Stability-based approaches in chemoproteomics.

Target deconvolution can help understand how compounds exert therapeutic effects and can accelerate drug discovery by helping optimise safety and efficacy, revealing mechanisms of action, anticipate off-target effects and identifying opportunities for therapeutic expansion. Chemoproteomics, a combination of chemical biology with mass spectrometry has transformed target deconvolution. This review discusses modification-free chemoproteomic approaches that leverage the change in protein thermodynamics induced by small molecule ligand binding. Unlike modification-based methods relying on enriching specific protein targets, these approaches offer proteome-wide evaluations, driven by advancements in mass spectrometry sensitivity, increasing proteome coverage and quantitation methods. Advances in methods based on denaturation/precipitation by thermal or chemical denaturation, or by protease degradation are evaluated, emphasising the evolving landscape of chemoproteomics and its potential impact on future drug-development strategies.

Psychometric Properties of the Pictorial Pain Interference Questionnaire for Assessing Functional Interference in Chronic Low Back Pain.

OBJECTIVE: To analyze the psychometric properties of the Pictorial Pain Interference Questionnaire (PPIQ) for evaluating functional interference in the population with chronic low back pain (CLBP). DESIGN: Cross-sectional study. SETTING: Rehabilitation Unit in a hospital. PARTICIPANTS: Ninety-nine patients with CLBP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional interference was assessed using PPIQ. The following data were also collected: sociodemographic data; pain intensity (Numeric Pain Rating Scale [NPRS]); physical functioning (30-s arm curl, 30-s chair stand [30CST], and timed Up and Go [TUG] tests), fitness (International Physical Activity Questionnaire); quality of life (Short-Form 12 Health Survey version 1 [SF-12v1]); sleep quality (Spanish-validated 12-item Medical Outcomes Study Sleep scale [12-MOS Sleep]); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); and social support (Duke-UNK Functional Social Support Questionnaire). Internal consistency was analyzed using Cronbach's alpha, structural validity using exploratory factor analysis (EFA), and discriminant and convergent validity using bivariate analysis. RESULTS: Ninety-nine patients with CLBP were included (age [mean ± SD]: 54.37±12.44 y); women, 67.7%). The EFA extracted 2 factors: "physical function and "social and sleep," which explained 57.75% of the variance. Excellent internal consistency was observed for the overall PPIQ score (Cronbach's α=0.866). Convergent validity was observed between the PPIQ and other functional measures (ρ: 0.52 and -0.47 for the TUG and 30CST, respectively; P<.001) and with the following variables: physical and mental component summaries of the SF-12v1 (ρ: -0. 55 and -0.52, respectively (P<.001); anxiety and depression of the HADS (ρ: 0.47 and 0.59, respectively (P<.001); NPRS (ρ: 0.45; P<.001); and index 9 of the 12-MOS Sleep scale (r: 0.49; P<.001). CONCLUSIONS: The PPIQ is a valid instrument with good psychometric properties for measuring functional interference in people with CLBP. This questionnaire appears to be a feasible alternative when language or communication barriers exist in CLBP population.

Comparison of Quantitative Mass Spectrometric Methods for Drug Target Identification by Thermal Proteome Profiling.

Thermal proteome profiling (TPP) provides a powerful approach to studying proteome-wide interactions of small therapeutic molecules and their target and off-target proteins, complementing phenotypic-based drug screens. Detecting differences in thermal stability due to target engagement requires high quantitative accuracy and consistent detection. Isobaric tandem mass tags (TMTs) are used to multiplex samples and increase quantification precision in TPP analysis by data-dependent acquisition (DDA). However, advances in data-independent acquisition (DIA) can provide higher sensitivity and protein coverage with reduced costs and sample preparation steps. Herein, we explored the performance of different DIA-based label-free quantification approaches compared to TMT-DDA for thermal shift quantitation. Acute myeloid leukemia cells were treated with losmapimod, a known inhibitor of MAPK14 (p38α). Label-free DIA approaches, and particularly the library-free mode in DIA-NN, were comparable of TMT-DDA in their ability to detect target engagement of losmapimod with MAPK14 and one of its downstream targets, MAPKAPK3. Using DIA for thermal shift quantitation is a cost-effective alternative to labeled quantitation in the TPP pipeline.

"Bronchogenic cyst impersonating a pericardial lesion": A case report.

