Nanocharacterization in Dentistry

About 80% of US adults have some form of dental disease. There are a variety of new dental products available, ranging from implants to oral hygiene products that rely on nanoscale properties. Here, the application of AFM (Atomic Force Microscopy) and optical interferometry to a range of dentistry issues, including characterization of dental enamel, oral bacteria, biofilms and the role of surface proteins in biochemical and nanomechanical properties of bacterial adhesins, is reviewed. We also include studies of new products blocking dentine tubules to alleviate hypersensitivity; antimicrobial effects of mouthwash and characterizing nanoparticle coated dental implants. An outlook on future “nanodentistry” developments such as saliva exosomes based diagnostics, designing biocompatible, antimicrobial dental implants and personalized dental healthcare is presented

Delays in maturation among adolescents with hemophilia and a history of inhibitors

Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV− adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors

Stromal Cell–Derived Factor–1 Genotype, Coreceptor Tropism, and HIV Type 1 Disease Progression

This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV‐1)–infected hemophiliacs to define the relationship between the SDF1‐3′A allele, the plasma HIV‐1 coreceptor tropism, and the natural history of HIV‐1 disease. Subjects heterozygous or homozygous for the SDF1‐3′A allele experienced higher rates of decline in CD4+ T cell counts over time than did those without the allele (P=.009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV‐1 RNA levels and CD4+ T cell counts or CCR5Δ32 and CCR2‐64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1‐3′A allele were also more likely to have detectable X4‐tropic viruses (P=.012), and, when tropism was included in the survival analyses, the effect of the SDF1‐3′A allele on disease progression was no longer significant. Therefore, the increased frequency of X4‐tropic viruses in subjects carrying the SDF1‐3′A allele may explain the observed adverse effect that this allele has on the natural history of HIV‐1 disease

Pulmonary hypertension in sickle cell disease.

BACKGROUND: Recurrent vaso-occlusive episodes lead to progressive end-organ damage in patients with sickle cell disease. We sought to determine the prevalence of pulmonary hypertension in adult patients with sickle cell disease and to identify factors associated with this life-threatening complication. METHODS: Sixty patients (\u3e or =18 years of age; mean [+/- SD] age, 37 +/- 13 years) followed at a University Medical Center were evaluated. They were selected by a systematic sampling of patients presenting to the clinic for routine follow-up visits. All enrolled subjects underwent a clinical examination, Doppler echocardiography, pulmonary function tests, and hematologic tests during a single visit. Pulmonary hypertension was defined using an age- and body mass index-adjusted nomogram. RESULTS: The prevalence of pulmonary hypertension was 30% (18/60). Ten patients had mild pulmonary hypertension (up to 44 mm Hg), 5 had moderate pulmonary hypertension (45 to 74 mm Hg), and 2 had severe pulmonary hypertension (\u3e or =75 mm Hg). In a logistic regression model, both lower fetal hemoglobin level and lower systolic blood pressure were associated with the presence of pulmonary hypertension. CONCLUSION: We found that the prevalence of pulmonary hypertension in adult patients with sickle cell disease was substantial, particularly in those with lower levels of fetal hemoglobin and lower systolic blood pressure

The importance of genetic factors for the development of arthropathy: a longitudinal study of children and adolescents with haemophilia A

Haemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic regression models were fit for each joint separately. A subset of SNP markers showing significant effects (p < 0.01) on the right and left sides for at least two joints were included in a full model fit using a multivariate generalised linear mixed model assuming an ordinal response. The models contained all ROM scores obtained at all visits. Twenty-five markers analysed in the full model showed either increased or decreased risk of ROM abnormalities at the p<0.001 level. Several genes identified at either the first or second stage of the analysis have been associated with arthritis in a variety of large studies. Our results support the likelihood that risk for haemophilic arthropathy is associated with genetic factors, the identification of which holds promise for further advancing the individualisation of treatment

Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD