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Anticholinergic toxicity typically presents with symptoms of cutaneous vasodilation, delirium, mydriasis, urinary retention, hyperthermia, anhidrosis, and tachycardia. This case report presents a 68-year-old female patient who exhibited some of these signs and symptoms after ingesting an unknown quantity of dicyclomine. However, she displayed one notable exception to the classic toxidrome. On hospital day 2, the patient experienced multiple incidences of prolonged sinus pause, culminating in witnessed asystole lasting 5-10 seconds. The patient continued to have numerous episodes of sinus pause that lasted 5-10 seconds each over the next two days. Treatment involved placement of multiple temporary transvenous pacemakers until the episodes of sinus pause eventually self-resolved, facilitating discharge home on hospital day 6. The patient recovered without any known complications. After considering alternative diagnoses such as sick sinus syndrome, electrolyte derangements, and intracranial hypertension, multiple hospital medical services ultimately attributed the arrhythmia to anticholinergic toxicity. There are no other documented cases of intermittent sinus pause associated with anticholinergic overdose. While rare, clinicians should consider anticholinergic toxicity as a potential cause of intermittent sinus pause, especially in patients taking anticholinergic medications. Increased clinical vigilance could impact treatment decisions, including potentially avoiding unnecessary procedures such as permanent pacemaker placement, if symptoms resolve with cessation of the offending agent., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Kwong et al.)

Background: Signs and symptoms of myocarditis may vary among men and women., Objectives: This study aimed to analyze sex-specific differences in the presentation and outcomes of patients with suspected myocarditis., Methods: Patients meeting clinical ESC criteria for suspected myocarditis were included from two tertiary centers between 2002 and 2021. Baseline characteristics, cardiac magnetic resonance (CMR), and outcomes (i.e. major adverse cardiovascular events (MACE), including all-cause death, ventricular tachycardia, hospitalization for heart failure, and recurrent myocarditis) in women and men were compared., Results: 776 consecutive patients (mean age 48 ± 16 years, 286 [36.9 %] women) were followed for a median of 3.7 years. Compared to men, women presented more often with severe dyspnea (NYHA III-IV: 25.9 % versus 19.2 % of men; p = 0.029), while chest pain was more frequent in men (39.8 % versus 32.2 % in women; p = 0.037). There was no difference in left ventricular ejection fraction at the time of presentation (women: 48.5 ± 15.4 % versus men: 48.6 ± 15.1 %;p = 0.954). Further, no sex-specific difference in the occurrence of MACE was noted; however, women were more often hospitalized for heart failure than men (women: 9.8 % versus men: 5.3 %, p = 0.018). Accordingly, female sex was independently associated with heart failure hospitalization in an adjusted model (HR: 2.31, 95 % CI:1.25-4.26; p = 0.007). The prognostic value of CMR markers was similar in both sex., Conclusion: Significant sex-specific differences in presentations and imaging findings are found in patients with suspected myocarditis. Female sex is associated with a twofold increase in the risk of heart failure hospitalization, which should be considered in risk stratification., Competing Interests: Declaration of competing interest B. Bernhard report a career development grant from the Swiss National Science Foundation. C. Gebhard was supported by grants from the Swiss National Science Foundation (SNSF), the Olga Mayenfisch Foundation, Switzerland, the OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, the Swissheart Foundation, the Helmut Horten Foundation, Switzerland, the EMDO Foundation, the Iten-Kohaut Foundation, Switzerland, the University Hospital Zurich Foundation, the University of Zurich (UZH) Foundation, and the LOOP, Zurich. R. Kwong has received research support from Bristol Myers Squibb, Alnylam Pharmaceuticals, Epirium Bio, and Bayer AG, outside of the submitted work. C. Gräni has no conflict of interest with regard to the current study. C. Gräni received funding from the Swiss National Science Foundation, Swissheart Foundation, InnoSuisse, CAIM foundation and GAMBIT foundation, outside of the submitted work. C. Gräni is Editor-in Chief of the International Journal of Cardiovascular Imaging. All other authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Group A streptococcus (GAS) manifests as a spectrum of illnesses, ranging from mild to life-threatening. While relatively rare in infants, GAS infections can present with grave consequences., Case Report: An eight-month-old infant was found to have GAS bacteremia complicated by sepsis and disseminated intravascular coagulation, resulting in lower extremity myositis and tissue ischemia. Tissue ischemia progressed to dry gangrene requiring below-knee amputation followed by six weeks of antibiotics., Conclusion: This case serves as a reminder of the critical importance of vigilance, prompt recognition, and aggressive intervention in the management of invasive GAS infections in infants.

