Flare-ups in endodontics and their relationship to various medicaments

The purpose of this research is to investigate the frequency of endodontic flare-ups using a visual analogue scale. Definitions of flare-ups vary widely as does their reported frequency. A flare-up was defined as an increase of 20 or more points on the visual analogue scale for a given tooth, within the periods of 4 h and 24 h after the initial treatment appointment. The data from a previous study were used to determine the incidence of flare-ups after using three modalities (Ledermix, calcium hydroxide and no medication) to manage patients presenting for relief of pain of endodontic origin. A statistical analysis showed that there were no significant differences in flare-up rates at both the 4-h and 24-h periods between the three modalities. Further research is required using the above definition of a flare-up and standardising treatment protocols.     

Obesity is Associated with Worse Outcomes Among Abdominal Trauma Patients Undergoing Laparotomy: A Propensity-Matched Nationwide Cohort Study

Introduction

Obesity is associated with increased morbidity and mortality in abdominal trauma patients. The characteristics of abdominal trauma patients with poor outcomes related to obesity require evaluation. We hypothesize that obesity is related to increased mortality and length of stay (LOS) among abdominal trauma patients undergoing laparotomies.

Methods

Abdominal trauma patients were identified from the National Trauma Data Bank between 2013 and 2015. Patients who received laparotomies were analyzed using propensity score matching (PSM) to evaluate the mortality rate and LOS between obese and non-obese patients. Patients without laparotomies were analyzed as a control group using PSM cohort analysis.

Results

A total of 33,798 abdominal trauma patients were evaluated, 10,987 of them received laparotomies. Of these patients, the proportion of obesity in deceased patients was significantly higher when compared to the survivors (33.1% vs. 26.2%, p < 0.001). Elevation of one kg/m² of body mass index independently resulted in 2.5% increased odds of mortality. After a well-balanced PSM, obese patients undergoing laparotomies had significantly higher mortality rates [3.7% vs. 2.4%, standardized difference (SD) = 0.241], longer hospital LOS (11.1 vs. 9.6 days, SD = 0.135), and longer intensive care unit LOS (3.5 vs. 2.3 days, SD = 0.171) than non-obese patients undergoing laparotomies.

Conclusions

Obesity is associated with increased mortality in abdominal trauma patients who received laparotomies versus those who did not. Obesity requires a careful evaluation of alternatives to laparotomy in injured patients.

     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Exposure to Fine Particulate Matter during Pregnancy and Risk of Preterm Birth among Women in New Jersey,Ohio, and Pennsylvania, 2000–2005

Background: Particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) has been variably associated with preterm birth (PTB).Objective: We classified PTB into four categories (20–27, 28–31, 32–34, and 35–36 weeks completed gestation) and estimated risk differences (RDs) for each category in association with a 1-μg/m³ increase in PM_2.5 exposure during each week of gestation.Methods: We assembled a cohort of singleton pregnancies that completed ≥ 20 weeks of gestation during 2000–2005 using live birth certificate data from three states (Pennsylvania, Ohio, and New Jersey) (n = 1,940,213; 8% PTB). We estimated mean PM_2.5 exposures for each week of gestation from monitor-corrected Community Multi-Scale Air Quality modeling data. RDs were estimated using modified Poisson linear regression and adjusted for maternal race/ethnicity, marital status, education, age, and ozone.Results: RD estimates varied by exposure window and outcome period. Average PM_2.5 exposure during the fourth week of gestation was positively associated with all PTB outcomes, although magnitude varied by PTB category [e.g., for a 1-μg/m³ increase, RD = 11.8 (95% CI: –6, 29.2); RD = 46 (95% CI: 23.2, 68.9); RD = 61.1 (95% CI: 22.6, 99.7); and RD = 28.5 (95% CI: –39, 95.7) for preterm births during 20–27, 28–31, 32–34, and 35–36 weeks, respectively]. Exposures during the week of birth and the 2 weeks before birth also were positively associated with all PTB categories.Conclusions: Exposures beginning around the time of implantation and near birth appeared to be more strongly associated with PTB than exposures during other time periods. Because particulate matter exposure is ubiquitous, evidence of effects of PM_2.5 exposure on PTB, even if small in magnitude, is cause for concern.Citation: Rappazzo KM, Daniels JL, Messer LC, Poole C, Lobdell DT. 2014. Exposure to fine particulate matter during pregnancy and risk of preterm birth among women in New Jersey, Ohio, and Pennsylvania, 2000–2005. Environ Health Perspect 122:992–997; http://dx.doi.org/10.1289/ehp.1307456     

