An Icon of Painless Parker.

The discovery of two unaccredited photographs purported to be of Painless Parker occasions a discussion of the notorious "outlaw" dentist's historical significance. It is argued that social media threaten to have performance eclipse clinical skills in dentistry - a process that can be sourced to Parker's vaudevillian antics.

The Stewardship of George Lewis Elliot: Canada's First Dean of Dentistry.

George Lewis Elliot has not been given his proper due as the first dean of dentistry in Canada. Elliot was in the center of a scandal, surrounding his establishment of a private dental school, the Canada College of Dentistry. Faced with a regulatory body whose leaders he perceived to be engaging in the practice "choking off" and "stamping out" their competitors, Elliot undertook to create an independent dental school to provide prospective licentiates with the means to pass the board exams, thereby also improving the profession.

Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory.

OBJECTIVES: The aim of this study was to create and validate severity levels for the central sensitization inventory (CSI), a valid and reliable patient-reported outcome instrument designed to identify patients whose presenting symptoms may be related to a central sensitivity syndrome (CSS; eg, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome), with a proposed common etiology of central sensitization (CS). METHODS: Based on CSI score means and standard deviations from previously published subject samples, the following CSI severity levels were established: subclinical = 0 to 29; mild = 30 to 39; moderate = 40 to 49; severe = 50 to 59; and extreme = 60 to 100. The concurrent validity of the CSI severity levels was then confirmed in a separate chronic pain patient sample (58% with a CSS diagnosis and 42% without) by demonstrating associations between CSI scores and (1) the number of physician-diagnosed CSSs; (2) CSI score distributions in both CSS and non-CSS patient samples; (3) patient-reported history of CSSs; and (4) patient-reported psychosocial measures, which are known to be associated with CSSs. RESULTS: Compared to the non-CSS patient subsample, the score distribution of the CSS patient subsample was skewed toward the higher severity ranges. CSI mean scores moved into higher severity levels as the number of individual CSS diagnoses increased. Patients who scored in the extreme CSI severity level were more likely to report previous diagnoses of fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, tension/migraine headaches, and anxiety or panic attacks (P < 0.01). CSI severity levels were also associated with patient-reported depressive symptoms, perceived disability, sleep disturbance, and pain intensity (P ≤ 0.02). CONCLUSION: This study provides support for these CSI severity levels as a guideline for healthcare providers and researchers in interpreting CSI scores and evaluating treatment responsiveness.

Current status of percutaneous right ventricular assist devices: First-in-man use of a novel dual lumen cannula.

Ventricular assist devices have become an accepted therapeutic solution for patients with severe left ventricular dysfunction when pharmacology fails to maintain sufficient cardiac output. Despite various technologies that have allowed left ventricular assist devices to become more reliable and versatile in the past decade, comparatively little attention has been applied to right heart assistance which is still in the early stage of its development. The extracorporeal devices developed thus far have been associated with mobility issues and complications common to ventricular assist devices in general, such as infection, bleeding, and thromboembolism. Designed to obviate the problems previously experienced by other right ventricle (RV)-focused devices, the Protek Duo (CardiacAssist, Pittsburgh, PA) is a novel, fully percutaneous, dual lumen cannula for RV support used in conjunction with the paracorporeal TandemHeart(®) (CardiacAssist, Pittsburgh, PA) pump. We describe our initial experience with the Protek Duo cannula in two different clinical scenarios. In addition, we summarize the current percutaneous mechanical support technology for RV assistance and propose modification of current technology to facilitate its application. © 2016 Wiley Periodicals, Inc.

Study design and rationale of the heterotopic implantation of the Edwards-Sapien XT transcatheter valve in the inferior VEna cava for the treatment of severe tricuspid regurgitation (HOVER) trial.

