Kv7/M-type potassium channels in rat skin keratinocytes.

Skin keratinocytes fulfil important signalling and protective functions. Immunocytochemical experiments revealed the unexpected presence of immunoreactivity for the M-type potassium channel subunit Kv7.2 in the keratinocyte layer of intact rat paw skin and in keratinocytes isolated from the skin of 1-day-old rats and cultured in vitro for 3-10 days. Application of the M-channel enhancer retigabine (3-10 μM) to isolated cultured rat keratinocytes: (a) increased outward membrane currents recorded under voltage clamp, (b) produced ~3 mV hyperpolarization at rest, (c) enhanced ~3-fold the release of ATP induced by the TRPV3 agonist carvacrol (1 mM) and (d) increased the amplitude of the carvacrol-induced intracellular Ca(2+) transient measured with Fura-2. The effect of retigabine on ATP release was prevented by the M-channel blocking agent XE991. We conclude that rat skin keratinocytes possess M-channels that, when activated, can modify their physiological properties, with potential significance for their sensory and other biological functions

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

Whole Atmosphere Climate Change: Dependence on Solar Activity

We conducted global simulations of temperature change due to anthropogenic trace gas emissions, which extended from the surface, through the thermosphere and ionosphere, to the exobase. These simulations were done under solar maximum conditions, in order to compare the effect of the solar cycle on global change to previous work using solar minimum conditions. The Whole Atmosphere Community Climate Model‐eXtended was employed in this study. As in previous work, lower atmosphere warming, due to increasing anthropogenic gases, is accompanied by upper atmosphere cooling, starting in the lower stratosphere, and becoming dramatic, almost 2 K per decade for the global mean annual mean, in the thermosphere. This thermospheric cooling, and consequent reduction in density, is less than the almost 3 K per decade for solar minimum conditions calculated in previous simulations. This dependence of global change on solar activity conditions is due to solar‐driven increases in radiationally active gases other than carbon dioxide, such as nitric oxide. An ancillary result of these and previous simulations is an estimate of the solar cycle effect on temperatures as a function of altitude. These simulations used modest, five‐member, ensembles, and measured sea surface temperatures rather than a fully coupled ocean model, so any solar cycle effects were not statistically significant in the lower troposphere. Temperature change from solar minimum to maximum increased from near zero at the tropopause to about 1 K at the stratopause, to approximately 500 K in the upper thermosphere, commensurate with the empirical evidence, and previous numerical models

Monitoring trends in HIV prevalence among young people, aged 15 to 24 years, in Manicaland, Zimbabwe

BACKGROUND: In June 2001, the United Nations General Assembly Special Session (UNGASS) set a target of reducing HIV prevalence among young women and men, aged 15 to 24 years, by 25% in the worst-affected countries by 2005, and by 25% globally by 2010. We assessed progress toward this target in Manicaland, Zimbabwe, using repeated household-based population serosurvey data. We also validated the representativeness of surveillance data from young pregnant women, aged 15 to 24 years, attending antenatal care (ANC) clinics, which UNAIDS recommends for monitoring population HIV prevalence trends in this age group. Changes in socio-demographic characteristics and reported sexual behaviour are investigated. METHODS: Progress towards the UNGASS target was measured by calculating the proportional change in HIV prevalence among youth and young ANC attendees over three survey periods (round 1: 1998-2000; round 2: 2001-2003; and round 3: 2003-2005). The Z-score test was used to compare differences in trends between the two data sources. Characteristics of participants and trends in sexual risk behaviour were analyzed using Student's and two-tailed Z-score tests. RESULTS: HIV prevalence among youth in the general population declined by 50.7% (from 12.2% to 6.0%) from round 1 to 3. Intermediary trends showed a large decline from round 1 to 2 of 60.9% (from 12.2% to 4.8%), offset by an increase from round 2 to 3 of 26.0% (from 4.8% to 6.0%). Among young ANC attendees, the proportional decline in prevalence of 43.5% (from 17.9% to 10.1%) was similar to that in the population (test for differences in trend: p value = 0.488) although ANC data significantly underestimated the population prevalence decline from round 1 to 2 (test for difference in trend: p value = 0.003) and underestimated the increase from round 2 to 3 (test for difference in trend: p value = 0.012). Reductions in risk behaviour between rounds 1 and 2 may have been responsible for general population prevalence declines. CONCLUSIONS: In Manicaland, Zimbabwe, the 2005 UNGASS target to reduce HIV prevalence by 25% was achieved. However, most prevention gains occurred before 2003. ANC surveillance trends overall were an adequate indicator of trends in the population, although lags were observed. Behaviour data and socio-demographic characteristics of participants are needed to interpret ANC trends

