Transfusional hemosiderosis in childhood cancer patients and survivors.

BACKGROUND: Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. OBJECTIVE: This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. METHODS: This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. RESULTS: Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p = .0043) and pituitary iron (p = .0101). In the 73 off-therapy patients, ferritin levels were lower (p = .0008) with higher correlation with liver iron concentration (LIC) (p = .0016) than on-therapy patients. Fifty-eight subjects were treated for IO. CONCLUSION: In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

Significant pituitary siderosis is common in transfusion-dependent sickle cell disease.

ABSTRACT: Chronically transfused patients with sickle cell disease typically do not exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.

Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol.

BACKGROUND: Obesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. METHODS AND DESIGN: Infants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DISCUSSION: Effective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. ETHICS AND DISSEMINATION: The University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03310983.

We Can Dance If We Want To (with Safety Measures).

This work considers the spread of SARS-CoV-2 during a multiday intensive dance camp occurring from 26 December 2021 to 1 January 2022 in Asheville, North Carolina. Approximately 370 dancers and performers were in attendance, and the data presented are the result of an anonymous survey distributed 10 days following the event. While some transmission occurred during the time span of the event, it appears that the majority of transmission occurred either through the result of individual interactions or activities outside the formal dance event rather than due to a buildup of airborne viral particles in the event space.

Development, Implementation, and Satisfaction With a Nurse Practitioner Professional Ladder: A Children's Hospital Experience.

This article describes the development and implementation of a nurse practitioner professional ladder (NPPL) at a large freestanding urban pediatric hospital. The NPPL was created to recognize advanced practice registered nurses and differentiate levels of clinical expertise, role development, leadership, and professional contributions into a three-tiered approach, designated as NP I, NP II, and NP III. The results of a nurse practitioner satisfaction survey at Year 2 and Year 4 after the development of the NPPL are summarized. The NPPL helped create an empowering environment for continued nurse practitioner professional growth.

No consistent association found between dental caries and body mass index in children.

Data sourcesPubMed, Embase, the Cochrane Library and reference lists of identified studies.Study selectionObservational studies comparing dental caries and body mass index (BMI) where BMI was clearly defined were considered.Data extraction and synthesisTwo reviewers independently abstracted data using standard forms with study quality being assessed using a modified version of the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. The weighted mean differences and corresponding 95% confidence intervals for dental caries between children with abnormal weight and those with normal weight were analysed.ResultsFourteen cross-sectional studies including 43,860 children (boys: 23,299; girls: 20,561) were included. Only two studies were considered to be of high quality, eight of medium quality and four of low quality. Four main patterns of associations between dental caries and BMI were found: five studies showed no association, five studies found a positive association, three an inverse association and one found a U-shaped pattern, which meant that the deft score was significantly higher in underweight children and there was a higher DMFT score in overweight and obese children.ConclusionsThis meta-analysis showed no differences in dental caries between underweight and normal weight children. Further studies are recommended using suitable sample sizes, to unify the criteria for BMI categorisation and the dental caries index, and investigate the confounding factors that might influence dental caries and BMI.

The relationship between childhood body weight and dental caries experience: an umbrella systematic review protocol.

BACKGROUND: Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? METHODS: This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. DISCUSSION: The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016047304.

Rubber dam may increase the survival time of dental restorations.

Data sourcesCochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, LILACS, SciELO, Chinese BioMedical Literature Database, VIP, China National Knowledge Infrastructure, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, OpenGrey and Sciencepaper Online databases. Handsearches in a number of journals.Study selectionRandomised controlled trials, including split-mouth studies assessing the effects of rubber dam isolation for restorative treatments in dental patients.Data extraction and synthesisTwo review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies.ResultsFour studies involving a total of 1,270 patients were included. The studies were at high risk of bias. One trial was excluded from the analysis due to inconsistencies in the presented data. Restorations had a significantly higher survival rate in the rubber dam isolation group compared to the cotton roll isolation group at six months in participants receiving composite restorative treatment of non-carious cervical lesions (risk ratio (RR) 1.19, 95% confidence interval (CI) 1.04 to 1.37, very low-quality evidence). The rubber dam group had a lower risk of failure at two years in children undergoing proximal atraumatic restorative treatment in primary molars (hazard ratio (HR) 0.80, 95% CI 0.66 to 0.97, very low-quality evidence). One trial reported limited data showing that rubber dam usage during fissure sealing might shorten the treatment time. None of the included studies mentioned adverse effects or reported the direct cost of the treatment, or the level of patient acceptance/satisfaction. There was also no evidence evaluating the effects of rubber dam usage on the quality of the restorations.ConclusionsWe found some very low-quality evidence, from single studies, suggesting that rubber dam usage in dental direct restorative treatments may lead to a lower failure rate of the restorations, compared with the failure rate for cotton roll usage. Further high quality research evaluating the effects of rubber dam usage on different types of restorative treatments is required.

Impact of smoking on tooth loss in adults.

DesignCohort studyCohort selectionParticipants were recruited between 1994 and 1998 from the general population with the preferred ages of 35 to 65 years in women and 40 to 65 years in men.Exposure measurementSmoking was assessed using a questionnaire from which pack years of smoking were calculated. Educational attainment, body mass index, hypertension, diabetes, alcohol consumption and vitamin or mineral supplements were assessed from measurements and questionnaires. Tooth loss was also assessed by questionnaire returned between 2004 and 2006. With the exception of the tooth loss data analysis was based on data collected at baseline.Data analysisThe 24,373 participants who returned the tooth loss questionnaire were analysed. Two hundred and eighty-six (1.2%) were excluded, as they did not respond to either of the tooth loss questions, and an additional 106 (0.4%) were excluded because they gave inconsistent responses to the questions on tooth loss. Four hundred and thirteen (1.7%) participants with missing data on cigarette smoking and 192 (0.8%) participants with missing data in any of the covariates were also excluded. The association between smoking and number of teeth at baseline was assessed using negative binomial regression models to obtain relative risks and 95% confidence intervals (CIs).ResultsThe sample of 23,376 included 9,032 men and 14,344 women of which 4,394 (19%) were current cigarette smokers, and 7,268 (31%) were cigarette smokers. 1,566 (6.7%) were edentulous at baseline. Compared with never smokers, current smokers were more likely to be male, less educated, more likely to be hypertensive, and less likely to take vitamins/mineral supplements, and they had higher alcohol consumption. Cigarette smoking was associated with higher prevalence of tooth loss at baseline as well as higher incidence of tooth loss during follow-up. The association between cigarette smoking and incident tooth loss during follow-up for the fully adjusted model (adjusted for age, sex, education, diabetes, body mass index, waist-to-hip ratio, hormone replacement therapy, contraception, intake of vitamin and mineral supplements, physical activity, alcohol intake, hypertension, and cardiovascular disease) is shown in the table.ConclusionsThere is a strong dose-dependent association between cigarette smoking and the risk of tooth loss. The risk declines after cessation of cigarette smoking; however, the risk may remain elevated for up to 20 years compared with never smokers. Efforts to improve the oral health of the population should include the prevention of smoking as well the promotion of smoking cessation.

Management of iron overload in hemoglobinopathies: what is the appropriate target iron level?

