Paper-Based Bi-Material Cantilever Actuator Bending Behavior and Modeling.

In this paper, the behavior of the Bi-Material Cantilever (B-MaC) response deflection upon fluidic loading was experimentally studied and modeled for bilayer strips. A B-MaC consists of a strip of paper adhered to a strip of tape. When fluid is introduced, the paper expands while the tape does not, which causes the structure to bend due to strain mismatch, similar to the thermal loading of bi-metal thermostats. The main novelty of the paper-based bilayer cantilevers is the mechanical properties of two different types of material layers, a top layer of sensing paper and a bottom layer of actuating tape, to create a structure that can respond to moisture changes. When the sensing layer absorbs moisture, it causes the bilayer cantilever to bend or curl due to the differential swelling between the two layers. The portion of the paper strip that gets wet forms an arc, and as the fluid advances and fully wets the B-MaC, the entire B-MaC assumes the shape of the initial arc. This study showed that paper with higher hygroscopic expansion forms an arc with a smaller radius of curvature, whereas thicker tape with a higher Young's modulus forms an arc with a larger radius of curvature. The results showed that the theoretical modeling could accurately predict the behavior of the bilayer strips. The significance of paper-based bilayer cantilevers lies in their potential applications in various fields, such as biomedicine, and environmental monitoring. In summary, the novelty and significance of paper-based bilayer cantilevers lie in their unique combination of sensing and actuating capabilities using a low-cost and environmentally friendly material.

Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning.

Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to HIV viral heterogeneity as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. However, it is too time-consuming and costly to determine the effect of the variants for all double mutant alleles through experiments. Therefore, we propose a combined GigaAssay/deep learning approach. As a first step to determine activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieved a 0.94 Pearson correlation coefficient when comparing the predicted to experimental activities. This hybrid approach can be extensible to more complex Tat alleles for a better understanding of the genetic control of HIV genome transcription.

Impact of Prediabetes on Cardiac Function Among Primary Care Patients.

Background: Prediabetes is a novel risk factor recently associated with changes in the left ventricle. Our aim is to determine if prediabetes is associated with heart failure (HF) and structural heart disease. Methods: We conducted a cross-sectional study and performed screening echocardiograms to consecutive primary care patients. We calculated the hemoglobin A1c (HbA1c) within 3 months of the echocardiogram and classified patients as having normal glucose, low-risk or high-risk prediabetes or diabetes. Our primary outcome was HF defined as an ejection fraction (EF) <50% and HF with preserved EF. Our secondary outcome was structural heart disease defined as having either a large atrium, left ventricular hypertrophy, or low EF. Results: We included 15,056 patients who underwent a screening echocardiogram and had a recorded HbA1c. Only 2794 patients had a normal blood glucose, 4201 had low-risk prediabetes, 2499 had high-risk prediabetes, and the remainder had diabetes. The adjusted odds ratio (ORs) of HF for low-risk prediabetes, high-risk prediabetes and diabetes were 1.38 [confidence interval (95% CI) 1.07-1.78] (P = 0.01), 1.47 (95% CI 1.05-2.01) (P = 0.01), and 1.60 (95% CI 1.16-2.01) (P < 0.01), respectively, when compared with normoglycemic patients. The adjusted OR of HF with preserved EF for low- and high-risk prediabetes and diabetes were 1.17 (95% CI 0.86-1.60) (P = 0.30), 1.60 (95% CI 1.15-2.21) (P < 0.01), and 1.63 (95% CI 1.24-2.13) (P < 0.01), respectively, when compared with normoglycemic patients. Conclusions: Prediabetes is a prevalent condition associated with structural heart disease and HF.

LITTLE MEMORY EDITORS LIVING INSIDE YOUR BRAIN.

We interact with the world continuously. However, memories of our experiences are stored as individual events. For example, when we go on a road trip, we do not remember what happens second by second. Instead, we remember only a few special moments or events from a trip, such as dancing around the campfire. Our brains constantly extract memorable events while we interact with the world, and we organize those events based on their relevance. This process is like grouping road trip photos under different folders on the computer, so we can efficiently and accurately retrieve those memories in the future. How does the brain create these memorable events? In this article, you will learn about two groups of neurons inside the brain that help achieve this remarkable feat. You will also learn about how the activation of these neurons shapes the formation and retrieval of memories.

3D Printed Patient-Specific Complex Hip Arthroplasty Models Streamline the Preoperative Surgical Workflow: A Pilot Study.

