bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving smoking cessation care in pregnancy at Aboriginal Medical Services: ‘ICAN QUIT in Pregnancy’ step-wedge cluster randomised study
Authors: Bar-Zeev Yael , Bovill Michelle , Bonevski Billie , Gruppetta Maree , Oldmeadow Christopher , Palazzi Kerrin , Atkins Louise , Reath Jennifer , Gould Gillian Sandra
Published: June 2019

Objectives

This study aimed to examine the impact of the ‘ICAN QUIT in Pregnancy’ intervention on individual health providers (HPs) smoking cessation care (SCC) knowledge, attitudes and practices in general, and specifically regarding nicotine replacement therapy (NRT) prescription.

Design

Step-wedge clustered randomised controlled study. HPs answered a preintervention and 1–6 months postintervention survey.

Setting

Six Aboriginal Medical Services (AMSs) in three states of Australia.

Participants

All HPs were invited to participate. Of 93 eligible, 50 consented (54%), 45 completed the presurvey (90%) and 20 the post (40%).

Intervention

Included three 1-hour webinar sessions, educational resource package and free oral NRT.

Outcomes

HPs knowledge was measured using two composite scores—one from all 24 true/false statements, and one from 12 NRT-specific statements. Self-assessment of 22 attitudes to providing SCC were measured using a five-point Likert scale (Strongly disagree to Strongly agree). Two composite mean scores were calculated—one for 15 general SCC attitudes, and one for 7 NRT-specific attitudes. Self-reported provision of SCC components was measured on a five-point Likert scale (Never to Always). Feasibility outcomes, and data collected on the service and patient level are reported elsewhere.

Results

Mean knowledge composite scores improved from pre to post (78% vs 84% correct, difference 5.95, 95% CI 1.57 to 10.32). Mean NRT-specific knowledge composite score also improved (68% vs 79% correct, difference 9.9, 95% CI 3.66 to 16.14). Mean attitude composite score improved (3.65 (SD 0.4) to 3.87 (SD 0.4), difference 0.23, 95% CI 0.05 to 0.41). Mean NRT-specific attitudes composite score also improved (3.37 (SD 0.6) to 3.64 (SD 0.7), difference 0.36, 95% CI 0.13 to 0.6). Self-reported practices were unchanged, including prescribing NRT.

Conclusions

A multicomponent culturally sensitive intervention in AMSs was feasible, and might improve HPs provision of SCC to pregnant Aboriginal women. Changes in NRT prescription rates may require additional intensive measures.

Trial registration number

ACTRN 12616001603404; Results.
The intermediate care unit as a cost-reducing critical care facility in tertiary referral hospitals: a single-centre observational study
Authors: Plate Joost D J , Peelen Linda M , Leenen Luke P H , Hietbrink Falco
Published: June 2019

Objectives

To determine whether and to what extent the surgical intermediate care unit (IMCU) reduces healthcare costs.

Design

Retrospective cohort study.

Setting

The mixed-surgical IMCU of a tertiary academic referral hospital.

Participants

All admissions (n=2577) from 2012 to 2015.

Primary and secondary outcome measures

The outcome measure was the hypothetical cost savings due to the presence of the IMCU. For this, each admission day was classified as either low-acuity or high-acuity, based on the Therapeutic Intervention Scoring System-28, the required specific nursing interventions and the indication for admission at the IMCU. Costs (2018) used were €463 per hospital ward, €1307 per IMCU and €2224 per intensive care unit (ICU) admission day. Savings were calculated by subtracting the actual IMCU costs from the hypothetical costs in the absence of the IMCU.

Results

There were 9037 admission days (n=2577 admissions) at the IMCU. The proportion of high-acuity admissions was 87.6%. Total costs at the IMCU were €11.808 888. Total hypothetical costs in absence of the IMCU were €18.115 284. Total cost savings were thus €6.306 395, or €1.576 599, per year.

Conclusions

The surgical IMCU may substantially reduce societal healthcare costs, making it a cost saving alternative to ICU care. Constant adequate triage is essential to optimise its potential.
Randomised controlled trial of a novel online cognitive rehabilitation programme for children with cerebral palsy: a study protocol
Authors: Wotherspoon Jane , Whittingham Koa , Boyd Roslyn N , Sheffield Jeanie
Published: June 2019

Introduction

Cerebral palsy (CP) is the most common cause of physical disability in children, with an estimated 600–700 infants born with CP in Australia each year. CP is typically associated with motor impairments, but nearly half of all children with CP also experience cognitive impairment, potentially impacting educational and vocational achievement. This paper reports the protocol for a randomised controlled trial of a computerised cognitive training intervention based on behavioural principles: Strengthening Mental Abilities through Relational Training (SMART). The study aims to investigate SMART’s effect on fluid reasoning, executive function and academic achievement in children with CP.

Methods and analysis

Sixty children with mild to moderate CP (Gross Motor Function Classification Scale I–IV) aged between 8 years and 12 years will be recruited. Participants will be randomly allocated to two groups: SMART cognitive training and waitlist control. Families will access the programme at home over a 4-month period. Assessments will be administered at baseline, 20 weeks and at 40 week follow-up for retention. The primary outcome will be fluid intelligence, while academic achievement, executive function and social and emotional well-being will be secondary outcomes.