Immune-mediated systemic inflammatory disorders present a latent threat for cardiovascular disease. Early involvement may be associated with constitutional symptoms, while clinical evidence of disease may manifest later in an insidious manner. Multimodality imaging is crucial to detect myocardial involvement, with transthoracic echocardiogram as a first-line imaging modality; however, cardiac MRI (CMRI) has the potential to significantly impact our diagnostic and therapeutic approaches through high-fidelity chamber quantification and parametric mapping techniques. Novel imaging techniques are currently under investigation, including stress CMRI, feature tracking CMR, late gadolinium enhancement (LGE) entropy, and 4 dimensional flow CMRI., Competing Interests: Disclosure B. Weber reports consulting/scientific advisory board fees from Novo Nordisk, Kiniksa Pharmaceuticals, Bristol Meyer Squib (BMS) and Horizon Therapeutics (now Amgen), unrelated to the current work. R. Kwong has no relevant disclosures. J.A. Aun: The views expressed in this article are those of Dr J.A. Aun and do not reflect the official policy of the United States Air Force, the Department of the Defense, the Defense Health Agency, or the United States Government. The identification of specific products or scientific instrumentation is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of Dr J.A. Aun, the Department of Defense, or any component agency. Funding: Dr B. Weber is supported by research grants from NHLBIK23 HL159276-01, AHA 21CDA851511. Dr R. Kwong is supported by research grants from Alynlam, Myocardia, and Cytokinetics. Dr J.A. Aun: N/A., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH., Methods: Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI., Results: Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/μL; P = .02) increased in the eplerenone- versus placebo-treated groups., Conclusions: RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo., Clinical Trials Registration: NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1)., Competing Interests: Potential conflicts of interest. S. S. was the recipient of a Gilead Sciences Research Scholars award. M. T. L. has received research funding from KOWA, MedImmune, AstraZeneca, Ionis, and Johnson & Johnson Innovation. T. H. B. is a paid member of the Scientific Advisory Board and has equity in Excision BioTherapeutics, Inc. C. R. d. receives consulting fees from Abbott Diagnostics, Quidel/Ortho, Roche Diagnostics, and Siemens Diagnostics. G. K. R. has received trials support from Leonard Meron Biosciences and consulting fees from Teradyne for clinical trial design and from SEED for COVID consulting. He is also an unpaid panel member of the Department of Health and Human Services (DHHS) Opportunistic Infections guidelines review committee and has provided expert medical review testimony for Tufts Medical Center. G. K. R. also reports unpaid participation on a Data Safety Monitoring Board or Advisory Board for Arterial Inflammation and Coronary Microvascular Dysfunction among Women with HIV: Missing Pieces to the MI Risk Puzzle (grant number R01HL146267). S. K. G. has received research funding from KOWA, Gilead, ViiV, and Theratechnologies and received consulting fees from Theratechnologies and ViiV. He is a member of the Scientific Advisory Board of Marathon Asset Management. M. D. reports grants or contracts paid to institutions from Gilead Sciences and Spectrum Dynamics; consulting fees from Sanofi and MedTrace Pharma; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Amgen. All disclosures are unrelated to this manuscript. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Disclosures None.

Objective: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC., Design: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs., Results: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells., Conclusions: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology.)

Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype-phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype-phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). "Cases of SCMR" is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. The COVID-19 Case Collection highlights the impact of coronavirus disease 2019 (COVID-19) on the heart as demonstrated on CMR. Each case in series consists of the clinical presentation and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2021 Cases of SCMR and the 2020 and 2021 COVID-19 Case Collection series of nine cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar literature search engine., (© 2022. The Author(s).)

