bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrative medicine: A useful approach for difficult conversations.
Authors: Hinyard Leslie J. , Wallace Cara L. , Trees April , Ohs Jennifer E.
Published: November 2019

6

Background: Narrative medicine (NM) is acknowledged as an effective approach for valuing patient and provider experiences. The NM approach requires developing narrative competence to “recognize, absorb, interpret, and honor” the stories of self and other (Charon, 2010). Given the difficulties providers face engaging in end-of-life (EOL) and advance care planning (ACP) conversations, this study reports the results of a NM workshop to 1) develop skills in attending and responding to the stories of others as part of ACP conversations and 2) reflect on their own stories of loss in relation to their professional practice. Methods: 80 health care professionals participated in a workshop on NM principles for end-of-life care and completed both pre- and post-workshop surveys. Workshop activities included a close reading on a professional’s story of personal loss and a reflective writing exercise sharing one’s own personal story of loss. Small groups debriefed after each exercise. 2 participants were current students and were dropped from analysis, for a final analytic sample of 78. Participants completed surveys at baseline and at the conclusion of the workshop. Surveys included questions on participant demographics, confidence for EOL conversations, and the ACP Self Efficacy scale. Descriptive statistics were calculated for sample demographics and post-workshop evaluation questions. A paired sample t-test was used to compare ACP Self Efficacy scores pre- and post-workshop. Confidence for EOL conversations was compared pre- and post-workshop using Kendall’s tau-b. Results: The mean age of the sample was 46.6 years (SD 13.1), 94% were female, and 82% were White. Social workers represented 84.6% of the sample. 53% of the sample reported having some type of advance care directive for themselves. Self-efficacy for engaging in ACP conversations increased from pre- to post-workshop (p < 0.0001) and there was a statistically significant improvement in confidence discussing death and dying from pre- to post-workshop (p = 0.004). Conclusions: NM competencies improve self-efficacy and confidence for engaging in ACP and EOL conversations. Providers find the NM approach to be a useful framework for engaging in difficult conversations about end-of-life.
Eflapegrastim, a novel, long-acting GCSF for reducing chemotherapy-induced neutropenia: Integrated results from two phase III trials in breast cancer patients.
Authors: Schwartzberg Lee S. , Bhat Gajanan , Bharadwaj Jayaram S. , Hlalah Osama , Restrepo Alvaro , Mehmi Inderjit , Chawla Shanta , Cobb Patrick Wayne
Published: November 2019

61

Background: Eflapegrastim (E) is a novel, long-acting GCSF comprised of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a PEG linker (MW, 72 kDa). E showed increased potency vs pegfilgrastim (P) in preclinical and Phase I and II trials. Two identically designed Phase III pivotal trials (NCT02643420, NCT02953340) were conducted globally with a fixed dose of 13.2 mg E containing 3.6 mg GCSF to evaluate E vs P (6 mg) in pts receiving chemotherapy for early-stage breast cancer. Methods: Each open-label trial randomized pts 1:1 to a single subcutaneous dose of E 13.2 mg/0.6 mL or P 6 mg/0.6 mL on Day 2 of each of four 21-day cycles following Day 1 adj/neoadj docetaxel 75 mg/m2 + cyclophosphamide 600mg/m2 (TC) . The primary endpoint was to demonstrate E non-inferiority (NI) to P as measured by mean duration of severe neutropenia (DSN) in Cycle 1. Results: A total 643 intent-to-treat pts (314 E/329 P) with median age 60 yrs (24–88) were enrolled. Cycle 1 mean (SD) DSN was 0.24 (0.581) vs 0.36 (0.789) days for E and P, confirming NI (p<.0001) and suggesting statistical superiority (p<.029). DSN NI was also shown across cycles 2–4. Among subgroups, including elderly (≥65 yrs) and overweight (>75kg) pts, DSN was reduced for E vs P. In Cycle 1, E showed an absolute risk reduction for severe neutropenia of 6.5% vs P (27.1% relative risk reduction, p<.043). Neutropenic complications (hospitalization and/or anti-infective use) were 2.9% and 4.0% for E and P (p=ns) in Cycle 1. Incidence of FN was low for both E and P, 1.6% vs 1.8% in Cycle 1 and 3.2% vs 3.0% overall. ANC profiles showed sustained increased levels for E vs P in the recovery phase across all cycles. Safety profiles including events of special interest, irrespective of grade, were mostly similar for E and P. The most common ≥ Grade 3 adverse events were hematologic due to chemotherapy. Conclusions: These integrated pivotal trial results confirm a similar safety profile and non-inferiority in reducing neutropenic risk for E at a lower GCSF dose vs P. The data also suggests the potential for increased potency of E to deliver improved clinical benefit, a possibility that warrants further clinical trials. Clinical trial information: NCT02643420 and NCT02953340.
Building a real-time clinical dashboard to identify and target supportive care interventions in patients with cancer: The Lung Cancer Report Card (LCRC).
Authors: Adonizio Christian S. , Wojtowicz Mark , Manikowski Jesse , Siegrist Cory , Hardenstine Jonathan , Belletti Daniel , Oberle Anne Marie ,   On behalf of the Thoracic Oncology Care Gaps addressed with Clinical Analytics (TOGAA) working group
Published: November 2019

