Ocean oxygenation in the wake of the Marinoan glaciation.

Metazoans are likely to have their roots in the Cryogenian period, but there is a marked increase in the appearance of novel animal and algae fossils shortly after the termination of the late Cryogenian (Marinoan) glaciation about 635 million years ago. It has been suggested that an oxygenation event in the wake of the severe Marinoan glaciation was the driving factor behind this early diversification of metazoans and the shift in ecosystem complexity. But there is little evidence for an increase in oceanic or atmospheric oxygen following the Marinoan glaciation, or for a direct link between early animal evolution and redox conditions in general. Models linking trends in early biological evolution to shifts in Earth system processes thus remain controversial. Here we report geochemical data from early Ediacaran organic-rich black shales (∼635-630 million years old) of the basal Doushantuo Formation in South China. High enrichments of molybdenum and vanadium and low pyrite sulphur isotope values (Δ(34)S values ≥65 per mil) in these shales record expansion of the oceanic inventory of redox-sensitive metals and the growth of the marine sulphate reservoir in response to a widely oxygenated ocean. The data provide evidence for an early Ediacaran oxygenation event, which pre-dates the previous estimates for post-Marinoan oxygenation by more than 50 million years. Our findings seem to support a link between the most severe glaciations in Earth's history, the oxygenation of the Earth's surface environments, and the earliest diversification of animals.

Effects of lithium isotopes on sodium/lithium co-transport and calcium efflux through the sodium/calcium/lithium exchanger in mitochondria.

The effects of lithium (Li) isotopes and their impact on biological processes have recently gained increased attention due to the significance of Li as a pharmacological agent and the potential that Li isotopic effects in neuroscience contexts may constitute a new example of quantum effects in biology. Previous studies have shown that the two Li isotopes, which differ in mass and nuclear spin, have unusual different effects in vivo and in vitro and, although some molecular targets for Li isotope fractionation have been proposed, it is not known whether those result in observable downstream neurophysiological effects. In this work we studied fluxes of Li+, sodium (Na+) and calcium (Ca2+) ions in the mitochondrial sodium/calcium/lithium exchanger (NCLX), the only transporter known with recognized specificity for Li+. We studied the effect of Li+ isotopes on Ca2+ efflux from heart mitochondria in comparison to natural Li+ and Na+ using Ca2+-induced fluorescence and investigated a possible Li isotope fractionation in mitochondria using inductively coupled plasma mass spectrometry (ICP-MS). Our fluorescence data indicate that Ca2+ efflux increases with higher concentrations of either Li+ or Na+. We found that the simultaneous presence of Li+ and Na+ increases Ca2+ efflux compared to Ca2+ efflux caused by the same concentration of Li+ alone. However, no differentiation in the Ca2+ efflux between the two Li+ isotopes was observed, either for Li+ alone or in mixtures of Li+ and Na+. Our ICP-MS data demonstrate that there is selectivity between Na+ and Li+ (greater Na+ than Li+ uptake) and, most interestingly, between the Li+ isotopes (greater 6Li+ than 7Li+ uptake) by the inner mitochondrial membrane. In summary, we observed no Li+ isotope differentiation for Ca2+ efflux in mitochondria via NCLX but found a Li+ isotope fractionation during Li+ uptake by mitochondria with NCLX active or blocked. Our results suggest that the transport of Li+ via NCLX is not the main pathway for Li+ isotope fractionation and that this differentiation does not affect Ca2+ efflux in mitochondria. Therefore, explaining the puzzling effects of Li+ isotopes observed in other contexts will require further investigation to identify the molecular targets for Li+ isotope differentiation.

Update on the epidemiology of pulmonary nontuberculous mycobacterial infections.

For decades, the incidence of pulmonary nontuberculous mycobacteria (NTM) has been reported to be increasing, yet formal epidemiological evaluation of this notion has been lacking until recently. Defining the epidemiology of NTM has been more challenging than with Mycobacterium tuberculosis (MTB). Unlike MTB, NTM are soil and water organisms, and infection is thought to be acquired from the environment rather than transmitted from person-to-person, with very rare exceptions. Due to their nearly ubiquitous presence in municipal water supplies, exposure to NTM is common. Further, NTM can colonize the respiratory tract without causing disease. NTM disease is not reportable to public health authorities; therefore, epidemiological and surveillance data are not readily available. Nonetheless, the prevalence of pulmonary NTM disease has increased dramatically in the United States and globally over the past 3 decades. Mycobacterium avium complex (MAC) accounts for the majority of NTM infections worldwide, but there is significant regional variability of various species. Additionally, novel species have been implicated in several countries in NTM pulmonary disease.

Global ocean redox changes before and during the Toarcian Oceanic Anoxic Event.