Renewable biofuel has a great potential in replacing the conventional transportation fuels as well as aiding the current issue of climate change and global warming. In the present scenario, tremendous initiatives have been implemented to encourage large-scale biofuel production and reduce greenhouse gas emissions. However, the information on the current biofuel status specifically in Canada and where it lacks in biofuel production, tax rebate and policies in comparison with other countries is limited. In this sense, the current work focuses on the liquid biofuel status, recent advancements and evaluation of programs aimed at reducing greenhouse gas emissions in coming years. Additionally, the role of private and government programs in scaling up the projects is elaborated using several examples of successful as well as failed attempts to commercialize biofuels. Moreover, the Canadian government regulations and policies for greenhouse gas mitigation, and biofuel blending policies are also briefly described. In summary, future aspects and suggestions to further increase biofuel production are portrayed in this review.

Anterior urethral syringocele is an uncommon congenital deformity characterized by cystic dilatation of bulbourethral gland ducts and is usually asymptomatic. We present a case on 4-day-old male neonate who presented with bilateral antenatal hydroureteronephrosis and renal impairment and found to have urethral syringocele and posterior urethral valves., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31 st December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms., Aim: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made., Method: Contacts were identified and risk categorized as 'close' or 'casual' for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2., Findings: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of 'close contact'. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period., Conclusion: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, should be the primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. These perspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. The evidence has changed considerably since the 2012 SIHD guideline, and the current perspectives represent the diversity of available evidence as to the optimal imaging strategy for evaluation of the symptomatic patient., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The prostate exhibits a unique metabolism that changes during initial neoplasia to aggressive prostate cancer (PCa) and metastasis. The study of PCa metabolism thus represents a new avenue for diagnostics, particularly early diagnosis of aggressive PCa cases., Results: Here, by clustering tissue transcriptomics data from The Cancer Genome Atlas (498 PCa patients), we identified six metabolic subgroups (C1-C6) of PCa that show distinct disease-free survival (DFS) outcomes (p < 0.0001). In particular, we identified at least two subgroups (C5 & C3) that exhibit significant poor prognosis (∼70% and 30-40% relapse within the first 72 months; hazards ratios of 9.4 and 4.4, respectively, relative to the best prognosis cluster C4 that showed <20% relapse even by 120 months). We were able to reproduce the subgroups in several independent datasets including B. S. Taylor et al. (2010) data; 215 patients; DFS p = 0.00088) using a multinomial regression classifier. The subgroups displayed distinct metabolic profiles vis-à-vis normal tissues, measured as 'deregulation' observed for 20 metabolic pathways (using Pathifier; Y. Drier and E. Domany, 2013). In particular, C5 and C3 showed considerable deregulation for pathways involved in synthesis and catabolism of complex forms of lipids and carbohydrates, and these were exhibited in parallel or in the face of glycolysis, a common form of energy production in cancer cells. The subgroups were significantly over-enriched for different sets of genetic alterations [BRCA1, MSH2, FOXA1, TP53 (C5), RB1 and STK11(C3); and AR (C1); p ≤ 8.6 × 10-4], suggesting that distinct sets of alterations underpinning the PCa subgroups that 'push' the subgroups towards their unique metabolic profiles. Finally, applying the classifier to blood protein expression profiles from 42 active surveillance (AS) and 65 advanced castrate resistant PCa (ACRPC) patients (D. Olmos et al., 2012) assigned 70.77% ACPRC and interestingly reassigned 59.52% AS patients to at least one of the poor prognosis subgroups with 35.71% to the metabolically active poor-prognosis subgroup C3., Conclusion: The identification of PCa subgroups displaying distinct clinical outcomes solely from metabolic expression profiles of PCa tumours reiterates the significant link between deregulated metabolism and PCa outcomes (E. Eidelman et al., 2017). On the other hand, the time to biochemical relapse (rise in PSA levels) was not indicative of early relapse seen for subgroups C3 and C5 (these show considerably late BCR compared to C4). Our study thus highlights specific processes (elevated lipid and carbohydrate metabolism pathways) that could be better indicators than PSA for early diagnosis of aggressive PCa., Availability: https://maxwellplus.com/research/metabolic-deregulation-in-prostate-cancer/.