66

Background: Many studies aiming to improve supportive care of patients with cancer have been single or bundled large population intervention(s). Potential use of unified clinical data architectures has not been realized in oncology, despite large patient-specific data sources generated during routine clinical care (electronic health records). Such systems can systematically apply clinical algorithms and data analytics to identify care gaps in individual patients with specific needs. Methods: Utilizing a design-think paradigm, we developed the LCRC, a near real-time interactive dashboard identifying actionable care gaps in all patients with lung cancer currently followed at Geisinger. Using an iterative process, data analysts served an expanded role in clinical delivery of targeted supportive oncology care, including recommending measures of risk for admission. Results: The table shows aggregate data as of 6/30/2019. Using the LCRC, we were able to identify 174 open care gaps in a population of 1199 active patients. We were also able to identify ‘high-risk’ clinical features in individual patients and the entire patient population. This was completed with analytics alone, without the need for lengthy chart review. Conclusions: By utilizing a population health view, the health system can more accurately estimate resources needed to better address patient needs. The LCRC can be used to directly determine the choice of supportive care interventions for specific patients with lung cancer. [Table: see text]
Who is at risk for palliative care misconceptions and how do we address them? A mixed-methods study of metastatic lung cancer patients.
Authors: McLouth Laurie , Gabbard Jennifer , Levine Beverly J , Nightingale Chandylen L , Furgurson Kate , Lycan Thomas , Petty William J. , Weaver Kathryn E.
Published: November 2019

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Background: A major misperception of palliative care (PC) is that it is only for people who are about to die. We recently identified this misperception as a barrier to PC in metastatic non-small cell lung cancer (mNSCLC) patients, patients who should all receive early PC per guidelines. The goal of this study was to assess patient characteristics associated with misperceptions about PC and to elicit patient perspectives on how to address them. Methods: We conducted a mixed-methods study of mNSCLC patients on immunotherapy or chemo-immunotherapy. A survey assessed sociodemographics, health literacy, and PC misperceptions. Semi-structured interviews queried perceptions of PC, experiences discussing PC with providers, and reactions to our institutional definition of PC. Qualitative data from interviews were analyzed using directed content analysis approach. Results: Sixty patients (Mean age = 63, 40% male; 18% African American, 45% inadequate health literacy) completed the survey. Twelve of the survey participants (Mean age = 65, 50% male, 25% African American, 67% inadequate health literacy; 50% with caregivers participating) also completed a semi-structured interview. Quantitative survey results showed equating PC with death and/or hospice did not differ based on gender, health literacy, rural vs. urban residence, or time since diagnosis (p’s > .05). Qualitative results showed patients and caregivers consistently associated PC with death (e.g., “the next step to the graveyard”) and hospice. Though some patients noted differences between our institution’s definition of PC and their perceptions (e.g., “delivered at any stage”), the definition did not increase interest and sometimes reinforced misperceptions (e.g., “See, that's a death spiral”). To address misconceptions, patients and caregivers suggested distinguishing PC from end of life and hospice, presenting it positively, and discussing it early into treatment. Conclusions: Lung cancer patients may associate PC with death even if they have adequate health literacy. Commonly used definitions of PC may not quell patient fears. PC needs to be presented as a positive service to patients early into treatment.
Current landscape of combined oncology/palliative care training in the United States.
Authors: Sedhom Ramy , Gupta Arjun , Smith Thomas J. , Kamal Arif
Published: November 2019

68

Background: Recent calls by ASCO and others recommend early integration of oncology and palliative care. The rapid growth of new cancer therapies (e.g. immunotherapy) and their associated side effects and prognostic uncertainty suggest the need for oncologists to have palliative care sub-specialization. Despite the logical integration of oncology and palliative care training, the current landscape of ACGME training programs for these fields is unknown. Methods: We explored the ERAS Fellowship Website (https://www.aamc.org/services/eras/) on June 15, 2019, and collected information on Medical oncology, Medical Oncology/Hematology, and Hospice and Palliative Medicine (HPM) Programs. We identified institutions/ health systems that offered both Medical Oncology and HPM programs. We also identified institutions/ health systems that offered other Fellowships combined with Medical Oncology. We validated information by verifying each training program's website. Results: 152 unique programs offered Medical Oncology fellowship (144 combined with hematology) and 131 unique programs offered HPM fellowship. 7 Medical Oncology programs had tracks that allowed combination with geriatrics or infectious disease. 73 unique institutions/ health systems offered both Medical Oncology and HPM training separately, but no programs offered a combined Medical Oncology/ HPM track. Conclusions: Despite the call to better integrate palliative care in oncology care, we did not find any published descriptions of tracks combining Medical Oncology and HPM training. Successful examples of integrating Medical Oncology with other disciplines such as geriatrics exist. Trainees may still forge their own pathway and do sequential fellowships in Medical Oncology and HPM, but investment by key stakeholders is essential to pilot novel educational programs to address workforce issues in this field. It remains unknown how many programs accommodate combined or sequential training for interested applicants, or how they are funded.
Breast cancer patients in a female sexual medicine and women’s health program: A cross-sectional retrospective study.
Authors: Carter Jeanne , Saban Sally , Arkema Ashley , Goldfrank Deborah J. , Goldfarb Shari Beth
Published: November 2019

