NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer.

Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.

Organoid models of human and mouse ductal pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.

Cholesterol in the cargo membrane amplifies tau inhibition of kinesin-1-based transport.

Intracellular cargos are often membrane-enclosed and transported by microtubule-based motors in the presence of microtubule-associated proteins (MAPs). Whereas increasing evidence reveals how MAPs impact the interactions between motors and microtubules, critical questions remain about the impact of the cargo membrane on transport. Here we combined in vitro optical trapping with theoretical approaches to determine the effect of a lipid cargo membrane on kinesin-based transport in the presence of MAP tau. Our results demonstrate that attaching kinesin to a fluid lipid membrane reduces the inhibitory effect of tau on kinesin. Moreover, adding cholesterol, which reduces kinesin diffusion in the cargo membrane, amplifies the inhibitory effect of tau on kinesin binding in a dosage-dependent manner. We propose that reduction of kinesin diffusion in the cargo membrane underlies the effect of cholesterol on kinesin binding in the presence of tau, and we provide a simple model for this proposed mechanism. Our study establishes a direct link between cargo membrane cholesterol and MAP-based regulation of kinesin-1. The cholesterol effects uncovered here may more broadly extend to other lipid alterations that impact motor diffusion in the cargo membrane, including those associated with aging and neurological diseases.

The EICAT+ framework enables classification of positive impacts of alien taxa on native biodiversity.

Species introduced through human-related activities beyond their native range, termed alien species, have various impacts worldwide. The IUCN Environmental Impact Classification for Alien Taxa (EICAT) is a global standard to assess negative impacts of alien species on native biodiversity. Alien species can also positively affect biodiversity (for instance, through food and habitat provisioning or dispersal facilitation) but there is currently no standardized and evidence-based system to classify positive impacts. We fill this gap by proposing EICAT+, which uses 5 semiquantitative scenarios to categorize the magnitude of positive impacts, and describes underlying mechanisms. EICAT+ can be applied to all alien taxa at different spatial and organizational scales. The application of EICAT+ expands our understanding of the consequences of biological invasions and can inform conservation decisions.

Considerations for developing and implementing a safe list for alien taxa.

Many species have been intentionally introduced to new regions for their benefits. Some of these alien species cause damage, others do not (or at least have not yet). There are several approaches to address this problem: prohibit taxa that will cause damage, try to limit damages while preserving benefits, or promote taxa that are safe. In the present article, we unpack the safe list approach, which we define as "a list of taxa alien to the region of interest that are considered of sufficiently low risk of invasion and impact that the taxa can be widely used without concerns of negative impacts." We discuss the potential use of safe lists in the management of biological invasions; disentangle aspects related to the purpose, development, implementation, and impact of safe lists; and provide guidance for those considering to develop and implement such lists.

Food and Nutrition Insecurity: Experiences That Differ for Some and Independently Predict Diet-Related Disease, Los Angeles County, 2022.

BACKGROUND: National surveillance shows that food insecurity affects ≥1 in 10 Americans each year. Recently, experts have advocated for surveillance of nutrition and food insecurity. Nutrition security refers to the nutritional adequacy of accessible food and factors that impact one's ability to meet food preferences. OBJECTIVES: This study presents representative estimates of food insecurity and nutrition insecurity for Los Angeles County, CA, United States; compares predictors of these constructs; and examines whether they independently predict diet-related health outcomes. METHODS: In December 2022, a representative sample of Los Angeles County adults participating in the Understanding America Study (N = 1071) was surveyed about household food insecurity and nutrition insecurity over the past 12 mo. Data were analyzed in 2023. RESULTS: Reported rates were similar for food insecurity (24%) and nutrition insecurity (25%), but the overlap of these subgroups was <60%. Logistic regression models indicated that non-Hispanic Asian individuals had higher odds of nutrition insecurity but not food insecurity. Moreover, nutrition insecurity was a stronger predictor of diabetes compared with food insecurity, and both constructs independently predicted poor mental health. CONCLUSIONS: Food and nutrition insecurity affect somewhat different populations. Both constructs are valuable predictors of diet-related health outcomes. Monitoring nutrition insecurity in addition to food insecurity can provide new information about populations with barriers to healthy diets.

Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy.

The stimulator of interferon genes (STING) cellular signaling pathway is a promising target for cancer immunotherapy. Activation of the intracellular STING protein triggers the production of a multifaceted array of immunostimulatory molecules, which, in the proper context, can drive dendritic cell maturation, antitumor macrophage polarization, T cell priming and activation, natural killer cell activation, vascular reprogramming, and/or cancer cell death, resulting in immune-mediated tumor elimination and generation of antitumor immune memory. Accordingly, there is a significant amount of ongoing preclinical and clinical research toward further understanding the role of the STING pathway in cancer immune surveillance as well as the development of modulators of the pathway as a strategy to stimulate antitumor immunity. Yet, the efficacy of STING pathway agonists is limited by many drug delivery and pharmacological challenges. Depending on the class of STING agonist and the desired administration route, these may include poor drug stability, immunocellular toxicity, immune-related adverse events, limited tumor or lymph node targeting and/or retention, low cellular uptake and intracellular delivery, and a complex dependence on the magnitude and kinetics of STING signaling. This review provides a concise summary of the STING pathway, highlighting recent biological developments, immunological consequences, and implications for drug delivery. This review also offers a critical analysis of an expanding arsenal of chemical strategies that are being employed to enhance the efficacy, safety, and/or clinical utility of STING pathway agonists and lastly draws attention to several opportunities for therapeutic advancements.

Integrated Advanced Molecular Tools Predict In Situ cVOC Degradation Rates: Field Demonstration.

Chlorinated volatile organic compound (cVOC) degradation rate constants are crucial information for site management. Conventional approaches generate rate estimates from the monitoring and modeling of cVOC concentrations. This requires time series data collected along the flow path of the plume. The estimates of rate constants are often plagued by confounding issues, making predictions cumbersome and unreliable. Laboratory data suggest that targeted quantitative analysis of Dehalococcoides mccartyi (Dhc) biomarker genes (qPCR) and proteins (qProt) can be directly correlated with reductive dechlorination activity. To assess the potential of qPCR and qProt measurements to predict rates, we collected data from cVOC-contaminated aquifers. At the benchmark study site, the rate constant for degradation of cis-dichloroethene (cDCE) extracted from monitoring data was 11.0 ± 3.4 yr-1, and the rate constant predicted from the abundance of TceA peptides was 6.9 yr-1. The rate constant for degradation of vinyl chloride (VC) from monitoring data was 8.4 ± 5.7 yr-1, and the rate constant predicted from the abundance of TceA peptides was 5.2 yr-1. At the other study sites, the rate constants for cDCE degradation predicted from qPCR and qProt measurements agreed within a factor of 4. Under the right circumstances, qPCR and qProt measurements can be useful to rapidly predict rates of cDCE and VC biodegradation, providing a major advance in effective site management.

Socio-ecological factors linked with changes in adults' dietary intake in Los Angeles County during the peak of the coronavirus 2019 pandemic.

OBJECTIVE: Comprehensive studies examining longitudinal predictors of dietary change during the coronavirus disease 2019 pandemic are lacking. Based on an ecological framework, this study used longitudinal data to test if individual, social and environmental factors predicted change in dietary intake during the peak of the coronavirus 2019 pandemic in Los Angeles County and examined interactions among the multilevel predictors. DESIGN: We analysed two survey waves (e.g. baseline and follow-up) of the Understanding America Study, administered online to the same participants 3 months apart. The surveys assessed dietary intake and individual, social, and neighbourhood factors potentially associated with diet. Lagged multilevel regression models were used to predict change from baseline to follow-up in daily servings of fruits, vegetables and sugar-sweetened beverages. SETTING: Data were collected in October 2020 and January 2021, during the peak of the coronavirus disease 2019 pandemic in Los Angeles County. PARTICIPANTS: 903 adults representative of Los Angeles County households. RESULTS: Individuals who had depression and less education or who identified as non-Hispanic Black or Hispanic reported unhealthy dietary changes over the study period. Individuals with smaller social networks, especially low-income individuals with smaller networks, also reported unhealthy dietary changes. After accounting for individual and social factors, neighbourhood factors were generally not associated with dietary change. CONCLUSIONS: Given poor diets are a leading cause of death in the USA, addressing ecological risk factors that put some segments of the community at risk for unhealthy dietary changes during a crisis should be a priority for health interventions and policy.

