Genome-scale evaluation of core one-carbon metabolism in gammaproteobacterial methanotrophs grown on methane and methanol.

Methylotuvimicrobium alcaliphilum 20Z is a promising platform strain for bioconversion of one-carbon (C1) substrates into value-added products. To carry out robust metabolic engineering with methylotrophic bacteria and to implement C1 conversion machinery in non-native hosts, systems-level evaluation and understanding of central C1 metabolism in methanotrophs under various conditions is pivotal but yet elusive. In this study, a genome-scale integrated approach was used to provide in-depth knowledge on the metabolic pathways of M. alcaliphilum 20Z grown on methane and methanol. Systems assessment of core carbon metabolism indicated the methanol assimilation pathway is mostly coupled with the efficient Embden-Meyerhof-Parnas (EMP) pathway along with the serine cycle. In addition, an incomplete TCA cycle operated in M. alcaliphilum 20Z on methanol, which might only supply precursors for de novo synthesis but not reducing powers. Instead, it appears that the direct formaldehyde oxidation pathway supply energy for the whole metabolic system. Additionally, a comparative transcriptomic analysis in multiple gammaproteobacterial methanotrophs also revealed the transcriptional responses of central metabolism on carbon substrate change. These findings provided a systems-level understanding of carbon metabolism and new opportunities for strain design to produce relevant products from different C1-feedstocks.

Dual Defibrillation is Highly Variable: An Analysis of Pulse Interval Delivered in Dual Defibrillation.

Background: Dual defibrillation (DD) is a technique where two external defibrillators are applied with two different pad configurations and discharged to treat refractory ventricular fibrillation (RVF). Although commonly called dual sequential defibrillation (DSD), if the delivered electrical pulses overlap with no pulse interval, the shocks are actually dual simultaneous defibrillation (DSiD). Manual DD technique is not standardized and the effect that the method of activation has on the delivered pulse interval has never been studied. Objectives: This study measured the timing of four methods of DD and the resulting inter-shock intervals, frequency with which they were either DSiD or DSD, and frequency which the true DSDs delivered any previously reported optimum pulse interval. Methods: This was a single-blinded prospective evaluation of a convenience sample of volunteer physicians, nurses, and paramedics each performing DD in our simulation center on two types of defibrillators using four techniques: single operator-simultaneous with 2 hands (SOSI), two operators-simultaneous (TOSI), single operator-sequential with 1 hand (SOSE1), and single operator-sequential with 2 hands (SOSE2). Results: The four DD methods generated a variable set of pulse intervals depending on the technique and defibrillator employed. The pulse intervals ranged from 0 msec (i.e., overlapping waveforms or DSiD) to 1800 msec. Of all DD attempts, 85.9% met the definition of DSD, 14.1% were DSiD, and 49.4% delivered any one of the optimum pulse intervals previously described in the literature. SOSI and TOSI techniques resulted in DSD between 47.2 and 87.6% of the time, depending on the technique and defibrillator. Shocks delivered sequentially on purpose (SOSE2 and SOSE1) were always DSD but with widely variable pulse intervals. SOSI resulted in the shortest pulse intervals, SOSE1 resulted in the longest, and TOSI and SOSE2 were the least skewed. Conclusion: DD using the various methods currently employed produces a highly variable set of pulse intervals even within a single method. It is difficult to reach a conclusion about the efficacy of DD unless the delivered pulse interval is measured or the method of activation reproducibly produces a precise pulse interval.

Estimating the footprint of pollution on coral reefs with models of species turnover.

Ecological communities typically change along gradients of human impact, although it is difficult to estimate the footprint of impacts for diffuse threats such as pollution. We developed a joint model (i.e., one that includes multiple species and their interactions with each other and environmental covariates) of benthic habitats on lagoonal coral reefs and used it to infer change in benthic composition along a gradient of distance from logging operations. The model estimated both changes in abundances of benthic groups and their compositional turnover, a type of beta diversity. We used the model to predict the footprint of turbidity impacts from past and recent logging. Benthic communities far from logging were dominated by branching corals, whereas communities close to logging had higher cover of dead coral, massive corals, and soft sediment. Recent impacts were predicted to be small relative to the extensive impacts of past logging because recent logging has occurred far from lagoonal reefs. Our model can be used more generally to estimate the footprint of human impacts on ecosystems and evaluate the benefits of conservation actions for ecosystems.

Synthetic Cannabinoid Abuse Resulting in ST-Segment Elevation Myocardial Infarction Requiring Percutaneous Coronary Intervention.