8

Background: Cancer treatment impacts sexual health and QOL with symptoms of vulvovaginal dryness, dyspareunia, and sexual dysfunction. There are limited data on specific sexual changes in patients with varying treatments. We examined patient-reported and exam outcomes of breast cancer patients’ initial consults at Female Sexual Medicine & Women’s Health Program (FSMWHP) at Memorial Sloan Kettering Cancer Center. Methods: We obtained a limited waiver to evaluate medical records and Female Sexual Medicine Clinic Assessment Forms (FSMCAFs) of initial consults at FSMWHP from 6/29/12–12/23/16. The FSMCAF is composed of a pelvic exam checklist, sexual function measures (Female Sexual Function Index-FSFI; Sexual Activity Questionnaire-SAQ), vulvovaginal health measures (Vaginal Assessment Scale—VAS; Vulvar Assessment Scale—VuAS), and questions about concerns. Descriptive statistics were calculated using SPSS. Results: 446 women were categorized by menopausal status and endocrine therapy. Subcohorts were: postmenopausal with aromatase inhibitors (AIs) alone (30%), tamoxifen followed by AI (22%), tamoxifen alone (16%) or no therapy (16%), and pre/peri-menopausal with tamoxifen alone (9%) or no therapy (5%). In postmenopausal women, initial consults avg. 3.3 yrs post-treatment (pre/peri avg. 1.8 yrs). Endocrine use avg. 3 yrs. across groups. 99% of postmenopausal women scored < 26.6 on FSFI, indicating sexual dysfunction (tamoxifen alone avg: 13.7; tamoxifen followed by AI avg: 10.4). Vulvovaginal dryness and severe dyspareunia were highest in postmenopausal women with endocrine exposure (AI alone: 83% and 36%; tamoxifen alone: 66% and 32%). Related exam outcomes (pH > 6.5, petechiae, vulvovaginal atrophy, minimal/no moisture) were also highest in postmenopausal women (AI alone: 30%, 13%, 78%, 89%; tamoxifen alone: 19%, 5%, 65%, 70% respectively). Conclusions: Sexual health concerns are common in breast cancer patients. Endocrine exposure and menopause can negatively impact tissue quality. Women exposed to AIs appear to have the poorest self-reported and clinical outcomes. Proactive sexual health interventions, including early counseling, are warranted in these patients.
Developing a population health tool to identify patients with serious mental illness at cancer diagnosis.
Authors: Pappano Catherine , Fung Vicki , Barry Maura , Zucconi Tanya , Chen Jing , Irwin Kelly
Published: November 2019

82

Background: Individuals with serious mental illness (SMI) experience increased cancer mortality and are less likely to receive timely cancer care. Despite increasing recognition that psychosocial care is essential for quality cancer care, mental illness remains underrecognized and undertreated. Involving psychiatry early may prevent cancer care disruptions. We developed an EHR-based algorithm to identify patients with SMI and cancer who may benefit from targeted interventions. Methods: We utilized structured codes from a widely-used, commercial EHR to identify patients with preexisting SMI and new breast, lung, head/neck, and gastrointestinal cancers seen in the Massachusetts General Cancer Center. We developed and refined an algorithm using ICD-10 diagnostic codes, medical history, appointment types, and consultations from across the health system. The algorithm updates every 24 hours to facilitate rapid intervention. We embedded a classification system to prioritize high-risk subgroups and key time points. We validated psychiatric diagnoses, cancer types, and appointments by randomly selecting 20 charts within each category and conducting a manual chart review. Results: Over 60 days from May to July 2019, the center saw 7674 patients in breast, thoracic, head/neck, and gastrointestinal oncology including 1674 patients (22%) with documented SMI. We identified 69 people (0.9%) with psychotic disorders, 111 (1.4%) with bipolar disorder, and 1,494 (19.5%) with major depression. Among patients with major depression, we prioritized recurrent major depression (N = 199), inpatient psychiatry consultation (N = 84), alcohol use disorders (N = 77), and opioid use disorders (N = 25). SMI was well-represented across cancers including 24% (916/3,815) of patients seen in breast, 25% (291/1,164) of thoracic, 24% (180/738) of head/neck, and 15% (287/1,956) of gastrointestinal oncology. Conclusions: We developed an EHR-based tool that identified a substantial population with SMI and cancer, prioritizing subgroups at high risk of cancer care disruptions. Leveraging data in the EHR is a feasible and promising strategy to detect a vulnerable population in need of targeted psychosocial interventions. Clinical trial information: NCT03360695.
Depression in lung cancer patients: A nationwide analysis.
Authors: Mariam Roy Arya , Konda Manojna , Mohanakumar Warrier Aravind , Arnaoutakis Konstantinos
Published: November 2019

