bluuebunny/crossref_metadata_2025 huggingface dataset:
The oncomir face of microRNA-206: A permanent miR-206 transfection study
Authors: Mihály Dóra , Papp Gergő , Mervai Zsolt , Reszegi Andrea , Tátrai Péter , Szalóki Gábor , Sápi Johanna , Sápi Zoltán
Published: August 2018

MiR-206 is a remarkable miRNA because it functions as a suppressor miRNA in rhabdomyosarcoma while at the same time, as previously showed, it can act as an oncomiRNA in SMARCB1 immunonegative soft tissue sarcomas. The aim of this study was to investigate the effect of miR-206 on its several target genes in various human tumorous and normal cell lines. In the current work, we created miR-206-overexpressing cell lines (HT-1080, Caco2, iASC, and SS-iASC) using permanent transfection. mRNA expression of the target genes of miR-206 (SMARCB1, ACTL6A, CCND1, POLA1, NOTCH3, MET, and G6PD) and SMARCB1 protein expression were examined with quantitative real-time polymerase chain reaction, immunoblotting, immunocytochemistry, and flow cytometry. MiRNA inhibition was used to validate our results. We found a diverse silencing effect of miR-206 on its target genes. While an overall tendency of downregulation was noted, expression profiles of individual cell lines showed large variability. Only CCND1 and MET were consistently downregulated. MiR-206 had an antiproliferative effect on a normal human fibroblast cell line. A strong silencing effect of SMARCB1 in miR-206 transfected SS-iASC was most likely caused by the synergic influence of the SS18-SSX1 fusion protein and miR-206. In the same cell line, a moderate decrease of SMARCB1 protein expression could be observed with immunocytochemistry and flow cytometry. In the most comprehensive analysis of miR-206 effects so far, a modest but significant downregulation of miR-206 targets on the mRNA level was confirmed across all cell lines. However, the variability of the effect shows that the action of this miRNA is largely cell context-dependent. Our results also support the conception that the oncomiR effect of miR-206 on SMARCB1 plays an important but not exclusive role in SMARCB1 immunonegative soft tissue sarcomas so it can be considered important in planning the targeted therapy of these tumors in the future.

Impact statement

Mir-206 is a very unique microRNA because it can act as a suppressor miRNA or as an oncomiRNA depending on the tumor tissue. In SMARCB1 negative soft tissue sarcomas miR-206 is overexpressed, so thus in epithelioid and synovial sarcomas it functions as an oncomiRNA. MiR-206 has diverse silencing effects on its target genes. We found that the action of miR-206 is largely cell context dependent. The oncomiR role of miR-206 is crucial but not exclusive in SMARCB1 negative soft tissue sarcomas and miR-206 has an antiproliferative effect on a normal human fibroblast cell line. Expressions of miR-206 targets observed in tumors can only be reproduced in the corresponding tumorous cell lines. This is the first study which examined the permanent effect of miR-206 on its target genes in normal, tumor, and genetically engineered cell lines.
A Unique Case Report on Hypersensitivity Vasculitis as an Allergic Reaction to the Herpes Zoster Vaccine
Authors: Puram Vikram , Lyon Danielle , Skeik Nedaa
Published: August 2018

Hypersensitivity vasculitis (HV) or leukocytoclastic vasculitis is a rare small-vessel vasculitis that may occur as a manifestation of the body’s extreme allergic reaction to a drug, infection, or other foreign substance. Characterized by the presence of inflammatory neutrophils in vessel walls, HV results in inflammation and damage to blood vessels, primarily in the skin. Histologically, when neutrophils undergo leukocytoclasia and release nuclear debris into the vasculature, vascular damage manifests as palpable purpura. The incidence of HV is unknown and its relationship and interaction with certain vaccinations is rare and poorly understood. Affected patients with HV generally have a good prognosis; however, fatality may occur if organs such as the central nervous system, heart, lungs, or kidneys are involved. We report a unique case of a 60-year-old man who presented with a serious case of HV after receiving the herpes zoster vaccine. A thorough literature review yielded only one similar case of vascular reaction to the varicella vaccine that was reported in the Annals of Internal Medicine in 1997; however, no other reported cases with regard to the herpes zoster vaccine have been found. Our case presents a rare glimpse into HV that may result from varicella vaccine administration.
Analytics for awareness in maritime surveillance: from data to tactical insight
Authors: Caelli Terry , Mukerjee Joyanto , Sparks Evan
Published: August 2018

Although significant effort has occurred into developing realistic simulation environments for maritime surveillance, relatively little attention has been given to objectively summarizing and providing platforms for querying the mission simulation outputs for post-mission debriefing purposes. In this paper we adopt recently proposed data analytic ideas for this context and illustrate the proposed approach using multi-layered statistical methods from visualization to Bayesian network-based data interpretation models. Analyzing example missions in these terms demonstrates the potential use for such technologies for objective and insightful post-mission analyses.
EBM: Rationalist Fever Dreams
Authors: Klein Devorah , Woods David , Klein Gary , Perry Shawna
Published: August 2018

