Concurrent Validity and Reliability of Video-Based Approach to Assess Physical Function in Adults With Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to determine the concurrent validity and reliability of the Osteoarthritis Research Society International recommended performance-based tests delivered by video-based in adults with knee osteoarthritis. METHODS: Thirty-two participants (aged 40-70 years; 15 men) undertook assessments of 4 performance-based tests via both video-based (real-time and recorded) and face-to-face approaches, on the same day. Outcome measures were performance-based test and the number of technical issues encountered. The performance-based tests included the 40-Meter Fast-Paced Walk Test (velocity, m/s), the 30-Second Chair Stand Test (number of repetitions), the Stair Climb Test (time, seconds), and the Timed "Up & Go" Test (time, seconds). The Bland-Altman limit of agreement measures, standard error of measurement (SEM), coefficient of variation (CV), minimal detectable changes, and bias (mean difference) were employed to analyze the concurrent validity between video-based and face-to-face approaches of the performance-based tests. Reliability was measured using intraclass correlation coefficients, CV, and SEM. RESULTS: A high degree of concurrent validity for the Timed "Up & Go" Test (bias = -0.22), the 30-Second Chair Stand Test (bias = -0.22), the Stair Climb Test (bias = -0.31), and the 40-Meter Fast-Paced Walk Test (bias = -0.06) was found. SEM and CV values were within the acceptable level for concurrent validity. There was a high degree of reliability demonstrated for all tests analyzed. Intraclass correlation coefficient measures ranged from 0.95 to 1.00 for intrarater reliability, and from 0.95 to 0.99 for interrater reliability. CONCLUSIONS: Video-based assessment of physical performance tests is a valid and reliable tool for measuring physical function among adults with knee osteoarthritis via Microsoft Teams (Microsoft Corp, Redmond, WA, USA). IMPACT: Video-based assessment is a promising public health tool to measure physical function in adults with knee osteoarthritis.

A network analysis of Hurricane Maria-related traumatic stress and substance use among Puerto Rican youth.

Youth exposed to natural disasters are at risk of developing trauma-related symptoms as well as engaging in substance use. Although previous research has established associations between disaster-related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3-12) from across Puerto Rico who completed a needs assessment 5-9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age- and binary gender-related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD-related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R2 = 8.5; friend, R2 = 7.9; or teacher/counselor, R2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed.

Update on vascular control of central chemoreceptors.

At least four mechanisms have been proposed to elucidate how neurons in the retrotrapezoid (RTN) region sense changes in CO2 /H+ to regulate breathing (i.e., function as respiratory chemosensors). These mechanisms include: (1) intrinsic neuronal sensitivity to H+ mediated by TASK-2 and GPR4; (2) paracrine activation of RTN neurons by CO2 -responsive astrocytes (via a purinergic mechanism); (3) enhanced excitatory synaptic input or disinhibition; and (4) CO2 -induced vascular contraction. Although blood flow can influence tissue CO2 /H+ levels, there is limited understanding of how control of vascular tone in central CO2 chemosensitive regions might contribute to respiratory output. In this review, we focus on recent evidence that CO2 /H+ -induced purinergic-dependent vasoconstriction in the ventral parafacial region near RTN neurons supports respiratory chemoreception. This mechanism appears to be unique to the ventral parafacial region and opposite to other brain regions, including medullary chemosensor regions, where CO2 /H+ elicits vasodilatation. We speculate that this mechanism helps to maintain CO2 /H+ levels in the vicinity of RTN neurons, thereby maintaining the drive to breathe. Important next steps include determining whether disruption of CO2 /H+ vascular reactivity contributes to or can be targeted to improve breathing problems in disease states, such as Parkinson's disease.

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

Development and Mechanical Characterization of Short Curauá Fiber-Reinforced PLA Composites Made via Fused Deposition Modeling.

The increase in the use of additive manufacturing (AM) has led to the need for filaments with specific and functional properties in face of requirements of structural parts production. The use of eco-friendly reinforcements (i.e., natural fibers) as an alternative to those more traditional synthetic counterparts is still scarce and requires further investigation. The main objective of this work was to develop short curauá fiber-reinforced polylactic acid (PLA) composites made via fused deposition modeling. Three different fiber lengths (3, 6, and 8 mm), and three concentrations in terms of weight percentage (2, 3.5, and 5 wt.%) were used to fabricate reinforced PLA filaments. Tensile and flexural tests in accordance with their respective American Society for Testing and Materials (ASTM) standards were performed. A thermal analysis was also carried out in order to investigate the thermal stability of the new materials. It was found that the main driving factor for the variation in mechanical properties was the fiber weight fraction. The increase in fiber length did not provide any significant benefit on the mechanical properties of the curauá fiber-reinforced PLA composite printed parts. The composites produced with PLA filaments reinforced by 3 mm 2% curauá fiber presented the overall best mechanical and thermal properties of all studied groups. The curauá fiber-reinforced PLA composites made via fused deposition modeling may be a promising innovation to improve the performance of these materials, which might enable them to serve for new applications.

Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial.

BACKGROUND: Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. METHODS: The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). RESULTS: Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was - 0.12 for MMSE (95% confidence interval [CI] - 0.88 to 0.63; P = 0.75), 0.05 (95% CI - 0.07 to 0.18; P = 0.40) for NTB, - 0.15 (95% CI - 0.30 to 0.01; P = 0.06) for CGNT, and - 0.96 (95% CI - 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. CONCLUSIONS: For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. TRIAL REGISTRATION: Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265 .

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018.

OBJECTIVE: To provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. STUDY DESIGN: We performed a cohort study of 799 016 infants treated in NICUs managed by the Pediatrix Medical Group from 2010 to 2018. We used 3 different methods to report counts of medication: exposure, courses, and days of use. We defined the change in frequency of medication administration by absolute change and relative change. We examined the Food and Drug Administration (FDA) package insert for each medication to determine whether a medication was labeled for use in infants and used PubMed to search for pharmacokinetics (PK) studies. RESULTS: The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants; of the 30 that are not labeled for use in infants, 13 (43%) had at least 2 published PK studies. The medications with the greatest relative increase in use from 2010 to 2018 included dexmedetomidine, clonidine, rocuronium, levetiracetam, atropine, and diazoxide. The medications with the greatest relative decrease in use included tromethamine acetate, pancuronium, chloral hydrate, imipenem + cilastatin, and amikacin. CONCLUSION: Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.

Mortality Risk Factors among Infants Receiving Dialysis in the Neonatal Intensive Care Unit.

OBJECTIVES: To identify risk factors associated with mortality for infants receiving dialysis in the neonatal intensive care unit (NICU). STUDY DESIGN: In this retrospective cohort study, we extracted data from the Pediatrix Clinical Data Warehouse on all infants who received dialysis in the NICU from 1999 to 2018. Using a Cox proportional hazards model with robust SEs we estimated the mortality hazard ratios associated with demographics, birth details, medical complications, and treatment exposures. RESULTS: We identified 273 infants who received dialysis. Median gestational age at birth was 35 weeks (interquartile values 33-37), median birth weight was 2570 g (2000-3084), 8% were small for gestational age, 41% white, and 72% male. Over one-half of the infants (59%) had a kidney anomaly; 71 (26%) infants died before NICU hospital discharge. Factors associated with increased risk of dying after dialysis initiation included lack of kidney anomalies, Black race, gestational age of <32 weeks, necrotizing enterocolitis, dialysis within 7 days of life, and receipt of paralytics or vasopressors (all P < .05). CONCLUSION: In this cohort of infants who received dialysis in the NICU over 2 decades, more than 70% of infants survived. The probability of death was greater among infants without a history of a kidney anomaly and those with risk factors consistent with greater severity of illness at dialysis initiation.

Puerto Ricans and Mexican immigrants differ in their psychological responses to patterns of lifetime adversity.

BACKGROUND: Puerto Ricans and Mexican immigrants are often exposed to multiple types of adversity across their lifetime (e.g., maltreatment, household dysfunction, discrimination) and this exposure can increase the risk for adult mental health problems. PURPOSE: The objective of this study was to (a) identify subgroups of individuals exposed to unique combinations of childhood adversity and lifetime discrimination among Puerto Ricans and Mexican immigrants, and (b) compare the prevalence of mental health problems across different risk profiles. METHOD: We used existing data from the HCHS/SOL Sociocultural Ancillary Study. Participants included Puerto Rican (N = 402) and Mexican adults (N = 1351) born outside but living in the continental U.S. FINDINGS: Through latent profile analysis, we selected a three-profile solution for Puerto Ricans: (a) Low Exposure (low on all adversity items; 58% of sample), (b) Adverse Childhood Experiences (ACEs) Only (high on ACEs items, average or lower than average on discrimination items; 32%), and (c) Dual Exposure (high on all adversity items; 10%). For Mexicans, we selected a four-profile solution: (a) Low Exposure (52%), (b) ACEs Only (24%), (c) Maltreatment and Discrimination (15%), and (d) Dual Exposure (9%). For Mexicans, we found that the Dual Exposure and the Maltreatment and Discrimination profiles had the highest levels of mental health problems. For Puerto Ricans, the Dual Exposure and ACEs Only profiles had the highest levels of mental health problems, suggesting that Puerto Ricans may be more vulnerable to the effects of childhood adversities as compared to Mexican immigrants. Results from our study indicate that different patterns of adversity exposure are linked to different levels of mental health outcomes, and therefore, may require different intervention dosage. Understanding which groups of individuals are at highest and lowest risk for mental health problems is critical for developing effective, tailored interventions to prevent the negative effects of childhood adversity and discrimination for Latinxs.

Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries.

Introduction: Hypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic, some countries have reduced access to supplemental oxygen, whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether variation in the nationally determined oxygen guidelines had any association with national mortality rates in COVID-19. Methods: Three independent investigators searched for, identified, and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied both parametric (Pearson's R) and non-parametric (Kendall's Tau B) tests of bivariate association to determine the relationship between case fatality rate (CFR) and target SpO2, and also between potential confounders and CFR. Results: Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden, and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. A statistically significant correlation was found between SpO2 and CFR both parametrically (R = -0.53, P < 0.01) and non-parametrically (-0.474, P < 0.01). Conclusion: Our study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed. In those nations that pursued a conservative oxygen strategy, there was an association with higher national mortality rates. We discuss the potential reasons for such an association.

High prevalence of sternal foramina in indigenous Bolivians compared to Midwest Americans and indigenous North Americans (sternal foramina in indigenous Bolivians).

The sternal foramen, usually an asymptomatic osteological defect, can lead to catastrophic consequences if not recognized prior to certain medical procedures. This study reports the prevalence of a sternal foramen in two South Amerindian populations compared with other published populations. We evaluated the presence of sternal foramina using thoracic computed tomography scans of 1334 (48% female) participants from two indigenous populations of Bolivia (n = 900 Tsimane, 434 Moseten). The prevalence of sternal foramina was compared to two U.S. populations of similar sex/age distribution (n = 572 Midwest Americans, 131 self-identified Native North Americans) via similar CT scans. A sternal foramen was significantly more common in the two Bolivian populations (prevalence ranging from 12.8 to 13.4%), compared to 4.4-5.1% in the two U.S. groups, consistent with prior estimates in studies from industrialized populations. Males had higher frequency of a sternal foramen compared to females in each of the four groups (OR = 1.904, 95% CI: 1.418-2.568, p < 0.001). Age was not associated with sternal foramen presence. These data show both a higher rate of sternal foramina in the South Amerindian populations versus comparator populations in North America and the highest rate of any studied living population. Although it is not possible to determine from our data the relative contribution of genetics versus early life or environmental causes to the higher rates of sternal foramen, we note that small prior studies have likewise demonstrated a higher prevalence in lower income countries. Further determination of the contributing factors warrants greater investigation and research.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate ß^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. ß^T was compared to the corresponding regression coefficient estimate ß^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis ß T = ß R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

A divide-and-conquer algorithm for quantum state preparation.

Advantages in several fields of research and industry are expected with the rise of quantum computers. However, the computational cost to load classical data in quantum computers can impose restrictions on possible quantum speedups. Known algorithms to create arbitrary quantum states require quantum circuits with depth O(N) to load an N-dimensional vector. Here, we show that it is possible to load an N-dimensional vector with exponential time advantage using a quantum circuit with polylogarithmic depth and entangled information in ancillary qubits. Results show that we can efficiently load data in quantum devices using a divide-and-conquer strategy to exchange computational time for space. We demonstrate a proof of concept on a real quantum device and present two applications for quantum machine learning. We expect that this new loading strategy allows the quantum speedup of tasks that require to load a significant volume of information to quantum devices.

Evaluation of 68Ga-DOTATATE uptake at the pituitary region and the biochemical response to somatostatin analogs in acromegaly.

PURPOSE: Acromegaly is associated with many comorbidities and increased mortality. The first-line treatment is transsphenoidal surgery. However, many patients also need adjuvant drug treatment after surgery. Somatostatin analog (SSA), which suppresses GH secretion by somatotrophs by binding to the SSTR2 receptor, is the first choice. Nevertheless, 50% of patients are partially or totally resistant to SSA, so predictive factors of response are helpful to individualize drug treatment. 68GaDOTATATE PET/CT has emerged as the gold-standard method in the diagnosis and follow-up of gastroenteropancreatic neuroendocrine tumors, which also express SSTR. Our objective was to evaluate whether 68Ga-DOTATATE uptake (SUV max) at the pituitary region of patients on SSA therapy would be useful as a drug response predictor without the need of tumoral tissue. METHODS: Fifteen acromegalics patients on SSA treatment for at least 6 months were underwent to 68Ga-DOTATATE PET/CT at the nuclear medicine service. There was an SSA complete response group (n = 5), defined as GH < 1 µg/L and IFG-1 in the normal range for gender and age, and a group that did not meet these criteria (n = 10). RESULTS: As a result, we did not find out a significantly higher SUV max in the complete response group (p = 0.0576) to SSA. However, we found a significant inverse relationship between postoperative GH values and the SUVmax at the sella turcica (p = 0.0188), probably reflecting tumor SSTR2 expression. CONCLUSION: Thus, after this initial evaluation, 68GaDOTATATE PET/CT should be better studied to assess its usefulness in the follow-up of acromegalic patients.

