Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial

Arruda AO, Senthamarai Kannan R, Inglehart MR, Rezende CT, Sohn W. Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S Abstract – Objectives: To determine the efficacy of 5% sodium fluoride (NaF) varnish application in reducing caries increments in the permanent dentition of rural Brazilian school children over the course of 12 months. Methods: A double‐blind, randomized, placebo‐controlled trial was conducted with 379 children aged 7–14 years who attended three schools in Brazil between January 2006 and December 2007. During this period, each school was visited four times at 6‐month interval for recruitment, dental examinations, and fluoride varnish applications. Recruited children were randomly assigned to either a treatment (5% NaF varnish, n = 198) or a control group (placebo, n = 181). Trained interviewers collected data on oral health habits and sociodemographic characteristics from the children. Information on the child’s diet was collected through a 7‐day food frequency diary. Caries examinations were conducted using the International Caries Detection and Assessment System (ICDAS). The efficacy of fluoride varnish application on caries prevention was reported as a preventive fraction (PF). Crude caries increments of decayed and filled surfaces (DFS) were compared between fluoride varnish and placebo groups. A generalized linear model (GLM) was constructed to test the differences in DFS increments between the groups after accounting for confounding factors. Results: Of the total sample (N = 379), 210 (55.4%) children had completed 12 months of follow‐up including one or two applications of fluoride varnish or placebo. At the baseline examination, the children in the treatment and control groups presented on average 6.2 and 5.6 DFS, respectively (P < 0.001). After 12 months of follow‐up, the children in the varnish group showed significantly lower DFS increments than did children in the control group (10.8 versus 13.3; P < 0.007), with PF of 40% (95% CI: 34.3–45.7%; P < 0.0001). Conclusions: The results of this study suggest that applications of 5% NaF varnish can be recommended as a public health measure for reducing caries incidence in this high‐caries‐risk population.     

The role of ethnicity and culture in body image and disordered eating among males

An increasing number of researchers have examined body image concerns, disordered eating, and other behaviors associated with increasing muscle size among men from different cultural groups. However, to date there has been no synthesis or evaluation of these studies. In this paper we specifically review studies which have included a comparison between males from different cultural groups with White males on body image concerns or other related behaviors. The groups include Blacks, Hispanic Americans, Asians, Native Americans, Pacific Islanders, and men from Middle Eastern countries. Overall, evidence suggests that males from a range of cultural groups engage in more extreme body change strategies and binge eating than Whites. On the other hand, there is no consistent pattern which summarizes the nature of body image concerns across the different cultures. Mediating and/or moderating variables are proposed to account for the inconsistent findings. These include body build, levels of acculturation, socio-economic status, media exposure, and internalization of the muscular and lean body ideal.     

Nutritional iron status in children with alpha+ thalassemia and the sickle cell trait in a malaria endemic area on the coast of Kenya

Although hemoglobinopathies such as alpha+ thalassemia and the sickle cell trait might contribute to anemia in African children, we hypothesized that they might also enhance iron absorption under circumstances of critical availability, and that this could attenuate their hematologic effects. We found no support for this hypothesis in a cohort of children living on the coast of Kenya.     

Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL

Cyclophosphamide, doxorubicin, vincristine, and prednisone, given every 3 weeks (CHOP-21), is standard chemotherapy for aggressive lymphomas. To determine whether biweekly CHOP (CHOP-14) with or without etoposide is more effective than CHOP-21, 689 patients ages 61 to 75 years were randomized to 6 cycles of CHOP-21, CHOP-14, CHOEP-21 (CHOP plus etoposide 100 mg/m2 days 1-3), or CHOEP-14. Patients in the 2-weekly regimens received granulocyte colony-stimulating factor (G-CSF) starting from day 4. Patients received radiotherapy (36 Gy) to sites of initial bulky disease and extranodal disease. Complete remission rates were 60.1% (CHOP-21), 70.0% (CHOEP-21), 76.1% (CHOP-14), and 71.6% (CHOEP-14). Five-year event-free and overall survival rates were 32.5% and 40.6%, respectively, for CHOP-21 and 43.8% and 53.3%, respectively, for CHOP-14. In a multivariate analysis, the relative risk reduction was 0.66 (P =.003) for event-free and 0.58 (P <.001) for overall survival after CHOP-14 compared with CHOP-21. Toxicity of CHOP-14 and CHOP-21 was similar, but CHOEP-21 and in particular CHOEP-14 were more toxic. Due to its favorable efficacy and toxicity profile, CHOP-14 should be considered the new standard chemotherapy regimen for patients ages 60 or older with aggressive lymphoma.     

Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone)

To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma older than 60 years (n=43) or not qualifying for high-dose chemotherapy (n=4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules. CEMP was well tolerated with little organ and moderate haematotoxicity. There was no difference in toxicity between bolus and continuous-infusion etoposide. Complete remission rate was 44% in patients relapsing >or=1 year, 27% in patients relapsing within the first year after achieving complete remission and 5% in primary refractory patients. Median event-free and overall survivals for all patients were 3 and 10 months, respectively. The observed equitoxicity and the more challenging logistics of a 60-h infusion make bolus injection the preferred application of etoposide. As the CEMP regimen is well tolerated and efficacious in elderly patients with relapsed or refractory aggressive non-Hodgkin's lymphoma for whom more aggressive therapies are not feasible, a three-weekly modification of CEMP should be tested in combination with rituximab.     

Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease

Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease-modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16–17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ⁺ thalassaemia; n = 52 HbSS/HbSβ⁰ thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ⁺ thalassaemia; n = 8 HbSS/HbSβ⁰ thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ⁰ thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ⁰ thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ⁺ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ⁺ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ⁰ thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.     

Derivation of na?ve human embryonic stem cells

The naïve pluripotent state has been shown in mice to lead to broad and more robust developmental potential relative to primed mouse epiblast cells. The human naïve ES cell state has eluded derivation without the use of transgenes, and forced expression of OCT4, KLF4, and KLF2 allows maintenance of human cells in a naïve state [Hanna J, et al. (2010) Proc Natl Acad Sci USA 107(20):9222–9227]. We describe two routes to generate nontransgenic naïve human ES cells (hESCs). The first is by reverse toggling of preexisting primed hESC lines by preculture in the histone deacetylase inhibitors butyrate and suberoylanilide hydroxamic acid, followed by culture in MEK/ERK and GSK3 inhibitors (2i) with FGF2. The second route is by direct derivation from a human embryo in 2i with FGF2. We show that human naïve cells meet mouse criteria for the naïve state by growth characteristics, antibody labeling profile, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile and development in the context of teratomas. hESCs can exist in a naïve state without the need for transgenes. Direct derivation is an elusive, but attainable, process, leading to cells at the earliest stage of in vitro pluripotency described for humans. Reverse toggling of primed cells to naïve is efficient and reproducible.It has become clear with the derivation of mouse epiblast stem cells (mEpiSCs) that pluripotency encompasses more than one stage of development (1, 2). The earlier “naïve” stage represents the preimplantation inner cell mass, typified by mouse ES cells (mESCs), and the “primed,” the postimplantation epiblast, typified by mEpiSCs and human ES cells (hESCs). The challenge in naïve cell maintenance has been protecting cells from differentiation stimuli. This has been achieved in mESCs through exposure to leukemia inhibitory factor (LIF), whereas addition of extracellular signal-regulated kinase (MEK) and glycogen synthase kinase 3 (GSK3) inhibitors (2i) in defined medium allows the cells to attain a homogeneous ground state (3). Defining characteristics of the naïve/ground vs. primed states are shown in Fig. S1A. In humans, the naïve stage has been difficult to capture as a stable in vitro state.There are practical advantages that come with a human naïve state. Among them is ease of trypsin passage and developmental capacity. Whole animals can be generated from good naïve mESCs through tetraploid complementation (4), and mEpiSCs cannot contribute to chimerism. Being more comparable to mESCs, naïve hESCs will likely allow increased developmental potential and a more accurate correlation to mESC data.It has been reported that human induced pluripotent cells (h-iPSCs) can be maintained in the naïve state if the pluripotency-inducing transgenes are not silenced (5). Only recently have hESCs been maintained in a naïve state without transgenes (6). Our primary aim was to generate naïve hESCs not dependent upon transgenes for stable culture. We toggled existing human ESC and mouse mEpiSC lines back from the primed state to grow under the influence of 2i without the need for Activin A. This helped us to define appropriate culture conditions for human naïve cells and allowed the de novo derivation of a naïve hESC line, Elf1. We report on the naïve state of human ESCs capable of unlimited culture in 2i.     

Disruption of structural and functional networks in long‐standing multiple sclerosis

Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter morphology and functional coactivation. We investigated, how gray matter and functional networks were affected within the same MS sample and examined their interrelationship. Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102 MS patients and 42 healthy controls. Gray matter networks were computed at the group‐level based on cortical thickness correlations between 78 regions across subjects. MEG functional networks were computed at the subject level based on the phase‐lag index between time‐series of regions in source‐space. In MS patients, we found a more regular network organization for structural covariance networks and for functional networks in the theta band, whereas we found a more random network organization for functional networks in the alpha2 band. Correlation analysis revealed a positive association between covariation in thickness and functional connectivity in especially the theta band in MS patients, and these results could not be explained by simple regional gray matter thickness measurements. This study is a first multimodal graph analysis in a sample of MS patients, and our results suggest that a disruption of gray matter network topology is important to understand alterations in functional connectivity in MS as regional gray matter fails to take into account the inherent connectivity structure of the brain. Hum Brain Mapp 35:5946–5961, 2014. © 2014 Wiley Periodicals, Inc.