In 2016, we examined the connection between naturalistic decision making and the trend toward best practice compliance; we used evidence-based medicine (EBM) in health care as an exemplar. Paul Falzer’s lead paper in this issue describes the historical underpinnings of how and why EBM came into vogue in health care. Falzer also highlights the epistemological rationale for EBM. Falzer’s article, like our own, questions the rationale of EBM and reflects on ways that naturalistic decision making can support expertise in the face of attempts to standardize practice and emphasize compliance. Our objectives in this commentary are first to explain the inherent limits of procedural approaches and second to examine ways to help decision makers become more adaptive.
Risk Factors for Violent Injuries and Their Severity Among Men in The Gambia
Authors: Bass Paul , Sanyang Edrisa , Lin Mau-Roung
Published: August 2018

A matched case-control study was conducted to identify risk factors for injury from physical violence and its severity in Gambian men. Study participants were recruited from eight emergency rooms and outpatient departments in two health administrative regions. Cases were male patients aged ⩾15 years who had been violently injured. A control patient for each case, matched for the hospital or health center, date of injury, gender, and age, was selected from those injured due to nonviolence causes. In total, 447 case-control pairs were recruited. Results of the conditional logistic regression analysis showed that case patients who worked as businessmen (odds ratio [OR], 1.93; 95% confidence interval [CI] [1.16, 3.20]), had monthly household income of ⩾US$311 (OR, 2.12; 95% CI [1.06, 4.24]), had two or more male siblings (OR, 2.20; 95% CI [1.15, 4.21]), had consumed alcohol in the past week (OR, 3.32; 95% CI [1.25, 8.84]), and had been physically abused (OR, 5.10; 95% CI [2.71, 9.62]) or verbally abused (OR, 1.63; 95% CI [1.04, 2.56]) in the past 12 months were significantly associated with the occurrence of injury from physical violence. Severe injuries during the violence were significantly associated with events that took place in public spaces, with certain injury mechanisms (being stabbed/cut/pierced, struck by an object, assaulted by fist punching/leg kicking/head-butting, and scalded/stoned), having injuries to the upper extremities, and smoked cigarettes in the past week. Specific public health programs aimed at preventing physical violence and severe injuries against men should be developed in The Gambia based on modifications of the identified risk factors.
Computed tomography-guided pericardiocentesis: a systematic review concerning contemporary evidence and future perspectives
Authors: Vilela Eduardo M. , Ruivo Catarina , Guerreiro Claudio E. , Silva Marisa P. , Ladeiras-Lopes Ricardo , Caeiro Daniel , Morais Gustavo P. , Primo João , Braga Pedro , Ferreira Nuno , Nunes José Pedro L. , Ribeiro Vasco Gama
Published: August 2018

Background:

Pericardial effusion (PE) can develop in several pathological scenarios, and is often initially evaluated by means of echocardiography. Computed tomography (CT) has been used as an aid in the management of patients presenting with PE, in selected cases. The role of CT-guided pericardiocentesis in contemporary practice, however, remains not fully ascertained. We aimed at presenting a systematic review concerning the state-of-the-art of this technique.

Methods:

A systematic review of published data on the use of CT for guiding pericardiocentesis was carried out (search performed on PubMed, ISI Web of Knowledge and Scopus databases).

Results:

From title and abstract analysis, 14 articles were included that met the prespecified criteria. After full-text analysis, six articles were excluded. The eight articles under analysis included a total of 635 procedures performed in 571 patients. CT guidance was mostly used in a postoperative setting (364 procedures). Most procedures were done mainly for therapeutic purposes (528 procedures). Success rates ranged from 94% to 100%. Complications ranged from 0% to 7.8%.

Conclusion:

CT-guided pericardiocentesis is a useful technique in the approach to PE, in several clinical scenarios. Its use can be especially relevant in the postoperative period, as well as in individuals with suboptimal image quality (as assessed by echocardiography, for the moment the first choice in the approach to most cases of PE).
The Provision of Primary and Revision Elbow Replacement Surgery in the NHS
Authors: Hay Stuart , Kulkarni Rohit , Watts Adam , Stanley David , Trail Ian , Van Rensburg Lee , Little Christopher , Samdanis Vas , Jenkins Paul , Eames Michael , Phadnis Joideep , Ali Amjid , Rangan Amar , Drew Steve , Amirfeyz Rouin , Conboy Veronica , Clark David , Brownson Peter , Connor Clare , Jones Val , Tennent Duncan , Falworth Mark , Thomas Michael , Rees Jonathan
Published: August 2018

BESS Surgical Procedure Guidelines (SPGs).

Optimising Surgical Outcomes for Shoulder and Elbow patients.

The British Elbow and Shoulder Society (BESS) SPGs are a series of evidence and consensus Best Practice Recommendations developed by BESS surgeons and physiotherapists to help drive quality improvement and achieve the best possible surgical outcomes for UK patients. This SPG on primary and revision elbow replacement surgery is supported and endorsed by both the British Orthopaedic Association (BOA) and the Getting It Right First Time (GIRFT) Programme.
Understanding the patterns of PPP renegotiations for infrastructure projects in Latin America
Authors: Neto Dimas de Castro e Silva , Cruz Carlos Oliveira , Sarmento Joaquim Miranda
Published: August 2018

The increased use of public–private partnerships (PPPs) around the world to build infrastructures and provide public services has led to several concerns. One of the main pitfalls of PPPs is an abnormal frequency of renegotiations, especially renegotiations occurring during the first years of contract. The Latin American experience has been the most relevant in terms of research on PPP renegotiations. Using the literature on PPP renegotiations in the Latin American context, this article focuses on the analysis and discussion of renegotiations. We use the experience from Brazil, at the State (region) level, of PPPs and renegotiations. From 2006 to 2016, Brazil developed 42 PPP projects in several sectors. From these, 27 were renegotiated at least once. We found a high number of renegotiations within a short period since the start of the contract for the first renegotiation to occur. The motives for renegotiations are mainly perceived from the public sector, particularly failure in planning, concept, and bidding. Electoral periods and the political connections of shareholders also have an impact on renegotiations. Based on the Brazilian experience, we drawn some policy implications.
Use of electronic medical record templates improves quality of care for patients with infantile spasms
Authors: Santoro Jonathan D , Sandoval Karamian Amanda G , Ruzhnikov Maura , Brimble Elise , Chadwick Whitney , Wusthoff Courtney J
Published: August 2018

Background:

Infantile spasms (IS) is a neurologic disorder of childhood where time to treatment may affect long-term outcomes. Due to the clinical complexity of IS, care can be delayed.

Objective:

To determine if the use of electronic medical record templates (EMRTs) improved care quality in patients treated for IS.

Method:

Records of patients newly diagnosed with IS were retrospectively reviewed both before and after creation of an EMRT for the workup and treatment of IS. Quality of care measures reviewed included delays in treatment plan, medication administration, obtaining neurodiagnostic studies and discharge. The need for repeat neurodiagnostic studies was also assessed. Resident physicians were surveyed regarding template ease of use and functionality.

Results:

Of 17 patients with IS, 7 received template-based care and 10 did not. Patients in the non-template group had more delays in treatment ( p = 0.010), delay in medication administration ( p = 0.10), delay in diagnostic studies ( p = 0.01) and delay in discharge ( p = 0.39). Neurodiagnostic studies needed to be repeated in 5 out of 10 patients in the non-template group and none of the 7 patients in the template group ( p = 0.04). Surveyed resident physicians reported improved coordination in care, avoidance of delays in discharge and improved ability to predict side effects of treatment with template use.

Conclusion:

In a single centre, the use of protocolised EMRTs decreased treatment delays and the need for repeated invasive procedures in patients with newly diagnosed IS and was reported as easy to use by resident physicians.

Implications:

The use of protocolised EMRTs may improve the quality of patient care in IS and other rare diseases.
Compliance With Subcutaneous Immunotherapy Appointments in an Urban Tertiary Care Setting
Authors: Keefe Katherine R. , Ngo-Howard Minhtran , Platt Michael P. , Brook Christopher D.
Published: August 2018

Introduction

Subcutaneous immunotherapy (SCIT) is an effective treatment for allergic disease such as allergic rhinitis and asthma. Reported adherence rates to SCIT have been low, ranging between 50% and 89%. This study sought to evaluate compliance to SCIT in an urban “safety net,” tertiary care center, and to evaluate for disparities in compliance based upon insurance and socioeconomic status.

Methods

A retrospective chart review of SCIT patients between 2003 and 2016 was performed. Demographic data, insurance carriers, and comorbidities were collected. Compliance was evaluated on treatment adherence (percentage of injections administered/scheduled appointments). Statistical analysis was performed using R statistical software. Linear regression analysis was performed to compare compliance to the variables, asthma, duration of therapy, payor, and age. Analysis of variance was used to compare mean compliance between payor groups.

Results

Two hundred five patients met our inclusion criteria and 28 were excluded. Insurance composition was Medicaid (67, 33%), Medicare (18, 9%), Health Safety Net (HSN) in Massachusetts (33, 16%), and commercial payors (82, 42%). Linear regression demonstrated that age, duration of therapy, and asthma status were not related to the percentage of missed doses ( P > .05). Payor status was statistically predictive of missed doses ( P = .02). When comparing average percentage of missed immunotherapy shots, Medicaid patients missed the most 34.2%, followed by Medicare 24.4%, commercial insurance 19.9%, and HSN in Massachusetts 18.5% ( P ≤ .02).