Ethics and dissemination

This study has approval from the Children’s Health Queensland Hospital and Health Service Research Ethics Committee (HREC/14/QRCH/377) and The University of Queensland (2017001806). If the computerised cognitive training programme is found to be effective, dissemination of these findings would assist children with CP by providing an accessible, cost-effective intervention that can be completed at home at the individual’s own pace.

Registration details

The study was registered prospectively on 10 November 2017 to present. Recruitment is now under way, and we aim to complete recruitment by June 2019, with data collection finalised by March 2020.

Trial registration number

ACTRN12617001550392; Pre-results.
How do residents perceive and narrate stories about communication challenges in patient encounters? A narrative study
Authors: Møller Jane Ege , Brøgger Matilde Nisbeth
Published: June 2019

Objective

This article investigated residents’ narratives to gain their understandings of which patterns are challenging in doctor–patient conversations.

Design

Qualitative narratological framework.

Participants

We analysed 259 narratives from 138 residents’ oral recounts of communication with patients in which they had felt challenged.

Results

The analysis identified an ideal narrative for the doctor–patient encounter with the resident as protagonist pursuing the object of helping the patient with his health problem. Disruptions of this ideal narrative were at play when challenges occurred. Regardless of medical setting, challenges were often related to the establishment of a common object, and the communication actants had to go through negotiations, disagreements or even battles when trying to reach a common object. Challenges also occurred when actants which in the ideal narrative should act as helpers become opponents. We find narratives where patients, relatives and colleagues become opponents.

Conclusions

Our study showed that communication challenges were the result of disruptions of the perceived ideal narrative. Residents found it especially challenging to establish a common object, and dealing with helpers turned opponents. Patient communication is thus a challenge in the transition phase from student to doctor, and doctor–patient communication is complex in nature and continuously perceived to be so by residents, despite pregraduate training.
Familial bilateral cryptorchidism is caused by recessive variants inRXFP2
Authors: Ayers Katie , Kumar Rakesh , Robevska Gorjana , Bruell Shoni , Bell Katrina , Malik Muneer A , Bathgate Ross A , Sinclair Andrew
Published: June 2019

Background

Cryptorchidism or failure of testicular descent is the most common genitourinary birth defect in males. While both the insulin-like peptide 3 (INSL3) and its receptor, relaxin family peptide receptor 2 (RXFP2), have been demonstrated to control testicular descent in mice, their link to human cryptorchidism is weak, with no clear cause–effect demonstrated.

Objective

To identify the genetic cause of a case of familial cryptorchidism.

Methods

We recruited a family in which four boys had isolated bilateral cryptorchidism. A fourth-degree consanguineous union in the family was reported. Whole exome sequencing was carried out for the four affected boys and their parents, and variants that segregated with the disorder and had a link to testis development/descent were analysed. Functional analysis of aRXFP2variant in cell culture included receptor localisation, ligand binding and cyclic AMP (cAMP) pathway activation.

Results

Genomic analysis revealed a homozygous missense variant in theRXFP2gene (c.1496G>A .p.Gly499Glu) in all four affected boys and heterozygous in both parents. No other variant with a link to testis biology was found. TheRXFP2variant is rare in genomic databases and predicted to be damaging. It has not been previously reported. Functional analysis demonstrated that the variant protein had poor cell surface expression and failed to bind INSL3 or respond to the ligand with cAMP signalling.

Conclusion

This is the first reported genomic analysis of a family with multiple individuals affected with cryptorchidism. It demonstrates that recessive variants in theRXFP2gene underlie familial cryptorchidism and solidifies the link between this gene and testicular descent in humans.
Single-cell RNA sequencing for the study of lupus nephritis
Authors: Der Evan , Suryawanshi Hemant , Buyon Jill , Tuschl Thomas , Putterman Chaim
Published: June 2019

Single-cell RNA sequencing (scRNA-seq) has recently undergone rapid advances in the development of this technology, leading to high throughput and accelerating discovery in many biological systems and diseases. The single-cell resolution of the technique allows for the investigation of heterogeneity in cell populations, and the pinpointing of pathological populations contributing to disease. Here we review the development of scRNA-seq technology and the analysis that has evolved with the ever-increasing throughput. Finally, we highlight recent applications of scRNA-seq to understand the molecular pathogenesis of lupus and lupus nephritis.
Effect of menthol cigarette and other menthol tobacco product bans on tobacco purchases in the RTI iShoppe virtual convenience store
Authors: Guillory Jamie , Kim Annice E , Nonnemaker James M , Bradfield Brian , Taylor Nathaniel Harlan , Dutra Lauren , Feld Ashley
Published: June 2019

Objective

To test how a potential US ban of menthol products or replacement with ‘green’ products and ads could influence tobacco purchases.

Methods

US adult menthol smokers (N=1197) were recruited via an online panel and randomly assigned to complete a shopping task in one of four versions (experimental conditions) of the RTI iShoppe virtual store: (1) no ban, (2) replacement of menthol cigarettes and ads with green replacement versions, (3) menthol cigarette ban and (4) all menthol tobacco product ban. Logistic regressions assessed the effect of condition on tobacco purchases.

Results

Participants in the menthol cigarette ban (OR=0.67, 95% CI 0.48 to 0.92) and all menthol product ban conditions (OR=0.60, 95% CI 0.43 to 0.83) were less likely to purchase cigarettes of any type than participants in the no ban condition. Participants in the green replacement (OR=1.74, 95% CI 1.13 to 2.70), menthol cigarette ban (OR=3.40, 95% CI 2.14 to 5.41) and all menthol product ban conditions (OR=3.14, 95% CI 1.97 to 5.01) were more likely to purchase a cigarette brand different from their usual brand than participants in the no ban condition.

Conclusions

Our findings suggest that menthol bans could have great public health impact by reducing cigarette purchases. However, tobacco marketing strategies, such as creating green (or other replacement) versions of menthol cigarettes, may undermine public health benefits of a menthol ban by prompting purchases of non-menthol cigarettes. Our findings highlight the importance of taking tobacco marketing tactics into consideration in tobacco product regulation.
High-intensity interval training followed by postexercise cold-water immersion does not alter angiogenic circulating cells, but increases circulating endothelial cells
Authors: Magalhães Flávio de Castro , Aguiar Paula Fernandes , Tossige-Gomes Rosalina , Magalhães Sílvia Mourão , Ottone Vinícius de Oliveira , Fernandes Tiago , Oliveira Edilamar Menezes , Dias-Peixoto Marco Fabrício , Rocha-Vieira Etel , Amorim Fabiano Trigueiro
Published: June 2019

High-intensity interval training (HIIT) induces vascular adaptations that might be attenuated by postexercise cold-water immersion (CWI). Circulating angiogenic cells (CAC) participate in the vascular adaptations and circulating endothelial cells (CEC) indicate endothelial damage. CAC and CEC are involved in vascular adaptation. Therefore, the aim of the study was to investigate postexercise CWI during HIIT on CAC and CEC and on muscle angiogenesis-related molecules. Seventeen male subjects performed 13 HIIT sessions followed by 15 min of passive recovery (n = 9) or CWI at 10 °C (n = 8). HIIT comprised cycling (8–12 bouts, 90%–110% peak power). The first and the thirteenth sessions were similar (8 bouts at 90% of peak power). Venous blood was drawn before exercise (baseline) and after the recovery strategy (postrecovery) in the first (pretraining) and in the thirteenth (post-training) sessions. For CAC and CEC identification lymphocyte surface markers (CD133, CD34, and VEGFR2) were used. Vastus lateralis muscle biopsies were performed pre- and post-training for protein (p-eNOSser1177) and gene (VEGF and HIF-1) expression analysis related to angiogenesis. CAC was not affected by HIIT or postexercise CWI. Postexercise CWI increased acute and baseline CEC number. Angiogenic protein and genes were not differently modulated by post-CWI. HIIT followed by either recovery strategy did not alter CAC number. Postexercise CWI increased a marker of endothelial damage both acutely and chronically, suggesting that this postexercise recovery strategy might cause endothelial damage.

Novelty HIIT followed by CWI did not alter CAC. HIIT followed by CWI increased CEC. Postexercise CWI might cause endothelial damage.
Investigation of particle breakage under one-dimensional compression of sand using X-ray microtomography
Authors: Zhao Budi , Wang Jianfeng , Andò Edward , Viggiani Gioacchino , Coop Matthew R.
Published: June 2019

Particle breakage alters particle-scale properties of granular soils including particle size, shape, and contact conditions, and changes macroscale properties including soil compressibility, shear strength, and permeability. This study monitors the crushing of natural quartz sands under one-dimensional compression with in situ X-ray tomography, i.e., X-ray scans during loading. We use the assembly-scale and particle-scale images to characterize particle failure patterns, e.g., chipping, major splitting, and comminution. Image processing and analysis enable us to determine the failure patterns around the yield stress, and the influence of initial density and particle morphology on the particle survival probability. We further quantify the degree of particle breakage with fractal dimension, breakage factor, and specific surface. Particle shape and coordination number both show a scale-dependent evolution pattern.
The importance of forensic soil science and geology being connected to mainstream forensic science
Authors: Kobus Hilton , Robertson James
Published: June 2019

Soil science and geology are specialist disciplines that can make a valuable contribution to forensic science investigations. Despite a resurgence in earth material examination associated with criminal investigations, its full potential has probably not been realized. This paper discusses some of the issues that impact on the effective participation of soil science and geology in a broad forensic science context and why it is important for meaningful partnerships between forensic science service providers and specialist soil science and geology institutions to be established.
Human Positron Emission Tomography Neuroimaging
Authors: Hooker Jacob M. , Carson Richard E.
Published: June 2019

Neuroimaging with positron emission tomography (PET) is the most powerful tool for understanding pharmacology, neurochemistry, and pathology in the living human brain. This technology combines high-resolution scanners to measure radioactivity throughout the human body with specific, targeted radioactive molecules, which allow measurements of a myriad of biological processes in vivo . While PET brain imaging has been active for almost 40 years, the pace of development for neuroimaging tools, known as radiotracers, and for quantitative analytical techniques has increased dramatically over the past decade. Accordingly, the fundamental questions that can be addressed with PET have expanded in basic neurobiology, psychiatry, neurology, and related therapeutic development. In this review, we introduce the field of human PET neuroimaging, some of its conceptual underpinnings, and motivating questions. We highlight some of the more recent advances in radiotracer development, quantitative modeling, and applications of PET to the study of the human brain.
Current and Future Considerations in the Use of Mechanical Circulatory Support Devices: An Update, 2008–2018
Authors: Simon Marc A. , Bachman Timothy N. , Watson John , Baldwin J. Timothy , Wagner William R. , Borovetz Harvey S.
Published: June 2019

Our review in the 2008 volume of this journal detailed the use of mechanical circulatory support (MCS) for treatment of heart failure (HF). MCS initially utilized bladder-based blood pumps generating pulsatile flow; these pulsatile flow pumps have been supplanted by rotary blood pumps, in which cardiac support is generated via the high-speed rotation of computationally designed blading. Different rotary pump designs have been evaluated for their safety, performance, and efficacy in clinical trials both in the United States and internationally. The reduced size of the rotary pump designs has prompted research and development toward the design of MCS suitable for infants and children. The past decade has witnessed efforts focused on tissue engineering–based therapies for the treatment of HF. This review explores the current state and future opportunities of cardiac support therapies within our larger understanding of the treatment options for HF.
A Contemporary Look at Biomechanical Models of Myocardium
Authors: Avazmohammadi Reza , Soares João S. , Li David S. , Raut Samarth S. , Gorman Robert C. , Sacks Michael S.
Published: June 2019

Understanding and predicting the mechanical behavior of myocardium under healthy and pathophysiological conditions are vital to developing novel cardiac therapies and promoting personalized interventions. Within the past 30 years, various constitutive models have been proposed for the passive mechanical behavior of myocardium. These models cover a broad range of mathematical forms, microstructural observations, and specific test conditions to which they are fitted. We present a critical review of these models, covering both phenomenological and structural approaches, and their relations to the underlying structure and function of myocardium. We further explore the experimental and numerical techniques used to identify the model parameters. Next, we provide a brief overview of continuum-level electromechanical models of myocardium, with a focus on the methods used to integrate the active and passive components of myocardial behavior. We conclude by pointing to future directions in the areas of optimal form as well as new approaches for constitutive modeling of myocardium.
Analysis of type 2 diabetes mellitus and arterial hypertension content in exercise physiology textbooks
Authors: de Lira Claudio Andre Barbosa , Viana Ricardo Borges , Luz Nina Franco , de Santana Marcos Gonçalves , Campos Mário Hebling , Vancini Rodrigo Luiz , Andrade Marília Santos
Published: June 2019

The textbook is a pedagogical tool that provides students and professionals with scientific information. As exercise is an important strategy for the prevention and treatment of noncommunicable diseases, such as type 2 diabetes mellitus (T2DM) and arterial hypertension, the presence of correct and up-to-date scientific information in exercise physiology textbooks is important. Our aim was to analyze T2DM and arterial hypertension content in exercise physiology textbooks and compare this content with the American College of Sports Medicine (ACSM) position stands. Comparative descriptions were made between information regarding T2DM and arterial hypertension found in textbooks ( n = 10) and similar information contained in the official ACSM position stands. The quality of the content was compared with current scientific information present in the ACSM position stands. In regards to T2DM, eight textbooks provided information regarding the purpose and benefits of exercise, two provided information regarding exercise prescription, seven provided information regarding the type of exercise, six provided information regarding general care and recommendations, and five provided information regarding the mechanisms involved. In regards to arterial hypertension, all textbooks provided information regarding the purpose and benefit of exercise, six provided information regarding exercise prescription, nine provided information regarding the type of exercise, two provided information regarding general care and recommendations, and seven provided information regarding the mechanisms involved. All textbooks analyzed contained information related to physical exercise for patients with T2DM and arterial hypertension. However, the textbooks differed in terms of the quality of the contents, especially in regard to exercise prescription.
Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep
Authors: McArdle Zoe , Pontes Roberto B. , Yao Song T. , Lankadeva Yugeesh R. , Singh Reetu R. , Hood Sally G. , Schlaich Markus P. , May Clive N. , Booth Lindsea C.
Published: June 2019