Background: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use., Objective: To determine whether the portion of plerixafor remaining in an opened vial of the Mozobil product after administration of a single dose is chemically stable, by comparison with the original product., Methods: Stability testing of partial drug contents of an opened vial, stored at room temperature or under refrigeration (4°C), was conducted using liquid chromatography-tandem mass spectrometry analysis. The mean concentration of plerixafor (μmol/L), standard deviation, coefficient of variation, and bias were determined on days 2, 3, 11, 17, 24, and 31. Method validation included determination of precision, sensitivity, recovery, dilution linearity, and carryover., Results: Throughout the 4-week testing period, measured plerixafor concentration in aliquots stored at room temperature and under refrigeration, tested in series over time, appeared similar. The mean residual drug concentration after initial opening was slightly, but not significantly, higher for the sample designated for storage at room temperature than the one designated for refrigerated storage (40.4 versus 39.9 μmol/L; p = 0.37)., Conclusions: Residual plerixafor after initial opening of a vial of the Mozobil product remained chemically stable for at least 2 weeks both at room temperature and under refrigeration. The results of this study provide in vitro evidence to support multiple uses, instead of single use, of vials of this drug in an aseptic, controlled environment., Competing Interests: Competing interests: None declared.

According to the so-called obesity paradox, obesity might present a protective role in patients with myocardial infarction. We aimed to assess the influence of the epicardial adipose tissue (EAT) volume on cardiac healing and remodeling in patients with acute ST-elevation myocardial infarction. We prospectively included 193 consecutive patients presenting a first STEMI without known coronary artery disease. Cardiac magnetic resonance imaging was performed at baseline and after a 3-month follow-up. EAT volume was computed, and the population was divided into quartiles: the highest quartile of EAT defining the high EAT group (h-EAT). h-EAT was associated with increased body mass index, higher rate of history of hypertension, and smaller infarct size at initial CMR assessment (18.3 ± 11.9% vs 23 ± 13.7% of total left ventricular [LV] mass, p = 0.041). Moreover, microvascular obstruction was less frequent in the h-EAT group (36.2% vs 59.3%, p = 0.006). There were no differences in LV ejection fraction (LVEF), LV volumes, systolic wall stress, coronary artery burden, and clinical events during the index hospitalization between the EAT groups at baseline and at follow-up. Linear regression analysis showed h-EAT to be associated with smaller infarct size at baseline (β coefficient = -3.25 [95% CI -5.89 to -0.61], p = 0.016). h-EAT also modified positively the effect of infarct size on LV remodeling, as assessed by the change in LVEF (p = 0.046). In conclusion, h-EAT was paradoxically related to smaller infarct size and acted as an effect modifier in the relation between the extent of infarct size and LVEF changes. Patients with higher extent of EAT presented better cardiac healing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Given the positive association between primary care and overall health, several health plans are offering doctors' visits without patient copay, with the intent to increase primary care use. However, the effectiveness of these offers has not been established in the literature., Objective: To evaluate the impact of a free primary care provider (PCP) office visit offered by a health plan on primary care-seeking behaviors., Methods: This nonrandomized concurrent control study used event/trials logistic regression to compare the differences in primary care utilization between new exchange enrollees in Mississippi who were offered a free nonpreventive PCP visit and concurrent controls from Georgia and Tennessee who were not offered a free visit, between January 1, 2014, and December 31, 2014, which was the first year of the exchange plans. Regression models adjusted for age, sex, plan type, rural-urban designation, and enrollment month. Visits to alternative sites of care were also assessed., Results: The adjusted number of nonpreventive PCP visits did not differ between the states (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.97-1.00). Mississippi residents were significantly more likely to go to the emergency department than the Georgia-Tennessee cohort (OR, 1.33; 95% CI, 1.28-1.39), but they were less likely to visit an urgent care center (OR, 0.10; 95% CI, 0.09-0.11) or a retail clinic (OR, 0.13; 95% CI, 0.11-0.17) than their counterparts., Conclusions: Despite being eligible for a free nonpreventive visit, enrollees in Mississippi were no more likely than their counterparts in Georgia and Tennessee to visit a PCP. These findings suggest that removing the cost barrier alone may be insufficient to change primary care-seeking behaviors, and other barriers to care should be addressed.