Conclusion

In a cohort of patients at a tertiary care “safety-net” center serving a low-income population, compliance to SCIT was found to be overall high but lower in the Medicaid population.
The dual nature of adaptive coordination in teams
Authors: Grote Gudela , Kolbe Michaela , Waller Mary J.
Published: August 2018

Adaptive team coordination is a central topic in the team dynamics literature. Most team adaptation research to date addresses team responses to demands for flexibility triggered by dynamic external forces. Little explicit attention has been paid to demands for stability created by continued pressures on efficiency and control. To capture this dual nature of adaptive coordination, we propose to characterize adaptation triggers in terms of stability and flexibility demands and suggest four modes of adaptive coordination that enable teams to adequately balance these demands. Grounded in team as well as organizational literatures, we explicate the specific patterns of coordination mechanisms comprising each mode of coordination, termed experiential, exploitative, exploratory, and ambidextrous coordination. The new insights offered into team adaptive coordination can spur research that further integrates team and organizational perspectives on adaptation processes.
Safety of right heart catheterization for pulmonary hypertension in very elderly patients
Authors: Ginoux Marylise , Cottin Vincent , Glérant Jean‐Charles , Traclet Julie , Philit François , Sénéchal Agathe , Mornex Jean‐Francois , Turquier Ségolène
Published: August 2018

Right heart catheterization (RHC) is the reference test in diagnosing pulmonary hypertension (PH). The increasing age of patients at the time of diagnosis raises the issue of the morbidity of this invasive test in elderly individuals. We hypothesized that the morbidity associated with RHC would be increased in elderly patients and highlight differences in hemodynamic characteristics compared to younger patients. A retrospective study was conducted in a regional referral center for PH. Data for all consecutive RHCs performed during the study period were analyzed. Over a five‐year period, 1060 RHCs were performed. Of the patients, 228 (21.5%) were aged ≥75 years and 832 (78.5%) were aged <75 years. Duration of the procedure and site of puncture did not differ according to age group (all P > 0.05). Nine procedures (0.9%) led to complications: three (1.3%) in patients aged >75 years and six (0.7%) in younger patients aged (P = 0.5). Eight were local vascular injuries, directly related to a femoral vein puncture (P < 0.001). Pulmonary arterial pressure and cardiac output were lower in patients aged >75 years than in younger patients (P = 0.001). RHC may be performed regardless of patient age. The rate of RHC complications is not increased in individuals aged >75 years. As most complications were related to femoral vein puncture, this route should be avoided whenever possible.
Doppler echocardiography for assessment of systemic vascular resistances in cardiogenic shock patients
Authors: Gaubert Mélanie , Resseguier Noémie , Thuny Franck , Paganelli Franck , Cautela Jennifer , Pinto Johan , Ammar Chloé , Laine Marc , Bonello Laurent
Published: August 2018

Objective:

Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock.

Methods:

This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment.

Results:

A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m2/cm5 and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m2/cm5. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution ( r=0.86, 95% confidence interval (CI) 0.74, 0.93; P<0.0001). The intraclass correlation coefficient was 0.84 (95% CI 0.72, 0.92). The mean bias was −111.95 dynes.s.m2/cm5 (95% CI −230.06, 6.16). Limits of agreement were −785.86, 561.96.

Conclusions:

Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.
The time of consumers: A review of researches and perspectives
Authors: Lallement Jeanne , Gourmelen Andrea
Published: August 2018

This article provides a synthesis of the research on consumer time. Based on a systematic review of studies from the past 25 years, it offers an original interpretative framework by grouping consumer time into two categories. In the first, the studies on ‘resource time’ reveal that time is perceived differently according to situational and individual antecedents. In the second, the research on ‘personality trait time’ presents time from a global (where time is perceived as a whole), comparative (comparing several time zones) or selective (positioned in a precise time zone) perspective, which is characterised according to the depth to which the time variable is anchored in an individual’s personality. Although this categorisation sheds light on the concept of consumer time, it was not possible to establish a unified theoretical anchoring. This research argues in favour of decompartmentalising the different approaches and methodologies.
Reliability of virtual non-contrast computed tomography angiography: comparing it with the real deal
Authors: Lehti Leena , Söderberg Marcus , Höglund Peter , Nyman Ulf , Gottsäter Anders , Wassélius Johan
Published: August 2018

Background

Computed tomographic angiography (CTA) may require a non-contrast enhanced dataset for the diagnostic workup. By using dual-energy acquisition, it is possible to obtain a virtual non-contrast-enhanced (VNC) dataset, thereby possibly eliminating the non-contrast acquisition and reducing the radiation dose.

Purpose

To compare image quality of VNC images reconstructed from arterial phase dual-energy CTA to true non-contrast (TNC) images, and to assess whether VNC images were of sufficient quality to replace TNC images.

Material and methods

Thirty consecutive patients with suspected abdominal aortic aneurysm, aortic dissection, or subacute control after EVAR/TEVAR were examined with dual-energy CT (DECT). The examination protocol included a single-energy TNC, DECT arterial phase (80 kV/Sn140 kV), and single-energy in venous phase of the aorta. A VNC dataset was obtained from the DE acquisition from arterial phase scans. Mean attenuation and image noise were measured within regions of interest at three levels in the aorta in TNC and VNC images. Comparison of the TNC and VNC images for artefacts was made side-by-side. Subjective evaluation included overall image quality on a 4-grade scale, and quantitative analysis of algorithm-induced artefacts by two experienced readers.

Results

For all cases, the aortic attenuation was significantly higher at VNC than at TNC. Image noise measured quantitatively was also significantly higher at VNC than at TNC. Subjective image quality was lower for VNC (mean = 3.1 for VNC, 3.7 = for TNC) but there were no cases rated non-diagnostic.