Catheter-based renal denervation (RDN) was introduced as a treatment for resistant hypertension. There remain critical questions regarding the physiological mechanisms underlying the hypotensive effects of catheter-based RDN. Previous studies indicate that surgical denervation reduces renin and the natriuretic response to saline loading; however, the effects on these variables of catheter-based RDN, which does not yield complete denervation, are largely unknown. The aim of this study was to investigate the effects of catheter-based RDN on glomerular-associated renin and regulation of fluid and sodium homeostasis in response to physiological challenges. First, immunohistochemical staining for renin was performed in normotensive sheep ( n = 6) and sheep at 1 wk ( n = 6), 5.5 mo ( n = 5), and 11 mo ( n = 5) after unilateral RDN using the same catheter used in patients (Symplicity). Following catheter-based RDN (1 wk), renin-positive glomeruli were significantly reduced compared with sham animals ( P < 0.005). This was sustained until 5.5 mo postdenervation. To determine whether the reduction in renin after 1 wk had physiological effects, in a separate cohort, Merino ewes were administered high and low saline loads before and 1 wk after bilateral RDN ( n = 9) or sham procedure ( n = 8). After RDN (1 wk), the diuretic response to a low saline load was significantly reduced ( P < 0.05), and both the diuretic and natriuretic responses to a high saline load were significantly attenuated ( P < 0.05). In conclusion, these findings indicate that catheter-based RDN acutely alters the ability of the kidney to regulate fluid and electrolyte balance. Further studies are required to determine the long-term effects of catheter-based RDN on renal sodium and water homeostasis.
Effect of spironolactone for 1 yr on endothelial function and vascular inflammation biomarkers in renal transplant recipients
Authors: Mortensen Line A. , Bistrup Claus , Stubbe Jane , Carlström Mattias , Checa Antonio , Wheelock Craig E. , Palarasah Yaseelan , Bladbjerg Else M. , Thiesson Helle C. , Jensen Boye L.
Published: June 2019

Kidney transplantation is associated with increased cardiovascular risk. Endothelial dysfunction and vascular inflammation contribute to negative outcome. In experimental models, mineralocorticoid receptor antagonists improved endothelial function and reduced inflammation. The present study tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone improves endothelial function and reduces vascular inflammation in renal transplant patients. Eighty prevalent renal transplant patients from an ongoing, double-blind randomized placebo-controlled trial were included. Paired plasma samples before and after 1 yr of treatment ( n = 39 in the spironolactone-treated group and 41 in the placebo-treated group) were used to determine markers of endothelial dysfunction (nitrite, nitrate, cGMP, arginine, citrulline, ornithine, asymmetric dimethylarginine, symmetric dimethylarginine, NG-monomethyl-l-arginine, von Willebrand factor, tissue-type plasminogen activator antigen, and plasminogen activator inhibitor 1 antigen) and markers of inflammation (intercellular adhesion molecule, vascular adhesion molecule, high-sensitivity C-reactive protein, and serum amyloid protein A). The median time since the transplantation was 4.6 (0.12–22.3) yr in the spironolactone-treated group and 2.1 (0.17–13.9) yr in the placebo-treated group ( P > 0.05). Spironolactone increased plasma aldosterone ( P < 0.001) and K+ ( P < 0.001). Blood pressure did not change significantly. No significant differences were detected between groups in any of the measured markers of endothelial dysfunction or inflammation except in the subgroup analysis of patients with diabetes, where spironolactone decreased nitrite compared with placebo. In this study, mineralocorticoid receptor antagonism did not improve biomarkers of endothelial dysfunction or vascular inflammation in prevalent renal transplant patients. Further studies are needed to evaluate the potential beneficial effect of early or late mineralocorticoid receptor antagonism on vascular outcomes in renal transplant patients.
Role of the glucocorticoid receptor in glomerular disease
Authors: Goodwin Julie E.
Published: June 2019

Glucocorticoids are potent anti-inflammatory agents that are commonly used in the treatment of various glomerular diseases. Data from in vitro and in vivo studies, in both animals and humans, convincingly demonstrate that glucocorticoids have many beneficial direct effects on glomeruli, including podocytes, suggesting that, in theory, systemic administration is not necessary to achieve therapeutic benefit. Indeed, it is increasingly recognized that systemic steroids often have an unfavorable risk-to-benefit ratio. As we move into an age of personalized medicine, strategies to develop targeted steroid delivery systems and individualized risk assessment algorithms are desirable in clinicians’ efforts to “first, do no harm.”
Vestibular neurons with direct projections to the solitary nucleus in the rat
Authors: Gagliuso Amelia H. , Chapman Emily K. , Martinelli Giorgio P. , Holstein Gay R.
Published: June 2019

Anterograde and retrograde tract tracing were combined with neurotransmitter and modulator immunolabeling to identify the chemical anatomy of vestibular nuclear neurons with direct projections to the solitary nucleus in rats. Direct, sparsely branched but highly varicose axonal projections from neurons in the caudal vestibular nuclei to the solitary nucleus were observed. The vestibular neurons giving rise to these projections were predominantly located in ipsilateral medial vestibular nucleus. The cell bodies were intensely glutamate immunofluorescent, and their axonal processes contained vesicular glutamate transporter 2, supporting the interpretation that the cells utilize glutamate for neurotransmission. The glutamate-immunofluorescent, retrogradely filled vestibular cells also contained the neuromodulator imidazoleacetic acid ribotide, which is an endogenous CNS ligand that participates in blood pressure regulation. The vestibulo-solitary neurons were encapsulated by axo-somatic GABAergic terminals, suggesting that they are under tight inhibitory control. The results establish a chemoanatomical basis for transient vestibular activation of the output pathways from the caudal and intermediate regions of the solitary nucleus. In this way, changes in static head position and movement of the head in space may directly influence heart rate, blood pressure, respiration, as well as gastrointestinal motility. This would provide one anatomical explanation for the synchronous heart rate and blood pressure responses observed after peripheral vestibular activation, as well as disorders ranging from neurogenic orthostatic hypotension, postural orthostatic tachycardia syndrome, and vasovagal syncope to the nausea and vomiting associated with motion sickness.

NEW & NOTEWORTHY Vestibular neurons with direct projections to the solitary nucleus utilize glutamate for neurotransmission, modulated by imidazoleacetic acid ribotide. This is the first direct demonstration of the chemical neuroanatomy of the vestibulo-solitary pathway.
How perceptual ambiguity affects response inhibition processes
Authors: Adelhöfer Nico , Chmielewski Witold X. , Beste Christian
Published: June 2019

The ability to inhibit responses is a central requirement for goal-directed behavior but has been dominated by a top-down or cognitive control view. Only recently, the role of bottom-up perceptual factors were focused in research. However, studies usually use clearly distinguishable stimulus categories to trigger response execution or inhibition. In the current study, we present a novel Gabor patch Go/No-go task to induce perceptual ambiguity during response inhibition. To examine the neurophysiological processes in detail, we use EEG recordings and combined temporal EEG signal decomposition methods with source localization analyses. We show that perceptual similarity between Go and No-go trials compromises response inhibition performance. Interestingly, the EEG data show that this is due to a modulation of stimulus-response transition or decision processes, and not purely stimulus-related processes. This was possible by applying a temporal EEG decomposition method. We provide evidence that a prefrontal P2 (pP2) likely reflects decision processes on action execution using stimulus information. These processes were associated with superior and middle prefrontal regions (BA8). When these processes fail, occasions to execute a response become misinterpreted as occasions to inhibit a response. Successful and unsuccessful decisions to inhibit a response under high perceptual ambiguity seem to further depend on how well “what-decisions,” supported by neural mechanisms in BA19, can be processed. However, these what-decisions seem to be closely linked to the specification of the required action. Stimulus processing is closely linked to response programming so that response control is already informed when uncertainty with regard to stimulus identity is detected.

NEW & NOTEWORTHY This study introduces a novel Go/No-go paradigm and shows what neurophysiological subprocesses and functional neuroanatomical are involved during inhibitory control when ambiguous stimulus input is provided. The results show that bottom-up perceptual processes are important to consider during top-down controlled response inhibition. Stimulus processing is closely linked to response programming so that response control is already informed when uncertainty with regard to stimulus identity is detected.
Action potentials and subthreshold potentials of dorsal horn neurons in a rat model of myositis: a study employing intracellular recordings in vivo
Authors: Hoheisel Ulrich , Chacur Marucia , Treede Rolf-Detlef , Mense Siegfried
Published: June 2019

Intracellular in vivo recordings from rat dorsal horn neurons were made to study the contribution of microglia to the central sensitization of spinal synapses induced by a chronic muscle inflammation. To block microglia activation, minocycline was continuously administered intrathecally during development of the inflammation. The aim was to test whether an inflammation-induced sensitization of dorsal horn neurons is mediated by changes in synaptic strength or other synaptic changes and how activated microglia influence these processes. Intracellular recordings were used to measure subthreshold excitatory postsynaptic potentials (EPSPs) and suprathreshold action potentials (APs). The muscle inflammation significantly increased the proportion of dorsal horn neurons responding with APs or EPSPs to electrical stimulation of the muscle nerve from 27 to 56% ( P < 0.01) and to noxious muscle stimulation (3 vs. 44%, P < 0.01). Neurons showing spontaneous ongoing AP or EPSP activity increased from 28 to 74% ( P < 0.01). Generally, the increases in suprathreshold AP responses did not occur at the expense of subthreshold EPSPs, because EPSP-only responses also increased. Intrathecal minocycline prevented the inflammation-induced increase in responsiveness to electrical (24%, P < 0.02) and mechanical stimulation (14%, P < 0.02); the effect was stronger on suprathreshold APs than on subthreshold EPSPs. The increase in ongoing activity was only partly suppressed. These data suggest that the myositis-induced hypersensitivity of the dorsal horn neurons to peripheral input and its prevention by intrathecal minocycline treatment were due to both an increase in the number of active synapses and an increased synaptic strength.

NEW & NOTEWORTHY During a chronic muscle inflammation (myositis), activated microglia controls both the increase in the number of active synapses and the increase in synaptic strength.
Directional interconnectivity of the human amygdala, fusiform gyrus, and orbitofrontal cortex in emotional scene perception
Authors: Frank David W. , Costa Vincent D. , Averbeck Bruno B. , Sabatinelli Dean
Published: June 2019

The perception of emotionally arousing scenes modulates neural activity in ventral visual areas via reentrant signals from the amygdala. The orbitofrontal cortex (OFC) shares dense interconnections with amygdala and has been strongly implicated in emotional stimulus processing in primates, but our understanding of the functional contribution of this region to emotional perception in humans is poorly defined. In this study we acquired targeted rapid functional imaging from lateral OFC, amygdala, and fusiform gyrus (FG) over multiple scanning sessions (resulting in over 1,000 trials per participant) in an effort to define the activation amplitude and directional connectivity among these regions during naturalistic scene perception. All regions of interest showed enhanced activation during emotionally arousing, compared with neutral scenes. In addition, we identified bidirectional connectivity between amygdala, FG, and OFC in the great majority of individual subjects, suggesting that human emotional perception is implemented in part via nonhierarchical causal interactions across these three regions.

