What is the optimal number of implants for fixed reconstructions: a systematic review

To assess the 5-year and 10-year survival and complication rates of implant-supported fixed reconstructions in partially and totally edentulous patients with regard to the optimal number and distribution of dental implants.

Moving along the mental number line: Interactions between whole-body motion and numerical cognition

Active head turns to the left and right have recently been shown to influence numerical cognition by shifting attention along the mental number line. In the present study, we found that passive whole-body motion influences numerical cognition. In a random-number generation task (Experiment 1), leftward and downward displacement of participants facilitated small number generation, whereas rightward and upward displacement facilitated the generation of large numbers. Influences of leftward and rightward motion were also found for the processing of auditorily presented numbers in a magnitude-judgment task (Experiment 2). Additionally, we investigated the reverse effect of the number-space association (Experiment 3). Participants were displaced leftward or rightward and asked to detect motion direction as fast as possible while small or large numbers were auditorily presented. When motion detection was difficult, leftward motion was detected faster when hearing small number and rightward motion when hearing large number. We provide new evidence that bottom-up vestibular activation is sufficient to interact with the higher-order spatial representation underlying numerical cognition. The results show that action planning or motor activity is not necessary to influence spatial attention. Moreover, our results suggest that self-motion perception and numerical cognition can mutually influence each other.

What is the optimal number of implants for removable reconstructions? A systematic review on implant-supported overdentures

The aim of this systematic review was to assess the optimal number of implants for removable reconstructions.

Efficient estimation of the total number of acini in adult rat lung

Pulmonary airways are subdivided into conducting and gas-exchanging airways. An acinus is defined as the small tree of gas-exchanging airways, which is fed by the most distal purely conducting airway. Until now a dissector of five consecutive sections or airway casts were used to count acini. We developed a faster method to estimate the number of acini in young adult rats. Right middle lung lobes were critical point dried or paraffin embedded after heavy metal staining and imaged by X-ray micro-CT or synchrotron radiation-based X-rays tomographic microscopy. The entrances of the acini were counted in three-dimensional (3D) stacks of images by scrolling through them and using morphological criteria (airway wall thickness and appearance of alveoli). Segmentation stopper were placed at the acinar entrances for 3D visualizations of the conducting airways. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean airspace volume of 0.907 (±0.108) μL per acinus were estimated. In 60-day-old rats neither the number of acini nor the mean acinar volume did correlate with the body weight or the lung volume.

Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest outbreak of the genus Ebolavirus to date. To better understand the spread of infection in the affected countries, it is crucial to know the number of secondary cases generated by an infected index case in the absence and presence of control measures, i.e., the basic and effective reproduction number. In this study, I describe the EBOV epidemic using an SEIR (susceptible-exposed-infectious-recovered) model and fit the model to the most recent reported data of infected cases and deaths in Guinea, Sierra Leone and Liberia. The maximum likelihood estimates of the basic reproduction number are 1.51 (95% confidence interval [CI]: 1.50-1.52) for Guinea, 2.53 (95% CI: 2.41-2.67) for Sierra Leone and 1.59 (95% CI: 1.57-1.60) for Liberia. The model indicates that in Guinea and Sierra Leone the effective reproduction number might have dropped to around unity by the end of May and July 2014, respectively. In Liberia, however, the model estimates no decline in the effective reproduction number by end-August 2014. This suggests that control efforts in Liberia need to be improved substantially in order to stop the current outbreak.

Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo.

The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R 0 = 5.2 (95% CI [4.0-6.7]). The model suggests that the net reproduction number Rt fell below unity 28 days (95% CI [25-34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.