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Background: Depression is a major ongoing problem with cancer patients and survivors. Depression can lead to functional impairment, decreased utilization of treatment, decreased quality of life and increased suicide risk. It also leads to an extended hospital stay and increased cost of treatment. Previous studies have shown that lung cancer has a high incidence for depression. Methods: We conducted a cross-sectional study using the National Inpatient Sample (NIS) database for the year 2016. Patients who were admitted with a principal diagnosis of Malignant Neoplasm of Bronchus and Lung (MNBL) and Major Depressive Disorder (MDD) were identified using ICD-10 codes. The prevalence of MDD and the risk factors contributing to MDD were studied. Statistical analysis was performed using STATA tool and tested with Pierson Chi-Square test. Results: A total of 79096 hospitalizations with a principal diagnosis of MNBL were identified. The prevalence of depression among lung cancer patients was found to be 12.49% (n = 9881). The mean age of lung cancer patients with depression was 62.27 ± 0.10. Females with lung cancer have more risk for MDD (15%, p < 0.001). Caucasian patients with lung cancer have a higher risk of MDD (13.6%, p < 0.001). It was also found that lung cancer patients who are ≤ 55 years have a higher risk of MDD (p < 0.001). The average length of stay for lung cancer patients with MDD was slightly higher than lung cancer patients without MDD (6.39 days and 5.99 days respectively). The average cost of stay also had a similar pattern. Severe morbidity was seen in a greater proportion of the MDD group. Conclusions: Younger patients who are ≤ 55 years of age, Caucasians or females with lung cancer have a higher risk of MDD. Particular attention should be given to them while being in the hospital which can decrease the morbidity, and will also help to improve their quality of life.
Mixed methods comparison of functional decline during chemotherapy, immunotherapy (IO), and/or targeted therapy in older adults with non-small cell lung cancer (NSCLC).
Authors: Wong Melisa L. , Smith Alexander K. , Miaskowski Christine , Musinipally Vivek , Cohen Harvey Jay , Lam Vivian , Mazor Melissa , Ursem Carling Jade , Loh Kah Poh , Cohen Jamie , Shumay Dianne , Levin Anna Ordin , Dixit Niharika , Grandi Janice , Walter Louise Christie
Published: November 2019

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Background: Functional decline during NSCLC treatment is critically important to older adults. Yet, data on functional decline—particularly during chemoIO, IO, and targeted therapy—remain limited. Additionally, the best measures to capture functional decline from the patient’s perspective remain unknown. Methods: We conducted a multisite, mixed methods prospective cohort study to characterize function during systemic NSCLC treatment and compare quantitative measures with gold standard qualitative descriptions of patients’ lived experience. Prior to and at 2 months after treatment initiation, 69 adults age >65 with advanced NSCLC starting chemo, IO, and/or targeted therapy underwent geriatric assessments including instrumental activities of daily living (IADL), EORTC QLQ-C30 Physical Functioning (PF), and Life-Space Assessment (LSA). LSA measures where a person goes in their environment, how frequently, and how independently. Pretreatment functional impairment and decline at 2 months were assessed. In a qualitative substudy, 16 purposively sampled patients with diverse pretreatment function completed two semi-structured interviews (pretreatment, 2 months) to explore treatment effects on daily functioning. Grounded theory was used to code for functional decline. Using the qualitative patient experience as the gold standard, sensitivity and specificity were calculated for each functional measure. Results: Mean age was 75 (range 65-94). NSCLC treatment included IO (36%), targeted therapy (28%), chemoIO (23%), and chemo (13%). Pretreatment functional impairment was common and ~25% of patients experienced functional decline on quantitative measures at 2 months (Table). Qualitatively, 50% described functional decline at 2 months. LSA had the highest sensitivity (71%) and similar specificity (88%) as IADL and PF. Conclusions: Functional decline during NSCLC treatment is common. LSA provides a sensitive and specific patient-centered measure of function. [Table: see text]
Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes
Authors: Baqar Sara , Kong Yee Wen , Chen Angela X , O’Callaghan Christopher , MacIsaac Richard J , Bouterakos Maree , Lambert Gavin W , Jerums George , Lambert Elisabeth E , Ekinci Elif I
Published: November 2019

Context

Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D).

Objective

To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo.

Design

We conducted a randomized, double-blinded, placebo-controlled crossover trial.

Setting

The study took place in a tertiary referral diabetes outpatient clinic.

Participants

Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included.

Intervention

Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered.

Main outcome measures

The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity.

Results

Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07).

Conclusions

In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.
Obesity Is Associated with Earlier Pubertal Onset in Boys
Authors: Busch Alexander S , Højgaard Brigitte , Hagen Casper P , Teilmann Grete
Published: November 2019

Context

Pubertal timing in boys is associated with body mass index (BMI). Studies consistently report an inverse correlation of BMI and pubertal timing within the normal BMI range. However, observations in obese boys are conflicting with different studies reporting either early or delayed pubertal onset in obese boys.

Objective

We aimed to assess the association of male pubertal timing with age-specific BMI (zBMI) in obese boys.

Design, Setting, and Participants

A total of 218 obese boys (zBMI > +2SD, with a median age at baseline of 10.8 years (range 4.2–17.0), were recruited as part of a prospective outpatient childhood obesity intervention program at Nordsjællands Hospital, Hillerød, Denmark, between 2009 and 2017. Serving as controls, we included 660 healthy boys participating in the population-based COPENHAGEN Puberty Study (-2SD < zBMI ≤ +2SD, 2006–2014). Subanalyses were performed on overweight controls (+1SD < zBMI ≤ +2SD). The clinical assessment of pubertal development by Tanner staging, including testis volume using a Prader’s orchidometer, was performed by trained physicians. The timing of pubertal milestones was estimated by probit analyses.

Main Outcome Measures

Timing of testicular volume ≥ 4 mL, genital stage ≥ 2, and pubarche.

Results

The mean (95% confidence interval [CI]) age of onset of pubertal event in obese boys was as follows: testicular volume ≥ 4 mL, 11.3 years (11.0–11.6); genital stage ≥ 2, 11.6 yrs (11.3–11.9); and pubarche, 11.9 years (11.5–12.3). Testicular volume ≥ 4 mL occurred significantly earlier in obese boys compared to controls (-2SD < zBMI ≤ +2SD) (P = 0.01). We did not observe significant differences for either the timing of pubarche nor the genital stage ≥ 2 (P = 0.06 and P = 0.94, respectively)

Conclusions

We demonstrate that testicular enlargement in obese boys occurs significantly earlier compared to a population-based normal-weight reference cohort.
Prenylflavonoid Icariin Induces Estrogen Response Element–Independent Estrogenic Responses in a Tissue-Selective Manner
Authors: Zhou Liping , Poon Christina Chui-Wa , Wong Ka-Ying , Cao Sisi , Yu Wenxuan , Dong Xiaoli , Lee Wayne Yuk-Wai , Zhang Yan , Wong Man-Sau
Published: November 2019

Icariin, a flavonoid phytoestrogen derived from Herba epimedii, has been reported to exert estrogenic effects in bone and activate phosphorylation of estrogen receptor (ER) α in osteoblastic cells. However, it is unclear whether icariin selectively exerts estrogenic activities in bone without inducing undesirable effects in other estrogen-sensitive tissues. The present study aimed to investigate the tissue-selective estrogenic activities of icariin in estrogen-sensitive tissues in vivo and in vitro. Long-term treatment with icariin effectively prevented bone of ovariectomized (OVX) rats from estrogen deficiency–induced osteoporotic changes in bone structure, bone mineral density, and trabecular properties. Moreover, icariin regulated the transcriptional events of estrogen-responsive genes related to bone remodeling and prevented dopaminergic neurons against OVX-induced changes by rescuing expression of estrogen-regulated tyrosine hydroxylase and dopamine transporter in the striatum. Unlike estrogen, icariin did not induce estrogenic effects in the uterus and breast in mature OVX rats or immature CD-1 mice. In vitro studies demonstrated that icariin exerted estrogen-like activities and regulated the expression of estrogen-responsive genes but did not induce estrogen response element–dependent luciferase activities in ER-positive cells. Our results support the hypothesis that icariin, through its distinct mechanism of actions in activating ER, selectively exerts estrogenic activities in different tissues and cell types.
BNC1 regulates cell heterogeneity in human pluripotent stem cell-derived epicardium
Authors: Gambardella Laure , McManus Sophie A. , Moignard Victoria , Sebukhan Derya , Delaune Agathe , Andrews Simon , Bernard William G. , Morrison Maura A. , Riley Paul R. , Göttgens Berthold , Gambardella Le Novère Nicolas , Sinha Sanjay
Published: November 2019

The murine developing epicardium heterogeneously expresses the transcription factors TCF21 and WT1. Here, we show that this cell heterogeneity is conserved in human epicardium, regulated by BNC1 and associated with cell fate and function. Single cell RNA sequencing of epicardium derived from human pluripotent stem cells (hPSC-epi) revealed that distinct epicardial subpopulations are defined by high levels of expression for the transcription factors BNC1 or TCF21. WT1+ cells are included in the BNC1+ population, which was confirmed in human foetal hearts. THY1 emerged as a membrane marker of the TCF21 population. We show that THY1+ cells can differentiate into cardiac fibroblasts (CFs) and smooth muscle cells (SMCs), whereas THY1− cells were predominantly restricted to SMCs. Knocking down BNC1 during the establishment of the epicardial populations resulted in a homogeneous, predominantly TCF21high population. Network inference methods using transcriptomic data from the different cell lineages derived from the hPSC-epi delivered a core transcriptional network organised around WT1, TCF21 and BNC1. This study unveils a list of epicardial regulators and is a step towards engineering subpopulations of epicardial cells with selective biological activities.
An interview with Kate Storey
Authors: Maartens Aidan
Published: November 2019

Kate Storey is Professor of Neural Development and Head of the Division of Cell and Developmental Biology at the University of Dundee in Scotland. Her lab works on neural differentiation in the developing spinal cord. A Fellow of The Royal Society of Edinburgh, the Academy of Medical Sciences and the Royal Society of Biology, in 2019 she was awarded the British Society for Developmental Biology's (BSDB) Waddington Medal, which recognises outstanding individuals who have made major contributions to UK developmental biology. After her award lecture, we caught up with Kate to survey her career and hear her thoughts on the field's future.
An interview with Bénédicte Sanson
Authors: Maartens Aidan
Published: November 2019