Conclusion

VNC images based on arterial phase CTA have significantly higher mean attenuation and higher noise levels compared to TNC.
PGE2 stimulates COX-2 expression via EP2/4 receptors and acts in synergy with IL-1β in human follicular dendritic cell-like cells
Authors: Nam Jihoon , Kwon Bongjae , Yoon Yongdae , Choe Jongseon
Published: August 2018

PGE2 is the major lipid mediator of inflammation produced by multiple cell types including follicular dendritic cells (FDCs) of the lymphoid tissue. We have investigated the immunoregulatory function of PGE2 and its production mechanism using FDC-like cells isolated from human tonsil. Our recent observation of COX-2-inducing effect of PGE2 prompted us to identify the responsible receptor in this study. Pharmacologic approaches were adopted and Western blotting was utilized to measure protein expression levels. Agonists selective for EP2 and EP4 significantly stimulated COX-2 expression, while antagonists for these receptors prevented PGE2 from triggering COX-2 induction. The combined addition of EP2 and EP4 antagonists resulted in further inhibition of PGE2. In contrast, EP1 and EP3 antagonists failed to exhibit the inhibitory effect on PGE2-induced COX-2 expression. Since PGE2 achieves COX-2 induction by repressing Akt activation in FDC-like cells, we confirmed EP2 and EP4 being the targets of PGE2 by examining the effects of E-prostanoid (EP) agonists and antagonists on the level of Akt phosphorylation. After the identification of PGE2 receptor, we examined the effect of PGE2 on IL-1β-induced COX-2 expression. PGE2 and IL-1β brought about a synergistic induction of COX-2 expression. Taken together, this study implies the impact of the combined role of eicosanoids and cytokines in inflammatory milieu.
A systematic review of treatments for acne scarring. Part 2: Energy-based techniques
Authors: Kravvas Georgios , Al-Niaimi Firas
Published: August 2018

Introduction:

Acne scarring is a very common problem, which can be extensive, and may lead to significant psychosocial morbidity. Multiple types of treatments are used to ameliorate atrophic scars with varying degrees of success. This paper provides an overview of the various energy-based modalities that are commonly employed against acne scarring.

Objectives and methods:

A comprehensive literature search of papers published since 2008 was performed in order to determine the efficacy and adverse reactions of commonly used energy-based treatments against post-acne scarring.

Results:

A total of 59 relevant articles were identified covering a multitude of different devices.

Discussion:

Ablative lasers seem to achieve the highest degree of efficacy, albeit this is associated with significant pain and downtime, and the risk for long-term pigmentary changes. Non-ablative fractional photothermolysis (FP) has a much safer profile but cannot achieve as good cosmetic results. The efficacies of fractional radiofrequency microneedling and radiofrequency are slightly inferior to that of FP but offer an even safer adverse profile. Little evidence is available on the remaining devices, with larger studies required in order to reach more solid conclusions.

Conclusion:

Multiple devices have been used with varying levels of efficacy and very different safety profiles. There is an overall lack of high-quality evidence about the effects of different interventions. Furthermore, no standardised scale is available for acne scarring, leading to variability in evaluation and interpretation of data in different studies.
Probation in Japan: Strengths and challenges and likely new tasks
Authors: Watson Andrew
Published: August 2018

Origins of the probation service in Japan, its administrative structure, the respective roles of Professional Probation Officers (PPOs), hogo kansatsu kan, and the nearly 50 times more numerous Volunteer Probation Officers (VPOs), hogo-shi, are described. Recruitment of VPOs, their backgrounds, increasing age, methods of work and training is outlined, followed by activities of local VPO Associations and Offender Rehabilitation Support Centres. Strengths of the distinctive Japanese VPO system are analysed, followed by challenges it faces. Chief amongst them being the introduction of partly suspended sentences coupled with probation for drug offenders and the need to build adequate medical, psychological, accommodation and employment support to prevent their reoffending and aid recovery. Consequences and new tasks for probation of the widely expected lowering of the age of criminal adulthood are also considered.
Utilization and Economic Impact of Posterolateral Fusion and Posterior/Transforaminal Lumbar Interbody Fusion Surgeries in the United States
Authors: Saifi Comron , Cazzulino Alejandro , Laratta Joseph , Save Akshay V. , Shillingford Jamal N. , Louie Philip K. , Pugely Andrew J. , Arlet Vincent
Published: August 2018

Study Design:

Retrospective database study.

Objective:

To analyze the economic and age data concerning primary and revision posterolateral fusion (PLF) and posterior/transforaminal lumbar interbody fusion (PLIF/TLIF) throughout the United States to improve value-based care and health care utilization.

Methods:

The National Inpatient Sample (NIS) database was queried by the International Classification of Diseases, Ninth Revision, Clinical Modification codes for patients who underwent primary or revision PLF and PLIF/TLIF between 2011 and 2014. Age and economic data included number of procedures, costs, and revision burden. The National Inpatient Sample database represents a 20% sample of discharges from US hospitals weighted to provide national estimates.

