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By age 40 years, over 90% of adults with Down syndrome have Alzheimer's disease pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with Down syndrome have elevated cerebrovascular disease markers that track with the clinical progression of Alzheimer's disease, suggesting a role of cerebrovascular disease that is hypothesized to be mediated by inflammatory factors. This study examined the pathways through which small vessel cerebrovascular disease contributes to Alzheimer's disease-related pathophysiology and neurodegeneration in adults with Down syndrome. One hundred eighty-five participants from the Alzheimer's Biomarkers Consortium-Down Syndrome [mean (SD) age = 45.2 (9.3) years] with available MRI and plasma biomarker data were included in this study. White matter hyperintensity (WMH) volumes were derived from T2-weighted fluid-attenuated inversion recovery MRI scans, and plasma biomarker concentrations of amyloid beta 42/40, phosphorylated tau 217, astrocytosis (glial fibrillary acidic protein) and neurodegeneration (neurofilament light chain) were measured with ultrasensitive immunoassays. We examined the bivariate relationships of WMH, amyloid beta 42/40, phosphorylated tau 217 and glial fibrillary acidic protein with age-residualized neurofilament light chain across Alzheimer's disease diagnostic groups. A series of mediation and path analyses examined statistical pathways linking WMH and Alzheimer's disease pathophysiology to promote neurodegeneration in the total sample and groups stratified by clinical diagnosis. There was a direct and indirect bidirectional effect through the glial fibrillary acidic protein of WMH on phosphorylated tau 217 concentration, which was associated with neurofilament light chain concentration in the entire sample. Amongst cognitively stable participants, WMH was directly and indirectly, through glial fibrillary acidic protein, associated with phosphorylated tau 217 concentration, and in those with mild cognitive impairment, there was a direct effect of WMH on phosphorylated tau 217 and neurofilament light chain concentrations. There were no associations of WMH with biomarker concentrations among those diagnosed with dementia. The findings from this cross-sectional study suggest that among individuals with Down syndrome, cerebrovascular disease promotes neurodegeneration by increasing astrocytosis and tau pathophysiology in the presymptomatic phases of Alzheimer's disease, but future studies will need to confirm these associations with longitudinal data. This work joins an emerging literature that implicates cerebrovascular disease and its interface with neuroinflammation as a core pathological feature of Alzheimer's disease in adults with Down syndrome.
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Renewable alternatives for nonelectrifiable fossil-derived chemicals are needed and plant matter, the most abundant biomass on Earth, provide an ideal feedstock. However, the heterogeneous polymeric composition of lignocellulose makes conversion difficult. Lignin presents a formidable barrier to fermentation of nonpretreated biomass. Extensive chemical and enzymatic treatments can liberate fermentable carbohydrates from plant biomass, but microbial routes offer many advantages, including concomitant conversion to industrial chemicals. Here, testing of lignin content of nonpretreated biomass using the cellulolytic thermophilic bacterium, Anaerocellum bescii, revealed that the primary microbial degradation barrier relates to methoxy substitutions in lignin. This contrasts with optimal lignin composition for chemical pretreatment that favors high S/G ratio and low H lignin. Genetically modified poplar trees with diverse lignin compositions confirm these findings. In addition, poplar trees with low methoxy content achieve industrially relevant levels of microbial solubilization without any pretreatments and with no impact on tree fitness in greenhouse.
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Biomassa , Fermentação , Lignina , Populus , Lignina/metabolismo , Populus/metabolismo , Populus/genética , Bactérias/metabolismo , Bactérias/genética , Plantas/metabolismoRESUMO
The anaerobic bacterium Anaerocellum (f. Caldicellulosiruptor) bescii natively ferments the carbohydrate content of plant biomass (including microcrystalline cellulose) into predominantly acetate, H2, and CO2, and smaller amounts of lactate, alanine and valine. While this extreme thermophile (growth Topt 78 °C) is not natively ethanologenic, it has been previously metabolically engineered with this property, albeit initially yielding low solvent titers (â¼15 mM). Herein we report significant progress on improving ethanologenicity in A. bescii, such that titers above 130 mM have now been achieved, while concomitantly improving selectivity by minimizing acetate formation. Metabolic engineering progress has benefited from improved molecular genetic tools and better understanding of A. bescii growth physiology. Heterologous expression of a mutated thermophilic alcohol dehydrogenase (AdhE) modified for co-factor requirement, coupled with bioreactor operation strategies related to pH control, have been key to enhanced ethanol generation and fermentation product specificity. Insights gained from metabolic modeling of A. bescii set the stage for its further improvement as a metabolic engineering platform.