Patients with thalassemia become iron overloaded from increased absorption of iron, ineffective erythropoiesis, and chronic transfusion. Before effective iron chelation became available, thalassemia major patients died of iron-related cardiac failure in the second decade of life. Initial treatment goals for chelation therapy were aimed at levels of ferritin and liver iron concentrations associated with prevention of adverse cardiac outcomes and avoidance of chelator toxicity. Cardiac deaths were greatly reduced and survival was much longer. Epidemiological data from the general population draw clear associations between increased transferrin saturation (and, by inference, labile iron) and early death, diabetes, and malignant transformation. The rate of cancers now seems to be significantly higher in thalassemia than in the general population. Reduction in iron can reverse many of these complications and reduce the risk of malignancy. As toxicity can result from prolonged exposure to even low levels of excess iron, and survival in thalassemia patients is now many decades, it would seem prudent to refocus attention on prevention of long-term complications of iron overload and to maintain labile iron and total body iron levels within a normal range, if expertise and resources are available to avoid complications of overtreatment.

Who Scared the Cat? A Molecular Crime Scene Investigation Laboratory Exercise.

This introductory laboratory exercise gives first-year life science majors or nonmajors an opportunity to gain knowledge and experience in basic bioinformatics and molecular biology laboratory techniques and analysis in the context of a mock crime scene investigation. In this laboratory, students determine if a human (Lady) or dog (Kona) committed the fictional crime of scaring a cat. Students begin by performing in silico PCR using provided dog- and human-specific PCR primers to determine the sequences to be amplified and predict PCR amplicon sizes. They then BLAST (Basic Local Alignment Search Tool) the in silico PCR results to confirm that the PCR primers are designed to amplify genomic fragments of the cardiac actin gene in both dogs and humans. Finally, they use DNA quantification techniques, PCR, and agarose gel electrophoresis to identify the culprit and they confirm results by analyzing Sanger sequencing. Student learning gains were demonstrated by successful execution of the lab and by analysis and interpretation of data in the completion of laboratory reports. The student learning gains were also demonstrated by increased performance on a post-laboratory assessment compared to the pre-assessment. A post-activity assessment also revealed that students perceived gains in the skills and conceptual knowledge associated with the student learning outcomes. Finally, assessment of this introductory molecular biology and bio-informatics activity reveals that it allows first-year students to develop higher-order data analysis and interpretation skills.

Patients give meaning to changes in health complaints before, during and after the replacement of amalgam restorations.

DESIGN: Qualitative, explorative and reflexive thematic analysis. METHODS: Semi-structured in-depth interviews were carried out with 12 participants who had all taken part in a previous amalgam removal trial. Follow-up; three months and one, three and five years after amalgam restoration removal and replacement. Interviews were carried out by two researchers at a different location from clinical follow-up. Transcripts were analysed by reading through the written material to establish common themes. NVivo9 software was used to assist further organising themes. Themes were then refined and condensed into the presented findings, which included selected quotes. RESULTS: The authors found the following themes to be important to patients in giving meaning to health complaints before, during and after amalgam removal: Something is not working: betrayed by the body. You are out there on your own. Not being sure of the importance of amalgam removal. The relief experienced after amalgam is removed. To accept, to give up, or to continue the search. CONCLUSIONS: For this group of patients, it was important to remove dental amalgam restorations. However, it remains uncertain of how critical this actually was in relation to their experienced changes in health complaints, as they did not feel that they could credit all positive change to the amalgam removal. For some participants it meant this was no longer a source of worry and for others it helped them move towards accepting their health status.

Genome Sequences of Six Paenibacillus larvae Siphoviridae Phages.

Six sequenced and annotated genomes of Paenibacillus larvae phages isolated from the combs of American foulbrood-diseased beehives are 37 to 45 kbp and have approximately 42% G+C content and 60 to 74 protein-coding genes. Phage Lily is most divergent from Diva, Rani, Redbud, Shelly, and Sitara.

Training and fairer payments would increase caries prevention in practice.

