Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.

Variant reclassification and clinical implications.

Genomic technologies have transformed clinical genetic testing, underlining the importance of accurate molecular genetic diagnoses. Variant classification, ranging from benign to pathogenic, is fundamental to these tests. However, variant reclassification, the process of reassigning the pathogenicity of variants over time, poses challenges to diagnostic legitimacy. This review explores the medical and scientific literature available on variant reclassification, focusing on its clinical implications.Variant reclassification is driven by accruing evidence from diverse sources, leading to variant reclassification frequency ranging from 3.6% to 58.8%. Recent studies have shown that significant changes can occur when reviewing variant classifications within 1 year after initial classification, illustrating the importance of early, accurate variant assignation for clinical care.Variants of uncertain significance (VUS) are particularly problematic. They lack clear categorisation but have influenced patient treatment despite recommendations against it. Addressing VUS reclassification is essential to enhance the credibility of genetic testing and the clinical impact. Factors affecting reclassification include standardised guidelines, clinical phenotype-genotype correlations through deep phenotyping and ancestry studies, large-scale databases and bioinformatics tools. As genomic databases grow and knowledge advances, reclassification rates are expected to change, reducing discordance in future classifications.Variant reclassification affects patient diagnosis, precision therapy and family screening. The exact patient impact is yet unknown. Understanding influencing factors and adopting standardised guidelines are vital for precise molecular genetic diagnoses, ensuring optimal patient care and minimising clinical risk.

FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

Phototrophic Fe(II) oxidation by Rhodopseudomonas palustris TIE-1 in organic and Fe(II)-rich conditions.

Rhodopseudomonas palustris TIE-1 grows photoautotrophically with Fe(II) as an electron donor and photoheterotrophically with a variety of organic substrates. However, it is unclear whether R. palustris TIE-1 conducts Fe(II) oxidation in conditions where organic substrates and Fe(II) are available simultaneously. In addition, the effect of organic co-substrates on Fe(II) oxidation rates or the identity of Fe(III) minerals formed is unknown. We incubated R. palustris TIE-1 with 2 mM Fe(II), amended with 0.6 mM organic co-substrate, and in the presence/absence of CO2 . We found that in the absence of CO2 , only the organic co-substrates acetate, lactate and pyruvate, but not Fe(II), were consumed. When CO2 was present, Fe(II) and all organic substrates were consumed. Acetate, butyrate and pyruvate were consumed before Fe(II) oxidation commenced, whereas lactate and glucose were consumed at the same time as Fe(II) oxidation proceeded. Lactate, pyruvate and glucose increased the Fe(II) oxidation rate significantly (by up to threefold in the case of lactate). 57 Fe Mössbauer spectroscopy revealed that short-range ordered Fe(III) oxyhydroxides were formed under all conditions. This study demonstrates phototrophic Fe(II) oxidation proceeds even in the presence of organic compounds, and that the simultaneous oxidation of organic substrates can stimulate Fe(II) oxidation.

Geospatial Analysis of Social Vulnerability, Race, and Firearm Violence in Chicago.

INTRODUCTION: Urban firearm violence (UFV) is associated with inequities rooted in structural racism and socioeconomic disparities. Social vulnerability index (SVI) is a composite measure that encompasses both. We sought to understand the relationship between SVI and the incidence of UFV in Chicago using geospatial analysis for the first time. MATERIALS AND METHODS: Firearm assaults in Chicago 2001-2019 were obtained from the Trace. Locations of incidents were geocoded using ArcGIS and overlaid with census tract vector files. These data were linked to 2018 SVI measures obtained from the Center for Disease Control and Prevention. Shooting rates were calculated by tabulating the total number of shootings per capita in each census tract. We used Poisson regression with robust error variance to estimate the incident rate of UFV in different levels of social vulnerability and Local Moran's I to evaluate spatial autocorrelation. RESULTS: In total, 642 census tracts were analyzed. The median shooting rate was 2.6 per 1000 people (interquartile 0.77, 7.0). When compared to those census tracts with very low SVI, census tracts with low SVI had a 1.7-time increased incident rate of shootings (incidence rate ratio [IRR] 1.74, 95% CI 1.08, 2.81), tracts with moderate SVI had a 3.1-time increased incident rate (IRR 3.07, 95% CI 2.31, 4.10), and tracts with high SVI had a 7-time increased incident rate (IRR 7.03, 95% CI 5.45, 9.07). CONCLUSIONS: In Chicago, social vulnerability has a significant association with rates of firearm violence, providing a focus point for policy intervention to address high rates of interpersonal violence in similar cities.

