bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-12p40 and sRAGE in serum correlate with chemically induced cleft palate in mice
Authors: Wang X-H , Peng Y , Meng L-Y
Published: July 2020

Cleft palate (CP), a congenital defect in the oral and maxillofacial regions, is difficult to detect prenatally. This study investigated the correlation between differentially expressed proteins in serum and CP induced by all-trans retinoic acid (atRA) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in mice. We studied 80 mice in the following groups: male mice (male; n = 6), nonpregnant female control mice (NP-CRL; n = 6), healthy pregnant controls (P-CRL; Con; n = 24), pregnant mice with CP induced by atRA ( n = 24), or pregnant mice with CP induced by TCDD (TCDD; n = 20). Pregnant mice were given with atRA (100 mg/kg) or TCDD (40 μg/kg), or corn oil by oral gavage at E10.5. The serum samples were collected and eight proteins—including interleukin (IL)-12p40, IL-12p70, receptor for advanced glycation end products (RAGE), interferon (IFN)-γ, IFN-β, IL-10, leukemia inhibitory factor (LIF), and epiregulin—were detected by enzyme-linked immunosorbent assay. Placental tissues were immunostained for IL-12p40 and RAGE from stages E13.5 to E16.5. In P-CRL mice, serum IL-12p40 was significantly increased at E13.5 and declined over E14.5–E16.5. P-CRL had lower IFN-γ levels at E13.5 compared with NP-CRL. The CP groups showed lower concentrations of IL-12p40 at E13.5–E14.5 and clearly higher concentrations of soluble RAGE (sRAGE) at E13.5 when compared with P-CRL. IL-12p40 immunostaining clearly decreased in placental tissue sections obtained from E13.5 to E14.5 in both CP groups. These findings suggest that reduced levels of IL-12p40 and increased levels of sRAGE in serum may be correlated with chemically induced CP in mice, but further studies would be required to establish this.
Clinical features, disease activity and outcomes of Malaysian children with paediatric systemic lupus erythematosus: A cohort from a tertiary centre
Authors: Lim Sern Chin , Chan Elaine Wan Ling , Tang Swee Ping
Published: July 2020

Background

Paediatric systemic lupus erythematosus is a rare autoimmune disease with a wide spectrum of clinical presentation in different populations. We present a cohort of paediatric systemic lupus erythematosus in Malaysia where the disease features and outcomes are still largely unknown.

Methods

A retrospective review of all paediatric systemic lupus erythematosus patients with at least 6 months follow-up at Selayang Hospital from 2004 to 2016. Epidemiological, clinical and outcome data were collected and analysed.

Results

A total of 141 paediatric systemic lupus erythematosus patients, 87.9% females, were followed up for a median 6.3 years (interquartile range 3.6–9.0). The median age at diagnosis was 10.8 years (interquartile range 9.0–12.0 years), positive family history of systemic lupus erythematosus was present in 12.1% and the majority (61.7%) were of Malay ethnicity. Common presentations included fever (87.2%), vasculitic rash (72.3%) and lethargy (69.5%). At diagnosis, leukopenia (51.1%), thrombocytopenia (41.8%) and cutaneous lupus (56%) predominate with significant renal involvement (39.7%). Renal (45.4%), liver (26%) and the central nervous system (17%) were important major organs involved during the course of the disease. At diagnosis, almost all (99.3%) patients had high disease activity (mean Systemic Lupus Erythematosus Disease Activity Index score 20.1 ± 9.6). The majority (62.4%) achieved remission or low disease activity after 6 months, maintained over the next 10 years. Damage occurred early (39.1% at 1 year) and increased with time. Ocular damage was the most common side effect (29%) and was predominantly corticosteroid related (93%). Growth retardation was significant (38.2%) with no gonadal failure or secondary malignancies. End-stage renal disease occurred in 3.1% patients whereas 53.1% had sustained renal remission. Overall mortality was 1.4%.

Conclusion

Despite high disease activity at diagnosis, the majority had good sustained response to treatment with low overall mortality. However, there was progressive accrual of organ damage, highlighting the need for further research and refinements into therapies for paediatric systemic lupus erythematosus.
Mixed-effects models for the design and analysis of stepped wedge cluster randomized trials: An overview
Authors: Li Fan , Hughes James P , Hemming Karla , Taljaard Monica , Melnick Edward R. , Heagerty Patrick J
Published: July 2020