Introduction: Surgical planning for complex total hip arthroplasty (THA) often presents a challenge. Definitive plans can be difficult to decide upon, requiring unnecessary equipment to be ordered and a long theatre list booked. We present a pilot study utilising patient-specific 3D printed models as a method of streamlining the pre-operative planning process. Methods: Complex patients presenting for THA were referred to the research team. Patient-specific 3D models were created from routine Computed Tomography (CT) imaging. Simulated surgery was performed to guide prosthesis selection, sizing and the surgical plan. Results: Seven patients were referred for this pilot study, presenting with complex conditions with atypical anatomy. Surgical plans provided by the 3D models were more detailed and accurate when compared to 2D CT and X ray imaging. Streamlined equipment selection was of great benefit, with augments avoided post simulation in three cases. The ability to tackle complex surgical problems outside of the operating theatre also flagged potential complications, while also providing teaching opportunities in a low risk environment. Conclusion: This study demonstrated that 3D printed models can improve the surgical plan and streamline operative logistics. Further studies investigating the optimal 3D printing material and workflow, along with cost-benefit analyses are required before this process is ready for routine use.

Erratum to "Prior cardiovascular risk and screening echocardiograms predict hospitalization and severity of coronavirus infection among elderly Medicare patients" [American Journal of Preventive Cardiology 3C (2020) 100090].

[This corrects the article DOI: 10.1016/j.ajpc.2020.100090.].

Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA.

BACKGROUND AND AIMS: Metformin has antiviral and anti-inflammatory effects and several cohort studies have shown that metformin lower mortality in the COVID population in a majority white population. There is no data documenting the effect of metformin taken as an outpatient on COVID-19 related hospitalizations. Our aim was to evaluate if metformin decreases hospitalization and severe COVID-19 among minority Medicare patients who acquired the SARS-CoV2 virus. METHODS: We conducted a retrospective cohort study including elderly minority Medicare COVID-19 patients across eight states. We collected data from the inpatient and outpatient electronic health records, demographic data, as well as clinical and echocardiographic data. We classified those using metformin as those patients who had a pharmacy claim for metformin and non-metformin users as those who were diabetics and did not use metformin as well as non-diabetic patients. Our primary outcome was hospitalization. Our secondary outcomes were mortality and acute respiratory distress syndrome (ARDS). RESULTS: We identified 1139 COVID-19 positive patients of whom 392 were metformin users. Metformin users had a higher comorbidity score than non-metformin users (p < 0.01). The adjusted relative hazard (RH) of those hospitalized for metformin users was 0.71; 95% CI 0.52-0.86. The RH of death for metformin users was 0.34; 95% CI 0.19-0.59. The RH of ARDS for metformin users was 0.32; 95% CI 0.22-0.45. Metformin users on 1000 mg daily had lower mortality, but similar hospitalization and ARDS rates when compared to those on 500-850 mg of metformin daily. CONCLUSIONS: Metformin is associated with lower hospitalization, mortality and ARDS among a minority COVID-19 population. Future randomized trials should confirm this finding and evaluate for a causative effect of the drug preventing disease.

Teaching Radial Endobronchial Ultrasound with a Three-Dimensional-printed Radial Ultrasound Model.

BACKGROUND: Peripheral pulmonary lesion (PPL) incidence is rising because of increased chest imaging sensitivity and frequency. For PPLs suspicious for lung cancer, current clinical guidelines recommend tissue diagnosis. Radial endobronchial ultrasound (R-EBUS) is a bronchoscopic technique used for this purpose. It has been observed that diagnostic yield is impacted by the ability to accurately manipulate the radial probe. However, such skills can be acquired, in part, from simulation training. Three-dimensional (3D) printing has been used to produce training simulators for standard bronchoscopy but has not been specifically used to develop similar tools for R-EBUS. OBJECTIVE: We report the development of a novel ultrasound-compatible, anatomically accurate 3D-printed R-EBUS simulator and evaluation of its utility as a training tool. METHODS: Computed tomography images were used to develop 3D-printed airway models with ultrasound-compatible PPLs of "low" and "high" technical difficulty. Twenty-one participants were allocated to two groups matched for prior R-EBUS experience. The intervention group received 15 minutes to pretrain R-EBUS using a 3D-printed model, whereas the nonintervention group did not. Both groups then performed R-EBUS on 3D-printed models and were evaluated using a specifically developed assessment tool. RESULTS: For the "low-difficulty" model, the intervention group achieved a higher score (21.5 ± 2.02) than the nonintervention group (17.1 ± 5.7), reflecting 26% improvement in performance (P = 0.03). For the "high-difficulty" model, the intervention group scored 20.2 ± 4.21 versus 13.3 ± 7.36, corresponding to 52% improvement in performance (P = 0.02). Participants derived benefit from pretraining with the 3D-printed model, regardless of prior experience level. CONCLUSION: 3D-printing can be used to develop simulators for R-EBUS education. Training using these models significantly improves procedural performance and is effective in both novice and experienced trainees.

