Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD ...raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.
A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.
Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54-25.45, p < 0.001, number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04-1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20-8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12-11.47, p = 0.03).
Despite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.
Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard ...task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.
We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross ...section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).
Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce ...this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis.
Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected.
In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results.
L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.
•LPS plus interferon-γ upregulate CB2 receptors in microglia.•LPS plus interferon-γ upregulate CB1-CB2 receptor complexes in microglia.•ß amyloid and LPS plus interferon-γ lead to similar activation ...traits in microglia.•Activated microglia is identified in pups of an Alzheimer’s disease model.•Dyskinesia in Parkinson’s correlates with CB1-CB2 receptor complex upregulation.
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB1 and circa 20 fold for CB2), whereas receptor levels were similar for CB1 and markedly upregulated for CB2; CB1-CB2Hets were also upregulated. Unlike in resting cells, CB2 receptors became robustly coupled to Gi in activated cells, in which CB1-CB2Hets mediated a potentiation effect. Hence, resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß1-42). Microglial activation markers were detected in the striatum of a Parkinson’s disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APPSw,Ind) mice, a transgenic Alzheimer’s disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APPSw,Ind and in cells from control animals activated using LPS plus IFN-γ. Expression of CB1-CB2Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment. In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB1-CB2Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB1-CB2 heteroreceptor complex in activated microglia have potential as targets in the treatment of neurodegenerative diseases.
The large majority of patients with HER2-positive metastatic breast cancer (MBC) will eventually develop resistance to anti-HER2 therapy and die of this disease. Despite, relatively high levels of ...stromal tumor infiltrating lymphocytes (sTILs), PD1-blockade has only shown modest responses. Monalizumab targets the inhibitory immune checkpoint NKG2A, thereby unleashing NK- and CD8 T cells. We hypothesized that monalizumab synergizes with trastuzumab by promoting antibody-dependent cell-mediated cytotoxicity.
In the phase II MIMOSA-trial, HER2-positive MBC patients were treated with trastuzumab and 750 mg monalizumab every two weeks. Following a Simon's two-stage design, 11 patients were included in stage I of the trial.
Treatment was well tolerated with no dose-limiting toxicities. No objective responses were observed. Therefore, the MIMOSA-trial did not meet its primary endpoint.
In summary, despite the strong preclinical rationale, the novel combination of monalizumab and trastuzumab does not induce objective responses in heavily pre-treated HER2-positive MBC patients.
•The MIMOSA trial investigated the novel combination of monalizumab and trastuzumab for HER2+ MBC.•The novel combination was well-tolerated, but no clinical responses were observed.•Combination strategies are warranted to induce a more inflamed tumor microenvironment.•Enrichment of inflamed HER2+ MBC with high TIL is likely to increase response to ICB.
The impact of the COVID-19 pandemic on the working, personal and health conditions of health professionals has been highlighted, although it is necessary to verify whether certain instruments used in ...research on this topic have sufficient psychometric support for their use. This need was the main motivation for undertaking the present study. We aimed to analyse the psychometric properties of the Utrecht Work Engagement Scale (UWES-9) in a sample of active health care workers during the pandemic.
A cross-sectional study was conducted from March to August 2020 with 2326 active health care workers (78.7% women). The instruments that were applied included the UWES-9 scale, the Sense of Coherence scale (SOC-13), the Goldberg General Health Questionnaire (GHQ-12) and an item on self-perceived health.
The three-factor structure related to the correlation of pairs of errors presented the best fit. The reliability of the UWES-9 was highlighted by the adequate internal consistency of the items, the existence of invariance according to gender, and its convergent and discriminant validity.
The findings of this work support the use of the UWES-9 to assess the work engagement of health personnel during the COVID-19 pandemic and identify it as an adequate measure of this psychological variable and the constructs that comprise it.
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