The stepped wedge cluster randomized design has received increasing attention in pragmatic clinical trials and implementation science research. The key feature of the design is the unidirectional crossover of clusters from the control to intervention conditions on a staggered schedule, which induces confounding of the intervention effect by time. The stepped wedge design first appeared in the Gambia hepatitis study in the 1980s. However, the statistical model used for the design and analysis was not formally introduced until 2007 in an article by Hussey and Hughes. Since then, a variety of mixed-effects model extensions have been proposed for the design and analysis of these trials. In this article, we explore these extensions under a unified perspective. We provide a general model representation and regard various model extensions as alternative ways to characterize the secular trend, intervention effect, as well as sources of heterogeneity. We review the key model ingredients and clarify their implications for the design and analysis. The article serves as an entry point to the evolving statistical literatures on stepped wedge designs.
Lt. Cmdr. Laura M. Cobb (1892–1981): Chief navy nurse who oversaw medical care in WWII civilian concentration camps
Authors: Lucchesi Emilie
Published: July 2020

Lt. Commander Laura M. Cobb was a chief nurse in the U.S. Navy during WWII who was imprisoned by Japan for more than three years in the Occupied Philippines. Under her direction, eleven other navy nurse POWs maintained rank and provided medical care to thousands of civilian inmates. Early in the war, Cobb courageously mislabeled quinine as baking soda in order to stop enemy medical corps from stealing the supply. She is credited with saving inmates from malaria. In 1943, she oversaw the creation of an infirmary at the Los Baños concentration camp where her nurses relied on scavenged supplies and local resources to provide medical care to more than 2,400 men, women and children. In U.S. military medical history, she is one of seventy-eight nurse POWs; and the only chief nurse in navy medical history to continue her duties while in enemy captivity. She received the Bronze Star with a gold star device and her citation honored her “dauntless determination, zealous efforts and unselfish devotion to duty in the face of unprecedented hardship.”
Chester R. Burns (1937–2006) and the origins of the American Osler Society
Authors: Malloy Michael H
Published: July 2020

The American Osler Society (AOS) traces its origin to a 1970 symposium on Humanism in Medicine in Galveston, Texas. Although John P. McGovern (1921–2007) receives credit for conceiving the symposium and spearheading formation of the AOS, Chester Ray Burns (1937–2006) played a key role that has not been sufficiently recognized. Burns, the first American-born physician to receive a doctorate in the history of medicine from the Johns Hopkins University, did much and perhaps most of the organizational work and brought to the symposium a perspective on the crossroads between medicine and the humanities that proved essential to the nascent organization’s success. Burns went on to a productive career at the University of Texas Medical Branch (UTMB) in Galveston, became the 35th president of the AOS, and is among the relatively few physician-historians to have published scholarly articles in the history of medicine, medical biography, medical ethics, and philosophy as related to medicine.
Determinants Linked to Executive Succession Planning in Public Sector Organizations
Authors: Al Suwaidi Muna , Jabeen Fauzia , Stachowicz-Stanusch Agata , Webb Matthew
Published: July 2020

Succession planning is important for organizational growth and business sustainability in the public sector. However, few organizations have attempted to introduce the concept and practice. This article aimed to identify and prioritize the factors that influence executive succession planning in the public sector in the United Arab Emirates (UAE), using the analytic hierarchy process. A model was developed with 5 criteria and 29 sub-criteria and tested using data collected from 40 interviews with top executives from various public sector organizations. The findings showed that succession planning strategy, organizational culture and leadership development opportunities were the most significant factors linked to executive succession planning in the UAE public sector. A framework for decision-makers was developed which could be used to overcome some of the challenges of executive succession planning. It is hoped that this study will help policymakers to formulate suitable policies and strategies to promote executive succession planning in public sector organizations. It will also help them to implement best practice in this field.
A review on multi-physics numerical modelling in different applications of magnetorheological fluids
Authors: Elsaady Wael , Oyadiji S Olutunde , Nasser Adel
Published: July 2020

Magnetorheological fluids involve multi-physics phenomena which are manifested by interactions between structural mechanics, electromagnetism and rheological fluid flow. In comparison with analytical models, numerical models employed for magnetorheological fluid applications are thought to be more advantageous, as they can predict more phenomena, more parameters of design, and involve fewer model assumptions. On that basis, the state-of-the-art numerical methods that investigate the multi-physics behaviour of magnetorheological fluids in different applications are reviewed in this article. Theories, characteristics, limitations and considerations employed in numerical models are discussed. Modelling of magnetic field has been found to be rather an uncomplicated affair in comparison to modelling of fluid flow field which is rather complicated. This is because, the former involves essentially one phenomenon/mechanism, whereas the latter involves a plethora of phenomena/mechanisms such as laminar versus turbulent rheological flow, incompressible versus compressible flow, and single- versus two-phase flow. Moreover, some models are shown to be still incapable of predicting the rheological nonlinear behaviour of magnetorheological fluids although they can predict the dynamic characteristics of the system.
Trends in the Utilization of Palliative Care in Patients With Gynecologic Cancer Who Subsequently Died During Hospitalization
Authors: Milki Anthony , Mann Amandeep Kaur , Gardner Austin , Kapp Daniel Stuart , English Diana , Chan John K.
Published: July 2020

Objective:

To determine factors associated with the utilization of palliative care (PC) in patients with metastatic gynecologic cancer who died while hospitalized.