NEW & NOTEWORTHY Due to the practical limitations of noninvasive recording methodologies, there is a scarcity of data regarding the interactions of human amygdala and orbitofrontal cortex (OFC). Using rapid functional MRI sampling and directional connectivity, we found that the human amygdala influences emotional perception via distinct interactions with late-stage ventral visual cortex and OFC, in addition to distinct interactions between OFC and fusiform gyrus. Future efforts may leverage these patterns of directional connectivity to noninvasively distinguish clinical groups from controls with respect to network causal hierarchy.
Airway Innervation and Plasticity in Asthma
Authors: Kistemaker L. E. M. , Prakash Y. S.
Published: June 2019

Airway nerves represent a mechanistically and therapeutically important aspect that requires better highlighting in the context of diseases such as asthma. Altered structure and function (plasticity) of afferent and efferent airway innervation can contribute to airway diseases. We describe established anatomy, current understanding of how plasticity occurs, and contributions of plasticity to asthma, focusing on target-derived growth factors (neurotrophins). Perspectives toward novel treatment strategies and future research are provided.
Ratiology and a Complementary Class of Metrics for Cardiovascular Investigations
Authors: Kerkhof Peter L. M. , Peace Richard A. , Handly Neal
Published: June 2019

Cardiovascular investigations often involve ratio-based metrics or differences: ejection fraction, arterial pressure augmentation index, coronary fractional flow reserve, pulse pressure. Focusing on a single number (ratio or difference) implies that information is lost. The lost companions constitute a well-defined but thus far unrecognized class, having additive value, a physical dimension, and often a physiological meaning. Physiologists should play a prominent role in exploring these complementary avenues and also define alternatives.
The Logic of Carotid Body Connectivity to the Brain
Authors: Zera Tymoteusz , Moraes Davi J. A. , da Silva Melina P. , Fisher James P. , Paton Julian F. R.
Published: June 2019

The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control of individual responses. We purport a remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response. This logic could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.
Discovery of Glabridin as Potent Inhibitor of Epidermal Growth Factor Receptor in SK-BR-3 Cell
Authors: Zhu Kun , Li Kang , Wang Haonan , Kang Li , Dang Chengxue , Zhang Yong
Published: June 2019

The breast cancer is the leading cause of death in women. Therefore, objective of the present study was to examine the antibreast cancer effect of glabridin (GBN) and to evaluate its mechanism of action. In this study, we have demonstrated that GBN causes reduction of cellular viability of human breast cancer SK-BR-3 in MTT assay. Results from Hoechst 33342 and propidium iodide staining assay suggested that GBN causes significant enhancement in the apoptosis. At the molecular level, in western blot analysis, GBN causes significant increase in c-PARP and c-caspases 3, 8, and 9 concentrations in a dose-dependent manner in breast cancer cells. The GBN further showed reduced level of p-epidermal growth factor receptor, p-AKT, p-ERK1/2, and cyclin D1 as the concentration rose in treated cells. Subsequent to this, GBN showed beneficial effect in 7,12-dimethylbenz[a]anthracene-induced breast cancer in experimental mice as confirmed by increase in body weight, reduction in tumor volume, oxidative stress, and dose-dependent restoration of all tested enzymes (phase I and II) in the treated group. GBN may, thus, play a protective role as an antibreast cancer drug for the prevention of breast cancer.
HTR2C Gene Variant and Salivary Cortisol Levels after Endurance Physical Activity: A Pilot Study
Authors: Bordoni Laura , Fedeli Donatella , Piangerelli Marco , Gabbianelli Rosita
Published: June 2019

Introduction: The 5-hydroxytryptamine 2C receptor (HTR2C) rs6318 polymorphism has been associated with increased sensitivity to stress. This study investigated whether the rs6318 genotype modified the cortisol response to endurance physical activity. Methods: The HTR2C SNP was genotyped in a population of agonistic cyclists, and salivary cortisol levels were measured before and after an endurance competition. Results and Conclusion: Salivary cortisol levels increased after the competition (from 20.72 ± 12.36 ng/mL to 33.80 ± 21.53 ng/mL; p = 3.189 × 10–5). rs6318 C carriers displayed higher baseline cortisol levels compared to G carriers (26.60 ± 9.35 ng/mL vs. 19.50 ± 12.63 ng/mL; p = 0.04). Baseline cortisol levels were able to predict the cortisol response to exercise (β = –0.846; p = 1.2 × 10–5). Although regression analysis did not identify an association between HTR2C genotype and change in cortisol levels, a secondary analysis in which the population was classified by median cortisol changes suggested that they might be weakly associated, thus warranting further investigation.
Vector Analysis of Femtosecond Laser-Assisted Arcuate Keratotomy for Post-Keratoplasty Astigmatic Correction
Authors: Elzarga Ali A.A. , Osman Amr A. , Gamal Mahmoud , Khafagy Mohamed M. , Osman Ihab S.
Published: June 2019

