Ethanol upregulates the P2X7 purinergic receptor in human macrophages

Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.     

Gender differences on benefits and risks associated with oral antithrombotic medications for coronary artery disease

Introduction: Despite the significant advances in the pharmacological and interventional management of patients with cardiovascular disease (CVD) over the last decades, cardiovascular mortality remains the leading cause of death. Large randomized clinical trials have investigated the efficacy and safety of different antithrombotic medications in patients with CVD. Although female gender is generally underrepresented in these clinical trials, most analyses clearly indicate that both men and women may accrue therapeutic benefits from antithrombotic management strategies.

Areas covered: This review aims to provide a comprehensive and focused update on gender-related comparative clinical studies of antithrombotic therapies in patients suffering from CVD.

Expert opinion: Current evidence supports the understanding of a similar therapeutic effect between genders with signals of an increased risk of bleeding in women. However, important gaps in evidence exist due to the overall limited percentage of women that have been enrolled in randomized controlled trials. A greater awareness of gender-related issues in antithrombotic therapy should be promoted among physicians and further evidence from large clinical trials looking at the safety and efficacy balance of different antithrombotic strategies in women is warranted.     

Treatment outcome in subgroups of uncooperative child dental patients: an exploratory study

Objectives. The principal aims of this study were to evaluate the treatment outcome in subgroups of uncooperative child dental patients and to test the validity of these subgroups, which were based on fear and personality characteristics. Design. An exploratory, intervention study using quantified questionnaire, interview and observation data. Sample and methods. Eighty‐six 4 to 12‐year‐old uncooperative child dental patients (of whom 81 were divided retrospectively into four subgroups) and their accompanying parents were followed up during treatment at a specialist paediatric dental clinic in Sweden. Treatment was based on behaviour management techniques, supported by nitrous oxide/oxygen sedation if necessary. At baseline, parents answered a questionnaire including questions on child dental and general fear, temperament and behaviour, and parental dental fear, emotional stress, locus of control, parenting efficacy and attitudes to dental care, some of which were repeated post‐treatment. The treating dentist rated child behaviour according to the acceptance of a maximum of 14 treatment steps at each visit. Results. Approximately 90% of all children managed to undergo the dental treatment. Child dental fear and parental emotional stress decreased during treatment. Externalizing, impulsive children showed lower acceptance. In fearful, inhibited children, integrated use of sedation appeared to facilitate acceptance. Validity of the subgroups characterized as ‘fearful, extrovert, outgoing’, ‘fearful, inhibited’ and ‘externalizing, impulsive’ was supported, while heterogeneity within the group of ‘non‐fearful, extrovert, outgoing’ children made validation difficult. Conclusion. Fear and personality characteristics may serve as diagnostic aids when planning treatment of uncooperative child dental patients. Controlled outcome studies using differentiated treatment methods for children with different fear and personality profiles are needed.     

Direct and indirect time spent on care of dental trauma: a 2-year prospective study of children and adolescents

Abstract – The aim was to account for the total time spent by professional care‐givers (direct time) and by patients and companions engaged as support and help (indirect time) to treat and otherwise attend to children and adolescents with dental trauma to primary and permanent teeth. The study was based on a random sample of 192 children and adolescents with dental traumas reported to an insurance company and prospectively followed up by telephone interviews over a period of 2 years after the trauma episode. On average, direct time represented 16% of total time for all visits for dental trauma to permanent teeth and 11% for trauma to primary teeth. The most extensive type of indirect time was transport time, which took up 30% of the total time spent on injuries to permanent teeth and 36% for injuries to primary teeth. Multiple regression analysis of the impact of dental and demographic injury variables on the time variables showed that complicated trauma was associated with extended time, direct as well as indirect, for permanent and primary teeth injuries. Our estimate of the average relative increase in total time spent by patients and companions in cases of complicated injury to permanent teeth was 117% (95% confidence interval [CI], 52–211) for patients and 112% (95% CI, 42–217) for companions. For transport time a strong predictor was access to a dental clinic near the place of residence. Lack of access could extend the average transport time by 180% (95% CI, 80–335) for patients and 163% (95% CI, 67–317) for their companions in cases of injuries to primary teeth.     

Resting State Functional Magnetic Resonance Imaging in Parkinson’s Disease

Next-generation sequencing technologies have tremendously increased the speed of gene discovery in monogenic epilepsies, enabling us to identify a genetic cause in an increasing proportion of patients, and to better understand the underlying pathophysiology of their disease. The rapid speed with which new genes are being described lately, confronts clinicians with the difficult task of keeping up to date with the continuous supply of new publications. This article aims to discuss some of the genes that were recently discovered in monogenic familial epilepsy syndromes or epileptic encephalopathies for which an underlying cause remained unknown for a long time.     

The morphometry of auditory cortex in the congenitally deaf measured using MRI

The study of congenitally deaf individuals provides a unique opportunity to understand the organization and potential for reorganization of human auditory cortex. We used magnetic resonance imaging (MRI) to examine the structural organization of two auditory cortical regions, Heschl's gyrus (HG) and the planum temporale (PT), in deaf and hearing subjects. The results show preservation of cortical volume in HG and PT of deaf subjects deprived of auditory input since birth. Measurements of grey and white matter, as well as the location and extent of these regions in the deaf showed complete overlap both with matched controls and with previous samples of hearing subjects. The results of the manual volume measures were supported by findings from voxel-based morphometry analyses that showed increased grey-matter density in the left motor hand area of the deaf, but no differences between the groups in any auditory cortical region. This increased cortical density in motor cortex may be related to more active use of the dominant hand in signed languages. Most importantly, expected interhemispheric asymmetries in HG and PT thought to be related to auditory language processing were preserved in these deaf subjects. These findings suggest a strong genetic component in the development and maintenance of auditory cortical asymmetries that does not depend on auditory language experience. Preservation of cortical volume in the deaf suggests plasticity in the input and output of auditory cortex that could include language-specific or more general-purpose information from other sensory modalities.     

Inter-Rater Reliability of the PIPES Tool: Validation of a Surgical Capacity Index for Use in Resource-Limited Settings

Introduction

In response to the need for simple, rapid means of quantifying surgical capacity in low resource settings, Surgeons OverSeas (SOS) developed the personnel, infrastructure, procedures, equipment and supplies (PIPES) tool. The present investigation assessed the inter-rater reliability of the PIPES tool.

Methods

As part of a government assessment of surgical services in Santa Cruz, Bolivia, the PIPES tool was translated into Spanish and applied in interviews with physicians at 31 public hospitals. An additional interview was conducted with nurses at a convenience sample of 25 of these hospitals. Physician and nurse responses were then compared to generate an estimate of reliability. For dichotomous survey items, inter-rater reliability between physicians and nurses was assessed using the Cohen’s kappa statistic and percent agreement. The Pearson correlation coefficient was used to assess agreement for continuous items.

Results

Cohen’s kappa was 0.46 for infrastructure, 0.43 for procedures, 0.26 for equipment, and 0 for supplies sections. The median correlation coefficient was 0.91 for continuous items. Correlation was 0.79 for the PIPES index, and ranged from 0.32 to 0.98 for continuous response items.

Conclusions

Reliability of the PIPES tool was moderate for the infrastructure and procedures sections, fair for the equipment section, and poor for supplies section when comparing surgeons’ responses to nurses’ responses—an extremely rigorous test of reliability. These results indicate that the PIPES tool is an effective measure of surgical capacity but that the equipment and supplies sections may need to be revised.