Motor vehicle collision characteristics and hospitalization outcomes associated with mild traumatic brain injury and concomitant whiplash injury.

OBJECTIVE: Few large studies have investigated the factors and outcomes related to concomitant injuries occurring alongside mild traumatic brain injury (mTBI) after motor vehicle collisions (MVCs). Thus, the objective of this study was to assess whether MVC characteristics predict which patients with mTBI will have concomitant whiplash injury, and whether concomitant whiplash injury affects care utilization for these patients. METHODS: This retrospective cohort study included 22,213 patients with mTBI after MVC identified from the American College of Surgeons Trauma Quality Programs dataset. A hierarchical logistic regression model was constructed to investigate patient and MVC factors associated with concomitant whiplash injury. Propensity score matching on whiplash status, in conjunction with a multivariable logistic regression model, assessed if concomitant whiplash affected odds of hospitalization. In the subgroup of patients who were hospitalized, associations with hospital length of stay (LOS) and discharge disposition were investigated. RESULTS: The median (IQR) age was 34 (24-51) years, with a median Glasgow Coma Scale score at presentation of 15 (15-15). Patients with concomitant whiplash were older (median 36 years vs 34 years, p = 0.03) and had higher rates of hospitalization (75% vs 64%, p < 0.001). In the hierarchical model for associations with concomitant whiplash injury, patients with blood alcohol content (BAC) greater than the federal driving limit had lower odds of concomitant whiplash (OR 0.63, 95% CI 0.49-0.81) along with those who had airbag deployment (OR 0.80, 95% CI 0.68-0.95), but seatbelt use was associated with greater odds (OR 1.41, 95% CI 1.16-1.71). After matching, concomitant whiplash was independently associated with increased odds of hospitalization (OR 1.67, 95% CI 1.40-1.99) while seatbelt use was associated with decreased odds (OR 0.88, 95% CI 0.81-0.95). Among hospitalized patients, concomitant whiplash was not associated with hospital LOS or discharge disposition. CONCLUSIONS: MVC characteristics such as alcohol consumption and airbag deployment were protective toward development of concomitant whiplash for mTBI patients, while seatbelt use was associated with higher risk. Concomitant whiplash increases the odds of hospitalization for mTBI patients but does not affect hospital LOS or discharge disposition, while seatbelt use is associated with lower rates of hospitalization and a more favorable hospital course. These findings provide context to injury patterns and care provision after a common mechanism of injury.

Modifiable Factors Related to Firearm Homicides: A Broader View of Our Lane.

