Calorically restricted diets decrease PCSK9 in overweight adolescents.

BACKGROUND AND AIMS: Nutritional therapy is the first line approach to treatment of hyperlipidemia in childhood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of plasma cholesterol levels and a target of novel lipid-lowering pharmacotherapies. We examined the effects of an intensive nutritional intervention on PCSK9 levels in overweight adolescents with cardiovascular disease (CVD) risk factors. METHODS AND RESULTS: Twenty seven obese and overweight adolescents with CVD risk factors were assigned to either a low fat or low glycemic load diet. During an 8-week "Intensive Phase," assigned meals were delivered to the home, and all participants received weekly in-person home nutrition counseling and phone calls. The subjects then underwent a 4-month "Maintenance Phase" without food provision and with no in-person contact. Anthropometric measurements, laboratory data, and serum PCSK9 protein levels were measured at baseline, 8 weeks, and 6 months. PCSK9 decreased by 16.5% at 8 weeks (201.2 ± 56.3 vs 165.6 ± 58.4 ng/mL; p < 0.001); PCSK9 levels returned to baseline levels at 6 months, after the Maintenance Phase. Change in PCSK9 was associated with change in fasting insulin, HOMA-IR, and AUC insulin, independent of weight loss. CONCLUSIONS: PCSK9 decreased in youth participating in an intensive dietary intervention. Change in HOMA-IR was associated with change in PCSK9, independent of weight loss, suggesting an important relationship with insulin sensitivity. ClinicalTrials.gov Identifier: NCT01080339.

Comparison of the visco-elastic behavior of a pre-impregnated reinforced glass fiber composite with resin-based composite.

OBJECTIVES: The visco-elastic behavior of a pre-impregnated reinforced glass fiber composite (everStick) was compared with a resin-based particulate composite (Filtek P60) by using dynamic mechanical analysis (DMA) to determine their storage modulus (E') and damping ratio (tandelta). METHODS: These materials were subjected to three-point bend tests using a PerkinElmer DMA7. In temperature mode, the temperature was increased from 26 to 140 degrees C at 1 Hz. In frequency mode, the range was 1-10 Hz at a constant temperature of 37 degrees C. RESULTS: In both temperature and frequency modes, E' for everStick was significantly higher and tandelta was significantly lower than those for Filtek P60, indicating that the stiffness of the pre-impregnated glass fiber composite was higher and its damping property was lower than those for resin-based particulate composite. SIGNIFICANCE: The glass fiber restorative composite appears to absorb less energy in repeated stress and is less likely to retain external energy as residual stress.

Estimating age using permanent molars and third cervical vertebrae shape with a novel semi-automated method.

Estimating chronological age accurately in young adults is difficult and additional methods are required to increase the accuracy. This study explored a new semi-automated method to assess shape change of third cervical vertebra (C3) with age in the living; comparing this as a method to determine whether individuals could be categorised into being less than 18 years of age (<18), or at least 18 years of age (≥18) with tooth formation of the second and third mandibular molars (M2 and M3). The sample was panoramic and lateral skull radiographs of 174 dental patients (78 males, 96 females aged 15-22 years). Twelve variables were compared in two age categories: younger than 18 and at least 18 years of age in males and females separately using a t-test. Tooth formation of M2 and M3 was assessed. Mean values of eight variables of C3 in males and one variable in females were significantly different between the two age categories (p < 0.05). Results for males showed that the best age indicator for age ≥18 was the ratio between height and width of C3 and for females, the ratio between diagonals. Results for molars showed that M2 was mature in 69% of males and 83% of females, within the expected age range of 14-16 years. M3 was highly variable ranging from stages 6-14 for both; M3 was missing in 24% of males and 28% of females and mature in 14% of males and 15% of females. The conclusion was that shape change of C3 has potential as an additional method to group individuals <18 and ≥ 18 years of age.

How do foster carers manage the oral health of children in foster care? A qualitative study.