Background: Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis., Methods and Results: We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men).One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7; P=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34-86.3]; P=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68-143]; P=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47-15.6]; P<0.001). There was no significant heterogeneity for any outcomes., Conclusions: LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis., (© 2016 American Heart Association, Inc.)

Opinion Statement: Combining the diagnostic utilities of cardiac structures, myocardial perfusion, and various tissue characterizing pulse sequence methods in matching scan planes within a single imaging session, cardiac magnetic resonance imaging (CMR) provides a novel interrogation of myocardial physiology and abnormal anatomy from various forms of cardiomyopathy. Establishment of technical imaging standards and clinical adaptation in the past years has helped recognize the distinguishing features of different cardiomyopathies, with CMR currently assuming a pivotal role in the diagnosis of cases of new-onset cardiomyopathy in experienced centers. Quantitative measurements such as ventricular volumes, myocardial iron content, and extent of late gadolinium enhancement can effectively monitor disease status, guide medical therapy, and impact patient outcomes in specific clinical settings. This chapter will aim to summarize these current CMR applications with case examples.

Background: High reproducibility of LV mass and volume measurement from cine cardiovascular magnetic resonance (CMR) has been shown within single centers. However, the extent to which contours may vary from center to center, due to different training protocols, is unknown. We aimed to quantify sources of variation between many centers, and provide a multi-center consensus ground truth dataset for benchmarking automated processing tools and facilitating training for new readers in CMR analysis., Methods: Seven independent expert readers, representing seven experienced CMR core laboratories, analyzed fifteen cine CMR data sets in accordance with their standard operating protocols and SCMR guidelines. Consensus contours were generated for each image according to a statistical optimization scheme that maximized contour placement agreement between readers., Results: Reader-consensus agreement was better than inter-reader agreement (end-diastolic volume 14.7 ml vs 15.2-28.4 ml; end-systolic volume 13.2 ml vs 14.0-21.5 ml; LV mass 17.5 g vs 20.2-34.5 g; ejection fraction 4.2 % vs 4.6-7.5 %). Compared with consensus contours, readers were very consistent (small variability across cases within each reader), but bias varied between readers due to differences in contouring protocols at each center. Although larger contour differences were found at the apex and base, the main effect on volume was due to small but consistent differences in the position of the contours in all regions of the LV., Conclusions: A multi-center consensus dataset was established for the purposes of benchmarking and training. Achieving consensus on contour drawing protocol between centers before analysis, or bias correction after analysis, is required when collating multi-center results.

Purpose: One important challenge in image-guided ablative therapies is the effect of heat diffusion which can cause damage to surrounding organs and limit the ability to achieve a conformal pattern of thermal damage. Furthermore, tissue properties such as perfusion and energy absorption can be dynamic and difficult to measure. This paper attempts to address these problems by proposing new control methods., Materials and Methods: A novel predictive approach was developed to compensate for the effect of heat diffusion using a minimally invasive rotating ultrasound heating applicator for ablative therapy. This method can be merged into any closed-loop control strategy. A binary controller, a previously developed adaptive proportional-integral controller, and a model reference adaptive controller were employed and compared, all with the predictive element incorporated. The reason for choosing these controllers was that none of them needed a model of the tissue or exact values of their parameters., Results: The effectiveness of these controllers was demonstrated through both simulation and experimental studies. The results were consistent and demonstrated equivalent performance between controllers., Conclusions: The dominant influence on radial targeting accuracy was the prediction element described in this paper. A binary controller with a predictive element may provide the best balance of performance and simplicity for this application.