Issues of methods and interpretation in the National Cancer Institute formaldehyde cohort study

In 2004, the International Agency for Research on Cancer (IARC) reclassified formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group 1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up through 1994 of the National Cancer Institute formaldehyde cohort study. To the contrary, in 2012, the Committee for Risk Assessment of the European Chemicals Agency disagreed with the proposal to classify FA as a known human carcinogen (Carc. 1A), proposing a lower but still protective category, namely as a substance which is presumed to have carcinogenic potential for humans (Carc. 1B). Thus, U.S. and European regulatory agencies currently disagree about the potential human carcinogenicity of FA. In 2013, the National Cancer Institute reported results from their follow-up through 2004 of the formaldehyde cohort and concluded that the results continue to suggest a link between FA exposure and NPC. We discuss in this commentary why we believe that this interpretation is neither consistent with the available data from the most recent update of the National Cancer Institute cohort study nor with other research findings from that cohort, other large cohort studies and the series of publications by some of the current authors, including an independent study of one of the National Cancer Institute's study plants. Another serious concern relates to the incorrectness of the data from the follow-up through 1994 of the National Cancer Institute study stemming from incomplete mortality ascertainment. While these data were corrected by the National Cancer Institute in subsequent supplemental publications, incorrect data from the original publications have been cited extensively in recent causal evaluations of FA, including IARC. We conclude that the NCI publications that contain incorrect data from the incomplete 1994 mortality follow-up should be retracted entirely or corrected via published errata in the corresponding journals, and efforts should be made to re-analyze data from the 2004 follow-up of the NCI cohort study. © 2014 Marsh et al.; licensee BioMed Central Ltd

Identification of major hemorrhage in trauma patients in the prehospital setting: diagnostic accuracy and impact on outcome.

BACKGROUND: Hemorrhage is the most common cause of potentially preventable death after injury. Early identification of patients with major hemorrhage (MH) is important as treatments are time-critical. However, diagnosis can be difficult, even for expert clinicians. This study aimed to determine how accurate clinicians are at identifying patients with MH in the prehospital setting. A second aim was to analyze factors associated with missed and overdiagnosis of MH, and the impact on mortality. METHODS: Retrospective evaluation of consecutive adult (≥16 years) patients injured in 2019-2020, assessed by expert trauma clinicians in a mature prehospital trauma system, and admitted to a major trauma center (MTC). Clinicians decided to activate the major hemorrhage protocol (MHPA) or not. This decision was compared with whether patients had MH in hospital, defined as the critical admission threshold (CAT+): administration of ≥3 U of red blood cells during any 60-minute period within 24 hours of injury. Multivariate logistical regression analyses were used to analyze factors associated with diagnostic accuracy and mortality. RESULTS: Of the 947 patients included in this study, 138 (14.6%) had MH. MH was correctly diagnosed in 97 of 138 patients (sensitivity 70%) and correctly excluded in 764 of 809 patients (specificity 94%). Factors associated with missed diagnosis were penetrating mechanism (OR 2.4, 95% CI 1.2 to 4.7) and major abdominal injury (OR 4.0; 95% CI 1.7 to 8.7). Factors associated with overdiagnosis were hypotension (OR 0.99; 95% CI 0.98 to 0.99), polytrauma (OR 1.3, 95% CI 1.1 to 1.6), and diagnostic uncertainty (OR 3.7, 95% CI 1.8 to 7.3). When MH was missed in the prehospital setting, the risk of mortality increased threefold, despite being admitted to an MTC. CONCLUSION: Clinical assessment has only a moderate ability to identify MH in the prehospital setting. A missed diagnosis of MH increased the odds of mortality threefold. Understanding the limitations of clinical assessment and developing solutions to aid identification of MH are warranted. LEVEL OF EVIDENCE: Level III-Retrospective study with up to two negative criteria. STUDY TYPE: Original research; diagnostic accuracy study

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity