bluuebunny/crossref_metadata_2025 huggingface dataset:
Public, health professional and legislator perspectives on the concept of psychiatric disease: a population-based survey
Authors: Tikkinen Kari A O , Rutanen Jarno , Frances Allen , Perry Brea L , Dennis Brittany B , Agarwal Arnav , Maqbool Amna , Ebrahim Shanil , Leinonen Janne S , Järvinen Teppo L N , Guyatt Gordon H
Published: June 2019

Objective

To assess which mental health-related states of being are perceived as diseases by psychiatrists, non-psychiatric physicians, nurses, parliament members and laypeople.

Design and setting

A population-based, mailed survey in Finland.

Participants

Respondents from a random sample of 3000 laypeople, 1500 physicians, 1500 nurses and all 200 members of the parliament (MPs) of Finland.

Primary outcome measures

Respondents’ perspectives on 20 mental health-related states of being as diseases, measuring the extent of agreement with the claim: ‘[This state of being] is a disease’.

Results

Of the 6200 people approached, we received 3259 eligible responses (53%). Two conditions (schizophrenia and autism) were considered to be diseases by at least 75% and two states (grief and homosexuality) were considered not to be diseases by at least 75% in each group. A majority (at least 50% in each group) considered seven states as diseases (anorexia, attention deficit hyperactivity disorder, bulimia, depression, generalised anxiety disorder, panic disorder and personality disorder) and three not to be diseases (absence of sexual desire, premature ejaculation and transsexualism). In six states, there was a wide divergence of opinion (alcoholism, drug addiction, gambling addiction, insomnia, social anxiety disorder and work exhaustion). Psychiatrists were significantly more inclined to considering states of being as diseases relative to other groups, followed by non-psychiatric physicians, nurses, MPs and laypeople.

Conclusions

Respondents agreed that some conditions, such as schizophrenia and autism, are diseases and other states, such as grief and homosexuality, are not; for others, there was considerable disagreement. Psychiatrists are more inclined to consider mental health-related states of being as diseases compared with other physicians, who, in turn, are more inclined than other constituencies. Understanding notions of disease may underlie important debates in public policy and practice in areas of mental health and behaviour, and have implications for resource allocation and stigma.
The utility of health belief model to explain self-protective behaviour against pneumoconiosis in Chinese underground coal miners: a cross-sectional study
Authors: Liu Qiong , Chen Wanli , Qi Renjie , Geng Yang , Liu Ya , Zhou Ying , Zhang Chenggang , Wang Xian , Wang Jiwei , Yu Jinming
Published: June 2019

Objectives

Coal workers’ pneumoconiosis is caused by exposure to respirable coal mine dust. The self-protection of underground coal miners (UCM) plays an irreplaceable role against this threat. The purpose of this study was to evaluate the predictors of self-protective behaviour (SPB) in Chinese UCM based on the health belief model (HBM).

Methods

A cross-sectional study was conducted among 341 UCM in January 2016 in Pingdingshan City, Henan Province, People’s Republic of China. Data was collected using a self-reported questionnaire, which included questions on sociodemographic characteristics, HBM variables and SPB. An exploratory factor analysis of the principal components with varimax rotation was carried out on the HBM-related items. Pearson’s correlation and multiple linear regression analysis were used to assess the relationship between sociodemographic characteristics, HBM variables and SPB.

Results

Multiple regression analysis demonstrated the monthly income (B=0.403, p=0.001), the internal cues to action (B=0.380, p<0.001) and external cues to action (B=0.401, p<0.001) as the predictors of UCM’s SPB, accounting for 24.8% of total variance (F=34.96, p<0.001), while the cognition variables of HBM were not significantly associated with SPB.

Conclusion

The results suggested that both internal and external cues to action were powerful predictors for SPB. These findings highlight that further efforts are required to provide the UCM with periodic health check-up reports and promote the active role of doctors and family members in miners’ decision-making to simulate them for better SPB.

Ethics approval

All data collection procedures received ethical approval from the Ethics Committee of Xuhui District Centre for Disease Control and Prevention (XHHEC-2016–7).
Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT) in the UK: study protocol for three population-based cohort studies emulating ‘target trials’ (the ADAPTT Study)
Authors: Pufulete Maria , Harris Jessica , Sterne Jonathan A C , Johnson Thomas W , Lasserson Daniel , Mumford Andrew , Doble Brett , Wordsworth Sarah , Benedetto Umberto , Rogers Chris A , Loke Yoon , Pithara Christalla , Redwood Sabi , Reeves Barnaby C
Published: June 2019

Introduction

‘Real world’ bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified.

Methods and analysis

We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three ‘target trials’ in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study’s main limitation—that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD.

Ethics and dissemination

This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders.

Trial registration number

76607611; Pre-results.
Metagenomics in ophthalmology: current findings and future prospectives
Authors: Borroni Davide , Romano Vito , Kaye Stephen B , Somerville Tobi , Napoli Luca , Fasolo Adriano , Gallon Paola , Ponzin Diego , Esposito Alfonso , Ferrari Stefano
Published: June 2019

Less than 1% of all microorganisms of the available environmental microbiota can be cultured with the currently available techniques. Metagenomics is a new methodology of high-throughput DNA sequencing, able to provide taxonomic and functional profiles of microbial communities without the necessity to culture microbes in the laboratory. Metagenomics opens to a ‘hypothesis-free’ approach, giving important details for future research and treatment of ocular diseases in ophthalmology, such as ocular infection and ocular surface diseases.
Expanding the spectrum of genes responsible for hereditary motor neuropathies
Authors: Previtali Stefano C. , Zhao Edward , Lazarevic Dejan , Pipitone Giovanni Battista , Fabrizi Gian Maria , Manganelli Fiore , Mazzeo Anna , Pareyson Davide , Schenone Angelo , Taroni Franco , Vita Giuseppe , Bellone Emilia , Ferrarini Moreno , Garibaldi Matteo , Magri Stefania , Padua Luca , Pennisi Elena , Pisciotta Chiara , Riva Nilo , Scaioli Vidmer , Scarlato Marina , Tozza Stefano , Geroldi Alessandro , Jordanova Albena , Ferrari Maurizio , Molineris Ivan , Reilly Mary M. , Comi Giancarlo , Carrera Paola , Devoto Marcella , Bolino Alessandra
Published: June 2019

Background

Inherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%–70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions. Thus, it is of paramount importance to identify novel causative variants in HMN/CMT2 patients to better predict clinical outcome and progression.

Methods

We designed a collaborative study for the identification of variants responsible for HMN/CMT2. We collected 15 HMN/CMT2 families with evidence for autosomal recessive inheritance, who had tested negative for mutations in 94 known IPN genes, who underwent whole-exome sequencing (WES) analyses. Candidate genes identified by WES were sequenced in an additional cohort of 167 familial or sporadic HMN/CMT2 patients using next-generation sequencing (NGS) panel analysis.

Results

Bioinformatic analyses led to the identification of novel or very rare variants in genes, which have not been previously associated with HMN/CMT2 (ARHGEF28,KBTBD13,AGRNandGNE); in genes previously associated with HMN/CMT2 but in combination with different clinical phenotypes (VRK1andPNKP), and in theSIGMAR1gene, which has been linked to HMN/CMT2 in only a few cases. These findings were further validated by Sanger sequencing, segregation analyses and functional studies.

Conclusions

These results demonstrate the broad spectrum of clinical phenotypes that can be associated with a specific disease gene, as well as the complexity of the pathogenesis of neuromuscular disorders.
CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
Authors: Jeppsson Anna , Wikkelsö Carsten , Blennow Kaj , Zetterberg Henrik , Constantinescu Radu , Remes Anne M , Herukka Sanna-Kaisa , Rauramaa Tuomas , Nagga Katarina , Leinonen Ville , Tullberg Mats
Published: June 2019

Objective

To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer’s disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders.

Methods

The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson’s disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer’s disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1).

Results

Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers.

Conclusions

The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.
Thinking with the living body: the biopsychosocial model and the cosmopolitics of existence
Authors: Schillmeier Michael
Published: June 2019

This paper argues that the ‘biopsychosocial’ model of the body highlights the importance of the psychosocial dimension for a better understanding of health and illness. Most importantly, by emphasising the fundamental relevance of values in the make-up of living systems, the biopsychosocial model radically challenges the common sense operation of evidence-based biomedical operations that bifurcate the body into the subjectivities of human perceptions and the non-subjective qualities of the nature of bodies. The biopsychosocial model protests against the manner by which only non-subjective qualities gain explanatory power in analysing, diagnosing and treating somatic and mental health issues. To accentuate the explanatory importance of values in understanding embodied human life, I will introduce Émile Durkheim’s seminal work about human society as a realitysui generisthat introduces the scientific realm for a ‘special psychology’ (Durkheim) to analyse ‘values’ as an emergent accomplishment of human social life. Still, as important Durkheim’s account is in understanding societal values, it is only partially valid for the biopsychosocial model since it iterates the common sense operation of bifurcation by dismissing individual perceptions as valid sources to gain knowledge about the realities of human social values. To avoid bifurcation and to give importance to the subjectivities of every mode of existence, I will introduce Tarde’s monadology that emphasises the value-laden psychosocial processes and societal organisation in understandingallbodies and things—human and non-human alike. A monadological reading of the body universalises the ‘biopolitics’ of human affairs and unfolds what I call the ‘cosmopolitics of existence’. With the shift from the biopolitics of human affairs to the cosmopolitics of existence this paper wishes to contribute to novel ways of thinking the biopsychosocial body beyond bifurcating mind and nature.
Multimodality imaging in carcinoid heart disease
Authors: Agha Ali M , Lopez-Mattei Juan , Donisan Teodora , Balanescu Dinu , Iliescu Cezar A , Banchs Jose , Kim Peter Y , Palaskas Nicolas L , Yusuf Syed , Gladish Greg , Hassan Saamir
Published: June 2019

Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart disease typically leads to valve dysfunction, but in rare instances, carcinoid tumours can also metastasise to the endocardium and myocardium. Cardiovascular imaging plays an integral role in the diagnosis and prognosis of carcinoid heart disease. The use of multimodality imaging techniques including echocardiography, cardiac MRI, cardiovascular CT and positron emission tomography have allowed for a more comprehensive assessment of carcinoid heart disease. In this review, we discuss the features of carcinoid heart disease observed on multimodality imaging, indications for obtaining imaging studies and their role in carcinoid heart disease management.
Impact of e-cigarette and cigarette prices on youth and young adult e-cigarette and cigarette behaviour: evidence from a national longitudinal cohort
Authors: Cantrell Jennifer , Huang Jidong , Greenberg Marisa S , Xiao Haijuan , Hair Elizabeth C , Vallone Donna
Published: June 2019

Introduction

Understanding the impact of prices for tobacco and nicotine products is critical for creating policies to prevent use among young people. This study examines the impact of electronic cigarette (e-cigarette) and cigarette prices on current e-cigarette and cigarette use among youth and young adults.

Methods

Data were from a national probability-based sample aged 15–21 collected in 2014 and followed every 6 months for 2.5 years through 2016. We conducted separate conditional likelihood logistic regression models with past 30-day e-cigarette use and past 30-day cigarette use outcomes on the sample of individuals who participated in at least two survey waves (n=11 578) with linked Nielsen market-level price data for rechargeable e-cigarettes and cigarettes. Models controlled for time-varying variables at the individual and state policy levels, and fixed effects at the individual, wave and market levels.

Results

Higher cigarette prices were associated with increased past 30-day e-cigarette use, indicating e-cigarettes may serve as a substitute for cigarettes. We did not find a statistically significant relationship between rechargeable e-cigarette prices and past 30-day e-cigarette use; neither did we find a significant relationship between rechargeable e-cigarette prices and past 30-day cigarette smoking.

Conclusion

This is the first study to examine e-cigarette and cigarette prices on e-cigarette and cigarette behaviour longitudinally among young people. Findings suggest the need for better measuring the costs associated with e-cigarette use among this population, as well as a careful assessment of price and tax policies that takes into account cross-product impact to sufficiently discourage e-cigarette and cigarette use among young people.
Exploring early life events including diet in cats presenting for gastrointestinal signs in later life
Authors: Kathrani Aarti , Blackwell Emily Jayne , Williams Jessica L , Gruffydd‐Jones Tim , Murray Jane K , Hezzell Melanie , Hall Edward J
Published: June 2019

Our study aimed to determine if certain early life events were more prevalent in cats presenting to veterinary practices specifically for gastrointestinal signs on at least two occasions between six months and 30 months of age. Data from an owner‐completed questionnaire for 1212 cats before 16 weeks of age and subsequent questionnaires for the same cats between six months and 30 months of age were reviewed. Of the 1212 cats included, 30 visited a veterinary practice for gastrointestinal signs on two or more occasions. Of the early life events recorded, cats reported with vomiting, diarrhoea or both, and/or those not exclusively fed commercial diet(s) that meets the World Small Animal Veterinary Association (WSAVA) Global Nutrition Committee (GNC) guidelines before 16 weeks of age were more likely to visit veterinary practices specifically for gastrointestinal signs on at least two occasions between six months and 30 months of age (P<0.001, odds ratio (OR)=2.64, 95 per cent confidence interval (CI)=1.66–4.22 and P=0.030, OR=1.51, 95 per cent CI=1.04–2.22, respectively). Ensuring cats exclusively consume commercial diet(s) that meets the WSAVA GNC guidelines and further studies identifying specific aetiologies for vomiting and diarrhoea before 16 weeks of age to enable prevention may reduce the number of cats subsequently presenting to primary care veterinary practices for repeated gastrointestinal signs.
Role of vitamin D in cell-cell interaction of fetal endothelial progenitor cells and umbilical cord endothelial cells in a preeclampsia-like model
Authors: Brodowski L. , Schröder-Heurich B. , Hubel C. A. , Vu T. H. , von Kaisenberg C. S. , von Versen-Höynck F.
Published: June 2019

Maternal endothelial dysfunction is a cental feature of preeclampsia (PE), a hypertensive disorder of pregnancy. Factors in the maternal circulation are thought to contribute to this endothelial dysfunction. Although understudied, factors in the fetal circulation may influence fetal endothelial cell interactions with endothelial progenitor cells as critical steps in placental angiogenesis. We hypothesize that cell-cell interactions that are important for pregnancy health are impaired by fetal serum from PE pregnancies and that 1,25(OH)2-vitamin D3 attenuates the negative effects of this serum on cell function. We tested the ability of fetal cord blood-derived endothelial progenitor cells [endothelial colony-forming cells (ECFCs)] to invade into established monolayers and capillary tubule-like structures of human fetal umbilical venous endothelial cells (HUVECs), while in the presence/absence of fetal cord serum from uncomplicated or PE pregnancies, and tested the ability of 1,25(OH)2-vitamin D3 to modulate the serum-mediated effects. PE cord serum reduced the invasion of fetal ECFCs into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. PE cord serum reduces the ability of fetal endothelial progenitor cells to incorporate into fetal endothelial cell networks. Physiologic concentrations of vitamin D reverse these PE serum-mediated effects. These data appear consistent with lines of evidence that vitamin D has antipreeclampsia effects.
Expression and distribution of PIEZO1 in the mouse urinary tract
Authors: Dalghi Marianela G. , Clayton Dennis R. , Ruiz Wily G. , Al-bataineh Mohammad M. , Satlin Lisa M. , Kleyman Thomas R. , Ricke William A. , Carattino Marcelo D. , Apodaca Gerard
Published: June 2019

The proper function of the organs that make up the urinary tract (kidneys, ureters, bladder, and urethra) depends on their ability to sense and respond to mechanical forces, including shear stress and wall tension. However, we have limited understanding of the mechanosensors that function in these organs and the tissue sites in which these molecules are expressed. Possible candidates include stretch-activated PIEZO channels (PIEZO1 and PIEZO2), which have been implicated in mechanically regulated body functions including touch sensation, proprioception, lung inflation, and blood pressure regulation. Using reporter mice expressing a COOH-terminal fusion of Piezo1 with the sequence for the tandem-dimer Tomato gene, we found that PIEZO1 is expressed in the kidneys, ureters, bladder, and urethra as well as organs in close proximity, including the prostate, seminal vesicles and ducts, ejaculatory ducts, and the vagina. We further found that PIEZO1 expression is not limited to one cell type; it is observed in the endothelial and parietal cells of the renal corpuscle, the basolateral surfaces of many of the epithelial cells that line the urinary tract, the interstitial cells of the bladder and ureters, and populations of smooth and striated muscle cells. We propose that in the urinary tract, PIEZO1 likely functions as a mechanosensor that triggers responses to wall tension.
Effects of cerebellar transcranial direct current stimulation on the cognitive stage of sequence learning
Authors: Ballard Hannah K. , Goen James R. M. , Maldonado Ted , Bernard Jessica A.
Published: June 2019

Though the cerebellum has been previously implicated in explicit sequence learning, the exact role of this structure in the acquisition of motor skills is not completely clear. The cerebellum contributes to both motor and nonmotor behavior. Thus, this structure not only may contribute to the motoric aspects of sequence learning but may also play a role in the cognitive components of these learning paradigms. Therefore, we investigated the consequence of both disrupting and facilitating cerebellar function using high-definition transcranial direct current stimulation (tDCS) before the completion of an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed cathodal ( n = 21) and anodal ( n = 23) tDCS (relative to sham), targeting the lateral posterior cerebellum, to temporarily modulate function and investigate the resulting effects on the acquisition of a sequential pattern of finger movements. Results indicate that cathodal stimulation has a positive influence on learning while anodal stimulation has the opposite effect, relative to sham. Though the cerebellum is presumed to be primarily involved in motor function and movement coordination, our results support a cognitive contribution that may come into play during the initial stages of learning. Using tDCS targeting the right posterior cerebellum, which communicates with the prefrontal cortex via closed-loop circuits, we found polarity-specific effects of cathodal and anodal stimulation on sequence learning. Thus, our results substantiate the role of the cerebellum in the cognitive aspect of motor learning and provide important new insights into the polarity-specific effects of tDCS in this area.

NEW & NOTEWORTHY The cerebellum contributes to motor and cognitive processes. Investigating the cognitive contributions of the cerebellum in explicit sequence learning stands to provide new insights into this learning domain, and cerebellar function more generally. Using high-definition transcranial direct current stimulation, we demonstrated polarity-specific effects of stimulation on explicit sequence learning. We speculate that this is due to facilitation of working memory processes. This provides new evidence supporting a role for the cerebellum in the cognitive aspects of sequence learning.
Whole-Cell cAMP and PKA Activity are Epiphenomena, Nanodomain Signaling Matters
Authors: Bers Donald M. , Xiang Yang K. , Zaccolo Manuela
Published: June 2019

Novel targeted fluorescent biosensors provide key insights into very local nanodomains of cAMP and PKA activity, and how they respond differently to β-adrenergic activation in cardiac myocytes. This unique spatiotemporal detail in living cells is not available with biochemical measurements of total cellular cAMP and PKA, and provides unique physiological insights.
Skeletal Muscle Atrophy: Discovery of Mechanisms and Potential Therapies
Authors: Ebert Scott M. , Al-Zougbi Asma , Bodine Sue C. , Adams Christopher M.
Published: June 2019

Skeletal muscle atrophy proceeds through a complex molecular signaling network that is just beginning to be understood. Here, we discuss examples of recently identified molecular mechanisms of muscle atrophy and how they highlight an immense need and opportunity for focused biochemical investigations and further unbiased discovery work.
Allergies and Asthma in Relation to Cancer Risk
Authors: Kantor Elizabeth D. , Hsu Meier , Du Mengmeng , Signorello Lisa B.
Published: June 2019

Background:

Allergies and asthma, conditions commonly characterized by immunoglobulin E–mediated atopic reactions, may decrease cancer risk via increases in immunosurveillance, but may increase risk due to persistent immune stimulation. Associations between allergies and asthma and cancer risk remain unclear, and it is unknown whether associations vary by race/ethnicity.

Methods:

We evaluated these associations in the Southern Community Cohort Study. At baseline (2002–2009), 64,170 participants were queried on history of allergies and asthma; participants were followed through 2011, during which time 3,628 incident, invasive cancers were identified, including 667 lung cancers, 539 breast cancers, and 529 prostate cancers. Cox proportional hazards regression was used to estimate multivariable-adjusted HRs and 95% confidence intervals (CI).

Results:

Neither allergies nor asthma was associated with risk of developing invasive cancer overall. Asthma was associated with increased lung cancer risk (HR, 1.25; 95% CI, 1.00–1.57), with no variation by race/ethnicity (Pinteraction = 0.84). Conversely, history of allergies was associated with decreased lung cancer risk (HR, 0.80; 95% CI, 0.65–1.00), with an inverse association observed among non-Hispanic whites (HR, 0.65; 95% CI, 0.45–0.94) but not non-Hispanic blacks (HR, 0.95; 95% CI, 0.73–1.25; Pinteraction = 0.10). No statistically significant associations were observed for risk of breast or prostate cancers, overall or by race/ethnicity.

Conclusions:

No associations were observed for risk of overall cancer, breast cancer, or prostate cancer. While asthma was associated with increased lung cancer risk, history of allergies was associated with decreased risk, an association driven by an inverse association among non-Hispanic whites.

Impact:

Associations pertaining to lung cancer merit follow up in a large, diverse study.
Comparison of Skin Structural and Functional Parameters in Well-Nourished and Moderately Undernourished Infants
Authors: Hughes-Formella Betsy , Wunderlich Oliver , Williams Ragna , Fernández Josefina , Kim Yun Zyong , Wigger-Alberti Walter , Pecquet Sophie , Moodycliffe Angus
Published: June 2019

Background: Little is known about the impact of nutrition on the development of skin structure and function in infants. Methods: We investigated epidermal, dermal, and subcutis parameters of aged-matched well-nourished and moderately undernourished infants in this single-center, cross-sectional, noninterventional study using noninvasive methods (skin caliper, 20-MHz sonography, transepidermal water loss, skin pH, and corneometry). Plasma fatty acids were determined as an indicator of nutritional differences. 310 infants from different age groups, i.e., 1 week, 4 weeks, and 6, 9, 12, 24, and 36 months were included. Approximately half of each age group was well-nourished (WHO reference values weight-for-height/length Zscore: –0.75 ≤ Z ≤ 0.75) and the other half was moderately undernourished (–3 ≤ Z < –2). Results: Structural maturational differences in the deeper dermis and subcutis regions of the skin and subtle functional changes in the epidermis were observed in moderately undernourished infants without notable clinical symptoms. Reduced skin barrier function or skin hydration were not observed in the undernourished infants, and skin pH shifted to more acidic values in this group. Conclusion: These findings reveal a greater impact of moderate undernutrition on the development of the dermis and subcutis and suggest that critical epidermal functions such as skin barrier and pH are mostly maintained.
Preschool Language Outcomes following Perinatal Hypoxic-Ischemic Encephalopathy in the Age of Therapeutic Hypothermia
Authors: Chin Eric M. , Jayakumar Srishti , Ramos Ezequiel , Gerner Gwendolyn , Soares Bruno P. , Cristofalo Elizabeth , Leppert Mary , Allen Marilee , Parkinson Charla , Johnston Michael , Northington Frances , Burton Vera Joanna
Published: June 2019

Early studies following perinatal hypoxic-ischemic encephalopathy (HIE) suggested expressive language deficits and academic difficulties, but there is only limited detailed study of language development in this population since the widespread adoption of therapeutic hypothermia (TH). Expressive and receptive language testing was performed as part of a larger battery with 45 children with a mean age of 26 months following perinatal HIE treated with TH. Overall cohort outcomes as well as the effects of gender, estimated household income, initial pH and base excess, and pattern of injury on neonatal brain MRI were assessed. The cohort overall demonstrated expressive language subscore, visual-reception subscore, and early learning composite scores significantly below test norms, with relative sparing of receptive language subscores. Poorer expressive language manifested as decreased vocabulary size and shorter utterances. Expressive language subscores showed a significant gender effect, and estimated socioeconomic status showed a significant effect on both receptive and expressive language subscores. Initial blood gas markers and modified Sarnat scoring did not show a significant effect on language subscores. Binarized MRI abnormality predicted a significant effect on both receptive and expressive language subscores; the presence of specific cortical/subcortical abnormalities predicted receptive language deficits. Overall, the language development profile of children following HIE in the era of hypothermia shows a relative strength in receptive language. Gender and socioeconomic status predominantly predict expressive language deficits; abnormalities detectable on MRI predominantly predict receptive language deficits.
Pregnancy with Chuvash Polycythaemia and Other Congenital Erythrocytosis
Authors: Dewarrat Natacha , Kaiser Julie , Baud David , Alberio Lorenzo , Gavillet Mathilde
Published: June 2019

This original report describes the management of a pregnant woman with congenital erythrocytosis (Chuvash polycythaemia) and reviews the scarce data available in the literature. Therapy consisted of low-dose aspirin and phlebotomies to maintain haematocrit <50% while monitoring iron stores to avoid severe deficiency detrimental to the foetus. Despite normal initial foetal growth, the pregnancy was complicated by preterm birth due to chorioamnionitis. The placenta showed no signs of thrombotic events. The published reports cover 13 pregnancies in 8 patients, showing 1 first-trimester miscarriage, 5 infants with intrauterine growth restriction and/or preterm birth and 1 maternal thrombotic event. These cases were managed with phlebotomies, low-dose aspirin and/or low-molecular-weight heparin, although inconsistently.
Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida
Authors: Möhrlen Ueli , Ochsenbein-Kölble Nicole , Mazzone Luca , Kraehenmann Franziska , Hüsler Margaret , Casanova Barbara , Biro Peter , Wille David , Latal Bea , Scheer Ianina , Bernet Vera , Moehrlen Theres , Held Leonhard , Flake Alan W. , Zimmermann Roland , Meuli Martin
Published: June 2019

Introduction: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. Materials and Methods: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. Results: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. Conclusion: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.
Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies
Authors: Gafter-Gvili Anat , Tibau Ariadna , Raanani Pia , Shepshelovich Daniel
Published: June 2019

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.
Albuminuria Testing by Race and Ethnicity among Patients with Hypertension with and without Diabetes
Authors: Lee Joi , Chu Chi , Guzman David , Fontil Valy , Velasquez Alexandra , Powe Neil R. , Tuot Delphine S.
Published: June 2019