Mesozoic oceanic anoxic events are recognized as widespread deposits of marine organic-rich mudrocks temporally associated with mass extinctions and large igneous province emplacement. The Toarcian Oceanic Anoxic Event is one example during which expanded ocean anoxia is hypothesized in response to environmental perturbations associated with emplacement of the Karoo-Ferrar igneous province. However, the global extent of total seafloor anoxia and the relative extent of euxinic (anoxic and sulfide-rich) and non-euxinic anoxic conditions during the Toarcian Oceanic Anoxic Event are poorly constrained. Here we present estimates of the global total anoxic and euxinic seafloor areas before and during the Toarcian Oceanic Anoxic Event based on rhenium and molybdenum enrichments, respectively, in organic-rich mudrocks of the Fernie Formation (British Columbia, Canada). We find that mass balance models depict an expansion of up to ~7% total seafloor anoxia, which was dominated by euxinia, at the onset of the Toarcian Oceanic Anoxic Event, followed by a contraction before the end of the event. The global ocean redox trends revealed by the rhenium data mirrors the collapse and recovery patterns of global ammonite and foraminiferal biodiversity.

Utilizing Post-Clerkship Surveys to Optimize Emergency Medicine Program Outcomes in the Match.

Purpose: The Match for Emergency Medicine residency has presented new challenges over the past 2 years (2022-2023). Use of a post-clerkship survey given to clerkship students could improve outcomes in The Match by helping the program identify its different strengths and weaknesses. Methods: A post-clerkship survey, sent after The Match, was sent to Emergency Medicine bound students who completed our Emergency Medicine clerkship. This data was then collected and analyzed and, in collaboration with our faculty and residents, changes were made to the clerkship and residency program with the intention that these changes would improve our program and therefore our competitiveness in the upcoming cycle of The Match. These changes were analyzed in the subsequent post-clerkship survey. The survey included questions that asked students to reflect on their experiences with various aspects of the program and how these experiences influenced their personal ranking of our program compared to other emergency medicine residency programs they might have interacted with. Results: Results from the initial post-clerkship survey revealed that students found our faculty and residents (55% ranked higher), County hospital (55% ranked higher), and SLOE transparency (64% ranked higher) as the main aspects of our program that led them to rank the program higher. Living in Lubbock, TX was found to be the biggest drawback for students, with 55% ranking our program lower. The 2023 post-clerkship survey revealed that the changes we made to our clerkship and program were effective, with an overall decrease of 10 points in students who ranked our program lower based on "Living in Lubbock, TX". We also were able to keep 4 of our rotators, as opposed to 2 the year before. Lastly, we also did not need to go as far down our rank list in the 2023 cycle of The Match. Conclusion: Using a post-clerkship survey to evaluate strengths and weaknesses of a program through a student's perspective can be an effective tool to help programs in their outcomes from The Match. Further study is necessary to validate these findings.

Technical comment on "Reexamination of 2.5-Ga 'whiff' of oxygen interval points to anoxic ocean before GOE".

Many lines of inorganic geochemical evidence suggest transient "whiffs" of environmental oxygenation before the Great Oxidation Event (GOE). Slotznick et al. assert that analyses of paleoredox proxies in the Mount McRae Shale, Western Australia, were misinterpreted and hence that environmental O2 levels were persistently negligible before the GOE. We find these arguments logically flawed and factually incomplete.

Cascade electrocatalysis via AgCu single-atom alloy and Ag nanoparticles in CO2 electroreduction toward multicarbon products.

Electrocatalytic CO2 reduction into value-added multicarbon products offers a means to close the anthropogenic carbon cycle using renewable electricity. However, the unsatisfactory catalytic selectivity for multicarbon products severely hinders the practical application of this technology. In this paper, we report a cascade AgCu single-atom and nanoparticle electrocatalyst, in which Ag nanoparticles produce CO and AgCu single-atom alloys promote C-C coupling kinetics. As a result, a Faradaic efficiency (FE) of 94 ± 4% toward multicarbon products is achieved with the as-prepared AgCu single-atom and nanoparticle catalyst under ~720 mA cm-2 working current density at -0.65 V in a flow cell with alkaline electrolyte. Density functional theory calculations further demonstrate that the high multicarbon product selectivity results from cooperation between AgCu single-atom alloys and Ag nanoparticles, wherein the Ag single-atom doping of Cu nanoparticles increases the adsorption energy of *CO on Cu sites due to the asymmetric bonding of the Cu atom to the adjacent Ag atom with a compressive strain.

Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Evolving epidemiologic characteristics of invasive group a streptococcal disease in Utah, 2002-2010.

