Perceived discrimination In Primary Healthcare in Europe: evidence from the cross‐sectional QUALICOPC study

Recent figures show that discrimination in healthcare is still persistent in the European Union. Research has confirmed these results but focused mainly on the outcomes of perceived discrimination. Studies that take into account socioeconomic determinants of discrimination limit themselves to either ethnicity, income or education. This article explores the influence of several socioeconomic indicators (e.g. gender, age, income, education and ethnicity) on perceived discrimination in 30 European countries. Data from the QUALICOPC study were used. These data were collected between October 2011 and December 2013 in the participating countries. In total, 7183 GPs (general practitioners) and 61932 patients participated in the study, which had an average response rate of 74.1%. Data collection was co‐ordinated by NIVEL (Dutch Institute for Research of Health Care). Bivariate binomial logistic regressions were used to estimate the impact of each socioeconomic indicator on perceived discrimination. Multivariate logistic regressions were used to estimate the unique effect of each indicator. Results indicate that in Europe, overall 7% of the respondents felt discriminated, ranging between 1.4% and 12.8% at the country level. With regard to socioeconomic determinants in perceived discrimination, income and age are both important indicators, with lower income groups and younger people having a higher chance to feel discriminated. In addition, we find significant influences of education, gender, age and ethnicity in several countries. In most countries, higher educated people, older people, women and the indigenous population appeared to feel less discriminated. In conclusion, perceived discrimination in healthcare is reported in almost all European countries, but there is large variation between European countries. A high prevalence of perceived discrimination within a country also does not imply a correlation between socioeconomic indicators and perceived discrimination.     

Feasibility of 7T MRI for imaging fascicular structures of peripheral nerves

Introduction: Evaluation of the nerve fascicular structure can be useful in diagnosing nerve damage, but it is a very challenging task with 3T MRI because of limited resolution. In this pilot study, we present the feasibility of high‐resolution 7T MRI for examining the nerve fascicular structure. Methods: A 3‐dimensional (3D) gradient‐spoiled sequence was used for imaging peripheral nerves in extremities. Images acquired with different in‐plane resolutions (0.42 × 0.42 mm vs. 0.12 × 0.12 mm), and different main field strengths (7T vs. 3T) were compared. Results: The individual nerve fascicles were identified at 0.12 × 0.12 mm resolution in both field strengths but not at 0.42 × 0.42 mm resolution. The fascicular structure was more sharply depicted in 7T images than in 3T images. Discussion: High‐resolution 3D imaging with 7T MRI demonstrated feasibility for imaging nerve fascicular structures. Muscle Nerve 57 : 494–498, 2018     

A small-molecule smoothened agonist prevents glucocorticoid-induced neonatal cerebellar injury

Glucocorticoids are used for treating preterm neonatal infants suffering from life-threatening lung, airway, and cardiovascular conditions. However, several studies have raised concerns about detrimental effects of postnatal glucocorticoid administration on the developing brain leading to cognitive impairment, cerebral palsy, and hypoplasia of the cerebellum, a brain region critical for coordination of movement and higher-order neurological functions. Previously, we showed that glucocorticoids inhibit Sonic hedgehog-Smoothened (Shh-Smo) signaling, the major mitogenic pathway for cerebellar granule neuron precursors. Conversely, activation of Shh-Smo in transgenic mice protects against glucocorticoid-induced neurotoxic effects through induction of the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) pathway. Here, we show that systemic administration of a small-molecule agonist of the Shh-Smo pathway (SAG) prevented the neurotoxic effects of glucocorticoids. SAG did not interfere with the beneficial effects of glucocorticoids on lung maturation, and despite the known associations of the Shh pathway with neoplasia, we found that transient (1-week-long) SAG treatment of neonatal animals was well tolerated and did not promote tumor formation. These findings suggest that a small-molecule agonist of Smo has potential as a neuroprotective agent in neonates at risk for glucocorticoid-induced neonatal cerebellar injury.     

Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo

A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing the influence on viability and mitochondria of hepatic stellate cells (HSC), the toxicity of the codrug was markedly reduced in comparison to that of tacrine. Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate-induced toxicity could be observed that was absent for the 1:1 mixture of components. In subsequent in vivo experiments in rats, in contrast to the effects seen after tacrine treatment, after administration of the codrug no hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a scopolamine-induced cognitive impairment model using Wistar rats, the codrug was as potent as tacrine in reversing memory dysfunction. The tacrine-silibinin codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive effects in vivo as tacrine, being superior to the physical mixture of tacrine and silibinin in all these regards.     

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune‐mediated arthritis

Objective

Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the 5 somatostatin receptor subtypes (SSTRs 1–5) is involved in these actions. The purpose of this study was to assess the effects of the stable somatostatin analogs octreotide and pasireotide (SOM230) in a mouse model of antigen‐induced arthritis (AIA).

Methods

Studies were performed in SSTR2‐deficient mice (SSTR2^–/–) and their wild‐type littermates (SSTR2^+/+). The expression of SSTR1, SSTR2A, SSTR3, and SSTR5 in dorsal root ganglia was examined by immunohistochemistry.

Results

Untreated SSTR2^–/– mice with AIA displayed joint swelling and mechanical hyperalgesia similar to that seen in SSTR2^+/+ mice. In wild‐type mice, both octreotide and pasireotide significantly attenuated knee joint swelling and histopathologic manifestations of arthritis to an extent comparable to that of dexamethasone. In SSTR2^–/– mice, the antiinflammatory effects of both octreotide and pasireotide were completely abrogated. Prolonged administration of pasireotide also inhibited joint swelling and protected against joint destruction during AIA flare reactions. In addition, both octreotide and pasireotide reduced inflammatory hyperalgesia. The antinociceptive actions of octreotide were abolished in SSTR2^–/– mice, but those of pasireotide were retained. In dorsal root ganglia of naive wild‐type mice, only SSTR1 and SSTR2A, but not SSTR3 or SSTR5, were detected in a subset of small‐ and medium‐diameter neurons.

Conclusion

Our findings indicate that the antinociceptive and antiinflammatory actions of octreotide and pasireotide are largely mediated via the SSTR2 receptor. In addition, we identified the SSTR1 receptor as a novel pharmacologic target for somatostatin‐mediated peripheral analgesia in inflammatory pain.