BACKGROUND: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration. CASE REPORT: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled "Scooby Snax Limited Edition Blueberry Potpourri." The patient was somnolent, but became agitated when stimulated and complained of chest pain. Vital signs were blood pressure 87/52 mm Hg and pulse 52 beats/min. The electrocardiogram demonstrated an inferior wall myocardial infarction. Coronary angiography identified an occluded obtuse marginal second branch that was successfully opened with a drug-eluting stent. The patient recovered uneventfully. Urine drug screen was negative for cocaine, and gas chromatography/mass spectrometry testing of the smoked material identified PB-22 and AMB-FUBINACA as the active ingredients. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians and cardiologists need to be aware that the mechanism of action of synthetic cannabinoids on the endocannabinoid system may result in acute ST-segment elevation myocardial infarction requiring percutaneous coronary intervention.

Coordination games, anti-coordination games, and imitative learning.

Bentley et al.'s scheme generates distributions characteristic of situations of high and low social influence on decisions and of high and low salience ("transparency") of rewards. Another element of decisions that may influence the placement of a decision process in their map is the way in which individual decisions interact to determine the payoffs. This commentary discusses the role of Nash equilibria in game theory, focusing especially on coordination and anti-coordination games.

Changes in Chinese students' academic emotions after examinations: Pride in success, shame in failure, and self-loathing in comparison.

BACKGROUND: Several attempts have been made to examine students' academic emotions (AEs) in Western contexts, but less is known about how students' self-reported emotions vary over time. AIMS: The study aimed to understand Chinese students' emotional responses to academic events and the impact of high-stakes testing on their AEs in the first year with a repeated-measures survey after the Semester 1 and Semester 2 mid-term examinations. SAMPLES: 351 first-year university students completed both surveys in an elite Chinese university, where the top 10% of first-year students were assigned to an honours programme. METHODS: Self-reported AEs survey responses were evaluated with confirmatory factor analysis. Invariance testing between honours and ordinary students and between semesters was used to examine between-group differences across time. RESULTS: A three-factor model of AEs (i.e., admired, shame, and self-loathing) was found in both semesters, with strong invariance between semesters. Mean scores between groups were equivalent and semester. However, self-loathing had the lowest mean (mean = 2.50; between mostly disagree and slightly agree), admired was at moderately agree (mean = 4.00), and shame was strongest at just over moderately agree (mean = 4.20). CONCLUSIONS: This study reveals a three-factor structure of AEs and the stability of these emotions among highly successful Chinese learners. Despite being elite students, this sample of Chinese learners felt shame and pride in response to mid-term examinations.

Developing the Metacognitive Awareness of Grit Scale for a better understanding of learners of English as a foreign language.

The prominent impact of metacognition on learners' academic achievement is widely discussed. Learners armed with appropriate metacognitive strategies should witness enhancement in learning performance. Similarly, the concept of grit is also valued as a crucial factor contributing to the improvement of academic achievement. Nevertheless, discussion of the relationship between metacognition and grit or their collective influence on other educational and psychological variables is limited, not to mention that an instrument measuring learners' metacognitive awareness of grit is a desideratum. Hence, by incorporating the constructs of metacognition and grit, the present research developed a measurement scale to address this need, named the Metacognitive Awareness of Grit Scale (MCAGS). The MCAGS consists of four components and initially included 48 items. It was later distributed to 859 participants for the purpose of scale validation. Confirmatory factor analysis was applied to evaluate the scale's validity and explore the factor-item relationship. A final model containing 17 items was retained. Implications and future directions were discussed.

Characterizing a novel and adjustable noninvasive murine joint loading model.

OBJECTIVE: Mechanical loading through a mechano-adaptive response modifies articular cartilage structure and contributes to osteoarthritis (OA). However, the specific mechanical stimuli involved in joint health and disease remain poorly defined, partly due to a lack of in vivo models of controlled loading. The present study was undertaken to develop and characterize a novel nonsurgical murine model in which applied loads to the knee joint are highly adjustable. METHODS: Animals experienced normal locomotion, except during loading. Loads were applied to the right knees of 8-week-old CBA mice, 3 times a week for 2 weeks (and assessed immediately or after 3 weeks of nonloading), or for 5 weeks, or just once (and assessed immediately or after 2 weeks of nonloading). Histologic features of loaded and control contralateral joints, including articular cartilage lesions, osteophyte formation, and pathologic features, were examined. Ex vivo visualization during loading was performed by microfocal computed tomography (micro-CT). RESULTS: Two weeks of loading produced articular cartilage lesions only at sites of maximal contact as exhibited by micro-CT; after 3 weeks without further loading, joints in another group of mice identically loaded revealed significant increases in mean lesion severity to levels seen following 5 weeks of loading. Single application of load also induced lesions, but in this case, 2 weeks of solely habitual use did not lead to further deterioration. Only repetitive loading induced loss of Safranin O staining. Loading also led to osteophyte formation, meniscal ossification, synovial hyperplasia and fibrosis, and cruciate ligament pathology, with a severity that was dependent upon the loading regimen utilized. CONCLUSION: We describe for the first time a noninvasive model of murine knee joint loading. This will further the study of mechanical and genetic interactions in joint health and in OA initiation and progression.