BACKGROUND: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity and mortality. Recent national surveillance data report stable rates of invasive GAS disease, although these may not capture geographic variation. METHODS: We performed a population-based, retrospective laboratory surveillance study of invasive GAS disease among Utah residents from 2002-2010. We used Intermountain Healthcare's electronic medical records and data warehouse to identify patients from whom GAS was isolated by culture. We defined clinical syndromes of invasive GAS disease on the basis of International Classification of Diseases, Ninth Revision codes. We abstracted demographic information, comorbidities, and microbiologic and laboratory findings. RESULTS: From 2002-2010, we identified 1514 cases of invasive GAS disease among Utah residents. The estimated mean annual incidence rate was 6.3 cases/100,000 persons, which was higher than the national rate of 3.6 cases/100,000 (P < .01). The incidence of invasive GAS disease in Utah rose from 3.5 cases/100,000 persons in 2002 to 9.8 cases/100,000 persons in 2010 (P = .01). Among children aged <18 years, the incidence of invasive GAS increased from 3.0 cases/100,000 children in 2002 to 14.1 cases/100,000 children in 2010 (P < .01). The increase in the pediatric population was due, in part, to an increase in GAS pneumonia (P = .047). The rate of invasive GAS disease in adults aged 18-64 years increased from 3.4 cases/100 000 persons in 2002 to 7.6 cases/100,000 persons in 2010 (P = .02). Rates among those aged ≥65 years were stable. The incidence of acute rheumatic fever declined from 6.1 to 3.7 cases/100,000 (P = .04). CONCLUSIONS: The epidemiologic characteristics of invasive GAS disease in Utah has changed substantially over the past decade, including a significant increase in the overall incidence of invasive disease-driven primarily by increasing disease in younger persons-that coincided temporally with a decrease in the incidence of acute rheumatic fever.

Impact of a Laboratory-Developed Phenotypic Rapid Susceptibility Test Directly From Positive Blood Cultures on Time to Narrowest Effective Therapy in Patients With Gram-Negative Bacteremia: A Prospective Randomized Trial.

Background: Antimicrobial susceptibility testing (AST) is often needed prior to antimicrobial optimization for patients with gram-negative bloodstream infections (GN-BSIs). Rapid AST (rAST) in combination with antimicrobial stewardship (AS) may decrease time to administration of narrower antibiotics. Methods: This was a prospective, nonblinded, randomized trial evaluating the impact of a phenotypic rAST method vs conventional AST (cAST) in hospitalized patients with GN-BSI and source control. The primary outcome was time to narrowest effective therapy. Results: Two hundred seventy-four patients were randomized and 205 underwent analysis (97 cAST, 108 rAST). Median (interquartile range [IQR]) time to susceptibility results was 23 hours shorter in the rAST group (cAST: 62 [59-67] hours vs rAST: 39 [IQR, 35-46] hours; P < .001). Median (IQR) time to narrowest effective therapy was similar between groups (cAST: 73 [44-138] hours vs rAST: 64 [42-92] hours; P = .10). Median (IQR) time to narrowest effective therapy was significantly shorter in a prespecified subgroup of patients not initially on narrowest therapy and during AS working hours (cAST: 93 [56-154] hours vs rAST: 62 [43-164] hours; P = .004). Significant decreases were observed in median (IQR) time to oral therapy (cAST: 126 [76-209] hours vs rAST: 91 [66-154] hours; P = .02) and median (IQR) length of hospital stay (cAST: 7 [4-13] days vs rAST: 5 [4-8] days; P = .04). Conclusions: In patients with GN-BSI, rAST did not significantly decrease time to narrowest effective therapy but did decrease time to oral antibiotics and length of hospital stay. Rapid AST using existing microbiology platforms has potential to optimize patient outcomes.

Distinguishing tuberculosis from nontuberculous mycobacteria lung disease, Oregon, USA.

To determine whether tuberculosis (TB) and nontuberculous mycobacteria (NTM) infection patients could be distinguished from one another with limited information, we compared pulmonary TB and NTM patients during 2005-2006. Our finding that age, birthplace, and presence of chronic obstructive pulmonary disease could differentiate TB and NTM disease could assist tuberculosis control efforts.

Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease.