Background: Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR)., Methods and Results: Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME ("l-NAME+S") showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks., Conclusions: Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy., Methods and Results: Two murine models of hypertension (n=18, with n=15 controls) induced by l-N(G)-nitroarginine methyl ester (L-NAME) and pressure overload (n=11) from transaortic constriction (TAC) were imaged by cardiac magnetic resonance at baseline and 7 weeks after L-NAME treatment or up to 7 weeks after TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size-dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin-stained sections. The τic correlated strongly with histological cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75, P<0.001). Histological cardiomyocyte diameters and cell volumes were higher in mice treated with L-NAME compared with controls (P<0.001). In the TAC model, cardiac magnetic resonance and histology showed cell hypertrophy at 2 weeks after TAC without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic between 2 and 7 weeks after TAC., Conclusion: The τic measured by contrast-enhanced cardiac magnetic resonance provides a noninvasive measure of cardiomyocyte hypertrophy. Extracellular volume fraction and τic can track myocardial tissue remodeling from pressure overload., Competing Interests: Disclosures: None.

Purpose: MRI-controlled interstitial ultrasound therapy is being developed as a minimally invasive, image-guided treatment for localized cancers. The method uses an interstitial multielement ultrasound applicator to deliver high-intensity ultrasound energy to tissue in order to achieve thermal coagulation in a target volume., Methods: A new temperature feedback control algorithm incorporating a proportional-integral controller is introduced to tackle a multiple-input single-output control problem arising in MRI-controlled interstitial ultrasound cancer therapy. The inputs to the controller block are the frequency, rotation rate, and applied power of an interstitial applicator and the output is the boundary temperature during treatment. Multiplanar magnetic resonance (MR) thermometry is acquired continuously during heating and used in the feedback control algorithm to achieve spatial control over treatment., Results: The method has been evaluated for prostate cancer treatment as an initial clinical application. Spatial treatment accuracy of a few millimeters is demonstrated in both simulations and experiments with the new controller. The spatial treatment accuracy of the new algorithm is shown to be equivalent or slightly improved over the existing approach implemented for this technology; however, the implementation of the new algorithm is much simpler, and does not involve time-intensive tuning of gain constants., Conclusions: The study demonstrates the potential advantages of a new automatic temperature control system adapted to image guided interstitial ultrasound therapy.

Calcium (Ca(2+)) is a key second messenger in eukaryotes and regulates diverse cellular processes, most notably via calmodulin (CaM). In Arabidopsis thaliana, IQD1 (IQ67 domain 1) is the founding member of the IQD family of putative CaM targets. The 33 predicted IQD proteins share a conserved domain of 67 amino acids that is characterized by a unique arrangement of multiple CaM recruitment motifs, including so-called IQ motifs. Whereas IQD1 has been implicated in the regulation of defense metabolism, the biochemical functions of IQD proteins remain to be elucidated. In this study we show that IQD1 binds to multiple Arabidopsis CaM and CaM-like (CML) proteins in vitro and in yeast two-hybrid interaction assays. CaM overlay assays revealed moderate affinity of IQD1 to CaM2 (K(d) ∼ 0.6 μm). Deletion mapping of IQD1 demonstrated the importance of the IQ67 domain for CaM2 binding in vitro, which is corroborated by interaction of the shortest IQD member, IQD20, with Arabidopsis CaM/CMLs in yeast. A genetic screen of a cDNA library identified Arabidopsis kinesin light chain-related protein-1 (KLCR1) as an IQD1 interactor. The subcellular localization of GFP-tagged IQD1 proteins to microtubules and the cell nucleus in transiently and stably transformed plant tissues (tobacco leaves and Arabidopsis seedlings) suggests direct interaction of IQD1 and KLCR1 in planta that is supported by GFP∼IQD1-dependent recruitment of RFP∼KLCR1 and RFP∼CaM2 to microtubules. Collectively, the prospect arises that IQD1 and related proteins provide Ca(2+)/CaM-regulated scaffolds for facilitating cellular transport of specific cargo along microtubular tracks via kinesin motor proteins.