Results:

From 2011 to 2014, the annual number of PLF and PLIF/TLIF procedures decreased 18% and increased 23%, respectively, in the Unites States. During the same period, the number of revision PLF decreased 19%, while revision PLIF/TLIF remained relatively unchanged. The average cost of PLF was lower than the average cost of PLIF/TLIF. The aggregate national cost for PLF was more than $3 billion, while PLIF/TLIF totaled less than $2 billion. Revision burden (ratio of revision surgeries to the sum of both revision and primary surgeries) remained constant at 8.0% for PLF while it declined from 3.2% to 2.9% for PLIF/TLIF.

Conclusion:

This study demonstrated a steady increase in PLIF/TLIF, while PLF alone decreased. The increasing number of PLIF/TLIF procedures may account for the apparent decline of PLF procedures. There was a higher average cost for PLIF/TLIF as compared with PLF. Revision burden remained unchanged for PLF but declined for PLIF/TLIF, implying a decreased need for revision procedures following the initial PLIF/TLIF surgery.
Verbal Response Times as a Potential Indicator of Cognitive Load During Conventional Speech Audiometry With Matrix Sentences
Authors: Meister Hartmut , Rählmann Sebastian , Lemke Ulrike , Besser Jana
Published: August 2018

This study examined verbal response times—that is, the duration from stimulus offset to voice onset—as a potential measure of cognitive load during conventional testing of speech-in-noise understanding. Response times were compared with a measure of perceived effort as assessed by listening effort scaling. Three listener groups differing in age and hearing status participated in the study. Testing was done at two target intelligibility levels (80%, 95%) and with two noise types (stationary and fluctuating). Verbal response times reflected effects of intelligibility level, noise type, and listener group. Response times were shorter for 95% compared with 80% target intelligibility, shorter for fluctuating compared with stationary noise, and shorter for young listeners compared with older listeners. Responses were also faster for the older listeners with near normal hearing compared with the older hearing-aid users. In contrast, subjective listening effort scaling predominantly revealed effects of target intelligibility level but did not show consistent noise-type or listener-group effects. These findings show that verbal response times and effort scalings tap into different domains of listening effort. Verbal response times can be easily assessed during conventional speech audiometry and have the potential to show effects beyond performance measures and subjective effort estimates.
Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats
Authors: Thow Lisa A. , MacDonald Kathleen , Holmes William M. , Muir Keith W. , Macrae I. Mhairi , Dewar Deborah
Published: August 2018

Background:

Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit.

Methods:

Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging.

Results:

Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group.

Conclusions:

Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear.
Vulvodynia: A Review of the Literature
Authors: Loflin Bobbi Jo , Westmoreland Kearsten , Williams Nancy Toedter
Published: August 2018

Objective: To evaluate the literature and educate the pharmacy community about the different treatment options for vulvodynia. Data Sources: Searches were performed through MEDLINE (1946-May 2018) using OVID and EBSCOhost, and Excerpta Medica (1974-May 2018) using EMBASE. Search terms included vulvar vestibulitis syndrome, vestibulodynia, vulvodynia, vulvar pain, provoked vulvar vestibulitis, and vulvodynia treatment. References of all relevant articles were then used to find additional applicable articles. Study Selection and Data Extraction: This review includes articles in the English language and human trial literature. Twenty-five trials explored the use of oral and topical medications in the treatment of vulvodynia. Data Synthesis: Vulvodynia is a poorly understood disease with an unknown etiology. Oral tricyclic antidepressants and gabapentin continue to be the most commonly used treatments for vulvodynia pain. This is due to their ease of use and patient preference. Topical treatments that have efficacy data are amitriptyline, gabapentin, lidocaine, baclofen, and hormones. This route of administration avoids systemic adverse effects and interpatient variability that accompanies oral administration. Alternative therapies more commonly used include physiotherapy, psychotherapy, and surgery. Treatment length may vary due to dose titrations and potential changes in medication therapy. Conclusions: Several medication and alternative therapies may be effective in treating vulvodynia. Current studies used wide dosing ranges, making it difficult to standardize therapy. No consistent method of assessing pain was used between studies, as well as a limited number being randomized and placebo controlled. Additional research is needed to increase knowledge and further develop vulvodynia treatments.
Normative Thyroid Volume by Ultrasonography in a Nigerian Pediatric Population
Authors: Idigo Felicitas Ugochinyere , Okon Ime Edet , Okeji Mark Chukwudi , Anakwue Angel-Mary Chukwunyelu
Published: August 2018