Methods:

Data were abstracted from the National Inpatient Sample database for patients with cervical, uterine, and ovarian cancers from 2005 to 2011. Chi-squared and logistic regression models were used for statistical analyses.

Results:

Of 4559 women (median age: 65 years; range: 19-102), 1066 (23.4%) utilized PC. Patients were 24.9% low socioeconomic status (SES), 23.9% low-middle, 23.7% middle-high, and 25.1% high SES. Medicare, Medicaid, and private insurance coverage were listed at 46.2%, 37.5%, 11.3% of patients; 36.2%, 21.1%, 18.1%, 24.6% were treated in the South, West, Midwest, and Northeast. Over the 7 year study period, the use of PC increased from 12% to 45%. Older age (odds ratio [OR]: 1.36; 95% CI: 1.11-1.68; P = .003), high SES (OR: 1.41; 95% CI: 1.12-1.78; P = .003), more recent treatment (OR: 9.22; 95% CI: 6.8-12.51; P < .0001), private insurance (OR: 1.81; 95% CI: 1.46-2.25; P < .001), and treatment at large-volume hospitals (OR: 1.36; 95% CI: 1.04-1.77; P = .02), Western (OR: 2.00; 95% CI: 1.61-2.49; P < .001) and Midwestern hospitals (OR: 1.35; 95% CI: 1.08-1.68; P = .001) were associated with higher utilization of PC.

Conclusions:

The use of inpatient PC for patients with gynecologic cancer increased over time. The lower utilization of PC for terminal illness was associated with younger age, lower SES, government-issued insurance coverage, and treatment in Southern and smaller volume hospitals, and warrants further attention.
Ferric Maltol: A New Oral Iron Formulation for the Treatment of Iron Deficiency in Adults
Authors: Khoury Adonice , Pagan Kaley A. , Farland Michelle Z.
Published: July 2020

Objective:

To review the pharmacology, efficacy, and safety of ferric maltol (FM), an oral iron formulation, for iron deficiency anemia (IDA).

Data Sources:

A MEDLINE/PubMed and EMBASE (January 1, 1985, to June 19, 2020) literature search was performed using the terms ferric maltol, accrufer, feraccru, iron maltol, ferric trimaltol, iron deficiency, iron deficiency anemia, inflammatory bowel disease, and chronic kidney disease. Additional data sources included prescribing information, abstracts, and the National Institutes of Health Clinical Trials Registry.

Study Selection/Data Extraction:

English language literature evaluating FM pharmacology, pharmacokinetics, efficacy, or safety in the treatment of IDA were reviewed.

Data Synthesis:

FM is a ferric, non–salt-based oral iron formulation demonstrating improved tolerance in patients with previous intolerance to other iron formulations. Phase 3 trials demonstrated significant improvements in anemia and serum iron parameters in patients with inflammatory bowel disease (IBD) and chronic kidney disease (CKD). Common adverse effects were gastrointestinal intolerance.

Relevance to Patient Care and Clinical Practice:

FM is an effective and well-tolerated alternative to oral iron salts for patients with IBD or CKD and IDA. Emerging data suggest that FM is noninferior to intravenous (IV) ferric carboxymaltose in patients with IBD and IDA. Prior to selecting FM over IV iron products, consideration should be given to time to normalization of Hb, ease of administration, cost, and tolerability.

Conclusion:

FM is a relatively safe, effective oral iron therapy that may be better tolerated than other oral iron formulations. FM may be an effective alternative to IV iron in patients with IBD.
Intraarticular Inflammatory Myofibroblastic Tumor of the Left Knee With ALK-CARS Fusion Detected With Archer Fusionplex Sarcoma NGS Panel: Case Report and Literature Review
Authors: Pineda-Díaz Janet , Solar Irit , Hershkovitz Dov , Drukman Ido , Sher Osnat
Published: July 2020

Inflammatory myofibroblastic tumor (IMT) is a lesion of intermediate biological potential with local recurrences and rare metastases found in multiple anatomical locations. We present a case of a pure intraarticular IMT of the knee, a location that has not been previously documented, with genetic confirmation of ALK-CARS fusion detected with next-generation sequencing. A 20-year-old healthy male was admitted to the orthopedic oncology department due to several months of pain and restriction in movement of his left knee. On magnetic resonance imaging, multiple intraarticular nodular lesions were seen. The patient underwent 2 synovectomies within the course of 1 year. The initial biopsy was interpreted as nodular fasciitis. The second biopsy revealed exuberant tissue displaying compact fascicles of spindle cells intermixed with myxoid areas in a background of inflammatory cells, highly suggestive for IMT. Due to the unusual intraarticular location, equivocal ALK immunostaining and the differential diagnosis with nodular fasciitis, we performed targeted next-generation sequencing using Archer FusionPlex Sarcoma panel, which can identify multiple fusions in a single assay. An ALK-CARS fusion was found, supporting the diagnosis of IMT. This report emphasizes the added value of broad molecular analysis in cases with unusual clinical presentation, equivocal immunohistochemistry, and a wide differential diagnosis.
Cannabis as a Gateway Drug for Opioid Use Disorder
Authors: Williams Arthur Robin
Published: July 2020