OBJECTIVE: This study aims to identify modifiable factors related to firearm homicide (FH). SUMMARY BACKGROUND DATA: Many socioeconomic, legislative and behavioral risk factors impact FH. Most studies have evaluated these risk factors in isolation, but they coexist in a complex and ever-changing American society. We hypothesized that both restrictive firearm laws and socioeconomic support would correlate with reduced FH rates. METHODS: To perform our ecologic cross-sectional study, we queried the Centers for Disease Control (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) and Federal Bureau of Investigation (FBI) Uniform Crime Reporting (UCR) for 2013-2016 state FH data. We retrieved firearm access estimates from the RAND State-Level Firearm Ownership Database. Alcohol use and access to care data were captured from the CDC Behavioral Risk Factor Surveillance System (BRFSS). Detached youth rates, socioeconomic support data and poverty metrics were captured from US Census data for each state in each year. Firearm laws were obtained from the State Firearms Law Database. Variables with significant FH association were entered into a final multivariable panel linear regression with fixed effect for state. RESULTS: A total of 49,610 FH occurred in 2013-2016 (median FH rate: 3.9:100,000, range: 0.07-11.2). In univariate analysis, increases in concealed carry limiting laws ( P =0.012), detached youth rates ( P <0.001), socioeconomic support ( P <0.001) and poverty rates ( P <0.001) correlated with decreased FH. Higher rates of heavy drinking ( P =0.036) and the presence of stand your ground doctrines ( P =0.045) were associated with increased FH. Background checks, handgun limiting laws, and weapon access were not correlated with FH. In multivariable regression, increased access to food benefits for those in poverty [ß: -0.132, 95% confidence interval (CI): -0.182 to -0.082, P <0.001] and laws limiting concealed carry (ß: -0.543, 95% CI: -0.942 to -0.144, P =0.008) were associated with decreased FH rates. Allowance of stand your ground was associated with more FHs (ß: 1.52, 95% CI: 0.069-2.960, P <0.040). CONCLUSIONS: The causes and potential solutions to FH are complex and closely tied to public policy. Our data suggests that certain types of socioeconomic support and firearm restrictive legislation should be emphasized in efforts to reduce firearm deaths in America.

Bariatric-metabolic surgery for NHS patients with type 2 diabetes in the United Kingdom National Bariatric Surgery Registry.

AIM: Bariatric-metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric-metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. METHODS: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric-metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. RESULTS: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39-3.79); p < 0.001), hypertension (OR: 2.32 (2.19-2.45); p < 0.001) and liver disease (OR: 1.73 (1.58-1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric-metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). CONCLUSION: NHS bariatric-metabolic surgery is used for people with T2DM much later in the disease process when it is less effective. National guidance on bariatric-metabolic surgery and data from multiple RCTs have had little impact on clinical practice.

A Pilot Machine Learning Study Using Trauma Admission Data to Identify Risk for High Length of Stay.

INTRODUCTION: Trauma patients have diverse resource needs due to variable mechanisms and injury patterns. The aim of this study was to build a tool that uses only data available at time of admission to predict prolonged hospital length of stay (LOS). METHODS: Data was collected from the trauma registry at an urban level one adult trauma center and included patients from 1/1/2014 to 3/31/2019. Trauma patients with one or fewer days LOS were excluded. Single layer and deep artificial neural networks were trained to identify patients in the top quartile of LOS and optimized on area under the receiver operator characteristic curve (AUROC). The predictive performance of the model was assessed on a separate test set using binary classification measures of accuracy, precision, and error. RESULTS: 2953 admitted trauma patients with more than one-day LOS were included in this study. They were 70% male, 60% white, and averaged 47 years-old (SD: 21). 28% were penetrating trauma. Median length of stay was 5 days (IQR 3-9). For prediction of prolonged LOS, the deep neural network achieved an AUROC of 0.80 (95% CI: 0.786-0.814) specificity was 0.95, sensitivity was 0.32, with an overall accuracy of 0.79. CONCLUSION: Machine learning can predict, with excellent specificity, trauma patients who will have prolonged length of stay with only physiologic and demographic data available at the time of admission. These patients may benefit from additional resources with respect to disposition planning at the time of admission.

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. SUMMARY BACKGROUND DATA: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. RESULTS: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore.

The IL-36 family of cytokines were first identified in 2000 based on their sequence homology to IL-1 cytokines. Over subsequent years, the ability of these cytokines to either agonise or antagonise an IL-1R homologue, now known as the IL-36 Receptor (IL-36R), was identified and these cytokines went through several cycles of renaming with the current nomenclature being proposed in 2010. Despite being identified over 20 years ago, it is only during the last decade that the function of these cytokines in health and disease has really begun to be appreciated, with both homeostatic functions in wound healing and response to infection, as well as pathological functions now ascribed. In the disease context, over activation of IL-36 has now been associated with many inflammatory diseases including Psoriasis and inflammatory bowel diseases, with roles in cancer also now being investigated. This review summarises the current knowledge of IL-36 biology, its role in inflammatory diseases and focuses on an emerging role for IL-36 in cancer.

