Geometric changes allow normal ejection fraction despite depressed myocardial shortening in hypertensive left ventricular hypertrophy

Objectives.This study of hypertensive left ventricular hypertrophy 1) assessed myocardial shortening in both the circumferential and long-axis planes, and 2) investigated the relation between geometry and systolic function.Background.In hypertensive left ventricular hypertrophy, whole-heart studies have suggested normal systolic function on the basis of ejection fraction-systolic stress relations. By contrast, isolated muscle data show that contractility is depressed. It occurred to us that this discrepancy could be related to geometric factors (relative wall thickness).Methods.We studied 43 patients with hypertensive left ventricular hypertrophy and normal ejection fraction (mean ± SD 69 ± 13%) and 50 clinically normal subjects. By echocardiography, percent myocardial shortening was measured in two orthogonal planes; circumferential shortening was measured at the endocardium and at the midwall, and long-axis shortening was derived from mitral annular motion (apical four-chamber view). Circumferential shortening was related to end-systolic circumferential stress and long-axis shortening to meridional stress.Results.Endocardial circumferential shortening was higher than normal (42 ± 10% vs. 37 ± 5%, p < 0.01) and midwall circumferential shortening lower than normal in the left ventricular hypertrophy group (18 ± 3% vs. 21 ± 3%, p < 0.01). Differences between endocardial and midwall circumferential shortening are directly related to differences in relative wall thickness. Long-axis shortening was also depressed in the left ventricular hypertrophy group (18 ± 6% in the left ventricular hypertrophy group, 21 ± 5% in control subjects, p < 0.05). Midwall circumferential shortening and end-systolic circumferential stress relations in the normal group showed the expected inverse relation; those for ∼33% of the left ventricular hypertrophy group were >2 SD of normal relations, indicating depressed myocardial function. There was no significant relation between long-axis shortening and meridional stress, indicating that factors other than afterload influence shortening in this plane.Conclusions.High relative wall thickness allows preserved ejection fraction and normal circumferential shortening at the endocardium despite depressed myocardial shortening in two orthogonal planes

The controversy in the management of the N0 neck for squamous cell carcinoma of the maxillary sinus

Squamous cell carcinoma (SCC) of the maxillary sinus is a relatively rare disease. As the reported incidence of regional metastasis varies widely, controversy exists as to whether or not the N0 classified neck should be treated electively. In this review, the data from published series are analyzed to decide on a recommendation of elective treatment of the neck in maxillary SCC. The published series consist of heterogeneous populations of different subsites of the paranasal sinuses, different histological types, different staging and treatment modalities used and different ways of reporting the results. These factors do not allow for recommendations based on high levels of evidence. Given this fact, the relatively high incidence rate of regional metastasis at presentation or in follow-up in the untreated N0 neck, and the relatively low toxicity of elective neck irradiation, such irradiation in SCC of the maxillary sinus should be considered

Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time

Ultrasonographic diagnosis of extremity masses

Radiographic examination of soft tissue extremity masses is frequently inconclusive. In 18 patients with normal or nonspecifically abnormal radiographs, gray scale ultrasonography provided useful additional information. It was possible to distinguish fluid collections from solid masses, and recurrent venous thrombosis from hematoma in anticoagulated patients. Occasionally, specific diagnoses were suggested on the basis of ultrasonic morphologic characteristics. Diagnoses included soft tissue neoplasms, hematomas, aneurysms, synovial cysts, abscesses, and a lymphocele.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46815/1/256_2004_Article_BF00347181.pd

Role of early second-trimester uterine artery Doppler screening to predict small-for-gestational-age babies in nulliparous women

Background Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. Objective We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. Study Design Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days’ and 22 weeks 6 days’ gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. Results Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. Conclusion In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies

MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy

An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified MECP2 as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRAS(G12C)-addicted cell line after KRAS down-regulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action

Setting our sights on infectious diseases

In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings

Review of research to inform California's climate scoping plan: Agriculture and working lands

Agriculture in California contributes 8% of the state's greenhouse gas (GHG) emissions. To inform the state's policy and program strategy to meet climate targets, we review recent research on practices that can reduce emissions, sequester carbon and provide other co-benefits to producers and the environment across agriculture and rangeland systems. Importantly, the research reviewed here was conducted in California and addresses practices in our specific agricultural, socioeconomic and biophysical environment. Farmland conversion and the dairy and intensive livestock sector are the largest contributors to GHG emissions and offer the greatest opportunities for avoided emissions. We also identify a range of other opportunities including soil and nutrient management, integrated and diversified farming systems, rangeland management, and biomass-based energy generation. Additional research to replicate and quantify the emissions reduction or carbon sequestration potential of these practices will strengthen the evidence base for California climate policy

Designing Hybrid Gifts

Hybrid gifting combines physical artefacts and experiences with digital interactivity to generate new kinds of gifts. Our review details how gifting is a complex social phenomenon and how digital gifting is less engaging than physical gifting for both givers and receivers. Employing a Research Through Design approach, we developed a portfolio of four hybrid gifting experiences: an augmented advent calendar; edible music tracks; personalised museum tours; and a narrated city walk. Our reflection addresses three concepts: hybrid wrapping where physical gifts become wrapped in digital media and vice versa; the importance of effortful interactions that are visible and pleasurable; and the need to consider social obligation, including opportunities for acknowledgement and reciprocation, dealing with embarrassment, and recognising the distinction between giving and sharing. Our concepts provide guidance to practitioners who wish to design future gifting experiences while helping HCI researchers engage with the concept of gifting in a nuanced way