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Factors that contribute to optimal chalcopyrite bioleaching by extremely thermoacidophilic archaea were examined for ten species belonging to the order Sulfolobales from the genera Acidianus (A. brierleyi), Metallosphaera (M. hakonensis, M. sedula, M. prunae), Sulfuracidifex (S. metallicus, S. tepriarius), Sulfolobus (S. acidocaldarius), Saccharlobus (S. solfataricus) and Sulfurisphaera (S. ohwakuensis, S. tokodaii). Only A. brierleyi, M. sedula, S. metallicus, S. tepriarius, S. ohwakuensis, and S. tokodai exhibited significant amounts of bioleaching and were investigated further. At 70-75 °C, Chalcopyrite loadings of 10 g/l were leached for 21 days during which pH, redox potential, planktonic cell density, iron concentrations and sulfate levels were monitored, in addition to copper mobilization. S. ohwakuensis proved to be the most prolific bioleacher. This was attributed to balanced iron and sulfur oxidation, thereby reducing by-product (e.g., jarosites) formation and minimizing surface passivation. Comparative genomics suggest markers for bioleaching potential, but the results here point to the need for experimental verification.
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Cobre , Ferro , Oxirredução , Enxofre , Enxofre/metabolismo , Cobre/metabolismo , Ferro/metabolismo , Archaea/metabolismo , Concentração de Íons de Hidrogênio , Temperatura , Sulfolobales/metabolismoRESUMO
Certain members of the family Sulfolobaceae represent the only archaea known to oxidize elemental sulfur, and their evolutionary history provides a framework to understand the development of chemolithotrophic growth by sulfur oxidation. Here, we evaluate the sulfur oxidation phenotype of Sulfolobaceae species and leverage comparative genomic and transcriptomic analysis to identify the key genes linked to sulfur oxidation. Metabolic engineering of the obligate heterotroph Sulfolobus acidocaldarius revealed that the known cytoplasmic components of sulfur oxidation alone are not sufficient to drive prolific sulfur oxidation. Imaging analysis showed that Sulfolobaceae species maintain proximity to the sulfur surface but do not necessarily contact the substrate directly. This indicates that a soluble form of sulfur must be transported to initiate cytoplasmic sulfur oxidation. Conservation patterns and transcriptomic response implicate an extracellular tetrathionate hydrolase and putative thiosulfate transporter in a newly proposed mechanism of sulfur acquisition in the Sulfolobaceae.IMPORTANCESulfur is one of the most abundant elements on earth (2.9% by mass), so it makes sense that the earliest biology found a way to use sulfur to create and sustain life. However, beyond evolutionary significance, sulfur and the molecules it comprises have important technological significance, not only in chemicals such as sulfuric acid and in pyritic ores containing critical metals but also as a waste product from oil and gas production. The thermoacidophilic Sulfolobaceae are unique among the archaea as sulfur oxidizers. The trajectory for how sulfur biooxidation arose and evolved can be traced using experimental and bioinformatic analyses of the available genomic data set. Such analysis can also inform the process by which extracellular sulfur is acquired and transported by thermoacidophilic archaea, a phenomenon that is critical to these microorganisms but has yet to be elucidated.