Commercial spaceflight participant G-force tolerance during centrifuge-simulated suborbital flight.

INTRODUCTION: Medical knowledge of the human body in microgravity and hypergravity is based upon studies of healthy individuals well-conditioned for such environments. Little data exist regarding the effects of spaceflight on untrained commercial passengers. We examined the responses of potential spaceflight participants (SFP) to centrifuge G-force exposure. METHODS: There were 77 individuals (65 men, 12 women), 22-88 yr old, who underwent 6 centrifuge runs over 48 h. Day 1 consisted of two +Gz runs (peak = 3.5+Gz, run 2) and two +Gx runs (peak = 6.0+Gx, run 4). Day 2 consisted of two runs approximating a suborbital spaceflight profile. Data included blood pressure, electrocardiogram, and postrun questionnaires regarding motion sickness, disorientation, greyout, and other symptoms. RESULTS: Of the 77 participants, average age was 50.4 +/- 12.7 yr. Average heart rate (HR) varied by sex and direction of G-exposure (+Gz: F 150 +/- 19, M 123 +/- 27; +Gx: F 135 +/- 30, M 110 +/- 27). Age and peak HR were inversely related (HR < 120 bpm: 60.2 +/- 12.2 yr, HR > 120: 47.1 +/- 10.9 yr). HR during peak G-exposure for the final run was associated with post-run imbalance (no imbalance: HR 126 +/- 26, imbalance: HR 145 +/- 21); no other significant hemodynamic change, sex, or age variation was associated with imbalance. Age and greyout were inversely associated; there was no association between greyout and vital sign change, sex, or G-force magnitude. Baseline/pretrial mean arterial pressure (MAP) was not associated with any symptoms. DISCUSSION: The results suggest that most individuals with well-controlled medical conditions can withstand acceleration forces involved in launch/landing profiles of commercial spaceflight vehicles. Further investigation will help refine which conditions present significant risk during suborbital flight and beyond.

The Hahnemann University Hospital Closure and What Matters: A Department Chair's Perspective.

The closure of Hahnemann University Hospital, which was announced on June 26, 2019, resulted in the most significant graduate medical education displacement in history, sending over 550 residents to new institutions within a month of the announcement. Over 2,000 physicians, nurses, and staff lost their jobs. While seemingly predictable in retrospect, the closure came as a cataclysmic event to all involved. In this Invited Commentary, a department chair reflects on the lessons learned from these unprecedented circumstances. These lessons cover areas that are not a typical concern for faculty who are focused on teaching their trainees, but are worthy of their attention. Corporate and organizational structure, leadership, and financing of the hospital were critical determining characteristics of the failure. The roles that the Accreditation Council for Graduate Medical Education and the Centers for Medicare and Medicaid Services played in this event were key stabilizers. However, examining their roles in this event offers opportunities to play a more active role in future events and alter how the next massive displacement unfolds, possibly preserving teaching programs. Highly competitive health systems should rethink noncollaborative strategies before allowing struggling institutions to succumb to market forces. Finally, a commitment by a hospital to the mission of academic medicine is a sacred trust with the faculty, trainees, and patients that it serves. It should not be undertaken by any enterprise that is not well resourced and equipped with the knowledge and expertise to meet this most serious of commitments.

An Unusual Case of Carbon Monoxide Poisoning from Formic and Sulfuric Acid Mixture.

Formic acid, when combined with sulfuric acid, gets dehydrated to form carbon monoxide (CO). A 27-year-old female was found unconscious inside a car, next to a container with a mixture of sulfuric acid and formic acid. Concentrations of up to 400 parts per million of CO were measured inside the car post ventilation. Serum carboxyhemoglobin level was 15% after receiving 100% oxygen for two hours. The patient received hyperbaric oxygen therapy after which she was extubated with normal mental status. On follow-up after three months, she demonstrated neurocognitive abnormalities suggestive of delayed neurological sequelae from CO exposure.