Prior cardiovascular risk and screening echocardiograms predict hospitalization and severity of coronavirus infection among elderly medicare patients.

BACKGROUND: The COVID-19 pandemic has disproportionally impacted the elderly. In the United States and Europe the mortality rate of elderly patients with COVID-19 is greater than 30%. Our aim is to determine predictors of COVID-19 related hospitalization and severity of disease among elderly Medicare patients in the United States. METHODS: We conducted a retrospective cohort study including elderly Medicare COVID-19 patients across eight states. We collected data from the inpatient and outpatient electronic health record, demographic, clinical and echocardiographic predictors. Our primary outcomes were hospitalization and adult respiratory distress syndrome (ARDS). Our secondary outcome was mortality. RESULTS: We identified 400 COVID-19 positive patients (incidence 5.2; (95% CI 4.7-5.7) per 1000 patients). The mean age of our patients was 72 â€‹± â€‹8, 60% were female, 82% were minorities and had a mean Charlson score of 2.9 â€‹± â€‹1.4. Two-hundred and forty-four patients were hospitalized due to COVID-19 (63%) and the mortality rate was 18%; 95% CI 14-22 with 1 patient still in the hospital. Age, socioeconomic status, Charlson score, systolic blood pressure, body mass index, grade 2 or 3 diastolic dysfunction, moderate or severe left ventricular hypertrophy were significant predictors of hospitalization and ARDS (p â€‹< â€‹0.05). CONCLUSIONS: Our study reports a lower incidence on a COVID-19 cohort than previously reported. Predictors of poor outcomes included socio-economic, cardiovascular risk and echocardiographic measures. High touch care with early cardiovascular risk factor modification could explain the low risk of events in our population.

Patients with elevated blood pressure or stage 1 hypertension have structural heart disease.

BACKGROUND: The 2017 American College of Cardiology (ACC) and the American Heart Association (AHA) recommendations lower the hypertension threshold to 130/80 mmHg and recommends treatment for high-risk patients. Our aim is to determine whether the new blood pressure categories are associated with left ventricular (LV) structural changes and whether echocardiograms can provide risk stratification and help treatment initiation. METHODS: We conducted a cross-sectional study and performed screening echocardiograms to consecutive primary care patients. We calculated the Framingham score to identify patients with a low or intermediate score who had structural heart disease.We classified everyone as having normal, elevated blood pressure, stage 1 or stage 2 hypertension according to the 2017 ACC/AHA guidelines. We defined structural heart disease as having LV hypertrophy and an abnormal LV mass index. RESULTS: We included 16 650 patients who underwent a screening echocardiogram and had recorded blood pressure. Out of the 16 650 patients, 1465 patients had a normal blood pressure, 1382 had elevated blood pressure, 1333 had stage 1 hypertension, and the remainder had stage 2 hypertension. The adjusted odds ratios of having structural heart disease for elevated blood pressure and stage 1 hypertension were 1.30; 95% CI, 1.112-1.64; P < 0.01 and 1.69; 95% CI, 1.25-2.30; P < 0.01, respectively. We identified 542 patients with stage 1 hypertension who had a low or intermediate Framingham score and 19% (95% CI, 16-23%) had structural heart disease. CONCLUSION: A quarter of patients identified as having elevated blood pressure or stage 1 hypertension have structural heart disease. Screening echocardiograms may help to risk stratify those patients deemed ineligible for treatment.

Three-dimensional printing in orthopaedic preoperative planning improves intraoperative metrics: a systematic review.

BACKGROUND: Three-dimensional (3D) printing has seen increasing interest in surgery, where it improves the visualization of difficult anatomy in complex cases. This literature review investigates the benefits and limitations of 3D printed models in preoperative planning in the field of orthopaedic surgery. METHODS: A literature search was performed using the Ovid platform on the Embase and MEDLINE databases using the terms '3D printing', 'Orthopaedics' and 'Surgical Planning'. Studies using 3D printed models as a part of preoperative planning were included. All others were excluded. Data regarding the metrics used to assess the benefit of the use of 3D models, surgical outcome, and surgeon or patient opinion on the technology were extracted. RESULTS: A total of 41 studies resulted. Eight (19.5%) were case-control studies, the remainder were case reports or case series. Assessment of benefit was mostly subjective, although the case-control studies included objective metrics such as operation time, intraoperative blood loss and intraoperative fluoroscopy time. The use of 3D printing technology showed subjective benefit for both patient and surgeon as well as indicating clinically significant improvements in intraoperative metrics. CONCLUSION: Despite the current absence of large scale trials, 3D printing has clear benefits in preoperative planning, particularly when utilized in complex cases. A streamlined workflow for case selection, in-house model creation and preoperative rehearsals is still required to be developed before the process is ready for routine use. Evidence supports an improvement in intraoperative metrics and patient engagement but data to support improved clinical outcome is lacking.

