Diagnostic strategy for suspected scaphoid fractures in the presence of other fractures in the carpal region

Bone scintigraphy will identify up to 25% of occult scaphoid bone fractures after negative scaphoid X-rays. Consequently, it deserves a place in the diagnostic process of suspected scaphoid fractures. However, the role of bone scintigraphy is less clear if scaphoid X-rays show other fractures in the carpal region. We analysed 111 consecutive patients with a suspected scaphoid fracture on physical examination. Scaphoid X-rays revealed 61 fractures. Fifty-five patients had scaphoid fractures only and six patients had other fractures in the carpal region but no scaphoid fracture. In 50 cases, no bone injury was seen on these X-rays. In three out of the six patients with other fractures in the carpal region, bone scintigraphy revealed four occult concomitant fractures: one scaphoid, one scaphoid and trapezial and one capitate fracture. In conclusion, bone scintigraphy is required when scaphoid X-rays do not confirm a suspected scaphoid fracture, even in the presence of other fractures in the carpal region.     

The role of P-glycoprotein in CNS antihistamine effects

Rationale

P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood–brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to antihistamines that are not P-gp transporter substrates.

Objectives

The present study explored whether P-gp contributes in similar ways to the occurrence of sedative effects of antihistamines in humans.

Methods

An fMRI study was conducted according to a double-blind, randomized, placebo-controlled, cross-over design in 13 healthy volunteers. Participants received cetirizine 15 mg (an antihistamine), verapamil 120 mg (a P-gp blocker), a combination of cetirizine + verapamil, and a placebo. Brain activity was assessed while conducting the attention network test (ANT) in a 3T magnetic resonance scanner. The ANT measures three independent attention domains: i.e., alerting, orienting, and executive attention. It was expected that the combined treatment of cetirizine with verapamil would prevent efflux of cetirizine from the CNS, thus increasing attentional impairment, as compared to cetirizine administered alone.

Results

The present study provides evidence that the P-gp transporter is involved in central antihistamine effects in humans. Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level-dependent response in the right superior temporal gyrus.

Conclusion

It is concluded that the affinity for the P-gp transporter may contribute to the lower incidence of CNS side effects of certain antihistamines.     

Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results

Genetic testing of cancer susceptibility genes is now widely applied in clinical practice to predict risk of developing cancer. In general, sequence-based testing of germline DNA is used to determine whether an individual carries a change that is clearly likely to disrupt normal gene function. Genetic testing may detect changes that are clearly pathogenic, clearly neutral, or variants of unclear clinical significance. Such variants present a considerable challenge to the diagnostic laboratory and the receiving clinician in terms of interpretation and clear presentation of the implications of the result to the patient. There does not appear to be a consistent approach to interpreting and reporting the clinical significance of variants either among genes or among laboratories. The potential for confusion among clinicians and patients is considerable and misinterpretation may lead to inappropriate clinical consequences. In this article we review the current state of sequence-based genetic testing, describe other standardized reporting systems used in oncology, and propose a standardized classification system for application to sequence-based results for cancer predisposition genes. We suggest a system of five classes of variants based on the degree of likelihood of pathogenicity. Each class is associated with specific recommendations for clinical management of at-risk relatives that will depend on the syndrome. We propose that panels of experts on each cancer predisposition syndrome facilitate the classification scheme and designate appropriate surveillance and cancer management guidelines. The international adoption of a standardized reporting system should improve the clinical utility of sequence-based genetic tests to predict cancer risk.     

Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects

The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.18 respectively for oxycodone 10mg/morphine 20mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20mg/morphine 40 mg. The effect on the laser-PtP amplitude of morphine at the highest dose (40 mg) and of oxycodone at all doses (10, 15, 20mg) was considered to be clinically relevant based on a difference from placebo of ≥ 2.5 μV. For both compounds, a statistically significant linear trend was observed between dose groups in at least 1 of the 2 main target variables (adjusted P value for both end points <.001 at all doses). Hyperalgesia developed over time vs baseline due to acute exposure to UVB irradiation and to topical/occlusive 1% capsaicin solution. For both compounds, the principal onset of analgesic/antihyperalgesic drug effects was around 0.5 hours with an average peak at about 1 to 2 hours and the effect lasting for more than 3 hours (morphine 20 and 30 mg) or 6 hours (morphine 40 mg and oxycodone all doses). In conclusion, the study demonstrated a solid outcome of a mixed objective/subjective human experimental algesimetric model to approach dose-response relationships and analgesic/antihyperalgesic effects of 2 opioids.     

Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio

During social interactions we automatically infer motives, intentions, and feelings from bodily cues of others, especially from the eye region of their faces. This cognitive empathic ability is one of the most important components of social intelligence, and is essential for effective social interaction. Females on average outperform males in this cognitive empathy, and the male sex hormone testosterone is thought to be involved. Testosterone may not only down-regulate social intelligence organizationally, by affecting fetal brain development, but also activationally, by its current effects on the brain. Here, we show that administration of testosterone in 16 young women led to a significant impairment in their cognitive empathy, and that this effect is powerfully predicted by a proxy of fetal testosterone: the right-hand second digit-to-fourth digit ratio. Our data thus not only demonstrate down-regulatory effects of current testosterone on cognitive empathy, but also suggest these are preprogrammed by the very same hormone prenatally. These findings have importance for our understanding of the psychobiology of human social intelligence.     

The air-abrasion technique versus the conventional acid-etching technique: A quantification of surface enamel loss and a comparison of shear bond strength.

The purpose of this study was to quantify the surface enamel loss that results when an air-abrasive technique is used and to compare the shear bond strength of different prebonding and bonding methods. Enamel loss was determined for 2 enamel-conditioning methods: acid etching with 37% phosphoric acid; and sandblasting with 50 microm aluminum oxide particles under different conditions. A profilometer was used to determine the surface enamel loss. Forty-two bovine teeth were divided into 7 groups (N = 6). The statistical comparison of the different groups was carried out by analysis of variance. The results showed that under certain conditions the enamel loss associated with sandblasting is equal to or smaller than that resulting from acid etching. In addition, the effectiveness of different prebonding and bonding techniques used in the bonding of orthodontic brackets was evaluated by means of shear bond strength measurements. For bonding, 1 resin and 1 glass ionomer cement were evaluated; for prebonding, a sandblaster, 2 different polyacrylic acids and phosphoric acid were tested. Seventy bovine teeth were divided into 7 groups (N = 10) and then stored in water for 24 hours. An Instrom testing machine was used to determine bond strengths, and the 7 groups were compared by means of analysis of variance. The significance of post hoc tests was predetermined at P <.003. The results showed that the bond strength of the sandblasted groups was significantly lower than that of the etching groups. This indicates that sandblasting is not an alternative for the acid-etching technique currently used in orthodontic practice.     

Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood–Brain Barrier System

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood–brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.