Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Barriers and Unequal Access to Timely Molecular Testing Results: Addressing the Inequities in Cancer Care Delays across Canada.

Genomic medicine is a powerful tool to improve diagnosis and outcomes for cancer patients by facilitating the delivery of the right drug at the right dose at the right time for the right patient. In 2023, a Canadian conference brought together leaders with expertise in different tumor types. The objective was to identify challenges and opportunities for change in terms of equitable and timely access to biomarker testing and reporting at the education, delivery, laboratory, patient, and health-system levels in Canada. Challenges identified included: limited patient and clinician awareness of genomic medicine options with need for formal education strategies; failure by clinicians to discuss genomic medicine with patients; delays in or no access to hereditary testing; lack of timely reporting of results; intra- and inter-provincial disparities in access; lack of funding for patients to access testing and for laboratories to provide testing; lack of standardized testing; and impact of social determinants of health. Canada must standardize its approach to biomarker testing across the country, with a view to addressing current inequities, and prioritize access to advanced molecular testing to ensure systems are in place to quickly bring innovation and evidence-based treatments to Canadian cancer patients, regardless of their place of residence or socioeconomic status.

In-hospital mortality trends after surgery for traumatic thoracolumbar injury: A national inpatient sample database study.

Introduction: Given the increasing incidence of traumatic thoracolumbar injuries in recent years, studies have sought to investigate potential risk factors for outcomes in these patients. Research question: The aim of this study was to investigate trends and risk factors for in-hospital mortality after fusion for traumatic thoracolumbar injury. Materials and methods: Patients undergoing thoracolumbar fusion after traumatic injury were queried from the National Inpatient Sample (NIS) from 2012 to 2017. Analysis was performed to identify risk factors for inpatient mortality after surgery. Results: Patients in 2017 were on average older (51.0 vs. 48.5, P = 0.004), had more admitting diagnoses (15.5 vs. 10.7, p < 0.001), were less likely to be White (75.8% vs. 81.2%, p = 0.006), were from a ZIP code with a higher median income quartile (Quartile 1: 31.4% vs. 28.6%, p = 0.011), and were more likely to have Medicare as a primary payer (22.9% vs. 30.1%, p < 0.001). Bivariate analysis of demographics and surgical characteristics demonstrated that patients in the in-hospital mortality group (n = 90) were older (70.2 vs. 49.6, p < 0.001), more likely to be male (74.4% vs. 62.8%, p = 0.031), had a great number of admitted diagnoses (21.3 vs. 12.7, p < 0.001), and were more likely to be insured by Medicare (70.0% vs. 27.0%, p < 0.001). Multivariate regression analysis found age (OR 1.06, p < 0.001) and Black race (OR 3.71, p = 0.007) were independently associated with in-hospital mortality. Conclusion: Our study of nationwide, traumatic thoracolumbar fusion procedures from 2012 to 2017 in the NIS database found older, black patients were at increased risk for in-hospital mortality after surgery.

Exploiting Vector Pattern Diversity of Molecular Scaffolds for Cheminformatics Tasks in Drug Discovery.

Chemical diversity is challenging to describe objectively. Despite this, various notions of chemical diversity are used throughout the medicinal chemistry optimization process in drug discovery. In this work, we show the usefulness of considering exploited vectors during different phases of the drug design process to provide a quantitative and objective description of chemical diversity. We have developed a concise and fast approach to enumerate and analyze the exploited vector patterns (EVPs) of molecular compound series, which can then be used in archetypal compound selection tasks, from hit matter identification to hit expansion and lead optimization. We first show that EVPs can be used to assess the progressibility of compounds in a fragment library design exercise. By considering EVPs, we then show how a set of compounds can be prioritized for hit expansion using EVP-based, customizable diversity sampling approaches, reducing the time taken and mitigating human biases. We also show that EVPs are a useful tool to analyze SAR data, offering the chance to uncover correlations between different vectors without predetermining the molecular scaffold structures. The codes used to perform these tasks are presented as easy-to-use Jupyter notebooks, which can be readily adapted for further related tasks.

Optically Transparent Lead Halide Perovskite Polycrystalline Ceramics.

We utilize room-temperature uniaxial pressing at applied loads achievable with low-cost, laboratory-scale presses to fabricate freestanding CH3NH3PbX3 (X- = Br-, Cl-) polycrystalline ceramics with millimeter thicknesses and optical transparency up to ∼70% in the infrared. As-fabricated perovskite ceramics can be produced with desirable form factors (i.e., size, shape, and thickness) and high-quality surfaces without any postprocessing (e.g., cutting or polishing). This method should be broadly applicable to a large swath of metal halide perovskites, not just the compositions shown here. In addition to fabrication, we analyze microstructure-optical property relationships through detailed experiments (e.g., transmission measurements, electron microscopy, X-ray tomography, optical profilometry, etc.) as well as modeling based on Mie theory. The optical, electrical, and mechanical properties of perovskite polycrystalline ceramics are benchmarked against those of single-crystalline analogues through spectroscopic ellipsometry, Hall measurements, and nanoindentation. Finally, γ-ray scintillation from a transparent MAPbBr3 ceramic is demonstrated under irradiation from a 137Cs source. From a broader perspective, scalable methods to produce freestanding polycrystalline lead halide perovskites with comparable properties to their single-crystal counterparts could enable key advancements in the commercial production of perovskite-based technologies (e.g., direct X-ray/γ-ray detectors, scintillators, and nonlinear optics).

Is Oncotype DX testing informative for breast cancers with low ER expression? A retrospective review from a biomarker testing referral center.

PURPOSE: It remains unclear whether patients with HER2-negative, low-estrogen receptor (ER-low)-positive early breast cancer (BC) benefit from Oncotype DX® (ODX) testing. METHODS: We conducted a retrospective review of cases referred for ODX testing over a seven-year period from a breast biomarker testing referral center (n = 854). For each case, we recorded the ODX Recurrence Score (RS) along with percentage of ER nuclear positivity and staining intensity on immunohistochemistry. Our criteria for ER-low was defined as ≤10% cells with nuclear positivity and/or weak intensity of staining. Slides from all ER-low cases were reviewed and the reported ODX ER gene scores were recorded. We randomly selected a comparator group of 56 patients with ER > 10% positivity and non-weak staining intensity (ER-high). RESULTS: We identified 27 cases (3.2%) that met our criteria for ER-low. Of these, 92.6% had a high RS (>25), and 7.4% had a RS of 25. All cases with ≤10% ER nuclear positivity had a high RS. Most ER-low cases (85.2%) had ODX quantitative ER gene scores in the negative range, whereas all (100%) ER-high cases had positive ER gene scores. CONCLUSION: ODX does not appear to add significant additional information to inform treatment decisions for most patients with ER-low BC. Incorporating weak ER staining intensity in addition to low percentage of nuclear positivity identifies about twice as many ER-low patients, although with reduced specificity for high RS. Our study supports the contention that most ER-low early BC should be regarded similarly to ER-negative BC.

Flat-Knit, Flexible, Textile Metasurfaces.

Lightweight, low-cost metasurfaces and reflectarrays that are easy to stow and deploy are desirable for many terrestrial and space-based communications and sensing applications. This work demonstrates a lightweight, flexible metasurface platform based on flat-knit textiles operating in the cm-wave spectral range. By using a colorwork knitting approach called float-jacquard knitting to directly integrate an array of resonant metallic antennas into a textile, we realize two textile reflectarray devices, a metasurface lens (metalens) and a vortex-beam generator. Operating as a receiving antenna, the metalens focuses a collimated normal-incidence beam to a diffraction-limited, off-broadside focal spot. Operating as a transmitting antenna, the metalens converts the divergent emission from a horn antenna into a collimated beam with peak measured directivity, gain, and efficiency of 21.30 dB, 15.30 dB, and -6.00 dB (25.12%), respectively. The vortex-beam generating metasurface produces a focused vortex beam with a topological charge of m = 1 over a wide frequency range of 4.1-5.8 GHz. Strong specular reflection is observed for our textile reflectarrays, caused by wavy yarn floats on the backside of the float-jacquard textiles. Our work demonstrates a novel approach for scalable production of flexible metasurfaces by leveraging commercially available yarns and well-established knitting machinery and techniques. This article is protected by copyright. All rights reserved.

The Relationship Between Uncertainty and Psychological Distress Among Family Caregivers of Patients With Delirium in Intensive Care Units: A Cross-Sectional Survey.

BACKGROUND: Although family caregivers experienced negative psychological symptoms associated with witnessing intensive care unit delirium in their loved ones, there is a lack of clear understanding of how delirium is associated with family caregiver psychological distress. Uncertainty could be a factor contributed to this association. OBJECTIVES: The aim of this study was to examine the relationship between uncertainty and psychological distress among family caregivers of patients with delirium in intensive care units. METHODS: A cross-sectional correlational design was used for this observational study of adult family caregivers of patients admitted to the intensive care unit and who reported witnessing delirium symptoms in their loved ones. Family caregivers completed an electronic survey in January 2022 that consisted of a family caregiver and patient demographic form, the Mishel Uncertainty in Illness Scale-Family Member, and the Kessler Psychological Distress Scale. Descriptive, correlational, and regression statistical analyses were applied. RESULTS: One hundred twenty-one adult family caregivers were enrolled. Family caregivers reported substantial uncertainty (mean, 106.15, on a scale of 31-155) and moderate to severe psychological distress (mean, 31.37, on a scale of 10-50) regarding their witnessing of delirium episodes in their loved ones. Uncertainty was significantly correlated with psychological distress among family caregivers (rs = 0.52, P < .001). Uncertainty significantly predicted psychological distress among family caregivers (regression coefficient, 0.27; P < .001). DISCUSSION: Family caregiver uncertainty was positively associated with psychological distress. This distress can interfere with family caregiver involvement in patient delirium care. These findings are essential to increase critical care nurse awareness and inform the development of nursing interventions to alleviate possible uncertainty and distress.

Punishment Leads to Greater Sensorimotor Learning But Less Movement Variability Compared to Reward.

When a musician practices a new song, hitting a correct note sounds pleasant while striking an incorrect note sounds unpleasant. Such reward and punishment feedback has been shown to differentially influence the ability to learn a new motor skill. Recent work has suggested that punishment leads to greater movement variability, which causes greater exploration and faster learning. To further test this idea, we collected 102 participants over two experiments. Unlike previous work, in Experiment 1 we found that punishment did not lead to faster learning compared to reward (n = 68), but did lead to a greater extent of learning. Surprisingly, we also found evidence to suggest that punishment led to less movement variability, which was related to the extent of learning. We then designed a second experiment that did not involve adaptation, allowing us to further isolate the influence of punishment feedback on movement variability. In Experiment 2, we again found that punishment led to significantly less movement variability compared to reward (n = 34). Collectively our results suggest that punishment feedback leads to less movement variability. Future work should investigate whether punishment feedback leads to a greater knowledge of movement variability and or increases the sensitivity of updating motor actions.

Tibial Spine Fractures in the Child and Adolescent Athlete: A Systematic Review and Meta-analysis.

BACKGROUND: Tibial spine fractures (TSFs) are uncommon injuries that may result in substantial morbidity in children. A variety of open and arthroscopic techniques are used to treat these fractures, but no single standardized operative method has been identified. PURPOSE: To systematically review the literature on pediatric TSFs to determine the current treatment approaches, outcomes, and complications. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A systematic review of the literature was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines using PubMed, Embase, and Cochrane databases. Studies evaluating treatment and outcomes of patients <18 years old were included. Patient demographic characteristics, fracture characteristics, treatments, and outcomes were abstracted. Descriptive statistics were used to summarize categorical and quantitative variables, and a meta-analytic technique was used to compare observational studies with sufficient data. RESULTS: A total of 47 studies were included, totaling 1922 TSFs in patients (66.4% male) with a mean age of 12 years (range, 3-18 years). The operative approach was open reduction and internal fixation in 291 cases and arthroscopic reduction and internal fixation in 1236 cases; screw fixation was used in 411 cases and suture fixation, in 586 cases. A total of 13 nonunions were reported, occurring most frequently in Meyers and McKeever type III fractures (n = 6) and in fractures that were treated nonoperatively (n = 10). Arthrofibrosis rates were reported in 33 studies (n = 1700), and arthrofibrosis was present in 190 patients (11.2%). Range of motion loss occurred significantly more frequently in patients with type III and IV fractures (P < .001), and secondary anterior cruciate ligament (ACL) injury occurred most frequently in patients with type I and II fractures (P = .008). No statistically significant differences were found with regard to rates of nonunion, arthrofibrosis, range of motion loss, laxity, or secondary ACL injury between fixation methods (screw vs suture). CONCLUSION: Despite variation in TSF treatment, good overall outcomes have been reported with low complication rates in both open and arthroscopic treatment and with both screw and suture fixation. Arthrofibrosis remains a concern after surgical treatment for TSF, but no significant difference in incidence was found between the analysis groups. Larger studies are necessary to compare outcomes and form a consensus on how to treat and manage patients with TSFs.

Social determinants of access to timely elective surgery in Ontario, Canada: a cross-sectional population level study.

BACKGROUND: Equitable access to surgical care has clinical and policy implications. We assess the association between social disadvantage and wait times for elective surgical procedures in Ontario. METHODS: We conducted a cross-sectional analysis using administrative data sets of adults receiving nonurgent inguinal hernia repair, cholecystectomy, hip arthroplasty, knee arthroplasty, arthroscopy, benign uterine surgery and cataract surgery from April 2013 to December 2019. We assessed the relation between exceeding target wait times and the highest versus lowest quintile of marginalization dimensions by use of generalized estimating equations logistic regression. RESULTS: Of the 1 385 673 procedures included, 174 633 (12.6%) exceeded the target wait time. Adjusted analysis for cataract surgery found significantly increased odds of exceeding wait times for residential instability (adjusted odd ratio [OR] 1.16, 95% confidence interval [CI] 1.11-1.21) and recent immigration (adjusted OR 1.12, 95% CI 1.07-1.18). The highest deprivation quintile was associated with 18% (adjusted OR 1.18, 95% CI 1.12-1.24) and 20% (adjusted OR 1.20, 95% CI 1.12-1.28) increased odds of exceeding wait times for knee and hip arthroplasty, respectively. Residence in areas where higher proportions of residents self-identify as being part of a visible minority group was independently associated with reduced odds of exceeding target wait times for hip arthroplasty (adjusted OR 0.82, 95% CI 0.75-0.91), cholecystectomy (adjusted OR 0.68, 95% CI 0.59-0.79) and hernia repair (adjusted OR 0.65, 95% CI 0.56-0.77) with an opposite effect in benign uterine surgery (adjusted OR 1.28, 95% CI 1.17-1.40). INTERPRETATION: Social disadvantage had a small and inconsistent impact on receiving care within wait time targets. Future research should consider these differences as they relate to resource distribution and the organization of clinical service delivery.

Future Role of Health Technology Assessment for Genomic Medicine in Oncology: A Canadian Laboratory Perspective.

Genome-based testing in oncology is a rapidly expanding area of health care that is the basis of the emerging area of precision medicine. The efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment, and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

Reinforcement-based processes actively regulate motor exploration along redundant solution manifolds.

From a baby's babbling to a songbird practising a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species' neural firing, gait patterns and reaching behaviour. The past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here, we test a fundamentally different idea-that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments, we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development or when recovering from a neurological disorder to discover and learn new motor actions.

Screening and testing practices for Lynch syndrome in Nova Scotians with endometrial cancer: a descriptive study.

BACKGROUND: Identifying people with Lynch syndrome, a genetic condition predisposing those affected to colorectal, endometrial and other cancers, allows for implementation of risk-reducing strategies for patients and their families. The goal of this study was to describe screening and testing practices for this condition among people with endometrial cancer in Nova Scotia, Canada, and to determine the prevalence of Lynch syndrome in this population. METHODS: All patients diagnosed with endometrial cancer in Nova Scotia between May 1, 2017, and Apr. 30, 2020 were identified through a provincial gynecologic oncology database. Patients from out of province were excluded. We collected age, body mass index, tumour mismatch repair protein immunohistochemistry results, personal and family histories, and germline testing information for all patients. RESULTS: We identified 465 people diagosed with endometrial cancer during the study period. Most were aged 51 years or older, and had obesity and low-grade early-stage endometrioid tumours. Tumour immunohistochemistry testing was performed in 444 cases (95.5%). Based on local criteria, 189 patients were eligible for genetic counselling, of whom 156 (82.5%) were referred to medical genetics. Of the 98 patients who underwent germline testing, 9 (9.2%) were diagnosed with Lynch syndrome. INTERPRETATION: The prevalence of Lynch syndrome was at least 1.9% (9/465) in this population. Our results illustrate successful implementation of universal tumour testing; however, there remains a gap in access to genetic counselling.

Long-term outcome of epileptic dogs treated with implantable vagus nerve stimulators.