The additive role of echocardiography in the screening for sudden death.

BACKGROUND: A clinically based sudden cardiac death (SCD) risk score has predictive value. Echocardiographic parameters predict SCD. Our aim was to evaluate the effect of adding echocardiographic parameters to the clinical SCD risk score for the prediction of all-cause mortality. METHODS: We conducted a retrospective cohort of screening echocardiograms performed on primary care patients. We calculated the SCD risk score and added the left ventricular (LV) mass index, LV hypertrophy, diastolic dysfunction, and LV ejection fraction (EF). We calculated the c-statistic, net reclassification index (NRI), and Hosmer-Lemeshow chi-square for the SCD score alone or combined with each echocardiographic parameter in predicting all-cause mortality. RESULTS: We included 6447 primary care patients who underwent a screening echocardiogram and had a SCD score. The c-statistic of the SCD score for mortality was 0.61; 95% CI 0.58-0.62 and the c-statistic for the score combined with LV mass index increased to 0.64; 95% CI 0.63-0.65 and for the score combined with LVEF, the c-statistic was 0.64;95% CI 0.63-0.67. When diastolic dysfunction and LV hypertrophy were added to the SCD score, the c-statistic did not significantly change (P > 0.05). The NRI for the addition of LV mass index and LVEF was 0.52 ± 0.02, and the Hosmer-Lemeshow statistic was nonsignificant (P > 0.05). CONCLUSIONS: Adding LV mass index or LVEF to the SCD risk score improves the ability to predict mortality, but in the primary care setting, the improvement is small and underscores the challenge of SCD prediction and prevention in the community.

High-touch care leads to better outcomes and lower costs in a senior population.

OBJECTIVES: There are several models of primary care. A form of high-intensity care is a high-touch model that uses a high frequency of encounters to deliver preventive services. The aim of this study is to compare the healthcare utilization of patients receiving 2 models of primary care, ​1 with high-touch care and 1 without. STUDY DESIGN: Retrospective cohort study. METHODS: We conducted a retrospective cohort study of 2 models of care used among Medicare Advantage populations. Model 1 is a high-touch care model, and model 2 is a standard care model. Compared with model 2, model 1 has smaller panel sizes and a higher frequency of encounters. We compared patients' healthcare utilization and hospitalizations between both models using a propensity score-matched analysis, matching by Charlson Comorbidity Index (CCI) score, age, and gender. RESULTS: We included 17,711 unmatched Medicare Advantage primary care patients and matched 5695 patients from both models of care. CCI scores, age, and gender were similar between both matched groups (P >.05). The median total per member per month healthcare costs in model 1 were $87 (95% CI, $26-$278) compared with $121 (95% CI, $52-$284) in model 2 (P <.01). The mean number of hospital admissions was lower in model 1 (0.10 ± 0.40) compared with model 2 (0.20 ± 0.58). The number of primary care physician visits and preventive medication use were higher in model 1 (P <.05 for both). CONCLUSIONS: In a propensity-matched sample of Medicare Advantage patients, those receiving high-touch care had lower healthcare costs and fewer hospitalizations. Potential explanations are higher preventive medication use and more frequent visits.

A screening echocardiogram to identify diastolic dysfunction leads to better outcomes.

BACKGROUND: Diastolic dysfunction (DD) can lead to heart failure and higher mortality. Echocardiograms can detect DD but are not indicated for screening in older adults. Our aim was to evaluate the prevalence of DD and the impact of identifying it in seniors. METHODS: We performed screening echocardiograms in 5227 consecutive patients between January 2014 and March 2015 in 36 senior-focused value-based clinics across six states. We determined the presence of the grade of DD and defined stage B grade II/III (asymptomatic) and of stage C grade II/III (symptomatic) DD by the presence or absence of typical HF symptoms. We obtained prescribed medications from the electronic health record to determine absolute changes in HF therapy before and after the echocardiogram. RESULTS: We included a group with no DD (n=649), a group with grade 1 DD (n=2875), and those with grades 2 and 3 (n=1357) who had normal ejection fraction. The prevalence of grade 2 or 3 DD with preserved ejection fraction was 25%; 95% CI: 24-26. The absolute change of ace-inhibitor use before and after the echocardiogram increased by 14, 19, 23, 27 in patients without DD, those with grade 1, grade 2 or 3 asymptomatic and grade 2 or 3 symptomatic, respectively. The use of ß-blocker, statin, and diuretic had similar trends. CONCLUSIONS: Seniors without previously known stage B or stage C heart failure have moderate-to-severe DD, 27% of whom were stage C. Identifying seniors with DD leads to improvement in care.