OBJECTIVES: This qualitative study explored how the foster family environment influenced children's oral health. It also aimed to better understand foster carers' oral health knowledge, attitudes and experiences of managing foster children's oral health behaviours and oral health care. METHODS: An interpretative phenomenological analysis (IPA) study design was used to recruit a purposive sample of foster carers in Tower Hamlets, United Kingdom, from a range of backgrounds (maximum variation sampling). Participants were aged 21 years and older and provided full-time foster care for children for a minimum of 1 year. The foster carers took part in focus groups that were audio-recorded and transcribed verbatim. Data analysis followed a five-step IPA process, which included reading the transcripts, note taking, identifying emerging themes, connecting related themes and writing up the final themes. Iterative data gathering and analysis continued to reach thematic saturation. RESULTS: Three focus groups were conducted, involving a total of 12 foster carers. Eight of the 12 participants had fostered children for more than 10 years and they were currently fostering 22 children aged five to 18 years old. Four themes emerged from within the context of the supportive and nurturing foster family environment that described how foster carers' responded to and managed the oral health of their foster children. Foster carers had adopted an oral health caregiving role, "in loco parentis" responding to the poor oral health of their vulnerable foster children. They were hypervigilant about establishing and monitoring children's oral health routines and taking their children to see a dentist; these were seen as an integral part of being good foster carers. They were knowledgeable about the causes of children's oral ill health, gained from their own dental experiences and from looking after their own children. Foster carers had experienced tensions while adopting this oral health caregiving role with dentists who had refused to see younger children. Foster carers had also experienced tensions with teenage foster children who questioned their parental authority and legitimate right to set rules about smoking and healthy eating. CONCLUSIONS: This is the first study to explore foster carers' oral health perspectives and the foster family environment within the oral health context. It highlights the unrecognized and important role that foster carers have in improving the oral health of vulnerable children. Further research is needed to explore the relationship between foster carers and dentists and to support the development of health and social care interventions to improve foster children's oral health.

A Novel Kinetic Method to Measure Apparent Solubility Product of Bulk Human Enamel.

Introduction: Tooth enamel mineral loss is influenced by its solubility product value, which is fundamental to the understanding of de- and remineralization resulting from a carious or erosive challenge. Published pKsp values for human enamel and hydroxyapatite range from 110 to 126 suggesting a heterogeneous nature of enamel solubility. However, this range of values may also result from the variety of methods used, e.g., some authors reporting values for suspensions of enamel powder and others for bulk enamel. The aim of this study was to develop a method to measure the solubility of bulk human enamel under controlled in vitro conditions simulating demineralization behavior of enamel within the oral environment using scanning microradiography (SMR). SMR was used to monitor real-time changes in enamel demineralization rates at increasing calcium concentrations in a caries simulating demineralization solution until the concentration at which thermodynamic equilibrium between enamel and solution was achieved. Method: 2 mm thick caries free erupted human enamel slabs with the natural buccal surfaces exposed were placed in SMR cells exposed to circulating caries-simulating 2.0 L 0.1 M pH = 4.0 acetic acid, at 25°C. SMR was used to continuously measure in real-time the decrease in mineral mass during the demineralization at 5 different points from on each slab. Demineralization rates were calculated from a linear regression curve of projected mineral mass against demineralization time. Changes in the demineralization rates were monitored following a series of successive increases in calcium (and phosphate at hydroxyapatite stoichiometric ratios of Ca:P 1.67) were added to the demineralizing solution, until demineralization ceased. The pH was maintained constant throughout. Results: Demineralization halted when the calcium concentration was ~30 mM. At higher calcium concentrations, mineral deposition (remineralization) occurred. By comparison with results from speciation software calculations for the calcium phosphate ternary system, this result suggests that the bulk solubility product of enamel (pKspBEnamel) under the conditions used is 121. Discussion: The apparent pKspBEnamel under these conditions was higher than many previous reported values, and much closer to those previously reported for HAp. However, this is a bulk value, and does not reflect that enamel is a heterogeneous material, nor the influence of ionic inclusions.

A novel frameshift MSX1 mutation in a Saudi family with autosomal dominant premolar and third molar agenesis.

OBJECTIVES: In this study, the aim was to investigate a consanguineous Saudi family with non-syndromic premolars and third molars agenesis and to identify the causal mutation(s) using whole exome sequencing. DESIGN: Family phenotype and family pedigree were constructed from clinical and radiographic examinations. Whole exome sequencing was performed in two affected members of the Saudi family using the SureSelect Human all Exon 50 Mb kit (Agilent Technologies, Inc., Santa Clara, CA) and then sequenced on an Illumina HiSeq. SNP and indel calling were performed using samtools version 0.18 and were annotated using the software ANNOVAR. RESULTS: The family pedigree showed that the inheritance was autosomal dominant. Whole exome sequencing revealed that the affected members in this family were heterozygous with a novel frameshift mutation in exon 2 of the MSX1 gene, (NM_002448:c.750_751insACCGGCTGCC, p.F251PfsX92). CONCLUSIONS: The novel MSX1 frameshift mutation was linked to a family with moderate to severe tooth agenesis phenotype affecting second premolars and third molars in both arches. This expands the genotype-phenotype of MSX1 associated conditions.

A 59-year-old liver-transplanted woman with fever, dyspnea and pulmonary infiltrates.

A 59-year-old woman was admitted to hospital 10 months after receiving a liver transplant (LT) for hepatitis C virus (HCV) cirrhosis because of fever, dyspnea and basal patchy peripheral infiltrates. Microscopic examinations and blood, sputum and BAL cultures were negative. Empirical anti-infective therapy was ineffective. Thoracoscopic lung biopsy was performed, and histology showed a pattern suggesting bronchiolitis obliterans organizing pneumonia (BOOP). Prednisone led to rapid clinical and radiologic improvement. BOOP has been anecdotally reported in LT cases, and this case was unrelated to any infectious agent. BOOP should be taken into account in the differential diagnosis of pneumonia in LT.

Direct measurement of LDL-C in children: performance of two surfactant-based methods in a general pediatric population.

OBJECTIVES: Several pediatric advisory groups have recommended selective screening for dyslipidemia in children. Low-density lipoprotein cholesterol (LDL-C) is measured clinically with the Friedewald calculation in fasting samples. Nonfasting measurement of LDL-C would be clinically useful in children. DESIGN AND METHODS: In the present study, we examine the performance of two surfactant-based direct LDL-C assays in paired samples, fasting and nonfasting, from 100 children. RESULTS: LDL-C in the fasting state was significantly lower with the Friedewald estimation: 2.43 +/- 0. 61 mmol/L, N-geneous (Genzyme Corp.) direct LDL-C: 2.30 +/- 0.59 mmol/L, and Roche (Roche Diagnostics) direct LDL-C: 2.32 +/- 0.57 mmol/L than with ultracentrifugation-dextran-sulfate-Mg(2+) precipitation (UC-DS): 2.47 +/- 0.64 mmol/L. Moreover, there was increased negative bias using nonfasting samples with N-geneous: 2. 25 +/- 0.56 mmol/L and Roche: 2.26 +/- 0.56 mmol/L compared with fasting UC-DS. Correlation with US-DS was highest for Friedewald (r = 0.974) and fasting N-geneous (r = 0.973), and lowest with nonfasting N-geneous (r = 0.849) and Roche in fasting (r = 0.891) and nonfasting samples (r = 0.747). The sensitivity at LDL-C concentration of 2.85 mmol/L for the two direct methods when either fasting or nonfasting samples were used, was lower than that obtained with Friedewald. CONCLUSION: Overall, these direct LDL-C assays demonstrated limited utility in screening children but may be useful in the management of lipid disorders.

Aneuploid polyclonality in image analysis.