Purpose: To study the astigmatic correction of high post-keratoplasty astigmatism using Femtosecond laser (FSL)-assisted Arcuate Keratotomy (FS-AK). Methods: A prospective interventional cohort study. We enrolled 17 eyes with high degree of irregular astigmatism, scheduled for FS-AK. FSL was used to perform paired arcuate incisions 1.00 mm inside the graft. Patients’ uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and astigmatic change were recorded and followed up to 1 year after surgery. Vector analysis using Alpins’ method was done to analyze the astigmatic correction. Results: FS-AK reduced the refractive astigmatism at final follow-up visit at 12 months (p = 0.0008, repeated-measures analysis of variance [ANOVA]). The procedure improved the UCVA over the follow-up period (p = 0.007, repeated-measures ANOVA), with a similar effect on the BCVA (p = 0.046, repeated-measures ANOVA). There was a mild correlation between the target-induced astigmatism and the surgically induced astigmatism (R2 = 0.245) with a tendency to overcorrect more than under correct the astigmatism. A constant rotational error in the counterclockwise direction was also detected. Conclusions: FS-AK improves the visual outcome and reduces the refractive cylinder in post-penetrating keratoplasty astigmatism. The predictability of astigmatism correction was variable in reducing post-keratoplasty astigmatism. Refinement of the treatment nomogram for such cases is highly recommended.
Hereditary Angio-Oedema for Dermatologists
Authors: Bygum Anette
Published: June 2019

Among angio-oedema patients, hereditary angio-oedema (HAE) should not be overlooked. Besides skin swellings, these patients might have very painful abdominal attacks and potentially life-threatening angio-oedema of the upper airway. They will not respond to traditional anti-allergic therapy with antihistamines, corticosteroids, and adrenaline, and instead need specific drugs targeting the kallikrein-kinin pathway. Classically, patients with HAE have a quantitative or qualitative deficiency of the C1 inhibitor (C1INH) due to different mutations in SERPING1, although a new subtype with normal C1INH has been recognised more recently. This latter variant is diagnosed based on clinical features, family history, or molecular genetic testing for mutations in F12, ANGPT1,or PLG.The diagnosis of HAE is often delayed due to a general unfamiliarity with this orphan disease. However, undiagnosed patients are at an increased risk of unnecessary surgical interventions or life-threatening laryngeal swellings. Within the last decade, new and effective therapies have been developed and launched for acute and prophylactic therapy. Even more drugs are under evaluation in clinical trials. It is therefore of utmost importance that patients with HAE are diagnosed as soon as possible and offered relevant therapy with orphan drugs to reduce morbidity, prevent mortality, and improve quality of life.
Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia
Authors: Zhang Yimin , Gu Haihui , Chen Qi , Zhang Ying , Cheng Hui , Yang Jianmin , Wang Jianmin , Hu Xiaoxia
Published: June 2019

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.
Lobar Quantification by Ventilation/Perfusion SPECT/CT in Patients with Severe Emphysema Undergoing Lung Volume Reduction with Endobronchial Valves
Authors: Kristiansen Jonas F. , Perch Michael , Iversen Martin , Krakauer Martin , Mortensen Jann
Published: June 2019

Background: Endoscopic lung volume reduction (ELVR) therapy using one-way valves is used to treat chronic obstructive pulmonary disease patients with severe heterogeneous emphysema. A successful treatment results in atelectasis of the treated pulmonary lobe with subsequent reduction of ventilation (V) and perfusion (Q). Objective: We evaluated the effects of ELVR on the targeted lobe using a new 3-dimensional ventilation and perfusion (V/Q) single-photon emission computed tomography (SPECT)/computed tomography (CT) analysis, which allows for simultaneous semi-automatic lobar pulmonary quantification of volume, ventilation and perfusion, on the first consecutive patients treated with ELVR at Rigshospitalet, Denmark. V/Q planar scintigraphy and V/Q SPECT/CT and lung function measurements were performed before and 6 months after intervention. Results: We included 24 subjects (60 years, range 46–74 years; 37.5% men) with a baseline FEV1 of 25% predicted and RV of 257% predicted. V/Q SPECT/CT-assessed volume of the targeted lobe decreased by a mean of –395 mL and a relative mean of –26.8%, whilst ventilation and perfusion decreased by a relative mean of –37.1 and –25.7%. There was a significant increase in the same parameters of the non-targeted lobe(s) on the ipsilateral side. None of these changes were found in the analysis of planar V/Q imaging. The total lung volume decreased on average by –420 mL. Six months after ELVR, FEV1 had increased by 22%. Significant correlations were found between changes in FEV1 and changes in the volume of the treated lobe (SPECT/CT). Conclusion: Semi-automatic SPECT/CT analysis can quantify volume, ventilation and perfusion changes in pulmonary lobes and may be used in the assessment of patient eligibility for ELVR, identifying target lobes, and evaluation of the regional effects of treatment.