Stereoselective Inhibition of the hERG1 Potassium Channel

A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1) channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom) is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Detection of exon deletions within an entire gene (CFTR) by relative quantification on the LightCycler

BACKGROUND: Cystic fibrosis (CF) is associated with at least 1 pathogen point sequence variant on each CFTR allele. Some symptomatic patients, however, have only 1 detectable pathogen sequence variant and carry, on the other allele, a large deletion that is not detected by conventional screening methods. METHODS: For relative quantitative real-time PCR detection of large deletions in the CFTR gene, we designed DNA-specific primers for each exon of the gene and primers for a reference gene (beta2-microglobulin). For PCR we used a LightCycler system (Roche) and calculated the gene-dosage ratio of CFTR to beta2-microglobulin. We tested the method by screening all 27 exons in 3 healthy individuals and 2 patients with only 1 pathogen sequence variant. We then performed specific deletion screenings in 10 CF patients with known large deletions and a blinded analysis in which we screened 24 individuals for large deletions by testing 8 of 27 exons. RESULTS: None of the ratios for control samples were false positive (for deletions or duplications); moreover, for all samples from patients with known large deletions, the calculated ratios for deleted exons were close to 0.5. In addition, the results from the blinded analysis demonstrated that our method can also be used for the screening of single individuals. CONCLUSIONS: The LightCycler assay allows reliable and rapid screening for large deletions in the CFTR gene and detects the copy number of all 27 exons.

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle

Voluntary exercise (VE) has a beneficial influence on the heart and mean lifespan. The present study evaluates structural adaptations of cardiomyocytes and their mitochondria due to VE by new, unbiased stereological methods. Female, 7-9-week-old mice were randomly assigned to a control (CG, n = 7) or VE group (EG, n = 7). EG animals were housed in cages with free access to a running wheel and had a mean running distance of 6.7 (1.8) km per day. After 4 weeks, the hearts of all mice were processed for light and electron microscopy. We estimated the number and volume of cardiomyocytes by the disector method and the number and volume of mitochondria by estimation of the Euler number. In comparison to CG, VE did not have an effect on the myocardial volume of the left ventricle (CG: 93 (10), EG: 103 (17) (mm(3))), the number of cardiomyocytes (CG: 2.81 (0.27), EG: 2.82 (0.43) (x10(6))) and their number-weighted mean volume. However, the composition of the cardiomyocytes changed due to VE. The total volume of mitochondria (CG: 21.8 (4.9), EG: 32.2 (4.3) (mm(3)), P < 0.01) and the total number (CG: 3.76 (0.44), EG: 7.02 (1.13) (x10(10)), P < 0.001) were significantly higher in EG than in CG. The mean number-weighted mitochondrial volume was smaller in EG than in CG (P < 0.05). In summary, VE does not alter ventricular volume nor cardiomyocyte volume or number but the oxidative capacity of cardiomyocytes by an increased mitochondrial number and total volume in the left ventricle. These structural changes may participate in the beneficial effects of VE.

Trial-to-trial size variability of motor-evoked potentials. A study using the triple stimulation technique

Motor-evoked potentials (MEPs) vary in size from one stimulus to the next. The objective of this study was to determine the cause and source of trial-to-trial MEP size variability. In two experiments involving 10 and 14 subjects, the variability of MEPs to cortical stimulation (cortical-MEPs) in abductor digiti minimi (ADM) and abductor hallucis (AH) was compared to those responses obtained using the triple stimulation technique (cortical-TST). The TST eliminates the effects of motor neuron (MN) response desynchronization and of repetitive MN discharges. Submaximal stimuli were used in both techniques. In six subjects, cortical-MEP variability was compared to that of brainstem-MEP and brainstem-TST. Variability was greater for MEPs than that for TST responses, by approximately one-third. The variability was the same for cortical- and brainstem-MEPs and was similar in ADM and AH. Variability concerned at least 10-15% of the MN pool innervating the target muscle. With the stimulation parameters used, repetitive MN discharges did not influence variability. For submaximal stimuli, approximately two-third of the observed MEP size variability is caused by the variable number of recruited alpha-MNs and approximately one-third by changing synchronization of MN discharges. The source of variability is most likely localized at the spinal segmental level.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.