Background: Detection of chronic kidney disease (CKD) with urine albumin-to-creatinine ratio (UACR) among patients with hypertension (HTN) provides an opportunity for early treatment, potentially mitigating risk of CKD progression and cardiovascular complications. Differences in UACR testing patterns among racial/ethnic populations at risk for CKD could contribute to known disparities in CKD complications. Methods: We examined the prevalence of UACR testing among low-income adult primary care patients with HTN, defined by a new administrative code for HTN or 2 clinic blood pressures >140/90 mm Hg between January 1, 2014, and January 1, 2017, in one public health-care delivery system with a high prevalence of end-stage kidney disease among race/ethnic minorities. Logistic regression was used to identify odds of UACR testing within 1 year of a HTN diagnosis, overall, and by racial/ethnic subgroup, adjusted for demographic factors, estimated glomerular filtration rate, and HTN severity. Models were also stratified by diabetes status. Results: The cohort (n = 16,414) was racially/ethnically diverse (16% White, 21% Black, 34% Asian, 19% Hispanic, and 10% other) and 51% female. Only 35% of patients had UACR testing within 1 year of a HTN diagnosis. Among individuals without diabetes, odds of UACR testing were higher among Asians, Blacks, and Other subgroups compared to Whites (adjusted OR [aOR] 1.19; 95% CI 1.00–1.42 for Blacks; aOR 1.33; 1.13–1.56 for Asians; aOR 1.30; 1.04–1.60 for Other) but were not significantly different between Hispanics and Whites (aOR 1.17; 0.97–1.39). Among individuals with diabetes, only Asians had higher odds of UACR testing compared to Whites (aOR 1.35; 1.12–1.63). Conclusions: Prevalence of UACR testing among low-income patients with HTN is low in one public health-care delivery system, with higher odds of UACR testing among racial/ethnic minority subgroups compared to Whites without diabetes and similar odds among those with diabetes. If generalizable, less albuminuria testing may not explain higher prevalence of kidney failure in racial/ethnic minorities.
Ocorrência de intercalação de rocha fosfática na Formação Ponta Grossa em Rio Verde de Mato Grosso, Mato Grosso do Sul: implicações paleoambientais
Authors: Montibeller Cibele Carolina , Zanardo Antenor , Navarro Guillermo Rafael Beltran
Published: June 2019

Entre as rochas da Formação Ponta Grossa, aflorantes no município de Rio Verde de Mato Grosso, é registrada a presença de camadas constituídas predominantemente por apatita, não fossilíferas, que ocorrem como estratos destacados intercalados em folhelhos cinzas-escuros a pretos. Petrograficamente, essa rocha fosfática apresenta estrutura sutilmente laminada e não são observadas feições indicativas de algas, restos fósseis ou de estruturas orgânicas. Possui teores de P2O5 variando entre 12,96 e 23,35%, teores de CaO variando entre 19,85 e 33,04%, e possui alta concentração de elementos terras raras (ETR) em relação à média da crosta continental superior. Essa ocorrência não possui evidências de ação biogênica — o que é confirmado pela microscopia eletrônica — e possui relictos de oxi-hidróxidos, preferencialmente de ferro, com pequena quantidade de manganês, sugerindo origem pela dessorção de fosfato por comportamento redox a partir desses relictos. As condições de formação dessas fosforitas — se não condicionadas a aporte externo de oxi-hidróxidos de ferro pela proximidade da costa, por ambientes deltaicos ou por contribuições hidrotermais e/ou vulcânicas — colocam as camadas fosfáticas de Rio Verde de Mato Grosso, Mato Grosso do Sul, em condições de ambiente marinho plataformal raso, com profundidade entre 200 e 300 m, de águas frias e com baixa salinidade, preferencialmente anóxico, e suscetível a estabelecimento de zona de ressurgência.
High-Power (40–50 W) Radiofrequency Ablation Guided by Unipolar Signal Modification for Pulmonary Vein Isolation
Authors: Pambrun Thomas , Durand Cyril , Constantin Marion , Masse Alexandre , Marra Céline , Meillet Valentin , Haïssaguerre Michel , Jaïs Pierre , Bortone Agustín
Published: June 2019

Background:

Although proposed to facilitate pulmonary vein isolation (PVI), high-power ablation may favor extracardiac damage. Negative component abolition of the unipolar signal reflects lesion transmurality. The present study sought to evaluate the safety and efficacy of high-power ablation using unipolar signal modification as a local end point.

Methods

High power and standard power were compared in 4 swine and 100 consecutive patients referred for PVI. The first 50 patients were included in the control group (25–30 W) and the last 50 patients in the study group (40–50 W). Atrial radiofrequency applications were stopped 2 s (study group and swine) or 5 s (control group) after unipolar signal modification. Ventricular radiofrequency applications of 500 J (25 W·20 s versus 50 W·10 s) were performed at the swine epicardium.

Results:

Swine gross necropsy did not show any extracardiac damage related to atrial lesions. At equal energy of 500 J, 50 W lesions were deeper (3±0.9 versus 2.6±1.1 mm;
P
=0.03) and wider (6.2±2 versus 5±2.3 mm;
P
=0.006) than 25 W lesions. No complications occurred during the clinical study, whatever the power output used for PVI. For a similar sinus rhythm maintenance at 12 months (90% versus 88%;
P
=0.75), the study group displayed higher first-pass PVI (92% versus 73%;
P
<0.001), lower acute pulmonary vein reconnection (2% versus 17%;
P
<0.001), reduced procedure time (73.1±18.2 versus 107.4±21.2 min;
P
<0.001), and ablation time (13±2.9 versus 30.3±8.8 min;
P
<0.001).

Conclusions:

High-power PVI guided by unipolar signal modification safely decreases procedural burden while ensuring robust 12-month outcomes.
Age at Menarche and Risk of Cardiovascular Disease Outcomes: Findings From the National Heart Lung and Blood Institute‐Sponsored Women's Ischemia Syndrome Evaluation
Authors: Lee Julie J. , Cook‐Wiens Galen , Johnson B. Delia , Braunstein Glenn D. , Berga Sarah L. , Stanczyk Frank Z. , Pepine Carl J. , Bairey Merz C. Noel , Shufelt Chrisandra L.
Published: June 2019

Background

Previous studies have reported an association between the timing of menarche and cardiovascular disease (
CVD
). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events (
MACE
).

Methods and Results

A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the
WISE
(Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse
CVD
outcomes.
MACE
was defined as the first occurrence of all‐cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self‐reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra–total estrogen time were calculated. Cox regression analysis was performed adjusting for
CVD
risk factors. Baseline age was 57.9 ± 12 years (mean ±
SD
), body mass index was 29.5 ± 6.5 kg/m
2
, total estrogen time was 32.2 ± 8.9 years, and supra–total estrogen time was 41.4 ± 8.8 years.
MACE
occurred in 172 (27%), and its adjusted regression model was J‐shaped. Compared with women with menarche at age 12 years, the adjusted
MACE
hazard ratio for menarche at ≤10 years was 4.53 (95%
CI
2.13‐9.63); and at ≥15 years risk for
MACE
was 2.58 (95%
CI
, 1.28‐5.21).

Conclusions

History of early or late menarche was associated with a higher risk for adverse
CVD
outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse
CVD
events.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00000554.
Revascularization of High-Grade Carotid Stenosis Restores Global Cerebral Energy Metabolism
Authors: Seiler Alexander , Kammerer Sara , Gühl Alexander , Schüre Jan Rüdiger , Deichmann Ralf , Nöth Ulrike , Pfeilschifter Waltraud , Hattingen Elke , Keese Michael , Pilatus Ulrich , Wagner Marlies
Published: June 2019

Background and Purpose—

Chronic cerebral hemodynamic impairment due to high-grade occlusive carotid disease may lead to compromised energy metabolism. This might result in chronic subtle tissue damage, even in patients without overt brain infarction. The aim of this study was to investigate hypoperfusion-related changes of cerebral energy metabolism and their potential restitution after revascularization. For this purpose, 3-dimensional
31
P magnetic resonance spectroscopy and oxygenation-sensitive T2′ magnetic resonance imaging were used (with 1/T2′=1/T2*−1/T2), which were expected to cross-validate each other.

Methods—

Ten patients with unilateral high-grade carotid artery stenosis resulting in a transient ischemic attack or a nondisabling cerebral ischemia were included. Then, high-energy metabolites, intracellular pH, and oxygenation-sensitive quantitative (q)T2′ values were determined in noninfarcted hypoperfused areas delineated on time-to-peak maps from perfusion-weighted imaging and in unaffected contralateral areas before and shortly after carotid stenting/endarterectomy. Repeated measures ANOVA was used to test for intervention effects.

Results—

Within dependent hypoperfused areas ipsilateral to the stenosis, qT2′ was significantly decreased (
P
<0.05) as compared to corresponding contralateral areas before carotid intervention. There was a significant effect of carotid intervention on qT2′ values in both hemispheres (
P
<0.001). No differences between hemispheres were found for qT2′ after revascularization. Intracellular pH and qT2′ values showed a significant negative relationship (
P
=0.005) irrespective of time point and hemisphere.

Conclusions—

After revascularization of unilateral high-grade carotid stenosis, previously decreased qT2′ in the dependent hypoperfused territory as marker of hypoxia reincreases not only in the dependent territory but also in corresponding contralateral brain tissue. This might indicate a restriction of the whole-brain oxygen metabolism in case of unilateral high-grade carotid stenosis and an improvement of whole-brain oxygenation after revascularization that goes beyond acute clinically apparent affection of the dependent territory. Furthermore, tissue oxygen supply seems to be closely linked to intracellular pH.