The objective was to establish normal thyroid volume in healthy infants and children, in a select Nigerian population. Using a portable ultrasound equipment with a 7.5-MHz transducer, 500 apparently healthy pediatric patients were sonographically evaluated. The volume for each thyroid lobe was obtained, as well as the summation of both left and right thyroid volumes, which represented the total volume. The mean and median thyroid volumes for the subgroups were 0.69 ± 0.38 cm3/0.7 cm3 (<1 year), 1.50 ± 0.68 cm3/1.4 cm3 (1–5 years), 2.75 ± 0.94 cm3/2.6 cm3 (6–10 years), 4.47 ± 2.83 cm3/3.7 cm3 (11–15 years), and 7.47 ± 4.81 cm3/5.9 cm3 (16 and 17 years). There was a significant difference ( P = .000) between the population studied and the World Health Organization/International Council for Control of Iodine Deficiency Disorders reference values. The baseline values derived for thyroid dimensions may form the basis for thyroid screening in these asymptomatic children.
Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis
Authors: Rice Lisa M. , Mantero Julio C. , Stratton Eric A. , Warburton Rod , Roberts Kari , Hill Nicholas , Simms Robert W. , Domsic Robyn , Farber Harrison W. , Layfatis Robert
Published: August 2018

Background

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is one of the leading causes of death in SSc. Identification of a serum-based proteomic diagnostic biomarker for SSc-PAH would allow for rapid non-invasive screening and could positively impact patient survival. Identification and validation of novel proteins could potentially facilitate the identification of SSc-PAH, and might also point to important protein mediators in pathogenesis.

Methods

Thirteen treatment-naïve SSc-PAH patients had serum collected at time of diagnosis and were used as the discovery cohort for the protein-expression biomarker. Two proteins, Midkine and Follistatin-like 3 (FSTL3) were then validated by enzyme-linked immunosorbent assays. Midkine and FSTL3 were tested in combination to identify SSc-PAH and were validated in two independent cohorts of SSc-PAH (n = 23, n = 11).

Results

Eighty-two proteins were found to be differentially regulated in SSc-PAH sera. Two proteins (Midkine and FSTL3) were also shown to be elevated in publicly available data and their expression was evaluated in independent cohorts. In the validation cohorts, the combination of Midkine and FSTL3 had an area under the receiver operating characteristic curve (AUC) of 0.85 and 0.92 with respective corresponding measures of sensitivity of 76% and 91%, and specificity measures of 76% and 80%.

Conclusions

These findings indicate that there is a clear delineation between overall protein expression in sera from SSc patients and those with SSc-PAH. The combination of Midkine and FSTL3 can serve as an SSc-PAH biomarker and are potential drug targets for this rare disease population.
Twice-daily insulin degludec/insulin aspart effectively improved morning and evening glucose levels and quality of life in patients previously treated with premixed insulin: an observational study
Authors: Fujimoto Kanta , Iwakura Toshio , Aburaya Megumi , Matsuoka Naoki
Published: August 2018

Background

Previous studies comparing insulin degludec/insulin aspart (IDegAsp) with premixed insulin twice daily among insulin users with type 2 diabetes have not thoroughly investigated differences in the glucose variability and psychological evaluations related to insulin regimen changes. We investigated changes in the daily and day-to-day glucose variability and quality of life (QOL) related to insulin use in patients with type 2 diabetes during a switch from premixed insulin preparations comprising either human insulin (BHI30) or insulin aspart (BIAsp30) to IDegAsp twice daily.

Methods

In this prospective observational study, 22 subjects (BHI30:BIAsp30 = 12:10) self-measured their blood glucose levels every morning, and before and after all meals each week. Premixed insulin was administered for the first 2 months, followed by IDegAsp for the next 2 months. Efficacy measures were evaluated during the last month or last day of both phases.

Results

The mean blood glucose levels (175.5 vs. 163.0 mg/dL; P = 0.004) and the M-values (53.9 vs. 27.6; P = 0.049) were significantly lower in the IDegAsp phase. However, no differences in the standard deviations of morning fasting glucose levels were observed between phases (premixed vs. IDegAsp, 20.0 vs. 19.3 mg/dL; P = 0.343). Compared to the premixed phase, the before-breakfast (145.3 vs. 126.0 mg/dL; P < 0.001), after-breakfast (190.3 vs. 170.7 mg/dL; P = 0.001), before-dinner (153.0 vs. 140.1 mg/dL; P  = 0.007), and after-dinner glucose levels (198.7 vs. 181.4 mg/dL; P = 0.018) were lower in the IDegAsp phase. However, the before-lunch (150.8 vs. 148.2 mg/dL; P  = 0.329) and after-lunch glucose levels (214.7 vs. 211.4 mg/dL; P = 0.308) did not significantly differ between phases. Regarding QOL, the total and therapy-related feeling Insulin Therapy Related-QOL (ITR-QOL) questionnaire scores favored IDegAsp, as did the ITR-QOL at Night questionnaire subscale score of glycemic control before breakfast.

Conclusions

Although the day-to-day variability of morning fasting glucose levels did not change, switching to IDegAsp improved daily glucose level variability, the morning and evening glucose control and QOL among patients treated with premixed insulin.

Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000021939. Prospectively registered 18 April 2016
Rise of the machines? Machine learning approaches and mental health: opportunities and challenges
Authors: Tiffin Paul A. , Paton Lewis W.
Published: August 2018

Machine learning methods are being increasingly applied to physical healthcare. In this article we describe some of the potential benefits, challenges and limitations of this approach in a mental health context. We provide a number of examples where machine learning could add value beyond conventional statistical modelling.