BACKGROUND: The long-term effect of implantable vagus nerve stimulators (VNS) on seizures has not been evaluated in epileptic dogs. OBJECTIVES: Report seizure frequency in medication-resistant epileptic dogs before and after VNS implantation. ANIMALS: Twelve client-owned dogs with idiopathic epilepsy and >1 seizure day per 3 weeks despite 3 months of appropriate use of 2 antiseizure medications and seizure diaries maintained 6 months before and >12 months after VNS implantation. METHODS: Uncontrolled, open-label, before and after study. Mean monthly seizures and inter-seizure periods obtained from contemporaneous seizure diaries in the 6 months before implantation were compared with 0 to 6 months, 7 to 12 months, and subsequent 12-month periods after implantation. The number of dogs with >50% decrease in seizure frequency, >3 times increase in inter-ictal period interval, and seizure freedom for >3 months at the time of death or last follow-up were recorded. RESULTS: Five of 12 dogs were euthanized <12 months after implantation. All 7 remaining dogs showed >50% decrease in seizure frequency until last follow-up, starting at a median of 37 to 48 months after implantation (range, 0-6 to 61-72 months) and a >3-fold increase in mean inter-seizure interval starting a median of 25 to 36 months after implantation (range, 0-6 months to 49-60 months), 3/7 dogs were seizure-free at death or last follow-up. CONCLUSIONS AND CLINICAL IMPORTANCE: Monthly seizure frequencies decreased and inter-seizure intervals increased in all dogs 2 to 3 years after VNS implantation, but a high proportion were euthanized before this time point. Prospective clinical trials are required to establish causality and the magnitude of this association.

Curriculum in Neuro-Ophthalmic Principles for National Football League Game Officials: Comparison of Pretraining and Posttraining Ratings of Knowledge.

BACKGROUND: We hypothesize that creation of a structured curriculum in neuro-ophthalmology principles might improve self-rated learner satisfaction and knowledge base of National Football League (NFL) game officials. Our initial objective is to create the said curriculum in coordination with game official experts and staff at the NFL to increase levels of understanding of neuro-ophthalmology principles. We reviewed the prior published literature on applicable neuro-ophthalmic principles in professional sports. Major neuro-ophthalmic principles reviewed include both the efferent (e.g., saccadic and pursuit eye movements and vestibulo-ocular reflex) and afferent (visual field, dynamic visual acuity during body movement, and selective attention deficits). METHODS: A 6-question survey pertaining to levels of understanding, future applicability, relevance, satisfaction, and interest in additional training was then given to 26 individuals before and after a lecture given by Dr. Andrew Lee in Plano, TX. The primary outcome measure was the creation of the curriculum followed by real-world testing for face and content validity and ending with a self-rated assessment. RESULTS: Twenty-one individuals completed the prelecture and postlecture survey out of 26 individuals who attended. Prelecture means for the level of understanding of oculomotor terms and the likelihood of using said terms were 3.4 and 3.2, respectively. Postlecture means were 8.9 and 8.8, respectively. The lecture was rated 9.2 of 10 for relevance to coaching and teaching officials, and individuals rated their interest in further content as 9.4 of 10. CONCLUSIONS: This study found that NFL game officials are interested in learning more about the science behind play-calling in terms of neuro-ophthalmology principles and practices. In addition, from our pilot survey, it is evident that even one lecture can improve participants' level of understanding and likelihood of learning more about neuro-ophthalmic principles.

Microbially Induced Calcium Carbonate Precipitation by Sporosarcina pasteurii: a Case Study in Optimizing Biological CaCO3 Precipitation.

Current production of traditional concrete requires enormous energy investment that accounts for approximately 5 to 8% of the world's annual CO2 production. Biocement is a building material that is already in industrial use and has the potential to rival traditional concrete as a more convenient and more environmentally friendly alternative. Biocement relies on biological structures (enzymes, cells, and/or cellular superstructures) to mineralize and bind particles in aggregate materials (e.g., sand and soil particles). Sporosarcina pasteurii is a workhorse organism for biocementation, but most research to date has focused on S. pasteurii as a building material rather than a biological system. In this review, we synthesize available materials science, microbiology, biochemistry, and cell biology evidence regarding biological CaCO3 precipitation and the role of microbes in microbially induced calcium carbonate precipitation (MICP) with a focus on S. pasteurii. Based on the available information, we provide a model that describes the molecular and cellular processes involved in converting feedstock material (urea and Ca2+) into cement. The model provides a foundational framework that we use to highlight particular targets for researchers as they proceed into optimizing the biology of MICP for biocement production.