A 32-year-old female presented with palpitations and chest discomfort. The patient had a history of pericardiotomy due to pericardial effusion. Multimodal imaging, including echocardiography, cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) showed a single mass in the pericardium as the cause of the symptoms. Furthermore, its location and potential complications were accurately defined. The patient underwent a successful surgical resection of the pericardial cyst, microscopic histopathological examination was compatible with a bronchogenic cyst, a very rare congenital malformation. The article discusses the rarity of bronchogenic cysts in the pericardium and the importance of accurate diagnosis and appropriate treatment.

Mitral valve prolapse in patients with atrial septal defect: A quantitative three-dimensional echocardiographic analysis.

INTRODUCTION AND OBJECTIVES: Mitral valve (MV) prolapse is highly prevalent in patients with atrial septal defect (ASD). Abnormal left ventricular geometry has been proposed as the main mechanism of MV prolapse in ASD, however, the changes in the morphology of the MV apparatus remain to be clarified. Our aim was to assess the MV geometry in patients with ASD and MV prolapse. METHODS: We evaluated 99 patients (73% female, median age 40 years) with ASD who underwent a three-dimensional transesophageal echocardiogram. Three-dimensional analysis of the MV was done using dedicated automated software. Transthoracic echocardiographic parameters were assessed post ASD closure in 28 patients. RESULTS: MV prolapse was found in 39% of patients. Although smaller left ventricular dimensions and greater interatrial shunt were found in patients with MV prolapse compared with those without prolapse, there was no difference in the subvalvular parameters. MV prolapse was associated with larger mitral anterior-posterior diameter, anterolateral-posteromedial diameter, anterior perimeter, posterior perimeter, total perimeter, and anterior leaflet area (all p < 0.05). Mitral regurgitation was more frequent in patients with MV prolapse (80 vs. 48%, p = 0.002). CONCLUSIONS: In patients with ASD, the main mechanism of MV prolapse is the presence of an organic primary process of the MV apparatus (excessive anterior mitral leaflet tissue and mitral annular enlargement).

A Case of Transient Mitral Regurgitation: Not Everything Is Always What It Seems.

Mitral regurgitation (MR) is a common form of valvular heart disease that is associated with significant morbidity and mortality. MR can be broadly classified into 2 different categories: primary and secondary MR. Primary MR usually is caused by leaflet abnormalities, whereas secondary MR is a chronic disease secondary to geometric distortion of both the annulus and subvalvular apparatus because of left ventricular remodeling. Without acute changes in loading conditions, myocardial blood flow, or rhythm disturbances, functional MR typically is not transient. In this E-Challenge, the authors show a transient and completely reversible acute and severe form of functional MR with the use of multimodal echocardiography.

Smartphone-based exercise intervention for chronic pain: PainReApp randomized clinical trial protocol.

AIM: To evaluate the effectiveness of PainReApp, an mHealth system, based on physical exercise recommendations for patients with chronic pain (low back pain, fibromyalgia and diabetic neuropathic pain) based on pain intensity, quality of life, anxiety and/or depression, and sleep quality. DESIGN: Single-blinded randomized controlled trial. METHODS: One hundred patients from three different chronic conditions (low back pain, fibromyalgia and neuropathic diabetic pain) will be recruited and randomized into two groups to receive the intervention with a physical activity program guided by the PainReApp system (experimental group) or with the program information in paper format (control group). All patients will attend a first face-to-face session in which the smartphone application usage (experimental group) and exercise execution will be explained (both groups). Data will be collected at baseline, 4, 12 and 24 weeks. Nevertheless, the users of the application will have a daily registry of the exercise performed and the self-perceived difficulty. The primary outcomes of the trial will be the intensity of pain and quality of life. Anxiety and/or depression and sleep quality will be also assessed to evaluate the influence of the physical activity at multiple levels. DISCUSSION: Physical exercise is becoming one of the leading evidence-based interventions to treat chronic pain. It needs to be adapted to the necessities of each pain condition. One of the major problems is the low adherence to the proposed program. New strategies that empower the patients, such as the m-Health, are reliable and useful tools to ease this end. IMPACT: To the best of our knowledge, this is the first long-term randomized controlled trial researching the impact of an m-health system on chronic pain from different origin. The intervention is based on international physical exercise recommendations and can be performed without specific material, allowing the home-based practice. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12621000783820).

Single-Cell Metabolomics by Mass Spectrometry Imaging.

Multicellular organisms achieve their complex living activities through the highly organized metabolic interplay of individual cells and tissues. This complexity has driven the need to spatially resolve metabolomics down to the cellular and subcellular level. Recent technological advances have enabled mass spectrometry imaging (MSI), especially matrix-assisted laser desorption/ionization (MALDI), to become a powerful tool for the visualization of molecular species down to subcellular spatial resolution. In the present chapter, we summarize recent advances in the field of MALDI-MSI, with respect to single-cell level resolution metabolomics directly on tissue. In more detail, we focus on advancements in instrumentation for MSI at single-cell resolution, and the applications towards metabolomic scale imaging. Finally, we discuss new computational tools to aid in metabolite identification, future perspective, and the overall direction that the field of single-cell metabolomics directly on tissue may take in the years to come.

The success of behavioral economics in improving patient retention within an intensive primary care practice.

BACKGROUND: A minority of the U.S. population comprises a majority of health care expenses. Health system interventions for high-cost populations aim to improve patient outcomes while reducing costly over-utilization. Missed and inconsistent appointments are associated with poor patient outcomes and increased health care utilization. PEAK Health- Mount Sinai's intensive primary care clinic for high-cost patients- employed a novel behavioral economics-based intervention to reduce the rate of missed appointments at the practice. Behavioral economics has accomplished numerous successes across the health care field; the effect of a clinic-based behavioral economics intervention on reducing missed appointments has yet to be assessed. METHODS: This was a single-arm, pre-post trial conducted over 1 year involving all active patients at PEAK Health. The intervention consisted of: a) clinic signage, and b) appointment reminder cards containing behavioral economics messaging designed to increase the likelihood patients would complete their subsequent visit; appointment cards (t1) were transitioned to an identical EMR template (t2) at 6 months to boost provider utilization. The primary objective, the success of scheduled appointments, was assessed with visit adherence: the proportion of successful over all scheduled appointments, excluding those cancelled or rescheduled. The secondary objective, the consistency of appointments, was assessed with a 2-month visit constancy rate: the percentage of patients with at least one successful visit every 2 months for 1 year. Both metrics were assessed via a χ2 analysis and together define patient retention. RESULTS: The visit adherence rate increased from 74.7% at baseline to 76.5% (p = .22) during t1 and 78.0% (p = .03) during t2. The 2-month visit constancy rate increased from 59.5% at baseline to 74.3% (p = .01) post-intervention. CONCLUSIONS: A low-resource, clinic-based behavioral economics intervention was capable of improving patient retention within a traditionally high-cost population. A renewed focus on patient retention- employing the metrics described here- could bolster chronic care efforts and significantly improve the outcomes of high-cost programs by reducing the deleterious effects of missed and inconsistent appointments.

Differences in physical and psychological health in patients with chronic low back pain: a national survey in general Spanish population.

PURPOSE: To estimate the prevalence of diagnosed and undiagnosed chronic low back pain (CLBP-D and CLBP-UD, respectively) in the general adult population in Spain and to compare the characteristics of these two groups with subjects without CLBP symptoms (No-CLBP). To establish CLBP-D patient sub-groups according to their self-perceived health status, mental health, level of pain and the impact of their pain on daily activities. METHODS: Data were obtained from the National Health Survey of Spain 2017 with a sample of 23,089 adults. Three groups were defined: CLBP-D, CLBP-UD and No-CLBP. In the CLBP-D group, a cluster analysis was performed to identify sub-groups. A multinomial regression model was constructed to determine the factors associated with each of the sub-groups identified. RESULTS: The prevalence of CLBP-D was 22% (95% CI 21.5-22.5) and that of CLBP-UD was 1.4% (95% CI 1.2-1.5). CLBP-D was more common in middle-aged females with a low educational level. They have a worse perceived health status, report more comorbidities, have worse mental health and more limitations in comparison with the populations without CLBP and with CLBP-UD. Three sub-groups of CLBP-D subjects were identified. Women and older subjects with a lower educational level, more occupational stress, less social support and with more physical limitations were the most likely subjects to be included in the group worst-affected. CONCLUSIONS: There is a high prevalence of CLBP among the adult population in Spain. Occupational stress and a lack of social support are common factors among subjects' worst-affected of CLBP-D and identifying the subjects with these risks is therefore a recommended strategy for improving the healthcare provided to CLBP patients.

Limitations in Activities of Daily Living in People With Chronic Pain: Identification of Groups Using Clusters Analysis.