Background: The myocardial extracellular volume fraction (MECVF) has been used to detect diffuse fibrosis. Estimation of MECVF relies on quantification of the T1 relaxation time after contrast enhancement, which can be sensitive to equilibrium transcytolemmal water-exchange. We hypothesized that MECVF, quantified with a parsimonious 2-space water-exchange model, correlates positively with the connective tissue volume fraction in a rodent model of hypertensive heart disease, whereas the widely used analysis based on assuming fast transcytolemmal water-exchange could result in a significant underestimate of MECVF., Methods and Results: Nω-nitro-L-arginine-methyl-ester (L-NAME) or placebo was administered to 22 and 15 wild-type mice, respectively. MECVF was measured at baseline and 7-week follow-up by pre- and postcontrast T1 cardiac magnetic resonance imaging at 4.7 T, using a 2-space water-exchange model. Connective tissue volume fraction was quantified, using Masson trichrome stain. L-NAME induced hypertrophy (weight-indexed left-ventricular mass 2.2±0.3 versus 4.1±0.4 μg/g, P<0.001), and increased connective tissue volume fraction (8.6%±1.5 versus 2.58%±0.6, P<0.001), were compared with controls. MECVF was higher in L-NAME-treated animals (0.43±0.09 versus 0.26±0.03, P<0.001), and correlated with connective tissue volume fraction and weight-indexed left-ventricular mass (r=0.842 and r=0.737, respectively, both P<0.0001). Neglecting transcytolemmal water-exchange caused a significant underestimate of MECVF changes. Ten patients with history of hypertension had significantly higher MECVF (0.446±0.063) compared with healthy controls (0.307±0.030, P<0.001)., Conclusions: Cardiac magnetic resonance allowed detection of myocardial extracellular matrix expansion in a mouse model and in patients with a history of hypertension. Accounting for the effects of transcytolemmal water-exchange can result in a substantial difference of MECVF, compared with assuming fast transcytolemmal water-exchange.

The clinical manifestations of Alzheimer's disease (AD) are secondary to the substantial loss of cortical neurons. To be effective, neuroprotective strategies will need to target the primary pathogenic mechanisms of AD prior to cell loss. The differences between neurons are largely determined by their specific repertoire of mRNAs. Thus, transcriptomic analyses that do not assume a priori etiological hypotheses are potentially powerful tools that can be used to understand the pathogenesis of complex diseases, including AD. The human brain comprises thousands of different cell types of both neuronal and non-neuronal origins. Information about individual cell-type-specific gene expression patterns will allow for a better understanding of the mechanisms that govern the progression of AD, which may lead to new therapeutic targets for prevention and treatment of the disease. This review provides an overview of the current technologies in use and the developments for single-cell extraction and transcriptome analysis. Recent transcriptome profiling studies on individual AD-afflicted brain cells are also discussed.

It can be difficult to identify endpoints that accurately reflect patient benefit in metastatic solid tumors. Overall survival (OS) is the gold standard although progression-free survival (PFS) is sometimes used as a surrogate for OS. Statistical modelling has suggested that the association between OS and PFS becomes weaker in diseases with longer survival post-progression (SPP). To evaluate these statistical hypotheses we determined the relationship between PFS and OS in control and experimental arms of randomised trials conducted in the last 10years, which have led to drug approval. Our data confirm that PFS is a poor surrogate for OS when SPP is long, but it is a better surrogate where SPP is short. In cancers with short SPP designing trials to show OS benefit is feasible and, therefore, remains the preferred approach. In tumours with long SPP, PFS is not clinically meaningful unless it is also associated with improvement in patient reported outcomes such as quality of life. The oncology community should consider the further development and validation of composite endpoints including patient reported outcomes and PFS across different disease sites. Such endpoints have been successfully used in cancer trials in the past. With improvements in therapy and prolonged survival of patients with many cancers, and with increasing pressure from healthcare payers to prove that treatment leads to patient benefit, the choice of optimal endpoints for clinical trials is increasingly important. Composite measures comprising patient reported outcomes and intermediate endpoints such as PFS may be the solution and should be investigated further., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The objective of this article is to discuss optimal imaging strategies for the evaluation of cardiac masses. The advantages and disadvantages of echocardiography, cardiac MRI, gated cardiac CT, and nuclear imaging will be discussed and specific techniques presented., Conclusion: Multimodality imaging plays a pivotal role in the diagnosis and surgical planning of cardiac masses. Clinical features, such as patient age, location, and imaging characteristics of the mass will determine the likely differential diagnosis.