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Oxirredução , Sulfolobaceae , Enxofre , Enxofre/metabolismo , Sulfolobaceae/metabolismo , Sulfolobaceae/genética , Fenótipo , Filogenia , Perfilação da Expressão Gênica , Genoma ArquealRESUMO
CLINICAL ISSUE: Carotid artery stenoses are constrictions of the common carotid artery and the internal carotid artery. They cause around 15% of all cerebral ischemia, which is why their detection and correct treatment play an important role in clinical practice. PRACTICAL RECOMMENDATIONS: Depending on the severity and clinical symptoms, carotid artery stenosis is treated conservatively, surgically or endovascularly by means of stent angioplasty. In the case of stent angioplasty in particular, correct drug therapy plays an important role in avoiding/reducing thromboembolic complications.
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Angioplastia , Estenose das Carótidas , Stents , Humanos , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Angioplastia/métodos , Estenose das Carótidas/terapia , Estenose das Carótidas/cirurgia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/instrumentação , Procedimentos Cirúrgicos Eletivos/métodos , Stents/efeitos adversosRESUMO
We present the case of a previously healthy 14-year-old boy who experienced two episodes of lightheadedness while sitting under the sun. The patient did not experience syncope and denied experiencing any other symptoms. Moreover, he exhibited great functional capacity. An electrocardiogram showed T-wave inversions in leads V1 to V4. Subsequent echocardiogram and cardiac magnetic resonance imaging confirmed the diagnosis of arrhythmogenic cardiomyopathy with severe features. Arrhythmogenic cardiomyopathy is a disorder characterized by fibrofatty degeneration of the myocardium and is a common cause of sudden cardiac death. This case highlights the significance of early investigation in any child who presents with seemingly benign symptoms, as they may be indicative of a serious cardiac disease.
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The complete genome sequence of the thermoacidophilic archaeon Metallosphaera sedula (DSM 5348) is reported here. M. sedula, originally isolated from a volcanic field in Italy, is a prolific iron-oxidizing archaeon with applications in bioleaching of sulfide minerals.
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BACKGROUND: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial. METHODS: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status. RESULTS: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status. CONCLUSION: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.
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Doença de Alzheimer , Transtornos Cerebrovasculares , Disfunção Cognitiva , Substância Branca , Idoso , Feminino , Humanos , Masculino , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/patologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Cognição , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Substância Branca/patologia , Ensaios Clínicos como AssuntoRESUMO
The complete genome sequence of the extremely thermophilic bacterium Anaerocellum (f. Caldicellulosiruptor) danielii (DSM:8977) is reported here. A. danielii is a fermentative anaerobe and capable of lignocellulose degradation with potential applications in biomass degradation and production of chemicals and fuels from renewable feedstocks.
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Reported here is the complete genome sequence (2,191,724 bp) for the thermoacidophilic archaeon Sulfuracidifex (f. Sulfolobus) metallicus DSM 6482 (Topt 65°C, pHopt 2.0). This obligately chemolithoautotrophic microorganism is a prolific metal and sulfur oxidizer and has application in metal bioleaching operations. A multi-assembly reconciliation approach enabled closure of the genome.