Heroin Adulterated with the Novel Synthetic Cannabinoid, 5F-MDMB-PINACA: A Case Series.

INTRODUCTION: Heroin can be adulterated with various substances that may or may not have pharmacological effects. Here we report a case series of 8 patients who presented to the emergency department after overdose with intravenous heroin preparation adulterated with the synthetic cannabinoid methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PINACA). CASE SERIES: Except for one patient, all of them presented with a typical initial opioid toxidrome consisting of central nervous system and respiratory depression along with pinpoint pupils. Naloxone was given to them, triggering severe agitation and combative behavior along with overlapping features of anticholinergic and sympathomimetic toxidrome. All patients required multiple doses of benzodiazepines. Three were successfully treated with physostigmine. DISCUSSION: 5F-MDMB-PINACA is a synthetic cannabinoid that was added to heroin in samples obtained from patients reported in this case series. Patients demonstrated significant agitation after receiving naloxone for opioid toxidrome, presumably because of the removal of the depressant effect of opioids, which unmasked the excitatory effects of the synthetic cannabinoids. Three patients required physostigmine along with the benzodiazepines for control of their agitation, urine retention and abnormal vitals, suggesting the possibility of an anticholinergic toxidrome to have developed in these patients. CONCLUSION: Heroin contaminated with 5F-MDMB-PINACA exhibits variable severities of anticholinergic effects, some on presentation and others only after opiate antagonism.

Physician assessment of changing lesion size of predominantly classic choroidal neovascular membranes in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To quantify the interpretation of fluorescein angiograms of evolving predominantly classic choroidal neovascularization in age-related macular degeneration. PATIENTS AND METHODS: Thirty-six fluorescein angiograms of predominantly classic choroidal neovascularization were used to define 22 fluorescein angiogram pairs. Imaging software was used to measure surface area and greatest linear dimension (GLD). Six retina physicians estimated the change in surface area and GLD for each pair before and after demarcation of the lesions' borders and GLD. RESULTS: For enlarging lesions, the smallest changes consistently detected by physicians were a 5% to 15% increase in surface area and a 5% to 15% increase in GLD; for shrinking lesions, they were a 5% to 15% decrease in surface area and a 5% to 15% decrease in GLD. Linear regression demonstrated moderate correlation between physician and software estimates of surface area and GLD change (r(2) = 0.50 and 0.67, respectively; P < .001), which was higher with lesion demarcation (r(2) = 0.91 and 0.93, respectively; P < .001). CONCLUSION: Computer-assisted demarcation of lesion surface area and GLD reduced variability in physicians' estimates of choroidal neovascularization size change and improved correlation with software measurements.

Smallpox, risks of terrorist attacks, and the Nash equilibrium: an introduction to game theory and an examination of the smallpox vaccination program.

INTRODUCTION: The smallpox vaccination emergency preparedness program has been unsuccessful in enrolling sufficient numbers of healthcare workers. OBJECTIVE: The objective of this study was to use game theory to analyze a pre-event vaccination versus post-event vaccination program using the example of a terrorist considering an attack with smallpox or a hoax. METHODS: A three-person game (normal and extensive form), and an in-person game are played for pre-event and post-event vaccinations of healthcare workers facing the possibility of a smallpox attack or hoax. RESULTS: Full pre-event vaccinations of all targeted healthcare workers are not necessary to deter a terrorist attack. In addition, coordinating vaccinations among healthcare workers, individual healthcare worker risk aversion, and the degree to which terrorists make the last move based on specific information on the status of pre-event vaccination all greatly impact strategy selection for both sides. A Nash Equilibrium of pre- and post-event vaccination strategies among a large number of healthcare professionals will tend to eliminate the advantage (of the terrorists) of a smallpox attack over a hoax, but may not eliminate some probability of a smallpox attack. CONCLUSIONS: Emergency preparedness would benefit from game theory analysis of the costs and payoffs of specific terrorism/counter-terrorism strategies.

Construct validity of the Motivated Strategies for Learning Questionnaire.

This study examined the construct validity of the motivational component of the Motivated Strategies for Learning Questionnaire using both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). 327 students enrolled in Bachelor of Education and Graduate Diploma Education courses at the University of Auckland participated in this study (278 women, 49 men). The results of the EFA did not generate support for either a six-factor or three-factor model. The CFA tested a six-factor correlated original model and a respecified model and found a good fit for the respecified model and a better fit of the original 31-item model in comparison with previous studies. In addition, alternative second-order and hierarchical models were tested, none of which showed better fit than the six-factor correlated models. The reasons for the lack of fit of the original model are discussed in light of nonnormality condition, specification error, and latent variables. Finally, possible explanations for the slight variation in patterns of subscale correlations are discussed.