BACKGROUND: Tricuspid regurgitation (TR) is an under treated disease. Although surgery for TR remains an effective therapy, many patients are considered to be at a high risk or otherwise inoperable. Caval valve implant (CAVI) offers an alternative to surgery in these patients. Trials assessing the safety and efficacy of caval valve implant are lacking. METHODS: The Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna cava for the treatment of severe Tricuspid Regurgitation (HOVER) trial is an FDA approved, physician initiated, prospective, non-blinded (open label), non-randomized safety and feasibility study to determine the safety and efficacy of the heterotopic implantation of the Edwards-Sapien XT valve in the inferior vena cava for the treatment of severe TR in patients who are at high risk or inoperable. Patients with severe TR in the absence of severe pulmonary hypertension will be recruited. They will be evaluated by a multi-disciplinary team who will agree by consensus that the patients' symptoms are from TR. They will undergo imaging to assess the size of the inferior vena cava (IVC) to determine feasibility of the procedure. If patients meet the inclusion criteria and are free from exclusion criteria, after informed consent they will be eligible for enrollment in the study. A total of 30 patients will be enrolled. The primary objective of the study will be to demonstrate procedural success at 30-days and patient success at 1-year. CONCLUSION: Caval valve implant may present an alternative for patients who are at high risk or inoperable for tricuspid valve surgery (TVS) for TR. © 2016 Wiley Periodicals, Inc.

Is multivessel intervention in ST-elevation myocardial infarction associated with early harm? Insights from observational data.

OBJECTIVES: Appraisal of evidence for recommendations for multivessel coronary intervention in ST-elevation myocardial infarction (STEMI). BACKGROUND: Multi-vessel disease (MVD) is common in patients with ST-segment elevation myocardial infarction (STEMI). Published observational data has suggested that multi-vessel percutaneous coronary intervention (MVPCI) at the time of initial hospitalization for STEMI may be harmful in contrast to evidence from recent randomized trials. METHODS: We queried the nationwide inpatient sample (NIS) to identify characteristics of hemodynamically stable STEMI patients undergoing MVPCI on index admission and subsequent mortality in raw and adjusted models. To compare our results with published observational data, we searched multiple databases from inception through July 15, 2015. RESULTS: From 2009-2012, excluding cardiac arrest or cardiogenic shock, there were 11,454 MVPCI and 157,011 single-vessel PCI (SVPCI) for STEMI patients in the NIS. Compared to SVPCI, MVPCI on index admission was not associated with higher in-hospital mortality in unadjusted or propensity-adjusted models (MVPCI 1.91% vs. SVPCI 5.32%, P < 0.001). Our analysis of index hospitalization MVPCI versus infarct-related artery (IRA)-only PCI in the meta-analysis of observational studies (19 studies, N = 76,399) demonstrated no difference in in-hospital mortality with MVPCI compared with IRA-only PCI (OR 0.87, 95% CI 0.65-1.17; P = 0.37), with confirmation in study sequential analysis. CONCLUSIONS: MVPCI is uncommonly performed during index hospitalization in hemodynamically stable STEMI patients, likely reflecting widespread adherence to prior guidelines. Based on observational data, there does not appear to be early harm associated with MVPCI on the index admission in hemodynamically stable STEMI patients. © 2016 Wiley Periodicals, Inc.

Does gestational diabetes affect fetal growth and pregnancy outcome in twin pregnancies?

