MARPOL Annex VI in 2020.

Human factors in preventing complications in anaesthesia: a systematic review.

Human factors in anaesthesia were first highlighted by the publication of the Anaesthetists Non-Technical Skills Framework, and since then an awareness of their importance has gradually resulted in changes in routine clinical practice. This review examines recent literature around human factors in anaesthesia, and highlights recent national reports and guidelines with a focus on team working, communication, situation awareness and human error. We highlight the importance of human factors in modern anaesthetic practice, using the example of complex trauma.

Orbital mass as first presentation of metastatic p16-positive oropharyngeal squamous cell carcinoma.

We describe a case in which a 67-year-old man was diagnosed with a metastatic recurrence of p16-positive oropharyngeal squamous cell carcinoma after presenting with a medial orbital mass in the region of the nasolacrimal apparatus. A review of the literature revealed that metastasis to the orbit from any malignancy is an uncommon occurrence, and no cases of p16-positive oropharyngeal squamous cell carcinoma have previously been reported. Our case highlights the importance of maintaining a high index of suspicion during surveillance visits with such patients.

Cold water immersion: kill or cure?

NEW FINDINGS: What is the topic of this review? This is the first review to look across the broad field of 'cold water immersion' and to determine the threats and benefits associated with it as both a hazard and a treatment. What advances does it highlight? The level of evidence supporting each of the areas reviewed is assessed. Like other environmental constituents, such as pressure, heat and oxygen, cold water can be either good or bad, threat or treatment, depending on circumstance. Given the current increase in the popularly of open cold water swimming, it is timely to review the various human responses to cold water immersion (CWI) and consider the strength of the claims made for the effects of CWI. As a consequence, in this review we look at the history of CWI and examine CWI as a precursor to drowning, cardiac arrest and hypothermia. We also assess its role in prolonged survival underwater, extending exercise time in the heat and treating hyperthermic casualties. More recent uses, such as in the prevention of inflammation and treatment of inflammation-related conditions, are also considered. It is concluded that the evidence base for the different claims made for CWI are varied, and although in most instances there seems to be a credible rationale for the benefits or otherwise of CWI, in some instances the supporting data remain at the level of anecdotal speculation. Clear directions and requirements for future research are indicated by this review.

A multistudy examination of organizational stressors, emotional labor, burnout, and turnover in sport organizations.

While a growing body of research has examined the types of organizational stressors encountered by individuals and their allied responses, little is known about how such individuals manage their emotional responses to these stressors or the consequences of such behaviors. This article presents novel findings from two studies examining the moderating role that emotional labor plays in the relationship between the frequency of organizational stressor experience, burnout, turnover intentions, and actual turnover in sport. In study 1, participants (n=487) completed measures of organizational stressors (OSI-SP), emotional labor (ELS), burnout (ABQ), and turnover intentions. In study 2, a 6-month longitudinal design was used to examine measures of organizational stressors (OSI-SP), emotional labor (ELS), turnover intentions, and actual turnover. Study 1 showed that surface acting moderated the relationship between the frequency of organizational stressors and burnout in sport. Further, surface acting acted as an important mechanism through which burnout mediated the relationship between the frequency of organizational stressors and turnover intentions. Study 2 showed that surface acting moderated the relationship between the organizational stressor frequency and turnover intentions-but not actual turnover-over time. These results highlight the importance of surface acting in understanding how individuals respond to organizational stressors encountered in sport, expanding our understanding of the positive and negative responses component of the meta-model of stress, emotions, and performance. These findings also highlight potentially deleterious emotion-management behaviors that practitioners might consider when aiming to support individuals encountering organizational stressors in sport.

Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.

INTRODUCTION: Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. METHODS: Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months. RESULTS: At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02). CONCLUSION: Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.

The SloR metalloregulator is involved in the Streptococcus mutans oxidative stress response.

SloR, a 25-kDa metalloregulatory protein in Streptococcus mutans modulates the expression of multiple genes, including the sloABC operon that encodes essential Mn2+ transport and genes that promote cariogenesis. In this study, we report on SloC- and SloR-deficient strains of S. mutans (GMS284 and GMS584, respectively) that demonstrate compromised survivorship compared with their UA159 wild-type progenitor and their complemented strains (GMS285 and GMS585, respectively), when challenged with streptonigrin and/or in growth competition experiments. The results of streptonigrin assays revealed significantly larger zones of inhibition for GMS584 than for either UA159 or GMS585, indicating weakened S. mutans survivorship in the absence of SloR. Competition assays revealed a compromised ability for GMS284 and GMS584 to survive peroxide challenge compared with their SloC- and SloR-proficient counterparts. These findings are consistent with a role for SloC and SloR in S. mutans aerotolerance. We also predicted differential expression of oxidative stress tolerance genes in GMS584 versus UA159 and GMS585 when grown aerobically. The results of quantitative RT-PCR experiments revealed S. mutans sod, tpx, and sloC expression that was upregulated in GMS584 compared with UA159 and GMS585, indicating that the impact of oxidative stress on S. mutans is more severe in the absence of SloR than in its presence. The results of electrophoretic mobility shift assays indicate that SloR does not bind to the sod or tpx promoter regions directly, implicating intermediaries that may arbitrate the SloR response to oxidative stress.