BACKGROUND: Chronic pain (CP) is a major public health problem affecting patients' lives and reducing physical activity. The aim is to establish subgroups of people with chronic pain (PCP) according to limitations in activities of daily living (ADLs), and to identify sociodemographic, pain-related, and psychosocial variables associated with each subgroup. METHODS: Nationwide cross-sectional study on a representative sample of the Spanish adult population. Information on pain characteristics and ADL limitations was collected via telephone survey. A cluster analysis was used to identify subgroups of subjects according to the limitations on ADLs. Multivariate analysis was performed to analyze the variables related to each subgroup. RESULTS: Out of the 1,957 surveys included in the original study, 325 PCP were identified according to the definition of the International Association for the Study of Pain. More than 50% reported some limitation in ADLs. Three groups of PCP were identified, with low, medium, and high ADL limitation. Older age, widespread and more intense pain, decrease in work activity, and belief that their pain affected the relationship with their friends were associated with higher limitations. CONCLUSIONS: The identification of the characteristics of people with higher limitations could help guide future prevention and treatment initiatives to minimize the disabling impact of chronic pain on patients' family, work, and social life.

Nanoparticle microarray for high-throughput microbiome metabolomics using matrix-assisted laser desorption ionization mass spectrometry.

A high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI)-MS-based metabolomics platform was developed using a pre-fabricated microarray of nanoparticles and organic matrices. Selected organic matrices, inorganic nanoparticle (NP) suspensions, and sputter coated metal NPs, as well as various additives, were tested for metabolomics analysis of the turkey gut microbiome. Four NPs and one organic matrix were selected as the optimal matrix set: α-cyano-4-hydroycinnamic acid, Fe3O4 and Au NPs in positive ion mode with 10 mM sodium acetate, and Cu and Ag NPs in negative ion mode with no additive. Using this set of five matrices, over two thousand unique metabolite features were reproducibly detected across intestinal samples from turkeys fed a diet amended with therapeutic or sub-therapeutic antibiotics (200 g/ton or 50 g/ton bacitracin methylene disalicylate (BMD), respectively), or non-amended feed. Among the thousands of unique features, 56 of them were chemically identified using MALDI-MS/MS, with the help of in-parallel liquid chromatography (LC)-MS/MS analysis. Lastly, as a proof of concept application, this protocol was applied to 52 turkey cecal samples at three different time points from the antibiotic feed trial. Statistical analysis indicated variations in the metabolome of turkeys with different ages or treatments. Graphical abstract ᅟ.

IL10 haplotypes are associated with diabetic nephropathy susceptibility in patients from western Mexico.

INTRODUCTION: Diabetic Nephropathy (DN) is the main cause of chronic kidney disease (CKD) in diabetic patients. An IL-10 imbalance could be related to renal hypertrophy and trigger to nephropathy. Three promoter polymorphisms (-1082G>A, -819C>T, and -592C>A) at IL10 gene have been associated with changes in the IL-10 expression and DN susceptibility. Therefore, the aim of this study was to analyze this association in Mexican patients with DN. METHODS: We conducted a case-control study on 128 patients with DN and 150 control subjects (CS) from western Mexico. All patients were tested for IL10 polymorphisms by PCR-RFLP. Allele frequencies, genotypes, and haplotypes were compared between groups. The significant haplotypes were correlated with patient clinical features. RESULTS: IL10 gene ATC haplotype (-1082A/-819T/-592C) was found significantly more frequent in DN patients than in CS (P < 0.001; OR = 3.6, 95% CI: 1.7-7.4). Similarly GTA (-1082G/-819T/-592A) haplotype was more frequent in DN patients than CS with significant differences (P < 0.05; OR = 4.02, 95% CI: 1.10-14.78). There were no correlations between IL10 haplotypes and clinical parameters in patients with DN. However, that there is a trend of higher serum urea levels and lower eGFR in ATC haplotype carriers compared to carriers of the other haplotypes (P < 0.05). CONCLUSIONS: These results indicate that IL10 promoter haplotypes ATC and GTA carriers have a higher risk factor to develop DN in the western Mexican population.

PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients.