BACKGROUND: Women with twin pregnancies are at increased risk for fetal growth restriction, which might be attributed to the limited maternal resources that are being shared by >1 fetus. Based on that, it may be hypothesized that the fetal effects of gestational diabetes mellitus (GDM) with respect to accelerated fetal growth may be less pronounced in twin gestations or alternatively may even have a beneficial role in decreasing the risk of fetal growth restriction in these pregnancies. However, available data are conflicting and are limited by the fact that many of the complications associated with GDM are less relevant for twin gestations, and that all women with GDM included in previous studies were monitored and treated to control maternal blood glucose levels. OBJECTIVE: We sought to assess the impact of GDM and milder degrees of glucose intolerance on fetal growth and pregnancy outcome in twin pregnancies. STUDY DESIGN: This was a retrospective cohort study of all women with twin pregnancies who underwent screening for GDM in a single tertiary referral center from October 2003 through December 2014. The diagnosis of GDM during the study period was based on the 2008 Canadian Diabetes Association (CDA) guidelines, which involve universal screening with a 50-g glucose challenge test (GCT) followed by a diagnostic 2-hour 75-g oral glucose tolerance test (OGTT). Fetal growth and pregnancy outcome were compared among 4 groups of women with increasing degree of glucose intolerance: (1) GCT-NEGATIVE, negative 50-g GCT; (2) OGTT-NEGATIVE, positive 50-g GCT followed by a negative 75-g OGTT; (3) GDM-IADPSG, positive 50-g GCT followed by a positive 75-g OGTT according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not the 2008 CDA criteria-because these women were not considered to have GDM during the study period they were not subjected to any form of treatment; and (4) GDM-CDA, positive 50-g GCT followed by a positive 75-g OGTT according to the 2008 CDA criteria. RESULTS: Overall 1393 women were eligible for the study: 1021 (73.3%) in the GCT-NEGATIVE group, 184 (13.2%) in the OGTT-NEGATIVE group, 99 (7.1%) in the GDM-IADPSG group, and 89 (6.4%) in the GDM-CDA group. There was a continuous relationship between the degree of glucose intolerance and fetal growth as reflected by a right shift of the distribution curve of birthweight percentiles and a greater likelihood of high birthweight percentile: OGTT-NEGATIVE = odds ratio (OR), 1.5; 95% confidence interval (CI), 1.07-2.2; GDM-IADPSG = OR, 1.7; 95% CI, 1.1-2.6; and GDM-CDA = OR, 1.9, 95% CI, 1.3-3.1 (using the GCT-NEGATIVE group as reference). Fetuses of women with glucose intolerance were more likely to experience asymmetric growth as reflected by an elevated abdominal circumference to head circumference ratio. CONCLUSION: GDM and milder degrees of glucose intolerance in twin pregnancies are associated with an increased risk of asymmetric overgrowth in a manner that is related to the degree of glucose intolerance.

Radial artery avulsion--a rare complication of transradial catheterization.

Transradial access is becoming the default mode of catheterization in a growing number of centers in the United States. The increasing utilization of transradial access has led to significant reduction in access site complications especially bleeding complications. We report a rare complication of transradial catheterization of radial artery avulsion, which was successfully treated in an endovascular fashion during the index procedure. © 2014 Wiley Periodicals, Inc.

Review of surgical prosthetic paravalvular leaks: diagnosis and catheter-based closure.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with surgical prosthetic valve implantation. Paravalvular leak can have significant clinical consequence such as congestive heart failure, haemolytic anaemia, and infective endocarditis. Recently, transcatheter therapy has been applied to the treatment of this disorder with reasonable procedural and clinical success. This review discusses the current state of PVLs, the utilization of multi-modality imaging in their diagnosis and treatment, and the available therapeutic options. Further aim of this review is to examine transcatheter therapy of PVLs including the principles, outcomes, and procedural-related complications.

Anesthetic efficacy of a combination of 0.9 M mannitol plus 68.8 mg of lidocaine with 50 µg epinephrine in inferior alveolar nerve blocks: a prospective randomized, single blind study.

The purpose of this prospective randomized, single blind study was to determine the anesthetic efficacy of 68.8 mg of lidocaine with 50 µg epinephrine compared to 68.8 mg lidocaine with 50 µg epinephrine plus 0.9 M mannitol in inferior alveolar nerve (IAN) blocks. Forty subjects randomly received 2 IAN blocks consisting of a 1.72-mL formulation of 68.8 mg lidocaine with 50 µg epinephrine and a 5-mL formulation of 68.8 mg lidocaine with 50 µg epinephrine (1.72 mL) plus 0.9 M mannitol (3.28 mL) in 2 separate appointments spaced at least 1 week apart. Mandibular anterior and posterior teeth were blindly electric pulp tested at 4-minute cycles for 60 minutes postinjection. No response from the subject to the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Total percent pulpal anesthesia was defined as the total of all the times of pulpal anesthesia (80 readings), for each tooth, over the 60 minutes. One hundred percent of the subjects had profound lip numbness with both inferior alveolar nerve blocks. The results demonstrated that the 5 mL-formulation of 68.8 mg lidocaine with 50 µg epinephrine plus 0.9 M mannitol was significantly better than the 1.72-mL formulation of 68.8 mg lidocaine with 50 µg epinephrine for all teeth, except the lateral incisor. We concluded that adding 0.9 M mannitol to a lidocaine with epinephrine formulation was significantly more effective in achieving a greater percentage of total pulpal anesthesia (as defined in this study) than a lidocaine formulation without mannitol. However, the 0.9 M mannitol/lidocaine formulation would not provide 100% pulpal anesthesia for all the mandibular teeth.