Psychosocial impacts of being nil-by-mouth as an adult: A scoping review.

AIM: To map existing evidence and identify gaps in the literature concerning psychosocial impacts of being nil by mouth (NBM) as an adult. DESIGN: A scoping review of the literature was undertaken using JBI guidance. A protocol was registered on the Open Science Framework (osf.io/43g9y). Reporting was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). METHODS: A comprehensive search of six databases (CINAHL, Embase, MEDLINE, PsycINFO, SCOPUS and Web of Science) was performed for studies published up to February 2023, with no restriction to study type. A scope of the grey literature was also undertaken. Two authors independently assessed eligibility and extracted data. Descriptive statistical analysis and narrative synthesis were used, and patient and public involvement included in funding discussions. RESULTS: A total of 23 papers were included in the review, consisting of 14 primary studies (7 qualitative and 7 quantitative) and 9 grey literature. Both global psychological distress and distress specific to being NBM (thirst, missing food and drink) were reported. Caregivers also experience distress from their family member being NBM. Furthermore, social impacts were reported for both patient and caregiver, primarily social isolation and subsequent low mood. CONCLUSION: Furthermore, research is needed to understand the prevalence of this population, how best to measure psychosocial impacts and to explore whether (and how) psychosocial impacts change over time. Advancement in this area would enable better service development to optimize care for this patient group. WHAT IS KNOWN ABOUT THIS TOPIC?: Eating and drinking provides more than nutrition and hydration. A wide range of conditions can lead to recommendations for no longer eating and drinking (nil by mouth). Being nil by mouth (NBM) for short periods such as pre-operative fasting causes distress; however, little is understood about impact on longer-term abstinence from eating and drinking. WHAT THIS PAPER ADDS?: Psychosocial consequences of being nil by mouth (NBM)have been investigated by both quantitative and qualitative studies. Being NBM impacts both patients and caregivers in various psychosocial aspects, including distress and social isolation. Several gaps remain, however, regarding ways to measure psychosocial impact of being NBM.

Revision reverse shoulder arthroplasty for the management of baseplate failure: an analysis of 676 revision reverse shoulder arthroplasty procedures.

BACKGROUND: Baseplate failure in reverse shoulder arthroplasty (RSA) is a rare but potentially catastrophic complication owing to poor patient outcomes and significant glenoid bone loss. The purpose of this study was to report on the prevalence, causes, and outcomes of revision RSA (rRSA) for baseplate failure or loosening. METHODS: A retrospective review of our institutional database was performed to identify all patients treated for a failed RSA from 2006 to 2021 who required revision to another RSA (rRSA) performed by a single surgeon. A total of 676 failed RSA procedures were identified, and further analysis identified 46 patients (6.8%) who underwent rRSA for baseplate failure with a confirmed loose baseplate at the time of rRSA. The primary outcome was repeated failure of the reimplanted baseplate following rRSA. The mode of failure associated with baseplate failure was stratified into 1 of 3 groups: aseptic, septic, or traumatic. Twenty-four patients underwent primary revision, and 22 had undergone >1 previous arthroplasty prior to undergoing re-revision. Five patients underwent previous rRSA for baseplate failure performed by an outside surgeon. The criteria for secondary outcome analysis of final American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, and range of motion were met by 32 patients and 23 patients at 1- and 2-year follow-up, respectively. RESULTS: Three patients (6.5%) had repeated baseplate failure requiring re-revision; 2 had baseplate failure at <1 year with associated periprosthetic infections and underwent conversion to hemiarthroplasty. The third patient experienced traumatic failure at 10 years and underwent successful rRSA. The mean American Shoulder and Elbow Surgeons scores at 1 and 2 years were 62.3 and 61.7, respectively. There was no significant difference in outcomes based on mode of baseplate failure (P = .232) or total arthroplasty burden (P = .305) at 1 year. There were 13 total complications in 11 patients, 5 of which required reoperation for reasons other than baseplate failure. CONCLUSION: In this study, rRSA for baseplate failure constituted 6.8% of all revisions performed over a period of 15 years. Re-revision for recurrent baseplate failure was required in 3 of 46 patients (6.5%). Complications and reoperation rates were higher than those for primary RSA but outcomes were comparable for revision of failed anatomic shoulder arthroplasty.