Pyrite formation from FeS and H2S is mediated through microbial redox activity.

The exergonic reaction of FeS with H2S to form FeS2 (pyrite) and H2 was postulated to have operated as an early form of energy metabolism on primordial Earth. Since the Archean, sedimentary pyrite formation has played a major role in the global iron and sulfur cycles, with direct impact on the redox chemistry of the atmosphere. However, the mechanism of sedimentary pyrite formation is still being debated. We present microbial enrichment cultures which grew with FeS, H2S, and CO2 as their sole substrates to produce FeS2 and CH4 Cultures grew over periods of 3 to 8 mo to cell densities of up to 2 to 9 × 106 cells per mL-1 Transformation of FeS with H2S to FeS2 was followed by 57Fe Mössbauer spectroscopy and showed a clear biological temperature profile with maximum activity at 28 °C and decreasing activities toward 4 °C and 60 °C. CH4 was formed concomitantly with FeS2 and exhibited the same temperature dependence. Addition of either penicillin or 2-bromoethanesulfonate inhibited both FeS2 and CH4 production, indicating a coupling of overall pyrite formation to methanogenesis. This hypothesis was supported by a 16S rRNA gene-based phylogenetic analysis, which identified at least one archaeal and five bacterial species. The archaeon was closely related to the hydrogenotrophic methanogen Methanospirillum stamsii, while the bacteria were most closely related to sulfate-reducing Deltaproteobacteria, as well as uncultured Firmicutes and Actinobacteria. Our results show that pyrite formation can be mediated at ambient temperature through a microbially catalyzed redox process, which may serve as a model for a postulated primordial iron-sulfur world.

Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing.

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70-80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.

Ictal aphasia in LGI1-related autosomal dominant epilepsy with auditory features.

Autosomal dominant epilepsy with auditory features (OMIM 600512) is characterised by focal seizures with distinctive auditory auras and/or ictal aphasia. We describe a 17-year-old girl with recurrent attacks of ictal aphasia and rare nocturnal convulsions. She had a four-generation paternal family history of epilepsy. Her father and aunt perceived bells ringing at the onset of seizures. Sequence analysis of the leucine-rich glioma-inactivated 1 (LGI1) gene identified a novel heterozygous variant in the proband and her father. LGI1-related genetic epilepsy has a benign clinical course with a favourable response to anti-seizure medications. Auditory or vertiginous seizures may be mistaken for peripheral audio-vestibular symptoms, while complex auditory ictal symptoms may be misattributed to primary psychiatric disorders. Recognising this distinctive inherited syndrome should prompt targeted analysis of the LGI1 gene.

Nitrate Removal by a Novel Lithoautotrophic Nitrate-Reducing, Iron(II)-Oxidizing Culture Enriched from a Pyrite-Rich Limestone Aquifer.