BACKGROUND: CD40 is a costimulatory molecule for B cells, and CD154 is a marker of CD4+ T cells activation. CD40-CD154 interaction promotes pro-inflammatory cytokines secretion and autoantibodies production. PTPN22 gene encodes LYP protein, an inhibitor of T- and B-cell activation. PTPN22 1858C>T polymorphism confers rheumatoid arthritis (RA) susceptibility. Hence, we evaluate the relationship between 1858C>T polymorphism with CD40 and CD154 expression and IFN-γ secretion in RA patients. METHODS: PTPN22 1858C>T polymorphism was genotyped in 315 RA patients and 315 control subjects (CS) using PCR-RFLP method. Later, we selected only ten anti-CCP-positive RA patients, naïve to disease-modifying antirheumatic drugs and ten CS, all with known 1858C>T PTPN22 genotype. The CD40 and CD154 membrane expressions were determined by flow cytometry in peripheral B and T cells, correspondingly. RESULTS: The B cells percentage and mCD40 expression were similar between RA and CS (P > 0.05) and we did not find an association between these variables and the 1858C>T polymorphism. The CD4+ T cells percentage was higher in RA patients than CS (P = 0.003), and in the RA group, the CD4+ T cells percentage and mCD154 expression were higher in the 1858 T allele carriers (P = 0.008 and P = 0.032, respectively). The IFN-γ levels were lower in RA patients carrying the PTPN22 risk allele (P = 0.032). CONCLUSION: The PTPN22 1858 T risk allele is associated with increased CD4+ T cells percentage and high mCD154 expression in RA patients, which could favor the pro-inflammatory cytokine release and the establishment of the inflammatory response at the seropositive RA.

High spatial resolution mass spectrometry imaging reveals the genetically programmed, developmental modification of the distribution of thylakoid membrane lipids among individual cells of maize leaf.

Metabolism in plants is compartmentalized among different tissues, cells and subcellular organelles. Mass spectrometry imaging (MSI) with matrix-assisted laser desorption ionization (MALDI) has recently advanced to allow for the visualization of metabolites at single-cell resolution. Here we applied 5- and 10 µm high spatial resolution MALDI-MSI to the asymmetric Kranz anatomy of Zea mays (maize) leaves to study the differential localization of two major anionic lipids in thylakoid membranes, sulfoquinovosyldiacylglycerols (SQDG) and phosphatidylglycerols (PG). The quantification and localization of SQDG and PG molecular species, among mesophyll (M) and bundle sheath (BS) cells, are compared across the leaf developmental gradient from four maize genotypes (the inbreds B73 and Mo17, and the reciprocal hybrids B73 × Mo17 and Mo17 × B73). SQDG species are uniformly distributed in both photosynthetic cell types, regardless of leaf development or genotype; however, PG shows photosynthetic cell-specific differential localization depending on the genotype and the fatty acyl chain constituent. Overall, 16:1-containing PGs primarily contribute to the thylakoid membranes of M cells, whereas BS chloroplasts are mostly composed of 16:0-containing PGs. Furthermore, PG 32:0 shows genotype-specific differences in cellular distribution, with preferential localization in BS cells for B73, but more uniform distribution between BS and M cells in Mo17. Maternal inheritance is exhibited within the hybrids, such that the localization of PG 32:0 in B73 × Mo17 is similar to the distribution in the B73 parental inbred, whereas that of Mo17 × B73 resembles the Mo17 parent. This study demonstrates the power of MALDI-MSI to reveal unprecedented insights on metabolic outcomes in multicellular organisms at single-cell resolution.

Factors Influencing Cognitive Impairment in Neuropathic and Musculoskeletal Pain and Fibromyalgia.

Objective: To assess cognitive performance of chronic pain (CP) patients diagnosed with three types of pain-neuropathic pain (NP), musculoskeletal (MSK), and fibromyalgia (FM)-and to analyze the factors influencing cognitive difficulties in each group. Methods: Two hundred fifty-four CP patients-104 NP, 99 MSK, 51 FM-and 72 pain-free subjects were included in the study. The "Test Your Memory" (TYM) scale was used to assess cognitive performance. Pain intensity was measured by means of the visual analog scale (VAS); the Hospital Anxiety and Depression scale was used to assess mental status, and the Medical Outcome Study (MOS) sleep scale to assess sleep quality. The relationships between cognitive performance and these factors were analyzed using linear regression models. Results: The mean score in the TYM was significantly lower (worse cognitive function) in CP patients than controls (40.5 vs 43.9, P < 0.001). In the separate analysis of each group, depression was observed to have a negative impact on MSK pain patients (ß = -0.37, 95% confidence interval [CI] = -0.53 to -0.2, P < 0.001) and on FM subjects (ß =-1.01, 95% CI = -1.05 to -2.38, P = 0.022). A significant interaction between pain intensity and depression was observed in the FM patients. In addition, a U-shaped association was found between the duration of pain and cognitive performance in the NP patients. Neither anxiety nor sleep impairment affected cognitive performance in any of the CP patients. Conclusions: These results highlight the importance of taking into account the type of pain when assessing cognitive performance in CP patients and demonstrate the influence of the emotional state of the patient, especially if depression is present.