Optimal Generators for Quantum Sensing.

We propose a computationally efficient method to derive the unitary evolution that a quantum state is most sensitive to. This allows one to determine the optimal use of an entangled state for quantum sensing, even in complex systems where intuition from canonical squeezing examples breaks down. In this paper we show that the maximal obtainable sensitivity using a given quantum state is determined by the largest eigenvalue of the quantum Fisher information matrix (QFIM) and the corresponding evolution is uniquely determined by the coinciding eigenvector. Since we optimize the process of parameter encoding rather than focusing on state preparation protocols, our scheme is relevant for any quantum sensor. This procedure naturally optimizes multiparameter estimation by determining, through the eigenvectors of the QFIM, the maximal set of commuting observables with optimal sensitivity.

Regional shear wave elastography of Achilles tendinopathy in symptomatic versus contralateral Achilles tendons.

OBJECTIVES: Ultrasound often corroborates clinical diagnosis of Achilles tendinopathy (AT). Traditional measures assess macromorphological features or use qualitative grading scales, primarily focused within the free tendon. Shear wave imaging can non-invasively quantify tendon elasticity, yet it is unknown if proximal structures are affected by tendon pathology. The purpose of the study was to determine the characteristics of both traditional sonographic measures and regional shear wave speed (SWS) between limbs in patients with AT. METHODS: Twenty patients with chronic AT were recruited. Traditional sonographic measures of tendon structure were measured. Regional SWS was collected in a resting ankle position along the entire length of the tendon bilaterally. SWS measures were extracted and interpolated across evenly distributed points corresponding to the free tendon (FT), soleus aponeurosis (SA), and gastrocnemius aponeurosis (GA). Comparisons were made between limbs in both traditional sonographic measures and regional SWS. RESULTS: Symptomatic tendons were thicker (10.2 (1.9) vs. 6.8 (1.8) mm; p < 0.001) and had more hyperemia (p = 0.001) and hypoechogenicity (p = 0.002) than the contralateral tendon. Regional SWS in the FT was lower in the symptomatic limb compared to the contralateral limb (11.53 [10.99, 12.07] vs. 10.97 [10.43, 11.51]; p = 0.03). No differences between limbs were found for the SA (p = 0.13) or GA (p = 0.99). CONCLUSIONS: Lower SWS was only observed in the FT in AT patients, indicating that alterations in tendon elasticity associated with AT were localized to the FT and did not involve the proximal passive tendon structures. KEY POINTS: • Baseline characteristics of a pilot sample of 20 subjects suffering from chronic Achilles tendinopathy showed differences in conventional sonographic measures of tendon thickness, qualitatively assessed hypoechogenicity, hyperemia, and quantitative measures of shear wave speed. • Regional shear wave speeds were lower in the free tendon but not in the proximal regions of the soleus or gastrocnemius aponeuroses in Achilles tendinopathy patients. • Using shear wave imaging to estimate tendon stiffness may prove beneficial for clinical validation studies to address important topics such as return to activity and the effectiveness of rehabilitation protocols.

Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation.

BACKGROUND: The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. METHODS: A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. RESULTS: Diagnosing mycobacterial disease among patients with hematologic disease and treatment-associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in-vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug-drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. CONCLUSION: The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes.

Transition Metal ß-Diketonate Adhesion Promoters in Epoxy-Anhydride Resin.

Epoxy to copper adhesion supports the reliability of numerous structures in electronic packaging. Compared to substrate pre-treatment, processing and cost considerations are in favor of adhesion promoters loaded in epoxy formulations. In this work, first row transition metal ß-diketonates present such a compelling case when added in epoxy/anhydride resins: over 30% (before moisture aging) and 50% (after moisture aging) enhancement in lap shear strength are found using Co(II) and Ni(II) hexafluoroacetylacetonate. From extensive X-ray photoelectron spectroscopy (XPS) analyses on the adhesively failed sample surfaces, increased population of oxygen-containing functional groups, especially esters, is linked to the adhesion improvement. Assisted by XPS depth profile on the fractured epoxy side and in situ Fourier-transform infrared spectroscopy (FTIR), the previously discovered latent cure characteristics endowed by the metal chelates interacting with phosphine catalysts are regarded pivotal for pacing the anhydride consumption and allowing interfacial esterification reactions to occur. Further examinations on the XPS binding energy shifts and dielectric properties of the doped epoxy also reveal metal-polymer coordination that contribute to the adhesion and moisture resistance properties. These findings should stimulate future research of functional additives targeting at cure kinetics control and polar group coordination ideas for more robust epoxy-Cu joints.

Folic Acid Inhibits Aging-Induced Telomere Attrition and Apoptosis in Astrocytes In Vivo and In Vitro.

Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0-40 µM) and were assigned to five groups: FA 0 µM (generation 5), FA 10 µM (generation 5), FA 20 µM (generation 5), FA 40 µM (generation 5), and FA 10 µM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.

Geospatial techniques for monitoring and mitigating climate change and its effects on human health.

This article begins by briefly examining the multitude of ways in which climate and climate change affect human health and wellbeing. It then proceeds to present a quick overview of how geospatial data, methods and tools are playing key roles in the measurement, analysis and modelling of climate change and its effects on human health. Geospatial techniques are proving indispensable for making more accurate assessments and estimates, predicting future trends more reliably, and devising more optimised climate change adaptation and mitigation plans.

Ecological risk and protective factors for food insufficiency in Los Angeles County during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic increased food insufficiency: a severe form of food insecurity. Drawing on an ecological framework, we aimed to understand factors that contributed to changes in food insufficiency from April to December 2020, in a large urban population hard hit by the pandemic. DESIGN: We conducted internet surveys every 2 weeks in April-December 2020, including a subset of items from the Food Insecurity Experience Scale. Longitudinal analysis identified predictors of food insufficiency, using fixed effects models. SETTING: Los Angeles County, which has a diverse population of 10 million residents. PARTICIPANTS: A representative sample of 1535 adults in Los Angeles County who are participants in the Understanding Coronavirus in America tracking survey. RESULTS: Rates of food insufficiency spiked in the first year of the pandemic, especially among participants living in poverty, in middle adulthood and with larger households. Government food assistance from the Supplemental Nutrition Assistance Program was significantly associated with reduced food insufficiency over time, while other forms of assistance such as help from family and friends or stimulus funds were not. CONCLUSIONS: The findings highlight that during a crisis, there is value in rapidly monitoring food insufficiency and investing in government food benefits.

Indications for Maternal Echocardiography in Detecting Disease and the Impact on Pregnancy Management.