The retrotrapezoid nucleus and the neuromodulation of breathing.

Breathing is regulated by a host of arousal and sleep-wake state-dependent neuromodulators to maintain respiratory homeostasis. Modulators such as acetylcholine, norepinephrine, histamine, serotonin (5-HT), adenosine triphosphate (ATP), substance P, somatostatin, bombesin, orexin, and leptin can serve complementary or off-setting functions depending on the target cell type and signaling mechanisms engaged. Abnormalities in any of these modulatory mechanisms can destabilize breathing, suggesting that modulatory mechanisms are not overly redundant but rather work in concert to maintain stable respiratory output. The present review focuses on the modulation of a specific cluster of neurons located in the ventral medullary surface, named retrotrapezoid nucleus, that are activated by changes in tissue CO2/H+ and regulate several aspects of breathing, including inspiration and active expiration.

Association between Nephrotoxic Drug Combinations and Acute Kidney Injury in the Neonatal Intensive Care Unit.

OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in infants exposed to nephrotoxic drug combinations admitted to 268 neonatal intensive care units managed by the Pediatrix Medical Group. STUDY DESIGN: We included infants born at 22-36 weeks gestational age, ≤120 days postnatal age, exposed to nephrotoxic drug combinations, with serum creatinine measurements available, and discharged between 2007 and 2016. To identify risk factors associated with a serum creatinine definition of AKI based on the Kidney Disease: Improving Global Outcomes criteria, we performed multivariable logistic and Cox regression adjusting for gestational age, sex, birth weight, postnatal age, race/ethnicity, sepsis, respiratory distress syndrome, baseline serum creatinine, and duration of combination drug exposure. The adjusted odds of AKI were determined relative to gentamicin + indomethacin for the following nephrotoxic drug combinations: chlorothiazide + ibuprofen; chlorothiazide + indomethacin; furosemide + gentamicin; furosemide + ibuprofen; furosemide + tobramycin; ibuprofen + spironolactone; and vancomycin + piperacillin-tazobactam. RESULTS: Among 8286 included infants, 1384 (17%) experienced AKI. On multivariable analysis, sepsis, lower baseline creatinine, and duration of combination therapy were associated with increased odds of AKI. Furosemide + tobramycin and vancomycin + piperacillin-tazobactam were associated with a decreased risk of AKI relative to gentamicin + indomethacin in both the multivariable and Cox regression models. CONCLUSIONS: In this cohort, infants receiving longer durations of nephrotoxic combination therapy had an increased odds of developing AKI.

DNAr: An R Package to Simulate and Analyze CRN and DSD Networks.

Chemical reaction networks (CRNs) have been proposed as an abstraction for molecular computing. DNA strand displacement (DSD) reactions are good candidates to realize this endeavor, since DNA strands can be wired to implement the desired dynamic behavior in a test tube. Specialists use simulators to help them design such chemical systems before experimental implementation. In this sense, we present the DNAr package, an alternative open-source tool, developed in R language, for users from multidisciplinary areas. The current version of our tool offers functions to simulate CRNs, convert a formal CRN into a DSD network, interpret results, export to Visual DSD, and create libraries. Here, we use the consensus CRN to show DNAr features and a neural network model to demonstrate scalability, simulating more than 600 chemical reactions in a few minutes.

Single-Molecule Observations Provide Mechanistic Insights into Bimolecular Knoevenagel Amino Catalysis.

While single-molecule (SM) methods have provided new insights to various catalytic processes, bimolecular reactions have been particularly challenging to study. Here, the fluorogenic Knoevenagel condensation of an aromatic aldehyde with methyl cyanoacetate promoted by surface-immobilized piperazine is quantitatively characterized using super-resolution fluorescence imaging and stochastic analysis using hidden Markov modeling (HMM). Notably, the SM results suggest that the reaction follows the iminium intermediate pathway before the formation of a fluorescent product with intramolecular charge-transfer character. Moreover, the overall process is limited by the turnover rate of the catalyst, which is involved in multiple steps along the reaction coordinate.