Solid tumors such as colorectal adenocarcinomas consist of biologically diverse cell subpopulations. Nuclear DNA content of tumor cells in colorectal carcinomas may be studied with different techniques of intranuclear DNA quantification. In the current study, the DNA ploidy of samples obtained from 68 patients with colorectal carcinoma (age ranging from 46 to 86 years, mean age 66 years), treated with radical surgery, between the years 1992 and 1995 was analyzed. DNA ploidy was assessed using a CAS 200 image analyzer and was evaluated on neoplastic tissue and undamaged healthy mucosa obtained from the edges of the surgical resection. Approximately 150-300 cells were analyzed for each sample. The aim of this study was to evaluate the prognostic significance of the polyclonal cases correlated with lymph node infiltration and disease free-survival. The pathological stage according to the TNM classification was compared to ploidy: an increase in multiple stemlines was observed in stage III cases, i.e., a progression towards aneuploidy and multiple stemlines was significantly associated with lymphatic metastasis (p<0.0003). Concerning distant metastasis, we found a correlation between stage IV and polyclonality. A significant correlation was observed between disease-free survival and aneuploid and polyclonal cases (p<0.0053). In polyclonal cases a nine fold greater relapse risk compared to the non-polyclonal cases was observed (p<0.0004). In two cases, the adeno-carcinoma of the sigma was polyclonal and its hepatic metastasis contained the predominant aneuploid clone with the same cytometric characteristics (DNA index) of the original lesion.

Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections.

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? A meta-analysis.

OBJECTIVES: To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors. DESIGN: Meta-analysis of randomised trials. SETTING: Outpatient clinics. SUBJECTS: 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials. INTERVENTIONS: Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics. MAIN OUTCOME MEASUREMENTS: Clinical failures and cures. RESULTS: Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)). Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)). The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality. CONCLUSIONS: Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis. Small differences in efficacy may exist, but are unlikely to be clinically important.

Synthesis and characterizations of a fluoride-releasing dental restorative material.

The aim was to develop an obturating material which has the tendency to release fluoride and minimize interfaces with tooth. Nano-fluorapatite (nFA) powder was synthesized by sol-gel. The composite based on polyurethane (PU) was obtained by chemically binding the nFA (10, 15, 20%wt/wt) to the diisocyanate component by utilizing in-situ polymerization. The procedure involved stepwise addition of monomeric units of PU, and optimizing the reagent concentrations to synthesize composite. The structural, phase and morphological analysis of nFA was evaluated. The structural, fluoride release and in-vitro adhesion analysis with tooth structure of PU/nFA was conducted. For fluoride release analysis the samples were stored in artificial saliva and deionized water for periodical time intervals. Bond strength of composites was analyzed by push-out test. Chemical linkage was achieved between PU and nFA without intermediate coupling agent. The insignificant difference of fluoride release pattern was observed in artificial saliva and (p≥0.05) deionized water. The PU/nFA composite provided sustained release of fluoride over a long period of time. The composite showed more adhesion toward tooth structure with the increase in concentration of nFA. Bond strength of composite was in accordance with root canal filling material, hence, the material with anti-cariogenic properties can be used as an obturating material.

Structural and in vitro adhesion analysis of a novel covalently coupled bioactive composite.

The interfacial adhesion between a restorative composite and tooth is one of the major factors that determine the ultimate performance of composite restoration. A novel polyurethane (PU) composite material was prepared by chemically binding the nano-hydroxyapatite (nHA) to the diisocyanate component in the PU backbone by utilizing solvent polymerization. The procedure involved stepwise addition of monomeric units of the PU and optimizing the reagent concentrations. The resultant materials were characterized structurally (Raman Spectroscopy) and in vitro bioactive analysis was conducted in modified-simulated body fluid for periodical time intervals. The in vitro study evaluated the push-out bond strength of existing obturating material and novel covalently linked PU/nHA composites to dentin after long-term storage in deionized water and artificial saliva. Human extracted molar roots were filled with experimental samples and analyzed at predetermined time intervals. The shear bond strength of samples was measured and surface morphologies were evaluated. Covalent bond formation was achieved between PU and nHA without intermediate coupling agent. With the increase in concentration of nHA, the composite showed more bioactivity and adhesion toward tooth structure. Bond strength of this new composite were in accordance with obutrating material, therefore, the material can be used as an obturating material because of its direct adhesion with tooth structure.

The cost of treating children and adolescents with injuries to their permanent incisors at a dental hospital in the United Kingdom.