OBJECTIVE: Few obstetric-specific guidelines detail the indications for screening echocardiography in pregnancy. The objective of the study is to examine the association of common indications for maternal echocardiography with the likelihood of abnormality identification, pregnancy management alteration, and conformity with current American College of Cardiology Foundation (ACCF) guidelines. STUDY DESIGN: This retrospective cohort analysis categorized all echocardiograms performed within pregnancy and the first month postpartum within a tertiary health system to correlate indications with abnormal findings. RESULTS: Data from 226 echocardiograms were analyzed from 205 women. The most common indication for initial echocardiography was cardiac symptoms (34.6%). History of cardiac disease was the only indication demonstrating a significant association with an abnormal finding on initial echocardiography (odds ratio [OR]: 2.6; p = 0.006). Postpartum status (OR: 4.9; p < 0.001), multiparity (p < 0.001), and tobacco use (OR: 2.2; p = 0.011) were demographic characteristics associated with the identification of abnormal findings on initial echocardiography. Abnormal echocardiographic findings were associated with changes in clinical management but did not correlate with adverse obstetric or neonatal outcomes, which may support the impact of a multidisciplinary programmatic approach. ACCF appropriateness criteria correlated well with identification of abnormal echocardiographic results (p = 0.034). CONCLUSION: Although the presence of cardiac symptoms or history of diabetes failed to demonstrate association with abnormal echocardiographic findings, a history of prior cardiac disease, tobacco use, multiparity, and postpartum status were factors associated with identification of abnormal findings on initial maternal echocardiography. The ACCF appropriateness criteria for obtaining echocardiography can be applied to pregnant women with consideration for these additional risk factors. KEY POINTS: · The ACCF criteria are applicable in pregnancy for appropriateness of echocardiography indications.. · Several clinical factors often prompt performance of echocardiography in pregnancy without merit.. · Consideration for multiparty, tobacco abuse, and postpartum state should coincide with ACCF criteria..

Effects of respiratory and cardiac motion on estimating radiation dose to the left ventricle during radiotherapy for lung cancer.

PURPOSE: Establish a workflow to evaluate radiotherapy (RT) dose variation induced by respiratory and cardiac motion on the left ventricle (LV) and left ventricular myocardium (LVM). METHODS: Eight lung cancer patients underwent 4D-CT, expiratory T1-volumetric-interpolated-breath-hold-examination (VIBE), and cine MRI scans in expiration. Treatment plans were designed on the average intensity projection (AIP) datasets from 4D-CTs. RT dose from AIP was transferred onto 4D-CT respiratory phases. About 50% 4D-CT dose was mapped onto T1-VIBE (following registration) and from there onto average cine MRI datasets. Dose from average cine MRI was transferred onto all cardiac phases. Cumulative cardiac dose was estimated by transferring dose from each cardiac phase onto a reference cine phase following deformable image registration. The LV was contoured on each 4D-CT breathing phase and was called clinical LV (cLV); this structure is blurred by cardiac motion. Additionally, LV, LVM, and an American Heart Association (AHA) model were contoured on all cardiac phases. Relative maximum/mean doses for contoured regions were calculated with respect to each patient's maximum/mean AIP dose. RESULTS: During respiration, relative maximum and mean doses on the cLV ranged from -4.5% to 5.6% and -14.2% to 16.5%, respectively, with significant differences in relative mean doses between inspiration and expiration (P < 0.0145). During cardiac motion at expiration, relative maximum and mean doses on the LV ranged from 1.6% to 59.3%, 0.5% to 27.4%, respectively. Relative mean doses were significantly different between diastole and systole (P = 0.0157). No significant differences were noted between systolic, diastolic, or cumulative cardiac doses compared to the expiratory 4D-CT (P > 0.14). Significant differences were observed in AHA segmental doses depending on tumour proximity compared to global LV doses on expiratory 4D-CT (P < 0.0117). CONCLUSION: In this study, the LV dose was highest during expiration and diastole. Segmental evaluation suggested that future cardiotoxicity evaluations may benefit from regional assessments of dose that account for cardiopulmonary motion.