Cannabis use in some individuals can meaningfully introduce de novo risk for the initiation of opioid use and development of opioid use disorder. These risks may be particularly high during adolescence when cannabis use may disrupt critical periods of neurodevelopment. Current research studying the combination of genetic and environmental factors involved in substance use disorders is poorly understood. More research is needed, particularly to identify which adolescents are most at risk and to develop effective interventions addressing contributing factors such as trauma and psychiatric comorbidity.
Is Litigation the Way to Combat the Opioid Crisis?
Authors: Ausness Richard C.
Published: July 2020

This paper examines the lawsuits brought by state and local government entities against prescription opioid producers and sellers. It examines their potential liability as well as some of the defenses they might raise. The paper also discusses multidistrict litigation and government lawsuits in state court. It concludes that litigation is not the best solution to the opioid crisis.
Multivariate recursive Bayesian linear regression and its applications to output-only identification of time-varying mechanical systems
Authors: Ma Zhi-Sai , Li Liqing , Ding Qian
Published: July 2020

This article focuses on the output-only recursive identification of time-varying systems by using parametric time-domain methods. A novel multivariate recursive Bayesian linear regression method is proposed based on the vector time-dependent autoregressive moving average model. The standard setup of univariate batch Bayesian linear regression is first extended to the multivariate case for multiple response signal modeling and further extended to the recursive case to meet the output-only recursive identification requirement of practical systems. A sliding window mechanism is finally applied to deemphasize data from the remote past and fix the computational complexity for each consecutive update, allowing the proposed method to be capable of tracking the time-varying dynamics online. The proposed multivariate recursive Bayesian linear regression method is first validated by a simple numerical system and subsequently applied to identify two mechanical systems with typical time-varying dynamics. Comparative identification results via Monte Carlo tests numerically and experimentally demonstrate the superior achievable accuracy and time-varying tracking capability of the proposed method.
Beyond Black and White: Mapping Misclassification of Medicare Beneficiaries Race and Ethnicity
Authors: Grafova Irina B. , Jarrín Olga F.
Published: July 2020

The Centers for Medicare and Medicaid Services administrative data contains two variables that are used for research and evaluation of health disparities: the enrollment database (EDB) beneficiary race code and the Research Triangle Institute (RTI) race code. The objective of this article is to examine state-level variation in racial/ethnic misclassification of EDB and RTI race codes compared with self-reported data collected during home health care. The study population included 4,231,370 Medicare beneficiaries who utilized home health care services in 2015. We found substantial variation between states in Medicare administrative data misclassification of self-identified Hispanic, Asian American/Pacific Islander, and American Indian/Alaska Native beneficiaries. Caution should be used when interpreting state-level health care disparities and minority health outcomes based on existing race variables contained in Medicare data sets. Self-reported race/ethnicity data collected during routine care of Medicare beneficiaries may be used to improve the accuracy of minority health and health disparities reporting and research.
Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis–related fatigue
Authors: Fitzgerald Kathryn C , Morris Bridget , Soroosh Aurash , Balshi Alexandra , Maher Dermot , Kaplin Adam , Nourbakhsh Bardia
Published: July 2020

Background:

Fatigue is the most common symptom of MS and has no effective pharmacotherapy.

Objective:

To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue.

Methods:

In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models.

Results:

In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (−0.10 point; 95% confidence interval (CI): −0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (−5.2 points; 95% CI: −10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (−13.5 point; 95% CI: −25.0, −1.98; p = 0.04).

Conclusions:

Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.
Visual field loss and structure–function relationships in optic neuritis associated with myelin oligodendrocyte glycoprotein antibody
Authors: Deschamps Romain , Philibert Manon , Lamirel Cedric , Lambert Jerome , Vasseur Vivien , Gueguen Antoine , Bensa Caroline , Lecler Augustin , Marignier Romain , Vignal Catherine , Gout Olivier
Published: July 2020

Background:

A paradoxical discrepancy between severe peripapillary retinal nerve fiber layer (pRNFL) atrophy and good visual outcome had been reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated optic neuritis (ON). However, only visual acuity (VA) was assessed.

Objectives:

To study visual field (VF) outcomes of patients with MOG-IgG-associated ON and evaluate the correlation between functional eye outcome and retinal structural changes assessed by optical coherence tomography.

Methods:

The records of 32 patients with MOG-IgG-associated ON who underwent ophthalmological examination at least 12 months after ON onset were reviewed. Degree of VF disability was determined by mean deviation (MD).