Nitrate removal in oligotrophic environments is often limited by the availability of suitable organic electron donors. Chemolithoautotrophic bacteria may play a key role in denitrification in aquifers depleted in organic carbon. Under anoxic and circumneutral pH conditions, iron(II) was hypothesized to serve as an electron donor for microbially mediated nitrate reduction by Fe(II)-oxidizing (NRFeOx) microorganisms. However, lithoautotrophic NRFeOx cultures have never been enriched from any aquifer, and as such, there are no model cultures available to study the physiology and geochemistry of this potentially environmentally relevant process. Using iron(II) as an electron donor, we enriched a lithoautotrophic NRFeOx culture from nitrate-containing groundwater of a pyrite-rich limestone aquifer. In the enriched NRFeOx culture that does not require additional organic cosubstrates for growth, within 7 to 11 days, 0.3 to 0.5 mM nitrate was reduced and 1.3 to 2 mM iron(II) was oxidized, leading to a stoichiometric NO3-/Fe(II) ratio of 0.2, with N2 and N2O identified as the main nitrate reduction products. Short-range ordered Fe(III) (oxyhydr)oxides were the product of iron(II) oxidation. Microorganisms were observed to be closely associated with formed minerals, but only few cells were encrusted, suggesting that most of the bacteria were able to avoid mineral precipitation at their surface. Analysis of the microbial community by long-read 16S rRNA gene sequencing revealed that the culture is dominated by members of the Gallionellaceae family that are known as autotrophic, neutrophilic, and microaerophilic iron(II) oxidizers. In summary, our study suggests that NRFeOx mediated by lithoautotrophic bacteria can lead to nitrate removal in anthropogenically affected aquifers. IMPORTANCE Removal of nitrate by microbial denitrification in groundwater is often limited by low concentrations of organic carbon. In these carbon-poor ecosystems, nitrate-reducing bacteria that can use inorganic compounds such as Fe(II) (NRFeOx) as electron donors could play a major role in nitrate removal. However, no lithoautotrophic NRFeOx culture has been successfully isolated or enriched from this type of environment, and as such, there are no model cultures available to study the rate-limiting factors of this potentially important process. Here, we present the physiology and microbial community composition of a novel lithoautotrophic NRFeOx culture enriched from a fractured aquifer in southern Germany. The culture is dominated by a putative Fe(II) oxidizer affiliated with the Gallionellaceae family and performs nitrate reduction coupled to Fe(II) oxidation leading to N2O and N2 formation without the addition of organic substrates. Our analyses demonstrate that lithoautotrophic NRFeOx can potentially lead to nitrate removal in nitrate-contaminated aquifers.

Using State Data to Predict a Single Institution Mortality for Patients That Fall.

BACKGROUND: Falls are the most common cause of injury-related death for patients older than 45.  We hypothesized that a machine learning algorithm developed from state-level registry data could make accurate outcome predictions at a level 1 trauma hospital. METHODS: Data for all patients admitted for fall injury during 2009 - 2019 in the state of Pennsylvania were derived from the state trauma registry.  Thirteen variables that were immediately available upon patient arrival were used for prediction modeling.  Data for the test institution were withheld from model creation.  Algorithms assessed included logistic regression (LR), random forest (RF), and extreme gradient boost (XGB).  Model discrimination for mortality was assessed with area under the curve (AUC) for each algorithm at our level 1 trauma center. RESULTS: 180,284 patients met inclusion criteria.  The mean age was 69 years ± 18.5 years with a mortality rate of 4.0%.  The AUC for predicting mortality in patients that fall for LR, RF, and XGB were 0.797, 0.876, and 0.880, respectively.  The variables which contributed to the prediction in descending order of importance for XGB were respiratory rate, pulse, systolic blood pressure, ethnicity, weight, sex, age, temperature, Glasgow Coma Scale (GCS) eye, race, GCS voice, GCS motor, and blood alcohol level. CONCLUSIONS: An extreme gradient boost model developed using state-wide trauma data can accurately predict mortality after fall at a single center within the state.  This machine learning model can be implemented by local trauma systems within the state of Pennsylvania to identify patients injured by fall that require greater attention, transfer to a higher level of care, and higher resource allocation.

Mercury Reduction by Nanoparticulate Vivianite.

Mercury (Hg) is a toxic trace element of global environmental concern which has been increasingly dispersed into the environment since the industrial revolution. In aquatic and terrestrial systems, Hg can be reduced to elemental Hg (Hg0) and escape to the atmosphere or converted to methylmercury (MeHg), a potent neurotoxin that accumulates in food webs. FeII-bearing minerals such as magnetite, green rusts, siderite, and mackinawite are recognized HgII reducers. Another potentially Hg-reducing mineral, which commonly occurs in Fe- and organic/P-rich sediments and soils, is the ferrous iron phosphate mineral vivianite (FeII3(PO4)2·8H2O), but its reaction with HgII has not been studied to date. Here, nanoparticulate vivianite (particle size ∼ 50 nm; FeII content > 98%) was chemically synthesized and characterized by a combination of chemical, spectroscopic, and microscopic analyses. Its ability to reduce HgII was investigated at circumneutral pH under anoxic conditions over a range of FeII/HgII ratios (0.1-1000). For FeII/HgII ratios ≥1, which are representative of natural environments, HgII was very quickly and efficiently reduced to Hg0. The ability of vivianite to reduce HgII was found to be similar to those of carbonate green rust and siderite, two of the most effective Hg-reducing minerals. Our results suggest that vivianite may be involved in abiotic HgII reduction in Fe and organic/P-rich soils and sediments, potentially contributing to Hg evasion while also limiting MeHg formation in these ecosystems.