RATIONALE: Respiratory specimens with nontuberculous mycobacteria (NTM) are increasingly common; however, pulmonary disease prevalence is unknown. OBJECTIVES: To determine the disease prevalence, clinical features, and risk factors for NTM disease, and to examine the predictive value of the microbiologic criteria of the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) pulmonary NTM case definition for true NTM disease. METHODS: We identified all Oregon residents during 2005-2006 with at least one respiratory mycobacterial isolate. From a population-based subset of these patients, we collected clinical and radiologic information and used the ATS/IDSA pulmonary NTM disease criteria to define disease. MEASUREMENTS AND MAIN RESULTS: In the 2-year time period, 807 Oregonians had one or more respiratory NTM isolates. Four hundred and seven (50%) resided within the Portland metropolitan region, among which 283 (70%) had evaluable clinical records. For those with records, 134 (47%) met ATS/IDSA pulmonary NTM disease criteria for a minimum overall 2-year period prevalence of 8.6/100,000 persons, and 20.4/100,000 in those at least 50 years of age within the Portland region. Case subjects were 66 years of age (median; range, 12-92 yr), frequently female (59%), and most with disease caused by Mycobacterium avium complex (88%). Cavitation (24.5%), bronchiectasis (16%), chronic obstructive pulmonary disease (28%), and immunosuppressive therapy (25.5%) were common. Eighty-six percent of patients meeting the ATS/IDSA microbiologic criteria for disease also met the full ATS/IDSA disease criteria. CONCLUSIONS: Respiratory NTM isolates frequently represent disease. Pulmonary NTM disease is not uncommon, particularly among elderly females. The ATS/IDSA microbiologic criteria are highly predictive of disease and could be useful for laboratory-based NTM disease surveillance.

High risk human papillomavirus DNA detection in pap tests with both atypical squamous cells of undetermined significance and Candida.

OBJECTIVE: We examined the detection rate of high risk human papillomavirus (hr-HPV) DNA in ThinPrep Pap tests with concurrent diagnoses of atypical squamous cells of undetermined significance (ASCUS) and fungal organisms morphologically consistent with Candida species. STUDY DESIGN: Gynecologic cytology records were searched to find reports with concurrent diagnoses of both ASCUS and Candida infection. Over a 19-month period, 309 cases with reflex brhHPV tests results were identified. The rate of hr-HPV detection in this group was compared to our laboratory's overall brhHPV rate for women in general and among 5-year age groupings. RESULTS: There was a significantly higher overall rate of hr-HPV detection in cases of ASCUS with Candida (44.7%, p < 0.001) compared to the overall ASCUS hr-HPV rate (34.1%). When age was stratified, the ASCUS with Candida < or = and 21-25 age-groups had significantly higher rates of hr-HPVde tection compared to the overall ASCUS rates (65.0% vs. 58.5, p < 0.001 and 61.6% vs. 50. 5, p < 0.04, respectively). CONCLUSION: Our study shows that the presence ofCa ndida does not exclude hr-HPV and that atypical cytologic features in the presence of Candida should not be entirely attributed to reactive cellular changes, especially in younger women.

Fully oxygenated water columns over continental shelves before the Great Oxidation Event.

Late Archaean sedimentary rocks contain compelling geochemical evidence for episodic accumulation of dissolved oxygen in the oceans along continental margins before the Great Oxidation Event. However, the extent of this oxygenation remains poorly constrained. Here we present thallium and molybdenum isotope compositions for anoxic organic-rich shales of the 2.5 billion-year-old Mount McRae Shale from Western Australia, which previously yielded geochemical evidence of a transient oxygenation event. During this event, we observe an anti-correlation between thalium and molybdenum isotope data, including two shifts to higher molybdenum and lower thalium isotope compositions. Our data indicate pronounced burial of manganese oxides in sediments elsewhere in the ocean at these times, which requires that water columns above portions of the ocean floor were fully oxygenated: all the way from the air-sea interface to well below the sediment-water interface. Well-oxygenated continental shelves were likely the most important sites of manganese oxide burial and mass-balance modeling results suggest that fully oxygenated water columns were at least a regional-scale feature of early-Earth's oceans 2.5 billion years ago.

Extensive marine anoxia during the terminal Ediacaran Period.

The terminal Ediacaran Period witnessed the decline of the Ediacara biota (which may have included many stem-group animals). To test whether oceanic anoxia might have played a role in this evolutionary event, we measured U isotope compositions (δ238U) in sedimentary carbonates from the Dengying Formation of South China to obtain new constraints on the extent of global redox change during the terminal Ediacaran. We found the most negative carbonate δ238U values yet reported (-0.95 per mil), which were reproduced in two widely spaced coeval sections spanning the terminal Ediacaran Period (551 to 541 million years ago). Mass balance modeling indicates an episode of extensive oceanic anoxia, during which anoxia covered >21% of the seafloor and most U entering the oceans was removed into sediments below anoxic waters. The results suggest that an expansion of oceanic anoxia and temporal-spatial redox heterogeneity, independent of other environmental and ecological factors, may have contributed to the decline of the Ediacara biota and may have also stimulated animal motility.

Pleural Effusion Caused by Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer.

Intravesical bacillus Calmette Guérin (BCG) instillation has been used as immunotherapy for early stage bladder cancer for >40 years. Complications from this therapy are rare but may result in a spectrum of infectious sequelae. Here we describe the case of an elderly man who presented with a pleural effusion and subcutaneous nodule several years after treatment with BCG.