Results:

At final assessment (median, 35 months), 4.2% of 48 affected eyes (AE) had VA ⩽ 0.1, 40% had abnormal MD, and among AE with final VA ⩾ 1.0, 31% had mild to moderate damage. Thinning of the inner retinal layers was significantly correlated with MD impairment. Analysis demonstrated a threshold of pRNFL thickness (50 µm), below which MD was significantly worse (mean, −2.27 dB vs −17.72 dB; p = 0.0003). ON relapse was significantly associated with poor visual outcome assessed by MD.

Conclusion:

Functional impairment measured with VF is not rare, and MD assessment better reflects actual structural damage.
Comparing sleep patterns between children with autism spectrum disorder and children with typical development: A matched case–control study
Authors: Tse Andy CY , Yu CCW , Lee Paul H
Published: July 2020

Children with autism spectrum disorder are often reported to have more sleep deficits and poorer sleep quality compared with children with typical development. However, most previous studies have serious methodological limitations, such as varying sample sizes in the comparison groups, wide age range of participants, and body mass index not matched between participants. This study investigated whether sleep patterns differed between children with autism spectrum disorder and those with typical development using a carefully matched case–control design and incorporating both actigraphy and sleep log assessments. A total of 78 children diagnosed with autism spectrum disorder were matched with 78 typical development controls in this study. The matched variables included age, gender, and body mass index. The results showed that children with autism spectrum disorder had shorter sleep duration, reduced sleep efficiency, longer sleep-onset latency, and longer wake after sleep onset than children with typical development ( ps < 0.05). Further studies are needed to explore the mechanisms underlying these sleep deficits in children with autism spectrum disorder.

Lay abstract

This study compared the sleep pattern between children with autism spectrum disorders and children with typical development using a matched case–control design (matched age, gender, and body mass index). Significant differences were found in night-time sleep duration (total amount of sleep at night), sleep efficiency (percentage of time spent asleep), sleep-onset latency (length of time that it takes to transit from awake to asleep), and wake after sleep onset (total amount of time spent awake after defined sleep onset). Findings showed that children with autism spectrum disorder had poorer sleep quality than children with typical development. Mechanisms underlying the differences should be further explored in order to develop an effective treatment intervention.
Pandemic and its metaphors: Sontag revisited in the COVID-19 era
Authors: Craig David
Published: July 2020

As the COVID-19 crisis spreads around the globe, the rhetoric about the pandemic evoked by journalists and politicians harks back to that of prior diseases and epidemics. This short article updates the framework of AIDS metaphors developed by critical theorist Susan Sontag to the COVID-19 era. Alongside the damage wrought by the virus itself, these discourses can inflict greater, even lethal damage, while thrusting into relief ongoing critical concerns around socio-cultural power, injustice, and inequality.
Use of a Steerable Sheath for Antegrade Catheterization of a Supra-aortic Branch of an Inner-Branched Arch Endograft via a Percutaneous Femoral Access
Authors: Settembrini Alberto M. , Kölbel Tilo , Rohlffs Fiona , Eleshra Ahmed , Debus E. Sebastian , Panuccio Giuseppe
Published: July 2020

Purpose: To describe the use of a steerable sheath from a femoral access for antegrade catheterization of the left common carotid artery (LCCA) in an inner-branched arch endograft. Technique: This technique is demonstrated in a patient with residual aortic dissection after replacement of the ascending aorta for acute type A aortic dissection. He presented 4 years later with aneurysmal degeneration of the thoracoabdominal aorta and a proximal tear located in the aortic arch. A 2-stage hybrid approach was devised to treat the patient. An axilloaxillary crossover graft (left to right) with plug occlusion of the innominate artery was performed initially. Later, a dual-branched custom-made device was implanted. To avoid an additional LCCA cutdown for retrograde branch access, an 18-F steerable sheath was used through a percutaneous femoral access. Two wires were delivered within the steerable sheath: the first one was directed into the left subclavian artery to stabilize the sheath position in the ascending aorta; the second wire was used to catheterize the first inner branch and the LCCA to deploy the covered bridging stent. Conclusion: Transfemoral access to catheterize antegrade branches for supra-aortic vessels is feasible using a large steerable sheath in branched endovascular arch repair.
Who Is Left Out? The Process of Validating Voter Registration Applications
Authors: Merivaki Thessalia
Published: July 2020

Whose voter registration requires further verification and why? And why are some prospective registrants left out from voter records? These questions can uncover challenges in the voter registration process, and potential implementation issues with federal and state law. In this article, I analyze “on hold” voter registration applications processed between November 2007 and September 2008 in Florida’s Hillsborough and Miami-Dade Counties. I evaluate why individuals were left out of the voter rolls, by matching their records to snapshots of the counties’ voter records from December 2008. I find that “on hold” applicants face persistent challenges in successfully registering to vote, particularly depending on when they attempt to register and what type of information they omit from a voter registration application.
MiR-7 Functions as a Tumor Suppressor by Targeting the Oncogenes TAL1 in T-Cell Acute Lymphoblastic Leukemia
Authors: Sun Hongbo , Zhang Zhifu , Luo Wei , Liu Junmin , Lou Ye , Xia Shengmei
Published: July 2020

