Conformational Change of Mitochondrial Complex I Increases ROS Sensitivity During Ischemia

Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities of reactive oxygen species (ROS) and resultant damage to mitochondrial enzymes is considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) and deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium in several tissues under ischemic conditions in vivo and investigated the sensitivity of both forms of the heart enzyme to ROS. Results: We found that in the heart, t(½) of complex I deactivation during ischemia was 10 min, and that reperfusion resulted in the return of A/D equilibrium to its initial level. The rate of superoxide generation by complex I was higher in ischemic samples where content of the D-form was higher. Only the D-form was susceptible to inhibition by H(2)O(2) or superoxide, whereas turnover-dependent activation of the enzyme resulted in formation of the A-form, which was much less sensitive to ROS. The mitochondrial-encoded subunit ND3, most likely responsible for the sensitivity of the D-form to ROS, was identified by redox difference gel electrophoresis. Innovation: A combined in vivo and biochemical approach suggests that sensitivity of the mitochondrial system to ROS during myocardial I/R can be significantly affected by the conformational state of complex I, which may therefore represent a new therapeutic target in this setting. Conclusion: The presented data suggest that transition of complex I into the D-form in the absence of oxygen may represent a key event in promoting cardiac injury during I/R. Antioxid. Redox Signal. 19, 1459–1468

American cultural regions mapped through the lexical analysis of social media

Cultural areas represent a useful concept that cross-fertilizes diverse fields in social sciences. Knowledge of how humans organize and relate their ideas and behavior within a society helps to understand their actions and attitudes towards different issues. However, the selection of common traits that shape a cultural area is somewhat arbitrary. What is needed is a method that can leverage the massive amounts of data coming online, especially through social media, to identify cultural regions without ad-hoc assumptions, biases or prejudices. This work takes a crucial step in this direction by introducing a method to infer cultural regions based on the automatic analysis of large datasets from microblogging posts. The approach presented here is based on the principle that cultural affiliation can be inferred from the topics that people discuss among themselves. Specifically, regional variations in written discourse are measured in American social media. From the frequency distributions of content words in geotagged Tweets, the regional hotspots of words' usage are found, and from there, principal components of regional variation are derived. Through a hierarchical clustering of the data in this lower-dimensional space, this method yields clear cultural areas and the topics of discussion that define them. It uncovers a manifest North-South separation, which is primarily influenced by the African American culture, and further contiguous (East-West) and non-contiguous divisions that provide a comprehensive picture of today's cultural areas in the US.Comment: 13 pages, 5 figures; contains Supplementary Informatio

Clarity of Microstamped Identifiers as a Function of Primer Hardness and Type of Firearm Action

The transfer of microstamped identifiers to the primers of fired cartridges was examined using a stereomicroscope and scanning electron microscope (SEM). The identifiers were placed on the firing pins of three different 9mm handguns, namely, a Sig Sauer, a Taurus, and a Hi-Point. Ten different brands of ammunition were fired from each handgun, 100 rounds being fired using each brand for a total of 1000 rounds fired per handgun. The quality of the markings was evaluated using a simple observation rubric. These results were compared to Vickers hardness values obtained from the ammunition primers and are discussed in light of the types of actions of firearms used

Home blood pressure monitors owned by participants in a large decentralised clinical trial in hypertension:the Treatment In Morning versus Evening (TIME) study

Various home blood pressure monitors (HBPMs) are available to the public for purchase but only some are validated against standardised protocols. This study aimed to assess whether HBPMs owned by participants taking part in a clinical trial were validated models. The TIME study is a decentralised randomised trial investigating the effect of antihypertensive medication dosing time on cardiovascular outcomes in adults with hypertension. No HBPMs were provided to participants in this trial but patients were asked to report if they already owned one. We identified the model of HBPM reported by participants, then cross-referenced this against lists of validated HBPMs produced by dabl Educational Trust and the British and Irish Hypertension Society (BIHS). Of 21,104 participants, 10,464 (49.6%) reported their model of HBPM. 7464 (71.3%) of these participants owned a monitor that could be identified from the participants’ entry. Of these, 6066 (81.3%) participants owned a monitor listed as validated by either dabl (n = 5903) or BIHS (n = 5491). Some were listed as validated by both. 1398 (18.7%) participants owned an identifiable HBPM that lacked clear evidence of validation. 6963 (93.3%) participants owned an upper arm HBPM and 501 (6.7%) owned a wrist HBPM. Validated HBPMs had a higher median online retail price of £45.00 compared to £20.00 for HBPMs lacking clear evidence of validation. A significant number of participants own HBPMs lacking evidence of validation

Factors influencing home blood pressure monitor ownership in a large clinical trial

Home blood pressure monitor (HBPM) ownership prevalence and the factors that influence it are unclear. This study aimed to investigate factors associated with HBPM ownership among participants in the Treatment in Morning versus Evening (TIME) hypertension study. This study is a sub-analysis of the TIME study, a randomised trial investigating the effect of day-time versus night-time dosing of antihypertensive medication on cardiovascular outcomes in adults with hypertension. As part of the TIME study online registration process, participants were asked to indicate whether they owned an HBPM. A multivariate logistic regression model was constructed to determine factors associated with HBPM ownership. Of 21 104 randomised participants, 11 434 (54.2%) reported owning an HBPM. The mean age of all participants at enrolment was 67.7 ± 9.3 years, 12 134 (57.5%) were male, and 8 892 (42.1%) reported a current or previous history of smoking. Factors associated with an increased likelihood of reporting HBPM owned include being male (OR:1.47; 95% CI 1.39-1.56) or residing in a less deprived socioeconomic region (IMD Decile 6-10) (OR:1.31; 95% CI 1.23-1.40). Participants with a history of diabetes mellitus (OR:0.74; 95% CI:0.64-0.86) or current smokers, compared to non-smokers, (OR:0.71; 95% CI:0.62-0.82) were less likely to report owning an HBPM. This study has identified important patient factors influencing HBPM ownership. Further qualitative research would be valuable to identify and explore potential patient-level barriers to engagement with self-monitoring of blood pressure