Genome-wide signals of positive selection in human evolution

The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes.The rate and patterns of positive selection are of fundamental interest for the study of human evolution. Population genomic studies should, in principle, allow us to quantify positive selection from its expected signatures in sequence polymorphism and divergence data. Surprisingly, despite the sequencing of thousands of human genomes (The 1000 Genomes Project Consortium 2012) and the availability of whole-genome sequences of closely related species, the extent to which adaptation has left identifiable signatures in the patterns of polymorphism in the human genome remains highly controversial (Akey 2009; Hernandez et al. 2011).On the one hand, recent studies have identified a large number of loci showing signatures of recent selective sweeps (Voight et al. 2006; Sabeti et al. 2007; Williamson et al. 2007; Pickrell et al. 2009; Grossman et al. 2013), and McDonald-Kreitman (MK) analyses inferred that ∼10%–20% of amino acid changes have been adaptive in human evolution (Boyko et al. 2008; Messer and Petrov 2013). Consistently, regions of high functional density, high rate of amino acid substitutions, and low recombination all show reduced levels of neutral diversity (Cai et al. 2009; Lohmueller et al. 2011), as expected under recurrent selective sweeps in functional regions.On the other hand, there are reasons to question the notion that adaptation left clear signatures in the human genome. First, different scans for positive selection have identified largely nonoverlapping sets of candidates (Akey 2009), which could be due to a high rate of false positives. Second, MK analyses can be confounded by a number of factors, such as perturbations left by demographic events and by the presence of slightly deleterious mutations (Eyre-Walker and Keightley 2009; Messer and Petrov 2013), and some MK analyses have failed to find evidence for adaptation in the human lineage (Eyre-Walker and Keightley 2009). Finally, it has been shown that background selection (BGS) (Charlesworth et al. 1993), a process in which deleterious mutations remove linked neutral variation from the population, reduces levels of polymorphism in regions of higher functional density and low recombination, providing an alternative explanation for the observation of these correlations in the human genome.One signature of positive selection—lower levels of neutral variation near functional substitutions (Andolfatto 2007; Macpherson et al. 2007; Cai et al. 2009)—is not generally expected under BGS and should therefore provide the clearest genomic evidence for the action of positive selection. While this signature was found in the human genome by Cai et al. (2009), it could not be detected by two recent studies using the newest large-scale data sets of human diversity (Hernandez et al. 2011; Lohmueller et al. 2011). In particular, Hernandez et al. (2011) searched for lower levels of neutral diversity near functional substitutions by contrasting levels of neutral diversity near nonsynonymous compared with synonymous substitutions. They did not find this signature in the human genome and, moreover, found that diversity might in fact be marginally higher near nonsynonymous substitutions. Simulations showed that this puts sharp limits on the amount of adaptation by classic selective sweeps in recent human evolution (Hernandez et al. 2011).However, it is likely that the study design of Hernandez et al. (2011) (also implemented in Drosophila by Sattath et al. 2011) is strongly biased against finding signatures of positive selection in the human genome and all other genomes with sharply variable levels of genomic constraint. This is because, as we show in the Results, nonsynonymous substitutions in the human genome tend to be located in regions of weaker constraint and thus weaker BGS compared with synonymous substitutions. These differences in levels of BGS should elevate neutral diversity near nonsynonymous compared with synonymous substitutions. The approach of Hernandez et al. (2011) would thus detect positive selection only if the reduction of diversity due to positive selection near nonsynonymous substitutions happens to be greater than the initial difference in the opposite direction due to BGS.Here we utilize a number of more sensitive approaches in the search for signatures of positive selection while attempting to reduce the confounding effects of BGS to the greatest extent possible. Our results suggest that positive selection was frequent in human history and might have involved adaptive mutations of substantial selective effect. We estimate that a few hundred strong adaptive events are likely to be detectable in the human genome, consistent with the latest scan for positive selection (Grossman et al. 2013). Moreover, we provide evidence that the majority of adaptive substitutions were due to cis-regulatory rather than protein-coding changes, consistent with the King and Wilson (1975) hypothesis that adaptive divergence is primarily driven by regulatory changes.     

Vesiculobullous Hailey-Hailey disease: Successful treatment with oral retinoids

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with lowdose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.     

Intracanal bisphosphonate does not inhibit replacement resorption associated with delayed replantation of monkey incisors

Abstract – Progressive replacement resorption following delayed replantation of avulsed teeth has proved to be an intractable clinical problem. A wide variety of therapeutic approaches have failed to result in the predictable arrest of resorption, with a good long‐term prognosis for tooth survival. Bisphosphonates are used in the medical management of a range of bone disorders and topically applied bisphosphonate has been reported to inhibit root resorption in dogs. This study evaluated the effectiveness of a bisphosphonate (etidronate disodium) as an intracanal medicament in the root canals of avulsed monkey teeth, placed before replantation after 1 h of extraoral dry storage. Incisors of six Macaca fascicularis monkeys were extracted and stored dry for 1 h. Teeth were then replanted after canal contamination with dental plaque (negative control) or after root canal debridement and placement of etidronate sealed in the canal space. A positive control of calcium hydroxide placed 8–9 days after replantation was also included. All monkeys were sacrificed 8 weeks later and block sections were prepared for histomorphometric assessment of root resorption and periodontal ligament status. Untreated teeth showed the greatest extent of root resorption (46% of the root surface), which was predominantly inflammatory in nature. Calcium hydroxide treated teeth showed the lowest overall level of resorption (<30% of the root surface), while the bisphosphonate‐treated group was intermediate (39%). Ankylosis, defined as the extent of the root surface demonstrating direct bony union to both intact and resorbed root surface, was the lowest in the untreated control group (15% of the root surface), intermediate in the calcium hydroxide group (27%) and the highest in the bisphosphonate group (41%). Bony attachment to the tooth root was divided approximately equally between attachment to intact cementum and to previously resorbed dentin. Overall, bisphosphonate resulted in a worse outcome than calcium hydroxide in terms of both root resorption and ankylosis.