Background:

T-cell acute lymphoblastic leukemia is a hematologic malignancy characterized by T-cell proliferation, and in many cases, the ectopic expression of the oncogenic transcription factor T-cell acute lymphocytic leukemia protein 1 (TAL1). MicroRNA-7 has been shown to play a critical role in proliferation, migration, and treatment sensitivity in a diverse array of cancers. In this study, we sought to establish a novel link between microRNA-7 and T-cell acute lymphoblastic leukemia oncogenesis.

Material and Method:

To do so, we characterized gene expression of microRNA-7 as well as TAL1 in both T-cell acute lymphoblastic leukemia patient-derived tissue and cell lines, as well as performing functional luciferase assays to assess microRNA-7 binding to the TAL1 3′-untranslated region. We also performed growth, apoptosis, and migration experiments using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide, Annexin V, and transwell assays in the context of microRNA-7 overexpression.

Results:

We found that microRNA-7 expression is attenuated and inversely correlated with TAL1 expression in TAL1 + T-cell acute lymphoblastic leukemia cells. Additionally, microRNA-7 directly targets and suppresses TAL1 levels. Finally, microRNA-7 overexpression reduces growth, motility, and migration while inducing apoptosis in T-cell acute lymphoblastic leukemia cells, phenotypes that can be rescued by concomitant overexpression of TAL1.

Conclusions:

These results indicate that microRNA-7 functions as a potent tumor suppressor by inhibiting the oncogene TAL1 and suggest microRNA-7 could function as a prognostic biomarker and possible therapeutic in the clinical management of T-cell acute lymphoblastic leukemia.
Backward Protective Stepping During Dual-Task Scenarios in People With Parkinson’s Disease: A Pilot Study
Authors: Peterson Daniel S. , Barajas Jordan S. , Denney Linda , Mehta Shyamal H.
Published: July 2020

Introduction. Reactive movements in response to a loss of balance are altered in people with Parkinson’s disease (PD) and are critical for fall prevention. Further, falls are more common while attention is divided. Although divided attention has been shown to impact postural responses in healthy older adults, the impact of dividing attention on reactive balance, and the natural prioritization across postural and cognitive tasks in people with PD is largely unknown. Objectives. To characterize (1) the impact of a secondary cognitive task on reactive postural control and (2) the prioritization across stepping and cognitive tasks in people with PD. Methods. Sixteen people with PD and 14 age-matched controls underwent step-inducing, support-surface perturbations from stance, with and without an auditory Stroop secondary cognitive task. Cognitive, neuromuscular, and protective stepping performance were calculated for single and dual task scenarios. Results. In PD and control participants, cognitive reaction times ( P = .001) and muscle onset latency ( P = .007), but not protective step outcomes ( P > .12 for all) were worse during dual tasking compared with single-task scenarios. Both PD and control groups prioritized the protective stepping task over the cognitive task. Overall, people with PD exhibited worse first-step margin of stability (a measure of protective step performance) than controls ( P = .044). Conclusion. This study provides preliminary evidence that people with PD, like age-matched controls, exhibit cognitive and neuromuscular, but not protective step, dual-task interference. The lack of dual-task interference on step performance indicates a postural prioritization for PD and healthy older adults during dual-task protective stepping.
α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of Euphorbia nivulia–Ham. in STZ-Induced Diabetic Rats
Authors: Younus Muhammad , Hasan Muhammad Mohtasheem ul , Ahmad Khalil , Sharif Ali , Asif Hafiz Muhammad , Aslam Muhammad Rahil , Haq Ihsan ul , Ahmad Zulfiqar
Published: July 2020

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.
Case Study and Narrative Inquiry as Merged Methodologies: A Critical Narrative Perspective
Authors: Sonday Amshuda , Ramugondo Elelwani , Kathard Harsha
Published: July 2020

Case study and narrative inquiry as merged methodological frameworks can make a vital contribution that seeks to understand processes that may explain current realities within professions and broader society. This article offers an explanation of how a critical perspective on case study and narrative inquiry as an embedded methodology unearthed the interplay between structure and agency within storied lives. This case narrative emerged out of a doctoral thesis in occupational therapy, a single instrumental case describing a process of professional role transition within school-level specialized education in the Western Cape, South Africa. This case served as an exemplar in demonstrating how case study recognized the multiple layers to the context within which the process of professional role transition unfolded. The embedded narrative inquiry served to clarify emerging professional identities for occupational therapists within school-level specialized education in postapartheid South Africa.
Flecainide is well-tolerated and effective in patient with atrial fibrillation at 12 months: a retrospective study
Authors: Muzzey Mikayla , Tellor Katie B. , Ramaswamy Karthik , Schwarze Martin , Armbruster Anastasia L.
Published: July 2020

Introduction:

Current atrial fibrillation (AF) guidelines recommend flecainide as a first-line rhythm control option in patients without structural heart disease. While there is proven efficacy in clinical trials and guideline support, it is hypothesized that flecainide may be underutilized due to negative outcomes in the CAST trial and that adverse effects are less common than previously perceived.

Methods:

This retrospective chart review evaluated patients ⩾18 years initiated on flecainide for AF from August 2011 to October 2016 by a cardiology provider at the study site. Exclusion criteria included: <5 days of flecainide therapy, AF due to a reversible cause, and inadequate documentation. The primary outcome was efficacy of flecainide at maintaining symptomatic control at 6 and 12 months. Secondary outcomes included characterization of alterations in rhythm control strategies and documented normal sinus rhythm per electrocardiogram at 6 and 12 months.

Results:

Of the 326 patients identified, 144 patients were included. After 6 and 12 months, 102 patients (70.8%) and 89 patients (61.8%) of the 144 were symptomatically controlled. Atenolol use ( p = 0.024), female sex ( p = 0.006), hypertension ( p = 0.040), and dronedarone failure ( p = 0.012) were associated with flecainide discontinuation at 6 months. At 12 months, only previous propafenone failure ( p = 0.032) was significant. Of the 144 patients, 16 (11.1%) reported adverse effects with dizziness, hot flashes, bradycardia, and headache (1.4% each) being the most common.

Conclusion:

Flecainide is a well-tolerated medication, even at 12 months, with very minor adverse effects. These results support the utility of flecainide in guideline recommended patient populations.
Prostanoids in pediatric pulmonary hypertension: clinical response, time‐to‐effect, and dose–response
Authors: Tella Joseph B. , Kulik Thomas J. , McSweeney Julia E. , Sleeper Lynn A. , Lu Minmin , Mullen Mary P.
Published: July 2020

For pediatric pulmonary arterial hypertension (PAH) patients treated with parenteral prostanoids, response predictors, and the dose–effect relationship are ill defined. We determined the following: (1) which pulmonary vascular hemodynamic variable, after initiating prostanoids, best correlates with a significant clinical response; (2) the time interval after treatment when if no pulmonary hemodynamic improvement has occurred, none is ever likely to; and (3) the relationship between the prostanoid dose and its hemodynamic effects. This is a retrospective cohort study of 31 pediatric patients with Group 1 PAH treated with parenteral prostanoids. We found the following: (1) A fall in mean pulmonary arterial pressure (mPAP) of ≥25% predicted freedom from adverse clinical events with 80.7% accuracy and was also associated with improved functional class. (2) Thirty‐three percent of patients who avoided an adverse clinical event demonstrated a ≥25% reduction in mPAP after 1 year of treatment, and 65% by 2 years. (3) Lower mPAP was seldom seen with doses of epoprostenol >60 ng/kg/min (100 ng/kg/min for treprostinil). Cardiac index was positively correlated with the dose of epoprostenol but not treprostinil; cardiac index >4 l/min/m2 was seen at modest as well as high doses. We conclude that a ≥25% fall in mPAP on prostanoids indicates a positive clinical response which, if validated in other studies, may be useful for patient management or clinical trials. Some patients take more than 2 years for this change. Exceptionally high doses were generally not more effective than lower, although we could not determine whether lower doses would have been as effective.
Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta‐analysis
Authors: de la Iglesia Daniel , Avci Bartu , Kiriukova Mariia , Panic Nikola , Bozhychko Maryana , Sandru Vasile , de Madaria Enrique , Capurso Gabriele
Published: July 2020

Background

Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta‐analysis.

Methods

Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer.

Results

A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55–86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07–10.54; p  = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37–6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.

Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.
A single-centre experience of the management of inguinal lymph nodes associated with penile squamous-cell carcinoma
Authors: Sharma Amit , Parab Sandesh , Goyal Gaurav , Patel Ajit , Andankar Mukund , Pathak Hemant
Published: July 2020

Background:

Twenty-two cases of penile carcinoma that were managed at our institution over a 5-year period were analysed on the basis of inguinal lymph node dissection (ILND), complications and follow-up.

Methods:

A total of 22 cases post penectomy were stratified into low risk (T1 G1 or G2 without lympho-vascular invasion and negative on fine-needle aspiration cytology (FNAC)) and high risk (T1 G3 and above and/or lympho-vascular invasion). Low-risk patients having palpable lymphadenopathy were given a course of antibiotics. If the lymph nodes were still palpable, FNAC was done, and patients then underwent superficial ILND (SILND) or even ILND in cases with positive frozen-section reports. In the high-risk group, all patients underwent SILND, and if required, underwent ILND. Two patients in the high-risk group were lost to follow-up after 9 months. Histopathology reports were noted, and patients were followed up for 2 years.