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Importance: By age 40 years over 90% of adults with Down syndrome (DS) have Alzheimer's disease (AD) pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with DS have elevated cerebrovascular disease (CVD) markers that track with the clinical progression of AD, suggesting a role for CVD that is hypothesized to be mediated by inflammatory factors. Objective: To examine the pathways through which small vessel CVD contributes to AD-related pathophysiology and neurodegeneration in adults with DS. Design: Cross sectional analysis of neuroimaging, plasma, and clinical data. Setting: Participants were enrolled in Alzheimer's Biomarker Consortium - Down Syndrome (ABC-DS), a multisite study of AD in adults with DS. Participants: One hundred eighty-five participants (mean [SD] age=45.2 [9.3] years) with available MRI and plasma biomarker data were included. White matter hyperintensity (WMH) volumes were derived from T2-weighted FLAIR MRI scans and plasma biomarker concentrations of amyloid beta (Aß42/Aß40), phosphorylated tau (p-tau217), astrocytosis (glial fibrillary acidic protein, GFAP), and neurodegeneration (neurofilament light chain, NfL) were measured with ultrasensitive immunoassays. Main Outcomes and Measures: We examined the bivariate relationships of WMH, Aß42/Aß40, p-tau217, and GFAP with age-residualized NfL across AD diagnostic groups. A series of mediation and path analyses examined causal pathways linking WMH and AD pathophysiology to promote neurodegeneration in the total sample and groups stratified by clinical diagnosis. Results: There was a direct and indirect bidirectional effect through GFAP of WMH on p-tau217 concentration, which was associated with NfL concentration in the entire sample. Among cognitively stable participants, WMH was directly and indirectly, through GFAP, associated with p-tau217 concentration, and in those with MCI, there was a direct effect of WMH on p-tau217 and NfL concentrations. There were no associations of WMH with biomarker concentrations among those diagnosed with dementia. Conclusions and Relevance: The findings suggest that among individuals with DS, CVD promotes neurodegeneration by increasing astrocytosis and tau pathophysiology in the presymptomatic phases of AD. This work joins an emerging literature that implicates CVD and its interface with neuroinflammation as a core pathological feature of AD in adults with DS.
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In forensic investigations, forensic intelligence is required for illicit drug profiling in order to allow police officers and law enforcements to recognize crime developments and adjust their actions. In the present paper, we propose a novel framework for Digital Forensic Drug Intelligence (DFDI) by fusing digital forensic and drug profiling data through intelligent cycles, where a targeted and iterative collection of evidence from diverse sources is a core step in the process of drug profiling. Drug profiling data combined with digital data from seized devices collected, examined, and analyzed will allow authorities to generate valuable information about illicit drug trafficking routes and manufacturing. Such data can be stored in seized illicit drug databases to build in an intelligent way, all findings, hypotheses and recommendations, allowing law enforcement to make decisions. Our framework will potentially provide a better understanding of profiling, trafficking and distribution of illicit drugs.
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BACKGROUND: Data regarding the reliability of predicted effective orifice area indexed (pEOAi) is scarce in transcatheter aortic valve replacement (TAVR). AIMS: To assess the validity of the pEOAi in TAVR by correlating its value with echocardiography-derived hemodynamic data. METHODS: A single-center retrospective cohort study of TAVR patients from 2012 to 2021 with available echocardiograms was conducted. Patient-prosthesis mismatch (PPM) was defined based on the Valve Academic Research Consortium 3 criteria. The main endpoints were the congruence of measured effective orifice area indexed (EOAi) and pEOAi with the hemodynamic data obtained by echocardiography. The secondary endpoint included a correlation of predicted PPM (pPPM) and measured PPM (mPPM) with postoperative New York Heart Association (NYHA) status. RESULTS: A total of 318 patients were included. pPPM was more frequent than mPPM (54 [17%]; all moderate PPM vs. 39 [12.3%]: 32 moderate and 7 severe PPM). Predicted and measured EOAi were statistically correlated with postprocedural transvalvular mean gradient and Doppler velocity index (all p < 0.001), including in both sex-based subgroups. The positive predictive value and negative predictive value (NPV) of pPPM for postprocedural transvalvular mean gradient ≥ 20 mmHg were 16% and 97%, respectively. Only pPPM was significantly more prevalent in the group in which NYHA failed to improve than in those with symptom improvement (30.1% vs. 16%, p = 0.027). CONCLUSION: Predicted PPM has an excellent NPV for postprocedural transvalvular mean gradient ≥ 20 mmHg and seems to be a good predictor of NYHA status evolution as opposed to measured PPM. Predicted EOAi can be used in procedural planning to reduce the risk of PPM in both TAVR male and female patients.