Climatic Drivers for Multi-Decadal Shifts in Solute Transport and Methane Production Zones within a Large Peat Basin.

Northern peatlands are an important source for greenhouse gases but their capacity to produce methane remains uncertain under changing climatic conditions. We therefore analyzed a 43-year time series of pore-water chemistry to determine if long-term shifts in precipitation altered the vertical transport of solutes within a large peat basin in northern Minnesota. These data suggest that rates of methane production can be finely tuned to multi-decadal shifts in precipitation that drive the vertical penetration of labile carbon substrates within the Glacial Lake Agassiz Peatlands. Tritium and cation profiles demonstrate that only the upper meter of these peat deposits was flushed by downwardly moving recharge from 1965 through 1983 during a Transitional Dry-to-Moist Period. However, a shift to a moister climate after 1984 drove surface waters much deeper, largely flushing the pore waters of all bogs and fens to depths of 2 m. Labile carbon compounds were transported downward from the rhizosphere to the basal peat at this time producing a substantial enrichment of methane in Δ14C with respect to the solid-phase peat from 1991 to 2008. These data indicate that labile carbon substrates can fuel deep production zones of methanogenesis that more than doubled in thickness across this large peat basin after 1984. Moreover, the entire peat profile apparently has the capacity to produce methane from labile carbon substrates depending on climate-driven modes of solute transport. Future changes in precipitation may therefore play a central role in determining the source strength of peatlands in the global methane cycle.

Effect of short-term heat acclimation with permissive dehydration on thermoregulation and temperate exercise performance.

We examined the effect of short-term heat acclimation with permissive dehydration (STHADe) on heat acclimation (HA) and cycling performance in a temperate environment. Ten trained male cyclists [mean (SD) maximal oxygen uptake: 63.3(4.0) mL/kg/min; peak power output (PPO): 385(40) W; training: 10 (3) h/week] underwent a STHADe program consisting of 5 days of exercise (maximum 90 min/day) in a hot environment (40 °C, 50% RH) to elicit isothermic heat strain [rectal temperature 38.64(0.27) °C]. Participants abstained from fluids during, and 30 min after, HA sessions. Pre- and post-STHADe HA was evaluated during euhydrated fixed-intensity exercise (60 min) in hot conditions; the effect of STHADe on thermoregulation was also examined under temperate conditions (20 min fixed-intensity exercise; 22 °C, 60% RH). Temperate cycling performance was assessed by a graded exercise test (GXT) and 20-km time trial (TT). STHADe reduced thermal and cardiovascular strain in hot and temperate environments. Lactate threshold [Δ = 16 (17) W] and GXT PPO [Δ = 6 (7) W] were improved following STHADe (P < 0.05), but TT performance was not affected (P > 0.05), although there was a trend for a higher mean power (P = 0.06). In conclusion, STHADE can reduce thermal and cardiovascular strain under hot and temperate conditions and there is some evidence of ergogenic potential for temperate exercise, but longer HA regimens may be necessary for this to meaningfully influence performance.

Peri-operative renal dysfunction: prevention and management.

Postoperative increases in serum creatinine concentration, by amounts historically viewed as trivial, are associated with increased morbidity and mortality. Acute kidney injury is common, affecting one in five patients admitted with acute medical disease and up to four in five patients admitted to intensive care, of whom one in two have had operations. This review is focused principally on the identification of patients at risk of acute kidney injury and the prevention of injury. In the main, there are no interventions that directly treat the damaged kidney. The management of acute kidney injury is based on correction of dehydration, hypotension, and urinary tract obstruction, stopping nephrotoxic drugs, giving antibiotics for bacterial infection, and commencing renal replacement therapy if necessary.

Mega-electron-volt ultrafast electron diffraction at SLAC National Accelerator Laboratory.

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition rate with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.

Relieving thermal discomfort: Effects of sprayed L-menthol on perception, performance, and time trial cycling in the heat.

L-menthol stimulates cutaneous thermoreceptors and induces cool sensations improving thermal comfort, but has been linked to heat storage responses; this could increase risk of heat illness during self-paced exercise in the heat. Therefore, L-menthol application could lead to a discrepancy between behavioral and autonomic thermoregulatory drivers. Eight male participants volunteered. They were familiarized and then completed two trials in hot conditions (33.5 °C, 33% relative humidity) where their t-shirt was sprayed with CONTROL-SPRAY or MENTHOL-SPRAY after 10 km (i.e., when they were hot and uncomfortable) of a 16.1-km cycling time trial (TT). Thermal perception [thermal sensation (TS) and comfort (TC)], thermal responses [rectal temperature (Trec ), skin temperature (Tskin )], perceived exertion (RPE), heart rate, pacing (power output), and TT completion time were measured. MENTHOL-SPRAY made participants feel cooler and more comfortable and resulted in lower RPE (i.e., less exertion) yet performance was unchanged [TT completion: CONTROL-SPRAY 32.4 (2.9) and MENTHOL-SPRAY 32.7 (3.0) min]. Trec rate of increase was 1.40 (0.60) and 1.45 (0.40) °C/h after CONTROL-SPRAY and MENTHOL-SPRAY application, which were not different. Spraying L-menthol toward the end of self-paced exercise in the heat improved perception, but did not alter performance and did not increase heat illness risk.