Rapid, label-free genetic detection of enteropathogens in stool without genetic isolation or amplification.

Current genetic detection methods require gene isolation, gene amplification and detection with a fluorescent-tagged probe. They typically require sophisticated equipment and expensive fluorescent probes, rendering them not widely available for rapid acute infection diagnoses at the point of care to ensure timely treatment of the diseases. Here we report a rapid genetic detection method that can detect the bacterial gene directly from patient stools using a piezoelectric plate sensor (PEPS) in conjunction with a continuous flow system with two temperature zones. With stools spiked with sodium dodecyl sulfate (SDS) in situ bacteria lysing and DNA denaturation occurred in the high-temperature zone whereas in situ specific detection of the denatured DNA by the PEPS occurred in the lower-temperature zone. The outcome was a rapid genetic detection method that directly detected bacterial genes from stool in < 40 min without the need of gene isolation, gene amplification, or expensive fluorescent tag but with polymerase chain reaction (PCR) sensitivity. In 40 blinded patient stools, it detected the toxin B gene of Clostridium difficile with 95% sensitivity and 95% specificity. The all-electrical, label-free nature of the detection further supports its potential as a low-cost genetic test that can be used at the point of care.

Single centre audit of early impact of inclusion of the three vessel and trachea view in obstetric screening.

Detection rates of congenital cardiac malformations have traditionally remained low. The NHS Fetal Anomaly Screening Programme (FASP) aims to increase these detection rates for various reasons, including influencing perinatal management and aiding parental decision making. The inclusion of the three vessel view and trachea (3VT) view in 2015 aimed to improve detection rates of arch abnormalities in particular. This study evaluated the early impact of the new initiative at one NHS Trust. Departmental screen-positive rates were compared for a full year before and after implementation. Referrals to, and opinions of, the foetal medicine unit (FMU) were assessed; as were undetected congenital heart defects for the two time periods. Compared with the pre-implementation (pre-3VT) period, the number of completed anomaly scans performed after implementation (post-3VT) increased by 3% and the number of FMU referrals increased by 625%. Departmental screen-positive rates for cardiac abnormalities increased from 40% (pre-3VT) to 91% (post-3VT). Over half (52%) of the FMU referrals were made due to a suspected abnormal 3VT view. Early evaluation of 3VT implementation at this NHS Trust indicates that it has been a success. Departmental screen-positive rates for congenital cardiac malformations have risen. However, this performance has come at a cost: Some abnormalities now being detected, such as loose vascular ring and PLSVC, are frequently asymptomatic and likely to be clinically insignificant. The implementation of 3VT achieves the aims of FASP but may begin to exceed what is expected from a low risk population screening programme.

Giant coral reef fishes display markedly different susceptibility to night spearfishing.

The humphead wrasse (Cheilinus undulatus) and bumphead parrotfish (Bolbometopon muricatum) are two of the largest, most iconic fishes of Indo-Pacific coral reefs. Both species form prized components of subsistence and commercial fisheries and are vulnerable to overfishing. C. undulatus is listed as Endangered and B. muricatum as Vulnerable on the IUCN Red List of Threatened Species. We investigated how night spearfishing pressure and habitat associations affected both species in a relatively lightly exploited setting; the Kia fishing grounds, Isabel Province, Solomon Islands. We used fisheries-independent data from underwater visual census surveys and negative binomial models to estimate abundances of adult C. undulatus and B. muricatum as a function of spearfishing pressure and reef strata. Our results showed that, in Kia, night spearfishing pressure from free divers had no measurable effect on C. undulatus abundances, but abundances of B. muricatum were 3.6 times lower in areas of high spearfishing pressure, after accounting for natural variations due to habitat preferences. It is likely the species' different nocturnal aggregation behaviors, combined with the fishers' use of night spearfishing by spot-checking underpin these species' varying susceptibility. Our study highlights that B. muricatum is extremely susceptible to night spearfishing; however, we do not intend to draw conservation attention away from C. undulatus. Our data relate only to the Kia fishing grounds, where human population density is low, the spot-checking strategy is effective for reliably spearing large numbers of fish, particularly B. muricatum, and fisheries have only recently begun to be commercialized; such conditions are increasingly rare. Instead, we recommend that regional managers assess the state of their fisheries and the dynamics affecting the vulnerability of the fishes to fishing pressure based on local-scale, fisheries-independent data, where resources permit.