Bénédicte Sanson is a Reader in Developmental Morphogenesis and Wellcome Trust Investigator at the Department of Physiology, Development and Neuroscience at the University of Cambridge. Her lab works on axis extension and compartmental boundary formation in the Drosophila embryo, combining genetics with quantitative and computational approaches. In 2019 she was awarded the British Society for Developmental Biology's Cheryll Tickle medal, which recognises outstanding achievements in developmental biology of mid-career female researchers. We caught up with Bénédicte in a café close to her lab and discussed how she started research not with flies but with phages and how collaboration and interdisciplinarity have always been at the core of her science.
Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts
Authors: Škalamera Dubravka , Stevenson Alexander J. , Ehmann Anna , Ainger Stephen A. , Lanagan Catherine , Sturm Richard A. , Gabrielli Brian
Published: November 2019

Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.
Experience-dependent tuning of early olfactory processing in the adult honey bee,Apis mellifera
Authors: Jernigan Christopher M. , Halby Rachael , Gerkin Richard C. , Sinakevitch Irina , Locatelli Fernando , Smith Brian H.
Published: November 2019

Experience-dependent plasticity in the central nervous system allows an animal to adapt its responses to stimuli over different time scales. In this study we explored the impacts of adult foraging experience on early olfactory processing by comparing naturally foraging honey bees, Apis mellifera, to those that experienced a chronic reduction in adult foraging experience. We placed age-matched sets of sister honey bees into two different olfactory conditions, in which animals were allowed to forage ad libitum. In one condition, we restricted foraging experience by placing honey bees in a tent in which both sucrose and pollen resources were associated with a single odor. In the second condition, honey bees were allowed to forage freely and therefore encounter a diversity of naturally occurring resource-associated olfactory experiences. We found that honey bees with restricted foraging experiences had altered antennal lobe development. We measured the glomerular responses to odors using calcium imaging in the antennal lobe, and found that natural olfactory experience also enhanced the inter-individual variation in glomerular response profiles to odors. Additionally, we found that honey bees with adult restricted foraging experience did not distinguish relevant components of an odor mixture in a behavioral assay as did their freely foraging siblings. This study highlights the impacts of individual experience on early olfactory processing at multiple levels.
Diffusive structural colour in Hoplia argentea
Authors: Kilchoer Cédric , Pirih Primož , Steiner Ullrich , Wilts Bodo D.
Published: November 2019

Nature's nanostructures can bring about vivid and iridescent colours seen in many insects, notably in beetles and butterflies. While the intense structural colours can be advantageous for display purposes, they may be also appealing to predators and therefore constitute an evolutionary disadvantage. Animals often employ absorption and scattering in order to reduce the directionality of the reflected light and thereby enhance their camouflage. Here, we investigate the monkey beetle Hoplia argentea using microspectrophotometry, electron microscopy, fluorimetry and optical modelling. We show that the dull green dorsal colour comes from the nanostructured scales on the elytra. The nanostructure consists of a multi-layered photonic structure covered by a filamentous layer. The filamentous layer acts as a spatial diffuser of the specular reflection from the multilayer and suppresses the iridescence. This combination leads to a colour-stable and angle-independent green reflection that likely enhances the camouflage of the beetles in their natural habitat.
Hypoxia-seeking behaviour, metabolic depression, and skeletal muscle function in an amphibious fish out of water
Authors: Rossi Giulia S. , Wright Patricia A.
Published: November 2019

Several animals enter a state of dormancy to survive harsh environmental conditions. During dormancy, metabolic depression can be critical for economizing on limited endogenous energy reserves. We used two isogenic strains (Strain 1 and Strain 2) of a self-fertilizing amphibious fish (Kryptolebias marmoratus) to test the hypothesis that animals seek hypoxic microhabitats that, in turn, accentuate metabolic depression during dormancy. Using custom-built tunnels that maintained a longitudinal O2 gradient (hypoxic to normoxic), we assessed the O2 preference of K. marmoratus during prolonged air-exposure. In support of our hypothesis, we found that one isogenic strain (Strain 2) spent more time in hypoxia compared to normoxia after 21 days in air. Prolonged air-exposure in both strains resulted in lower O2 consumption rates compared to active fish (35% depression), which was accentuated (51% depression) when fish were exposed to aerial hypoxia acutely. We then tested the hypothesis that chronic aerial hypoxia acclimation would protect endogenous energy reserves and skeletal muscle integrity, thereby maintaining locomotor performance, possibly due to hypoxic hypometabolism. We found that air-acclimated fish from both strains were in poorer body condition relative to fish acclimated to aerial hypoxia. Furthermore, aerial hypoxia-acclimation minimized glycogen usage (Strain 1), lipid catabolism (Strain 2), and white muscle atrophy (Strain 2), as well as preserved terrestrial locomotor performance compared to fish in air (Strain 2). Overall, our findings suggest that some K. marmoratus strains seek microhabitats that accentuate metabolic depression during dormancy, and that microhabitat O2 availability may have significant implications for energy metabolism, and the structure and function of skeletal muscle. Furthermore, the differential responses between isogenic strains suggests that genetic factors also contribute to phenotypic differences in the emersion behaviour and physiology of this species.
The energetics of ‘airtime’: estimating swim power from breaching behaviour in fishes and cetaceans
Authors: Halsey Lewis G. , Iosilevskii Gil
Published: November 2019