Declaration of interest

None.
Structural and Functional Biology of Aldo-Keto Reductase Steroid-Transforming Enzymes
Authors: Penning Trevor M , Wangtrakuldee Phumvadee , Auchus Richard J
Published: August 2018

Aldo-keto reductases (AKRs) are monomeric NAD(P)(H)-dependent oxidoreductases that play pivotal roles in the biosynthesis and metabolism of steroids in humans. AKR1C enzymes acting as 3-ketosteroid, 17-ketosteroid, and 20-ketosteroid reductases are involved in the prereceptor regulation of ligands for the androgen, estrogen, and progesterone receptors and are considered drug targets to treat steroid hormone–dependent malignancies and endocrine disorders. In contrast, AKR1D1 is the only known steroid 5β-reductase and is essential for bile-acid biosynthesis, the generation of ligands for the farnesoid X receptor, and the 5β-dihydrosteroids that have their own biological activity. In this review we discuss the crystal structures of these AKRs, their kinetic and catalytic mechanisms, AKR genomics (gene expression, splice variants, polymorphic variants, and inherited genetic deficiencies), distribution in steroid target tissues, roles in steroid hormone action and disease, and inhibitor design.
Aldosterone LC-MS/MS Assay-Specific Threshold Values in Screening and Confirmatory Testing for Primary Aldosteronism
Authors: Guo Zeng , Poglitsch Marko , McWhinney Brett C , Ungerer Jacobus P J , Ahmed Ashraf H , Gordon Richard D , Wolley Martin , Stowasser Michael
Published: August 2018

Context

Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values.

Objective

To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate performances of proposed LC-MS/MS–specific cutoffs for PA screening and confirmatory testing.

Patients and Intervention

Forty-one patients underwent aldosterone/renin ratio (ARR) testing to screen for, and fludrocortisone suppression testing (FST) to confirm or exclude, PA. Renin (DRC) was measured by chemiluminescent immunoassay.

Results

Median serum PACLC-MS/MS was 27.8% lower (P < 0.05) than plasma PACRIA in 164 pairs of FST samples. A positive correlation (Spearman coefficient, 0.894, P < 0.01; Pearson r coefficient, 0.861, P < 0.01) was observed between the two assays. Thirty-seven patients showed consistent FST diagnoses (29 positive, 8 negative), whereas four showed inconsistent FSTs by the two assays. Good agreement (κ coefficient, 0.736; P < 0.01) was observed between the current FST diagnostic PACRIA cutoff of 165 pmol/L and the proposed PACLC-MS/MS cutoff of 133 pmol/L. Among 37 patients with consistent FST results, no differences were observed in sensitivity (89.7% vs 93.1%) or specificity (87.5% vs 87.5%) for PA screening between the current ARR cutoff of 70 pmol/mU (PACRIA/DRC) and the proposed cutoff of 55 pmol/mU (PACLC-MS/MS/DRC).

Conclusions

Adjustment of the current cutoffs for PA diagnostic testing is necessary if PAC is measured by LC-MS/MS. Our preliminary results suggest that the proposed LC-MS/MS cutoffs for ARR and FST perform as well as current RIA cutoffs.
Serum Human Chorionic Gonadotropin Among Women With and Without Obesity After Single Embryo Transfers
Authors: Brady Paula C , Farland Leslie V , Ginsburg Elizabeth S
Published: August 2018

Context

Serum human chorionic gonadotropin (hCG) levels are essential for diagnosing and monitoring early pregnancy. Obesity is a health care epidemic; however, the performance of this vital serum hormone in women with an elevated body mass index (BMI) is unknown.

Objective

To investigate the association of BMI with serum hCG values and rate of hCG increase.

Design

Retrospective cohort study.

Setting

University-based infertility clinic.

Patients

Women undergoing fresh vs frozen in vitro fertilization cycles with single-day three or five embryo transfers resulting in singleton live births (≥24 weeks’ gestational age) from 2008 to 2015.

Intervention(s)

None.

Main Outcome Measure(s)

The initial hCG (mIU/mL, 16 days after oocyte retrieval) and 2-day percentage of hCG increases among BMI categories were compared using multivariable linear and logistic regression, adjusted a priori for the day of embryo transfer.

Results

The initial serum hCG values correlated inversely with the BMI (P < 0.0001, test for trend). Low initial hCG values (<100 mIU/mL) were significantly more common across increasing BMI classes, from 1.4% of normal weight patients to 15.6% of those with a BMI ≥40 kg/m2 (P = 0.001, test for trend). The mean 2-day hCG increases were similar and normal (≥53%) across the BMI groups.

Conclusions

Patients with obesity achieving live births had statistically significantly lower initial serum hCG values compared with patients who were nonobese. However, the mean 2-day percentage of increases in hCG were similar across BMI categories. The initial hCG values might lack sensitivity for live births in patients with obesity. The rate of hCG increase remains the mainstay of monitoring very early pregnancies after in vitro fertilization. Future studies should investigate whether serum analyte ranges should be adjusted according to the BMI.