Functional Degeneracy in Paracoccus denitrificans Pd1222 Is Coordinated via RamB, Which Links Expression of the Glyoxylate Cycle to Activity of the Ethylmalonyl-CoA Pathway.

Metabolic degeneracy describes the phenomenon that cells can use one substrate through different metabolic routes, while metabolic plasticity, refers to the ability of an organism to dynamically rewire its metabolism in response to changing physiological needs. A prime example for both phenomena is the dynamic switch between two alternative and seemingly degenerate acetyl-CoA assimilation routes in the alphaproteobacterium Paracoccus denitrificans Pd1222: the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). The EMCP and the GC each tightly control the balance between catabolism and anabolism by shifting flux away from the oxidation of acetyl-CoA in the tricarboxylic acid (TCA) cycle toward biomass formation. However, the simultaneous presence of both the EMCP and GC in P. denitrificans Pd1222 raises the question of how this apparent functional degeneracy is globally coordinated during growth. Here, we show that RamB, a transcription factor of the ScfR family, controls expression of the GC in P. denitrificans Pd1222. Combining genetic, molecular biological and biochemical approaches, we identify the binding motif of RamB and demonstrate that CoA-thioester intermediates of the EMCP directly bind to the protein. Overall, our study shows that the EMCP and the GC are metabolically and genetically linked with each other, demonstrating a thus far undescribed bacterial strategy to achieve metabolic plasticity, in which one seemingly degenerate metabolic pathway directly drives expression of the other. IMPORTANCE Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. Understanding the underlying mechanisms of metabolic control in bacteria is of importance for applications in health (e.g., targeting of metabolic pathways with new antibiotics, development of resistances) and biotechnology (e.g., metabolic engineering, introduction of new-to-nature pathways). In this study, we use the alphaproteobacterium P. denitrificans as model organism to study functional degeneracy, a well-known phenomenon of bacteria to use the same carbon source through two different (competing) metabolic routes. We demonstrate that two seemingly degenerate central carbon metabolic pathways are metabolically and genetically linked with each other, which allows the organism to control the switch between them in a coordinated manner during growth. Our study elucidates the molecular basis of metabolic plasticity in central carbon metabolism, which improves our understanding of how bacterial metabolism is able to partition fluxes between anabolism and catabolism.

Preoperative Opioid Prescribers and Lumbar Fusion: Their Effect on Clinical Outcomes and Postoperative Opioid Usage.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the impact of multiple preoperative opioid prescribers on postoperative patient opioid usage and patient-reported outcome measures after single-level lumbar fusion. SUMMARY OF BACKGROUND DATA: Prior literature has identified opioid prescriptions from multiple postoperative providers increase opioid usage rates. However, there is limited evidence on how multiple preoperative opioid prescribers affect postoperative opioid usage or clinical outcomes after a single-level lumbar fusion. PATIENTS AND METHODS: A retrospective review of single-level transforaminal lumbar interbody fusion or posterolateral lumbar fusions between September 2017 and February 2020 at a single academic institution was performed. Patients were excluded if they were not identifiable in our state's prescription drug-monitoring program. Univariate comparisons and regression analyses identified factors associated with postoperative clinical outcomes and opioid usage. RESULTS: Of 239 patients, 160 (66.9%) had one or fewer preoperative prescribers and 79 (33.1%) had >1 prescribers. On regression analysis, the presence of multiple preoperative prescribers was an independent predictor of increased improvement in Visual Analog Scale (∆VAS) Back (ß=-1.61, P =0.012) and the involvement of a nonoperative spine provider was an independent predictor of increased improvement in ∆VAS Leg (ß = -1.53, P = 0.034). Multiple preoperative opioid prescribers correlated with an increase in opioid prescriptions postoperatively (ß = 0.26, P = 0.014), but it did not significantly affect the amount of morphine milligram equivalents prescribed (ß = -48.79, P = 0.146). A greater number of preoperative opioid prescriptions predicted worse improvements in VAS Back, VAS Leg, and Oswestry Disability Index and predicted increased postoperative opioid prescriptions, prescribers, and morphine milligram equivalents. CONCLUSIONS: Multiple preoperative opioid prescribers predicted increased improvement in postoperative back pain, whereas preoperative involvement of a nonoperative spine provider predicted improvements in leg pain after surgery. The number of preoperative opioid prescriptions was a better metric for predicting poor postoperative outcomes and increased opioid consumption compared with the number of preoperative opioid prescribers.