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Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Masculino , Feminino , Substituição da Valva Aórtica Transcateter/efeitos adversos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Resultado do Tratamento , Hemodinâmica , Desenho de PróteseRESUMO
A type II VapB14 antitoxin regulates biofilm dispersal in the archaeal thermoacidophile Sulfolobus acidocaldarius through traditional toxin neutralization but also through noncanonical transcriptional regulation. Type II VapC toxins are ribonucleases that are neutralized by their proteinaceous cognate type II VapB antitoxin. VapB antitoxins have a flexible tail at their C terminus that covers the toxin's active site, neutralizing its activity. VapB antitoxins also have a DNA-binding domain at their N terminus that allows them to autorepress not only their own promoters but also distal targets. VapB14 antitoxin gene deletion in S. acidocaldarius stunted biofilm and planktonic growth and increased motility structures (archaella). Conversely, planktonic cells were devoid of archaella in the ΔvapC14 cognate toxin mutant. VapB14 is highly conserved at both the nucleotide and amino acid levels across the Sulfolobales, extremely unusual for type II antitoxins, which are typically acquired through horizontal gene transfer. Furthermore, homologs of VapB14 are found across the Crenarchaeota, in some Euryarchaeota, and even bacteria. S. acidocaldarius vapB14 and its homolog in the thermoacidophile Metallosphaera sedula (Msed_0871) were both upregulated in biofilm cells, supporting the role of the antitoxin in biofilm regulation. In several Sulfolobales species, including M. sedula, homologs of vapB14 and vapC14 are not colocalized. Strikingly, Sulfuracidifex tepidarius has an unpaired VapB14 homolog and lacks a cognate VapC14, illustrating the toxin-independent conservation of the VapB14 antitoxin. The findings here suggest that a stand-alone VapB-type antitoxin was the product of selective evolutionary pressure to influence biofilm formation in these archaea, a vital microbial community behavior. IMPORTANCE Biofilms allow microbes to resist a multitude of stresses and stay proximate to vital nutrients. The mechanisms of entering and leaving a biofilm are highly regulated to ensure microbial survival, but are not yet well described in archaea. Here, a VapBC type II toxin-antitoxin system in the thermoacidophilic archaeon Sulfolobus acidocaldarius was shown to control biofilm dispersal through a multifaceted regulation of the archaeal motility structure, the archaellum. The VapC14 toxin degrades an RNA that causes an increase in archaella and swimming. The VapB14 antitoxin decreases archaella and biofilm dispersal by binding the VapC14 toxin and neutralizing its activity, while also repressing the archaellum genes. VapB14-like antitoxins are highly conserved across the Sulfolobales and respond similarly to biofilm growth. In fact, VapB14-like antitoxins are also found in other archaea, and even in bacteria, indicating an evolutionary pressure to maintain this protein and its role in biofilm formation.
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Antitoxinas , Toxinas Bacterianas , Antitoxinas/metabolismo , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Sulfolobales , BiofilmesRESUMO
Background: Patient reviews provide an important referral source for physicians and an opportunity to improve practice performance. This study's objective was to characterize the online reviews of hip and knee arthroplasty surgeons published by three of the industry's leading platforms. Methods: A random sample of 1000 hip and knee arthroplasty surgeons across all 50 US states (10 hip and 10 knee surgeons per state) was generated using Google Search. A total of 7842 online reviews posted for those surgeons on Healthgrades, Vitals, and Google were analyzed. A range of surgeons, affiliated hospitals, and reviewer attributes was compared to identify significant predictors of patient satisfaction. Results: The study cohort had 98.1% male surgeons with a mean age of 53.55 ± 8.94 years and mean experience of 26.43 ± 9.21 years. Younger age (p < 0.001), shorter years of experience (p < 0.001), and arthroplasty fellowship training (p < 0.001) were associated with more positive ratings. Reviewer anonymity, observed in 30.93% of all reviews, tended to correlate with more negative ratings (p < 0.001). Overall, 86.93% of patient remarks were positive, and only 74.81% of remarks centered on physician attributes. The five leading components of patient satisfaction were perceptions of physician competence (34.81%, p < 0.001), bedside manner (23.83%, p = 0.002), and communication (16.17%, p = 0.94); interactions with physician extenders (14.75%, p < 0.001); and wait time (2.73%, p < 0.001). Conclusion: While most ratings of hip and knee arthroplasty surgeons were positive, more than a quarter of reviews were either not directly related to the individual surgeons or were submitted anonymously. Caution is advised regarding overreliance on patient experience surveys as predictors of physician performance.