Coexisting bicuspid aortic and pulmonary valves diagnosed by 3D transthoracic echocardiography.

Coexisting bicuspid aortic and pulmonary valves is an extremely rare condition, and there have been few published cases. Diagnosis of bicuspid aortic valve is straightforward with 2D echocardiography; however, analysis of the morphology of the pulmonary valve is challenging. In this study, we report on a case of a 32-year-old man with bicuspid aortic and pulmonary valves diagnosed by 2D and 3D transthoracic echocardiography. The enlarged pulmonary artery without any obvious etiology led us to suspect a pulmonary valve anomaly; thus, we comprehensively evaluated it with 2D and 3D echocardiography, which confirmed the diagnosis of bicuspid pulmonary valve.

Severe Craniofacial Involvement due to Amniotic Band Sequence.

BACKGROUND: Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. OBJECTIVE: We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. RESULTS: The craniofacial deformities were delimited by peripheral sharply demarcated scarring. CONCLUSION: When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

Relationship Between Using Clinical Practice Guidelines for Pain Treatment and Physicians' Training and Attitudes Toward Patients and the Effects on Patient Care.

AIMS: To determine the use of clinical practice guidelines (CPGs) for chronic pain (CP) management; analyze the effects of training in pain and the attitudes of physicians toward pain and CP patients on the adherence to these CPGs; and assess the impact of adherence to CPGs on patient care. METHOD: This was a cross-sectional study in a sample of physicians involved in CP patient management. Information on the use of CPGs for CP management, their training in pain, and their attitudes toward pain, patients, and patient care was collected. Descriptive and bivariate analyses were performed, and a multinomial logistic regression model was constructed to analyze factors associated with the use of CPGs. RESULTS: Of the 257 physicians surveyed, 46.6% were physiatrists, 26.7% were general practitioners, and 26.7% were medical oncologists. Although 96.5% claimed to have received training in pain, only 10.1% had received college training, and 76.3% expressed having gaps in their knowledge; 53.9% stated they applied CPGs often/always, and 12.5% rarely/never. Limited knowledge on pain, reduced involvement in training activities, more negative attitudes toward patients, and having experienced CP were the factors related to reduced adherence to CPGs, especially among the youngest respondents. The greater the use of CPGs, the better the patient care was. CONCLUSIONS: Access to scientific information and specialized training are factors related to the use of CPGs for pain treatment. Therefore, the inclusion of CP training in university and during medical specialty training will be essential measures to improve adherence to CPG, thereby improving patient care and pain control.

"Like parent, like child": Attention deficit hyperactivity disorder-like characteristics in parents of ADHD cases.

The objective of this study was to characterize an attention deficit hyperactivity disorder (ADHD) endophenotype in non-affected parents of adolescents with a history of ADHD, based on the relationship between performance on a sustained attention test (continuous performance task, or CPT) and polymorphisms of the DRD4 gene. In a sample of 25 non-affected parents of adolescents with ADHD history obtained from a longitudinal study of a nonclinical population, and 25 non-affected parents of adolescents with no ADHD history, four groups were evaluated with respect to the presence or absence of the long allele polymorphism of the DRD4 gene (i.e., over seven repeats). Comparisons of CPT performance among the four study groups included the number of commission errors, the number of omission errors, mean reaction time on correct responses (MRT), and reaction time (RT) variability (mean standard deviation of RT in each block [SDRT, as variability], and the sigma and tau components of the ex-Gaussian approach). The group of non-affected parents of adolescents with ADHD history and at least one long allele of the DRD4 gene showed greater RT variability (measured by SDRT), which is best explained by the greater frequency of abnormally slow responses (measured by tau). An association between the presence of the long allele of the DRD4 gene polymorphism and ADHD-like failure in CPT performance was evident in the non-affected parents of adolescents with ADHD in childhood. These findings suggest that certain traits of CPT performance could be considered an ADHD endophenotype.