Screening echocardiograms in a senior focused value based primary care improves systolic heart failure detection and clinical management.

BACKGROUND: Screening echocardiograms are not indicated. Our aim is to evaluate the impact of screening echocardiograms on improving clinical management among older adults. METHODS: We performed screening echocardiograms for all consecutive patients and defined incident systolic heart failure (HF) as an ejection fraction of less than 50% among patients without a previous HF diagnosis. We reviewed medical record data to determine if the new cases where Stage B or C. We obtained prescribed medications and vital signs from the electronic health record to determine absolute changes before and after the echocardiogram. RESULTS: We performed an echocardiogram in 6,417 patients with a mean age of 71.4±6. The echocardiogram identified 292 seniors with new cases of systolic HF (5.34%; 95% CI: 4.7-5.9) and 239 were stage B HF. The increase in the use of ace-inhibitor, beta blocker when comparing the pre and post echocardiogram periods was highest in those with Stage C and those with ejection fraction lower than 40%. Systolic blood pressure (SBP) decreased from 140±19 to 136±15 (P<0.01) and low density lipoprotein (LDL) from 105±36 to 97±33 (P<0.01). CONCLUSIONS: Performing echocardiograms in senior-focused value-based primary care improves evidence-based cardiovascular treatment and short-term clinical outcomes, including lowering SBP and LDL.

Cardiac performance, biomarkers and gene expression studies in previously sedentary men participating in half-marathon training.

BACKGROUND: The mechanisms through which exercise reduces cardiovascular disease are not fully understood. We used echocardiograms, cardiac biomarkers and gene expression to investigate cardiovascular effects associated with exercise training. METHODS: Nineteen sedentary men (22-37 years) completed a 17-week half-marathon training program. Serial measurements of resting heart rate, blood pressure, maximum oxygen consumption, lipids, C-reactive protein, cardiac troponin T, echocardiograms and blood for gene expression were obtained from baseline to peak training. Controls included 22 sedentary men who did not exercise. RESULTS: Among the training group, VO2 max increased from 37.1 to 42.0 ml/kg/min (p < 0.001). Significant changes were seen in left ventricular wall thickness and mass, stroke volume, resting heart rate and blood pressure (p < 0.001). The control group demonstrated no significant changes. Expression profiling in the training group identified 10 significantly over-expressed and 53 significantly under-expressed loci involved in inflammatory pathways. Dividing the training group into high and low responders based on percent change in VO2 max identified loci that differentiated these two groups at baseline and after training. CONCLUSION: Intensive exercise training leads to significant increase in cardiac and hemodynamic performance, and significant changes in expression of genes involved in immune and inflammatory response.

Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1.

MEKK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the MAPK JNK and is required for microtubule inhibitor-induced apoptosis in B cells. Here, we find that apoptosis induced by actin disruption via cytochalasin D and by the protein phosphatase 1/2A inhibitor okadaic acid also requires MEKK1 activation. To elucidate the functional requirements for activation of the MEKK1-dependent apoptotic pathway, we created mutations within MEKK1. MEKK1-deficient cells were complemented with MEKK1 containing mutations in either the ubiquitin interacting motif (UIM), plant homeodomain (PHD), caspase cleavage site or the kinase domain at near endogenous levels of expression and tested for their sensitivity to each drug. We found that both the kinase activity and the PHD domain of MEKK1 are required for JNK activation and efficient induction of apoptosis by drugs causing cytoskeletal disruption. Furthermore, we discovered that modification of MEKK1 and its localization depends on the integrity of the PHD.

Journey in antithrombotic strategies for ST-elevation myocardial infarction.

Our understanding and treatment of the ST-elevation myocardial infarction (STEMI) has led to a tremendous improvement in the care and preservation of life affecting millions yearly. As the medical community continues to discover novel strategies in therapeutics and innovations in prevention, it is imperative to understand the scientific journey the treatment of STEMI has traveled. Furthermore, the research pillars that led to our understanding of the current paradigm of STEMI will be highlighted in an effort to illuminate the foundation on which we now stand.