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The genome sequences of three extremely thermophilic, lignocellulolytic Caldicellulosiruptor species were closed, improving previously reported multiple-contig assemblies. All 14 classified Caldicellulosiruptor spp. now have closed genomes. Genome closure will enhance bioinformatic analysis of the species, including identification of carbohydrate-active enzymes (CAZymes) and comparison against other Caldicellulosiruptor species and lignocellulolytic microorganisms.
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Reported here are complete genome sequences for two anaerobic, thermophilic bacteria isolated from wheat straw, i.e., the (hemi)cellulolytic Thermoclostridium stercorarium subspecies strain RKWS1 (3,029,933 bp) and the hemicellulolytic Thermoanaerobacter species strain RKWS2 (2,827,640 bp). Discovery of indigenous thermophiles in plant biomass suggests that high-temperature microorganisms are more ubiquitous than previously thought.
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BACKGROUND: There is currently no consensus regarding the optimal anesthetic technique for total hip and knee arthroplasty (THA, TKA). This study aimed to compare the utilization rates and safety of spinal vs. general anesthesia in contemporary THA/TKA practice. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), a retrospective review of 307,076 patients undergoing total hip or knee arthroplasty under either spinal or general anesthesia between January 2015 and December 2018 was performed. Propensity matching was used to compare differences in operative times, hospital length of stay, discharge destination, and 30-day adverse events. The annual utilization rates for both techniques between 2011 and 2018 were also assessed. RESULTS: Patients receiving spinal anesthesia had a shorter length of stay (P < 0.001) for TKA while no statistical differences in length of stay were observed for THA. Patients were also less likely to experience any 30-day complication (OR = 0.82, P <0.001 and OR = 0.92, P < 0.001 for THA and TKA, respectively) while being more likely to be discharged to home (OR = 1.46, P < 0.001 and OR = 1.44, P < 0.001 for THA and TKA, respectively). Between 2011 and 2018, spinal anesthesia utilization only increased by 1.4% for THA (P < 0.001) and decreased by 0.2% for TKA (P < 0.001), reaching 38.1% and 40.3%, respectively. CONCLUSION: Spinal anesthesia remains a grossly underutilized tool despite providing better perioperative outcomes compared to general anesthesia. As orthopedic surgeons navigate the challenges of value-based care, spinal anesthesia represents an invaluable tool that should be considered the gold standard in elective, primary total hip and knee arthroplasty.
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Caldicellulosiruptor species are proficient at solubilizing carbohydrates in lignocellulosic biomass through surface (S)-layer bound and secretomic glycoside hydrolases. Tapirins, surface-associated, non-catalytic binding proteins in Caldicellulosiruptor species, bind tightly to microcrystalline cellulose, and likely play a key role in natural environments for scavenging scarce carbohydrates in hot springs. However, the question arises: If tapirin concentration on Caldicellulosiruptor cell walls increased above native levels, would this offer any benefit to lignocellulose carbohydrate hydrolysis and, hence, biomass solubilization? This question was addressed by engineering the genes for tight-binding, non-native tapirins into C. bescii. The engineered C. bescii strains bound more tightly to microcrystalline cellulose (Avicel) and biomass compared to the parent. However, tapirin overexpression did not significantly improve solubilization or conversion for wheat straw or sugarcane bagasse. When incubated with poplar, the tapirin-engineered strains increased solubilization by 10% compared to the parent, and corresponding acetate production, a measure of carbohydrate fermentation intensity, was 28% higher for the Calkr_0826 expression strain and 18.5% higher for the Calhy_0908 expression strain. These results show that enhanced binding to the substrate, beyond the native capability, did not improve C. bescii solubilization of plant biomass, but in some cases may improve conversion of released lignocellulose carbohydrates to fermentation products.