Maximum swimming behaviour is rare in the laboratory or the wild, limiting our understanding of the top-end athletic capacities of aquatic vertebrates. However, jumps out of the water - exhibited by a diversity of fish and cetaceans - might sometimes represent a behaviour of maximum burst effort. We collected data on such breaching behaviour for 14 fish and cetacean species primarily from online videos, to calculate breaching speed. From newly derived formulae based on the drag coefficient and hydrodynamic efficiency we also calculated the associated power. The fastest breaching speeds were exhibited by species 2 m in length, peaking at nearly 11 m/s; from this length, as species size decreases the fastest breaches become slower, while species larger than 2 m do not show a systematic pattern. The power associated with the fastest breaches was consistently about 50 W/kg (equivalent to 200 W/kg muscle) in species from 20 cm to 2 m in length; this value may represent a universal (conservative) upper boundary. And it is similar to the maximum recorded power output per muscle mass recorded in any species of similar size, suggesting that some breaches could indeed be representative of maximum capability.
Cardiorespiratory Fitness, Physical Activity, and Insulin Resistance in Children
Authors: HAAPALA EERO A. , WIKLUND PETRI , LINTU NIINA , TOMPURI TUOMO , VÄISTÖ JUUSO , FINNI TAIJA , TARKKA INA M. , KEMPPAINEN TITTA , BARKER ALAN R. , EKELUND ULF , BRAGE SOREN , LAKKA TIMO A.
Published: November 2019

Purpose

Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycemia and insulin resistance and their interactions with physical activity (PA) and sedentary time among 452 children age 6 to 8 yr.

Methods

We assessed CRF with a maximal cycle ergometer exercise test and used allometrically scaled maximal power output (W
max) for lean body mass (LM1.13) and body mass (BM1) as measures of CRF. The BF% and LM were measured by dual-energy X-ray absorptiometry, fasting glycemia by fasting plasma glucose, and insulin resistance by fasting serum insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The PA energy expenditure, moderate-to-vigorous PA (MVPA), and sedentary time were assessed by combined movement and heart rate sensor.

Results

W
max/LM1.13 was not associated with glucose (β = 0.065, 95% confidence interval [CI] = −0.031 to 0.161), insulin (β = −0.079, 95% CI = −0.172 to 0.015), or HOMA-IR (β = −0.065, 95% CI = −0.161 to 0.030). W
max/BM1 was inversely associated with insulin (β = −0.289, 95% CI = −0.377 to −0.200) and HOMA-IR (β = −0.269, 95% CI = −0.359 to −0.180). The BF% was directly associated with insulin (β = 0.409, 95% CI = 0.325 to 0.494) and HOMA-IR (β = 0.390, 95% CI = 0.304 to 0.475). Higher W
max/BM1, but not W
max/LM1.13, was associated with lower insulin and HOMA-IR in children with higher BF%. Children with higher BF% and who had lower levels of MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR.

Conclusions

Children with higher BF% together with less MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Cardiorespiratory fitness appropriately controlled for body size and composition using LM was not related to insulin resistance among children.
Corticospinal Modulations during Motor Imagery of Concentric, Eccentric, and Isometric Actions
Authors: GROSPRÊTRE SIDNEY , PAPAXANTHIS CHARALAMBOS , MARTIN ALAIN
Published: November 2019

Purpose

It is not known yet whether the neurophysiological specificity of eccentric, concentric, and isometric contractions can also be observed when these are mentally simulated. Therefore, our aim was to assess corticospinal excitability during motor imagery (MI) of different contraction types and to test whether a passive movement during MI could have additional effects.

Methods

Twelve young participants imagined contractions of the wrist flexors, firstly with the arm motionless (static mode) and second, with a congruent passive movement (wrist extension during eccentric MI and wrist flexion during concentric MI). Motor-evoked potentials (MEP) and H-reflexes were elicited in flexor carpi radialis (FCR) at rest and during the three types of MI. As a secondary outcome, the MEP of one antagonist (extensor carpi radialis), elicited concomitantly with FCR MEP recording, were also analyzed.

Results

In static mode, FCR MEP were facilitated during isometric (P = 0.046) and concentric (P = 0.039) MI, but not during eccentric MI (P = 0.902). With passive congruent movements, FCR MEP were enhanced during all imagined contraction types, including eccentric (P = 0.047). FCR H-reflexes increased only during eccentric MI accompanied with wrist extension (P = 0.003). Extensor carpi radialis MEP were modulated only when a passive congruent movement was provided (P = 0.040).

Conclusions

Like actual contractions, eccentric MI exhibits specific neural correlates, compared with isometric and concentric MI, which should be considered when using this modality for training. The present results showed that adding passive movements congruent to the eccentric MI task would enhance its impact over corticospinal structures.
Isometric Exercise with Large Muscle Mass Improves Redox Balance and Blood Pressure in Hypertensive Adults
Authors: OLHER RAFAEL REIS , ROSA THIAGO SANTOS , SOUZA LUIZ HUMBERTO RODRIGUES , OLIVEIRA JOSÉ FERNANDO , SOARES BRANDE RANTER ALVES , RIBEIRO THIAGO BELARMINO ALVES , SOUZA IORANNY RAQUEL CASTRO , NEVES RODRIGO VANERSON PASSOS , SOUSA CAIO VICTOR , DEUS LYSLEINE ALVES , MARCHETTI PAULO HENRIQUE , SIMOES HERBERT GUSTAVO , MORAES MILTON ROCHA
Published: November 2019

Purpose

The aim of this study was to investigate the hemodynamic, oxidative stress (OS), and nitric oxide (NO−) responses to a submaximal isometric exercise session (IES) involving large muscle mass.