Anaerobic Neutrophilic Pyrite Oxidation by a Chemolithoautotrophic Nitrate-Reducing Iron(II)-Oxidizing Culture Enriched from a Fractured Aquifer.

Neutrophilic microbial pyrite (FeS2) oxidation coupled to denitrification is thought to be an important natural nitrate attenuation pathway in nitrate-contaminated aquifers. However, the poor solubility of pyrite raises questions about its bioavailability and the mechanisms underlying its oxidation. Here, we investigated direct microbial pyrite oxidation by a neutrophilic chemolithoautotrophic nitrate-reducing Fe(II)-oxidizing culture enriched from a pyrite-rich aquifer. We used pyrite with natural abundance (NA) of Fe isotopes (NAFe-pyrite) and 57Fe-labeled siderite to evaluate whether the oxidation of the more soluble Fe(II)-carbonate (FeCO3) can indirectly drive abiotic pyrite oxidation. Our results showed that in setups where only pyrite was incubated with bacteria, direct microbial pyrite oxidation contributed ca. 26% to overall nitrate reduction. The rest was attributed to the oxidation of elemental sulfur (S0), present as a residue from pyrite synthesis. Pyrite oxidation was evidenced in the NAFe-pyrite/57Fe-siderite setups by maps of 56FeO and 32S obtained using a combination of SEM with nanoscale secondary ion MS (NanoSIMS), which showed the presence of 56Fe(III) (oxyhydr)oxides that could solely originate from 56FeS2. Based on the fit of a reaction model to the geochemical data and the Fe-isotope distributions from NanoSIMS, we conclude that anaerobic oxidation of pyrite by our neutrophilic enrichment culture was mainly driven by direct enzymatic activity of the cells. The contribution of abiotic pyrite oxidation by Fe3+ appeared to be negligible in our experimental setup.

Organic Matter from Redoximorphic Soils Accelerates and Sustains Microbial Fe(III) Reduction.

Microbial reduction of Fe(III) minerals is a prominent process in redoximorphic soils and is strongly affected by organic matter (OM). We herein determined the rate and extent of microbial reduction of ferrihydrite (Fh) with either adsorbed or coprecipitated OM by Geobacter sulfurreducens. We focused on OM-mediated effects on electron uptake and alterations in Fh crystallinity. The OM was obtained from anoxic soil columns (effluent OM, efOM) and included-unlike water-extractable OM-compounds released by microbial activity under anoxic conditions. We found that organic molecules in efOM had generally no or only very low electron-accepting capacity and were incorporated into the Fh aggregates when coprecipitated with Fh. Compared to OM-free Fh, adsorption of efOM to Fh decelerated the microbial Fe(III) reduction by passivating the Fh surface toward electron uptake. In contrast, coprecipitation of Fh with efOM accelerated the microbial reduction, likely because efOM disrupted the Fh structure, as noted by Mössbauer spectroscopy. Additionally, the adsorbed and coprecipitated efOM resulted in a more sustained Fe(III) reduction, potentially because efOM could have effectively scavenged biogenic Fe(II) and prevented the passivation of the Fh surface by the adsorbed Fe(II). Fe(III)-OM coprecipitates forming at anoxic-oxic interfaces are thus likely readily reducible by Fe(III)-reducing bacteria in redoximorphic soils.