Shift-to-shift handoffs in the NICU: lessons learned from a large scale audit.

OBJECTIVE: Describe the frequency of best practice behaviors during NICU provider and nursing shift-to-shift handoffs and identify strengths and opportunities for improvement. STUDY DESIGN: Observational study of handoff characteristics among 40 centers participating in a learning collaborative over a 10-month period. Data were gathered using a handoff audit tool that outlined best practices. Comparisons of behaviors between nurse-to-nurse and provider-to-provider handoffs were made where appropriate. RESULTS: Overall, 946 audits of shift-to-shift handoffs were analyzed. While many behaviors were demonstrated reliably, differences between nurse-to-nurse vs provider-to-provider handoffs were noted. Families were present for 5.9% of handoffs and, among those who were present, 48.2% participated by contributing information, asking questions, and sharing goals. CONCLUSIONS: Observation and measurement of handoff behaviors can be used to identify opportunities to improve handoff communication, family participation, and human factors that support handoff. Auditing handoffs is feasible and necessary to improve these critical transitions in infants' care.

Vacuum thrombectomy of large right atrial thrombus.

We report a novel technique for percutaneous removal of the right heart thrombi using a suction cannula. This method allowed complete en bloc removal of the right atrial thrombus avoiding surgical procedure in a high risk patient.

The development and psychometric validation of the central sensitization inventory.

Central sensitization (CS) has been proposed as a common pathophysiological mechanism to explain related syndromes for which no specific organic cause can be found. The term "central sensitivity syndrome (CSS)" has been proposed to describe these poorly understood disorders related to CS. The goal of this investigation was to develop the Central Sensitization Inventory (CSI), which identifies key symptoms associated with CSSs and quantifies the degree of these symptoms. The utility of the CSI, to differentiate among different types of chronic pain patients who presumably have different levels of CS impairment, was then evaluated. Study 1 demonstrated strong psychometric properties (test-retest reliability = 0.817; Cronbach's alpha = 0.879) of the CSI in a cohort of normative subjects. A factor analysis (including both normative and chronic pain subjects) yielded 4 major factors (all related to somatic and emotional symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the CSI was administered to 4 groups: fibromyalgia (FM); chronic widespread pain without FM; work-related regional chronic low back pain (CLBP); and normative control group. Analyses revealed that the patients with FM reported the highest CSI scores and the normative population the lowest (P < 0.05). Analyses also demonstrated that the prevalence of previously diagnosed CSSs and related disorders was highest in the FM group and lowest in the normative group (P < 0.001). Taken together, these 2 studies demonstrate the psychometric strength, clinical utility, and the initial construct validity of the CSI in evaluating CS-related clinical symptoms in chronic pain populations.

Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A.

Evidence suggests that exposure to UV-A radiation can liberate nitric oxide from skin cells eliciting vasodilation in-vivo. However, the duration of nitric oxide release in skin cells after UV exposure is not well studied, with emphasis on UV-B mediated iNOS upregulation. The current study demonstrated persistence of nitric oxide release in a dark reaction after moderate UV-A exposure, peaking around 48 h post exposure; this effect was shown in keratinocytes, fibroblasts and endothelial cells from neonatal donors and keratinocytes from aged donors and confirmed the hypothesis that UV-A exposure appeared to upregulate cNOS alongside iNOS. Release of nitric oxide in the skin cells induced by a moderate exposure to UV-A in sunlight may be especially beneficial for some demographic groups such as the elderly, hypertensive patients or those with impaired nitric oxide function, not only during exposure but many hours and days after that.

Isolation of five different primary cell types from a single sample of human skin.