Objective: The objectives of this article are to discuss key radiologic features that differentiate primary and secondary cardiac masses. Clinical scenarios are included to highlight stepwise radiologic workup of tumors of the pericardium, epicardium, myocardium, valves, and chambers. The involvement of key cardiac anatomic structures will also be emphasized to determine resectability and guide surgical planning., Conclusion: Multimodality imaging plays a pivotal role in diagnosis and surgical planning of cardiac masses. Clinical features, such as patient age, location, and imaging characteristics of the mass will determine the likely differential diagnosis. In addition to radiologic evaluation of the mass itself, involvement of valvular apparatus, extent of myocardial involvement, or presence of associated coronary artery involvement is necessary to determine resectability and surgical technique.

Purpose: The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported., Patients and Methods: Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared., Results: For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P < .001) and OS (P = .02). The median monthly prices for standard doses of drugs were $5375 for group A, $5644 for group B, and $6584 for group C (P = .87)., Conclusion: New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.).

Background: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking., Methods: We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype., Results: The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy., Conclusions: Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.)

The adaptive growth of the uterus is a critical event that involves changes in cellular phenotypes throughout pregnancy. In early pregnancy, uterine growth is due to hyperplasia of uterine smooth muscle cells (SMCs) within the myometrium; however, the major component of myometrial growth occurs after mid-gestation. This study sought to test the hypothesis that increase in myometrial growth seen during late pregnancy is due to SMC hypertrophy caused by mechanical stretch of uterine tissue by a growing fetus(es) by providing direct measurements of individual SMC size. We employed a stereological approach to calculate the average cell volumes of uterine myocytes through diameter measurements using the Stereoinvestigator statistical software. Uterine tissues were collected from nonpregnant Wistar rats, as well as from gravid and nongravid horns of unilaterally pregnant animals on gestational days (d) 8 (early gestation), 14 (mid-gestation), 19 (late gestation), 22 (term), and 4 days post partum. Anti-caveolin-1 immunostaining was used to clearly delineate SMC boundaries. The stereological analysis revealed that the dramatic increase in myometrial growth seen during late gestation (d19-22) is due to a threefold increase in the size of uterine myocytes. A significant increase in SMC volumes was detected in the gravid uterine horn as compared with the corresponding empty horn of unilateral term pregnant animals (day 22, mean cell volume 1114 vs 361 microm(3), P<0.05), indicating the effect of uterine occupancy. The restriction of the hypertrophy to cells within the gravid horn suggests that it may be a response to the biological mechanical stretch of uterine walls by the growing fetus(es) and placenta(s).

A board-level broadband frequency domain photon migration (mini-FDPM) instrument has been constructed to replace a conventional network-analyzer-based FDPM instrument. The mini-FDPM instrument with four wavelengths (681, 783, 823, and 850 nm), matches conventional FDPM instrument in performance (-88 dBm noise level, 100 dB dynamic range) and bandwidth (1 GHz), and recovers the same optical properties within about 6% in absorption and 4% in reduced scattering for liquid phantoms covering a wide range of relevant optical properties. Compared to the conventional FDPM instrument, the mini-FDPM instrument is more than 5x faster (approximately 200 ms per 401 modulation frequencies) and several orders of magnitude less in size and cost. Standard fiber-optic-based probes can be used with the mini-FDPM instrument, which increases applications in a number of clinically relevant measurement scenarios. By drastically reducing size and cost, FDPM miniaturization lowers barriers to access and will help promote FDPM in clinical research problems. The mini-FDPM instrument forms the core of a modular broadband diffuse optical spectroscopy instrument that can be used for a variety of clinical problems in imaging and functional monitoring (i.e., breast/skin cancer, brain activation, and exercise physiology).