Methods

Fourteen hypertensive (HTG: age = 35.9 ± 8.1 yr, height = 1.73 ± 0.10 m, total body mass = 78.0 ± 15.8 kg) and 10 normotensive (NTG: age = 41.1 ± 9.4 yr, height = 1.71 ± 0.12 m, total body mass = 82.3 ± 22.4 kg) participants performed two experimental sessions in the leg press and bench press: (i) control session and (ii) 8 sets × 1 min contraction at 30% maximal voluntary isometric contraction with 2-min rest interval. Blood pressure (BP) was measured at rest and during 60 min postexercise. Blood samples were collected at rest, immediately after the session, and 60 min postexercise. NO− was obtained through the Griess reaction method. OS parameters were analyzed using commercial kits. A repeated-measures ANOVA with Bonferroni post hoc test was used to analyze all dependent variables.

Results

A significant decrease in systolic BP was observed only for HTG at 45 and 60 min postexercise (baseline vs 45 min: P = 0.03, Δ% = 4.44%; vs 60 min: P = 0.018, Δ% = 5.58%). NO− increased immediately postexercise only for HTG (P = 0.008, Δ% = 16.44%). Regarding OS parameters, thiobarbituric acid reactive substances presented a significant reduction 60 min after the IES for NTG and HTG; catalase increased in both groups.

Conclusions

The data showed that only 8 min of IES with a large muscle mass elicits an elevated pro-oxidant activity leading to a greater NO− bioavailability, increases antioxidant reaction, and consequently reduces BP in hypertensive patients.
IMPACTS OF SEDIMENTATION ON STONY CORALS
Authors: Hadi Tri Aryono
Published: November 2019

PENGARUH SEDIMENTASI PADA KARANG KERAS. Aktivitas manusia baik di darat maupun di laut membawa banyak pengaruh negatif terhadap ekosistem laut. Terumbu karang yang utamanya disusun oleh karang keras mengalami degradasi akibat turunnya kualitas perairan, terutama akibat sedimentasi dan eutrofikasi. Secara umum hal ini akan menyebabkan menurunnya kelimpahan dan diversitas karang batu, dan secara khusus akan memengaruhi proses fisiologis karang. Proses fotosintesis menurun sebagai imbas dari menurunnya penetrasi cahaya akibat tingginya turbiditas dan sedimen yang menempel di permukaan karang. Untuk menanggulangi defisit energi, maka karang meningkatkan aktivitas menangkap makanan sekaligus proses respirasi. Reproduksi dan rekruitmen juga akan menurun seiring rusaknya sperma karang dan tertutupnya substrat untuk perlekatan larva. Sedimen juga akan memicu penyakit karang karena produksi mukus yang berlebihan. Pengkayaan nutrien di laut akan meningkatkan proses fotosintesis sebagaimana tersedianya senyawa anorganik yang penting untuk transfer energi dan kandungan dari zooxanthellae, namun apabila berlebihan akan menimbulkan gangguan pada proses reproduksi dan meningkatkan wabah penyakit karang. Meskipun karang mampu merespon gangguan tersebut, untuk jangka waktu yang panjang akan menimbulkan effek yang mematikan. Oleh karena itu perlu dilakukannya evaluasi mengenai aktivitas manusia disekitar wilayah pesisir untuk meminimalisir dampak negatif pada ekosistem pesisir.
Atrial Fibrillation: Should Lifelong Athletes Be Worried?
Authors: Drum Scott N. , Donath Lars , Dehlin Chris , Kashou Anthony , Noseworthy Peter A. , Zacher Jonas
Published: November 2019

Atrial fibrillation (AF) in lifetime athletes (e.g., ≥5 years of participation) is a growing concern but remains enigmatic. Intriguingly, a direct relationship between lifetime training hours and risk of developing AF exists. Professionals in exercise and sport science are at the forefront to help recognize symptoms and direct the athlete to appropriate medical clinicians for expedient care. Although AF in athletes is usually not accompanied by structural heart disease or stroke risk factors (i.e., termed lone AF), it may, nonetheless, pose health risks. In this study, we review various types of AF, proposed mechanisms, and treatment strategies for athletes with AF.
Using the Nordic Hamstring Exercise to Reduce Hamstring Injuries in Gaelic Football
Authors: Brown Justin R. , Macklin Ian , Waller Michael
Published: November 2019

Various modes of football, such as soccer, rugby, Gaelic football (GF), and Australian rules football (ARF), have been carefully examined regarding injuries, risk factors, and training to prevent injury. To date, few studies have examined hamstring injury (HI) in GF. Other modes of football have received a considerable amount of research. The research indicates many HIs are common during movements such as high-speed running, deceleration, and kicking. The purpose of this article is to introduce the Nordic hamstring exercise as an exercise used to increase eccentric hamstring muscle strength and reduce HI.