We have developed a technique to isolate primary keratinocytes, melanocytes, fibroblasts, preadipocytes, and microvascular endothelial cells from an individual sample of human skin. The protocol describes step-by-step instructions for processing, cells isolation, and culture of neonatal foreskin, with adaptation for more demanding adult tissues. The availability of multiple isogenic cell types derived from individual skin samples offers the ability to investigate various areas of biology, in the context of cell-type specificity without potential confounding influence of inter-individual or genetic differences. For complete details on the use and execution of this protocol, please refer to Holliman et al. (2017), Horvath et al. (2019), Horvath et al. (2018), Kabacik et al. (2018), Lowe et al. (2020), Lu et al. (2019), and Lu et al. (2018).

Amnioreduction with rescue cerclage at advanced cervical dilation or gestational age.

OBJECTIVE: To determine the feasibility of rescue cerclage and amnioreduction at advanced cervical dilation or gestational age. METHODS: We present a retrospective case series of women who underwent rescue cerclage at either an advanced gestational age (24 + 0 to 24 + 6 weeks) or cervical dilation (≥4 cm), with a subset undergoing amnioreduction prior to cerclage placement. RESULTS: Nine women were included and amnioreduction was performed in 7 (78%). A bi-modal distribution of obstetric outcomes was observed, with 5 (56%) women delivering ≥34 weeks gestation, 3 (33%) of which delivered at term. Two (22%) women experienced intra-operative rupture of membranes and subsequent perinatal deaths. Two (22%) women delivered extremely premature, with one resulting in infant death. DISCUSSION: Our data show that rescue cerclage with amnioreduction may be successful at advanced gestational ages or cervical dilations, suggesting that these women should be included in prospective studies to better establish the efficacy and safety of this procedure.

The relationship between epigenetic age and the hallmarks of aging in human cells.

Epigenetic clocks are mathematically derived age estimators that are based on combinations of methylation values that change with age at specific CpGs in the genome. These clocks are widely used to measure the age of tissues and cells1,2. The discrepancy between epigenetic age (EpiAge), as estimated by these clocks, and chronological age is referred to as EpiAge acceleration. Epidemiological studies have linked EpiAge acceleration to a wide variety of pathologies, health states, lifestyle, mental state and environmental factors2, indicating that epigenetic clocks tap into critical biological processes that are involved in aging. Despite the importance of this inference, the mechanisms underpinning these clocks remained largely uncharacterized and unelucidated. Here, using primary human cells, we set out to investigate whether epigenetic aging is the manifestation of one or more of the aging hallmarks previously identified3. We show that although epigenetic aging is distinct from cellular senescence, telomere attrition and genomic instability, it is associated with nutrient sensing, mitochondrial activity and stem cell composition.

Chronic irradiation of human cells reduces histone levels and deregulates gene expression.

Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6-20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology.

Variability in the systems of care supporting critical neonatal intensive care unit transitions.

OBJECTIVE: Assess practices supporting care transitions for infants and families in the neonatal intensive care unit (NICU) using a model of four key drivers: communication, teamwork, family integration, and standardization. STUDY DESIGN: Single-day audit among NICUs in the Vermont Oxford Network Critical Transitions collaborative addressing policies and practices supporting the four key drivers during admission, discharge, shift-to-shift handoffs, within hospital transfers, and select changes in clinical status. RESULTS: Among 95 NICUs, the median hospital rate of audited policies in place addressing the four key drivers were 47% (inter-quartile range (IQR) 35-65%) for communication, 67% (IQR 33-83%) for teamwork, 50% (IQR 33-61%) for family integration, and 70% (IQR 56-85%) for standardization. Of the 2462 infants included, 1066 (43%) experienced ≥1 specified transition during the week prior to the audit. CONCLUSIONS: We identified opportunities for improving NICU transitions in areas of communication, teamwork, family integration, and standardization.

Evaluation of artificial intelligence-based telemedicine screening for retinopathy of prematurity.

Retrospective evaluation of a deep learning-derived retinopathy of prematurity (ROP) vascular severity score in an operational ROP screening program demonstrated high diagnostic performance for detection of type 2 or worse ROP. To our knowledge, this is the first report in the literature that evaluated the use of artificial intelligence for ROP screening and represents a proof of concept. With further prospective validation, this technology might improve the accuracy, efficiency, and objectivity of diagnosis and facilitate earlier detection of disease progression in patients with potentially blinding ROP.