The aim was to estimate the total cost, including the direct costs (outpatient costs) and indirect costs (missed working day) of treating children and adolescents with traumatic injuries to their incisors. Factors such as the number of treatment visits and the success of outcome were also investigated. The sample was taken from patients who attended the dental trauma clinic at a London teaching hospital between 1990 and 2001. Eighty-one patients, with 111 traumatized incisors were included in this study. The mean age was 9.9 (SD = 2.33) years and the male:female ratio was 3:2. The median number of visits and median treatment duration were eight visits and 21 months, respectively. Sixty-two per cent of the patients lived >5 miles and 25% lived >10 miles from the hospital; 44% of the patients had uncomplicated and 56% had complicated trauma to their incisors. Accidental falls, falls involving a second person, sport-related injuries and road accidents accounted for 30, 22, 22 and 17% of the total injuries. For uncomplicated trauma, 97% of the patients had a successful outcome but this was reduced to 58% for complicated trauma. The average total cost of treating a patient with one traumatic injury was 856 pounds. The best predictor for higher number of visits and unsuccessful outcome was complicated trauma with odd ratios of 4.5 and 24 (95% CI 1.5-13.7 and 2.9-194.2), respectively. It was concluded that the indirect cost was a considerably large proportion (39%) of the total cost. More specialists in paediatric dentistry are needed to improve access to care locally and thus reducing the indirect travelling cost.

[Clinical and molecular epidemiology of an outbreak of infusion-related Acinetobacter baumannii bacteremia in an Intensive Care Unit] / Epidemiologia clinica e molecolare di una epidemia di batteriemie da Acynetobacter baumannii correlate ad infusioni in una Unita di Terapia Intensiva.

Objective: To describe the clinical and molecular epidemiology of an outbreak of infusion-related Acinetobacter baumannii bacteremia in an intensive care unit (ICU). Methods: Six cases of A. baumannii bacteremia identified in the Foligno Hospital ICU, Italy, were peer reviewed. Antibiotic susceptibility and genotyping (PFGE and RAPD) of A. baumannii isolates were carried out. Results: All A. baumannii blood isolates and a strain isolated from parenteral solution had an identical genotype. The strains were susceptible to carbapenems and the combination of meropenem plus amikacin or piperacillin/ tazobactam plus netilmicin was synergistic. A. baumannii bacteremia persisted for several days in almost all patients; catheter tip cultures were always positive for A. baumannii. Three patients, with an elevated Apache II score, died of sepsis. Conclusions: The outbreak was related to contaminated parenteral solutions improperly prepared in the ward. Aseptic preparation in the hospital pharmacy allowed for an interruption of the outbreak.

Large trials vs meta-analysis of smaller trials: how do their results compare?

OBJECTIVE: To evaluate the results of large clinical trials vs the pooled results of smaller trials. DATA IDENTIFICATION: Meta-analyses with at least 1 "large" study were identified from the Cochrane Pregnancy and Childbirth Database and from MEDLINE (1966-1995). STUDY SELECTION: We used a sample size approach to select 79 meta-analyses with at least 1 large study of 1000 or more patients. We used a statistical power approach to select 61 meta-analyses with at least 1 large study based on statistical power considerations. DATA EXTRACTION: The outcome of interest for each meta-analysis was the primary one stated in the original publication or, when not clearly specified, was decided on clinically. DATA SYNTHESIS: By random effects calculations, we found agreement between large and smaller trials in 90% of the meta-analyses selected by the sample size approach and in 82% of the meta-analyses selected by the statistical power approach. Twice as many disagreements appeared when the variability among large studies and among smaller studies was not considered (ie, fixed effects calculations). Of the 15 disagreements between results of large and smaller trials using the random effects model, plausible explanations were identified in 10 meta-analyses: 5 with differences in the control rate of events between large and smaller trials, 4 with specific protocol or study differences, and 1 with potential publication bias. Two other disagreements were not clinically important, and tentative reasons could be identified for 2 of the remaining 3 disagreements. CONCLUSIONS: Results of smaller studies are usually compatible with the results of large studies, but discrepancies do occur even when the diversity among both large studies and smaller studies is considered. Clinically important differences without a potential explanation are extremely uncommon. Future research should further examine sources of heterogeneity between the results of large and smaller trials.