DATA SOURCES: PubMed, Embase, PsycoInfo, Scielo, Scopus, Web of Science, BBO, Lilacs and York databases supplemented by Google scholar. STUDY SELECTION: Qualitative studies with findings derived from individual or group interviews and structured questionnaires reporting factors that drove dentists towards or away from incorporating caries preventive measures were considered. Two reviewers conducted selection independently. DATA EXTRACTION AND SYNTHESIS: Data were abstracted independently by two reviewers and a qualitative metasummary carried out. This involves the extraction, grouping and formatting of findings and the calculation of frequency and intensity effect sizes in order to provide mixed research syntheses and to conduct a posteriori analyses of the relationship between reports and findings. RESULTS: Seven qualitative studies and 41 surveys (36,501 participants) were included. The reports were grouped together into six categories that were judged to be topically similar; education and training, personal beliefs, work conditions, remuneration, gender, place of residence and patients. Biologicism (27%), low remuneration (25%), length of time since graduation (22%) and male dentists (19%) were found to be the highest frequency effect size driving dentists away from using preventive approaches, and team work (21%), post-graduation (12%) and professional understanding of the benefits (12%) were identified as the main reasons for dentists' adherence to preventive measures. CONCLUSIONS: Despite the questionable quality of the included reports the evidence that emerged seems to indicate that further education and training coupled with a fairer pay scheme would be a reasonable approach to change the balance in favour of the provision of dental caries preventive measures by dentists. The results of this review could be of value in the planning and decision-making processes aimed at encouraging changes in professional dental practice that could result in the improvement of the oral health care provided to the population in general.

Treatment of alpha(0)-thalassemia (--(SEA)/--(SEA)) via serial fetal and post-natal transfusions: Can early fetal intervention improve outcomes?

OBJECTIVE AND IMPORTANCE: Homozygous Southeast Asian alpha-thalassemia mutation (--(SEA)/--(SEA)) results in deletion of all alpha-globin genes (alpha(0)-thalassemia). Since all alpha-globin chains are absent, hemoglobin F cannot be synthesized, and hemoglobin Bart's becomes the dominant fetal hemoglobin. Hemoglobin Bart's is a γ tetramer with a very high oxygen affinity, thus oxygen delivery to the tissues is poor. Clinical manifestations include severe fetal anemia, hydrops fetalis, fetal demise, and high risk of neurodevelopmental impairment in the rare survivors. CLINICAL PRESENTATION: A 39-year-old Vietnamese woman presented to our center at 28 0/7 weeks' gestation with fetal alpha(0)-thalassemia (--(SEA)/--(SEA) type deletion) and ultrasound markers suggestive of severe fetal anemia. INTERVENTION: The fetus was treated with four intrauterine transfusions followed by post-natal chronic transfusions. Formal neurodevelopmental testing (Battelle Developmental Inventory, Second Edition) was performed at 18 months of age, and the developmental quotient was 93 (32nd percentile) with all subdomains noted within normal limits, indicating overall intact neurodevelopment. CONCLUSION: We posit that earlier diagnosis and fetal treatment, prior to clinical findings suggestive of fetal anemia, may improve long-term outcomes by enhancing oxygen delivery to the tissues of the developing fetus.

Targeting Critical Thinking Skills in a First-Year Undergraduate Research Course.

TH!NK is a new initiative at NC State University focused on enhancing students' higher-order cognitive skills. As part of this initiative, I explicitly emphasized critical and creative thinking in an existing bacteriophage discovery first-year research course. In addition to the typical activities associated with undergraduate research such as review of primary literature and writing research papers, another strategy employed to enhance students' critical thinking skills was the use of discipline-specific, real-world scenarios. This paper outlines a general "formula" for writing scenarios, as well as several specific scenarios created for the described course. I also present how embedding aspects of the scenarios in reviews of the primary literature enriched the activity. I assessed student gains in critical thinking skills using a pre-/posttest model of the Critical Thinking Assessment Test (CAT), developed by Tennessee Technological University. I observed a positive gain trend in most of the individual skills assessed in the CAT, with a statistically significant large effect on critical thinking skills overall in students in the test group. I also show that a higher level of critical thinking skills was demonstrated in research papers written by students who participated in the scenarios compared with similar students who did not participate in the scenario activities. The scenario strategy described here can be modified for use in biology and other STEM disciplines, as well as in diverse disciplines in the social sciences and humanities.