Results:

In the low-risk group, seven patients had palpable lymph nodes and underwent SILND. The remaining five patients were put on surveillance. Amongst the seven who underwent SILND, six were positive at frozen section, requiring ILND. Nine patients in the high-risk group underwent ILND. Four patients in the ILND group had a minor wound infection. Lymphoedema was seen in two patients which was managed conservatively, and lymphorrhoea was seen in one patient. Flap necrosis occurred in one patient. Recurrences were seen in three patients in the high-risk group. Two who had deep node involvement and who had early nodal recurrence underwent bilateral ILND. One patient in the high-risk group had late ipsilateral nodal recurrence and underwent ipsilateral ILND. There were no regional recurrences.

Conclusion:

Carcinoma of the penis has high morbidity because of delayed presentation, lack of awareness and poor compliance. This necessitates staging SILND in all high-risk cases for therapeutic and prognostic purposes.
Management of 760-g Extremely Premature Infant With Dextro-Transposition of the Great Arteries
Authors: Khazaal Jawad R. , Sowinski Heather A. , Ratnasamy Christopher , Vettukattil Joseph J. , Haw Marcus P.
Published: July 2020

Extremely low birth weight neonates with complex congenital heart disease have increased mortality risk. Multi-organ dysfunction, pulmonary disease, fluctuating pulmonary vascular resistance, and complex cardiovascular anatomy create a challenge for effective management. We present the case of a 760-g neonate with dextro-transposition of the great arteries, ventricular septal defect, patent ductus arteriosus, and single coronary artery with proximal intramural segment of the right coronary artery branch. We describe features of preoperative care, surgical intervention, and postoperative course that enabled this infant to survive.
Improved Technique for Interventional Extracardiac Fontan
Authors: Prabhu Sudesh , Maiya Shreesha , Shetty Riyan , Murthy Keshava , Ramachandra Prakash , Karl Tom Roland
Published: July 2020

We have previously reported a simple technique for preparatory staging and subsequent interventional completion of an extracardiac Fontan procedure that anatomically and hemodynamically closely mimics a standard extracardiac Fontan. We describe herein modifications that simplify the original procedural sequence and that may allow wider application. Percutaneous completion can be achieved even without a radiofrequency probe, using electrocautery. Fenestration is also easy to perform if there is a clinical indication.
Surgical Valvuloplasty Versus Balloon Dilation for Congenital Aortic Stenosis in Pediatric Patients
Authors: Herrmann Jeremy L. , Clark Aaron J. , Colgate Cameron , Rodefeld Mark D. , Hoyer Mark H. , Turrentine Mark W. , Brown John W.
Published: July 2020

Background:

For children with congenital aortic stenosis (AS) who are candidates for biventricular repair, valvuloplasty can be achieved by surgical aortic valvuloplasty (SAV) or by transcatheter balloon aortic dilation (BAD). We aimed to evaluate the longer term outcomes of SAV versus BAD at our institution.

Methods:

We retrospectively reviewed the outcomes of 2 months to 18 years old patients who underwent SAV or BAD at our institution between January 1990 and July 2018. Baseline and follow-up characteristics were assessed by echocardiography. Long-term survival, freedom from reintervention, freedom from aortic valve replacement (AVR), and aortic regurgitation were evaluated.

Results:

A total of 212 patients met inclusion criteria (SAV = 123; BAD = 89). Age, sex, aortic insufficiency (AI), and aortic valve gradient were similar between the groups. At 10 years, 27.9% (19/68) of SAV patients and 58.3% (28/48) of BAD patients had moderate or worse AI ( P = .001), and reintervention occurred in 39.2% (29/74) of SAV patients and 78.6% (44/56) of BAD patients ( P < .001). Kaplan-Meier analysis revealed overall survival was 96.8% (119/123) for SAV and 95.5% (85/89) for SAV ( P = .87). At 10 years, 35% (23/66) of SAV patients and 54% (23/43) of BAD patients underwent AVR ( P = .213).

Conclusions:

Surgical aortic valvuloplasty demonstrated greater gradient reduction, less postoperative and long-term AI, and a lower reintervention rate at 10 years than BAD. There was no difference in survival or AVR reintervention rate. Surgical aortic valvuloplasty is a durable and efficacious intervention and should continue to be considered a favorable choice for palliation of valvular AS.
Invited Commentary: Efficacy of Nitric Oxide Administration During Neonatal Cardiopulmonary Bypass
Authors: Hornik Christoph P.
Published: July 2020

This editorial accompanies an original research article by Dr Elzein and colleagues describing findings of a randomized, placebo-controlled trial of nitric oxide administration during cardiopulmonary bypass surgery in infants undergoing the Norwood procedure.