Immunological tools: engaging students in the use and analysis of flow cytometry and enzyme-linked immunosorbent assay (ELISA).

Flow cytometry and enzyme-linked immunosorbent assay (ELISA) are commonly used techniques associated with clinical and research applications within the immunology and medical fields. The use of these techniques is becoming increasingly valuable in many life science and engineering disciplines as well. Herein, we report the development and evaluation of a novel half-semester course that focused on introducing undergraduate and graduate students to advance conceptual and technical skills associated with flow cytometry and ELISA, with emphasis on applications, experimental design, and data analysis. This course was offered in the North Carolina State University Biotechnology Program over three semesters and consisted of weekly lectures and laboratories. Students performed and/or analyzed flow cytometry and ELISA in three separate laboratory exercises: (1) identification of transgenic zebrafish hematopoietic cells, (2) analysis of transfection efficiency, and (3) analysis of cytokine production upon lipopolysaccharide stimulation. Student learning outcomes were achieved as demonstrated by multiple means of assessment, including three laboratory reports, a data analysis laboratory practicum, and a cumulative final exam. Further, anonymous student self-assessment revealed increased student confidence in the knowledge and skill sets defined in the learning outcomes.

Making heads or tails: planarian stem cells in the classroom.

Stem cells hold great promise in the treatment of diseases ranging from cancer to dementia. However, as rapidly as the field of stem cell biology has emerged, heated political debate has followed, scrutinizing the ethical implications of stem cell use. It is therefore imperative to promote scientific literacy by educating students about stem cell biology. Yet, there is a definite lack of material to engage students in this subject at the basic science level. Therefore, we have developed and implemented a hands-on introductory laboratory module that introduces students to stem cell biology and can be easily incorporated into existing curricula. Students learn about stem cell biology using an in vivo planarian model system in which they down-regulate two genes important in stem cell differentiation using RNA interference and then observe the regenerative phenotype. The module was piloted at the high school, community college, and university levels. Here, we report that introductory biology students enrolled at a community college were able to demonstrate gains in learning after completion of a one-hour lecture and four 45-minute laboratory sessions over the course of three weeks. These gains in learning outcomes were objectively evaluated both before and after its execution using a student quiz and experimental results. Furthermore, students' self-assessments revealed increases in perceived knowledge as well as a general interest in stem cells. Therefore, these data suggest that this module is a simple, useful way to engage and to teach students about stem cell biology.

Barriers to providing dental care for older people.

DATA SOURCES: The Medline, Embase and CINAHL databases were searched together with the reference lists of selected publications. STUDY SELECTION: Studies published since January 1990 and published in English that looked at barriers, experienced by dentists, to delivering oral health care to people over the age of 65 were included. Study quality was assessed independently using criteria developed by the Dutch Cochrane Centre. DATA EXTRACTION AND SYNTHESIS: Study assessment and data extraction were carried out independently by two reviewers and a qualitative summary presented. RESULTS: Seven cross-sectional studies were included. The focus was primarily on dentists delivering oral health care to older people in care homes with only one focused on barriers experienced by dentists working in their own practice and delivering oral health care to community-dwelling older people. The most common barriers to delivering oral health care to older people were identified respectively as: the lack of adequate equipment in a care home and no area for treatment available (n = 4) and the lack of adequate reimbursement for working in a care home (n = 5). In addition, the inadequate training and experience in delivering oral health care to older care home residents (n = 2) were mentioned. Four publications indicated the loss of time from private practice as a barrier to delivering oral health care in a care home. CONCLUSIONS: Most articles retrieved described barriers experienced by dentists delivering oral health in care homes: much less is known about oral health care for community-dwelling older people. Therefore, we suggest that additional research should be initiated to investigate in more detail the barriers dentists experience in delivering oral health care to older people in their own dental practices.