OSU-6162, a Sigma1R Ligand in Low Doses,Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes

Neurotoxicity Research - Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer...     

Allergen immunotherapy during the COVID‐19 pandemic—A survey of the German Society for Allergy and Clinical Immunology

BackgroundWhen the coronavirus pandemic 2019 (COVID‐19) emerged, concerns were also raised regarding the safety of allergen immunotherapy (AIT). The German Society for Allergology and Clinical Immunology (DGAKI) conducted a survey to collect real‐world data on the daily routine of administering subcutaneous AIT (SCIT) and sublingual AIT (SLIT) during the COVID‐19 pandemic.MethodsA web‐based retrospective survey using the online platform survio with 26 standardized questions was used to survey physicians treating allergic patients during the pandemic.ResultsThree hundred and forty‐five physicians who regularly offer and perform AIT in German‐speaking countries responded to the questions. 70.4% of the respondents stated that they regularly initiated and dosed up SCIT for inhalant allergies (41.4% venom‐SCIT, 73.6% SLIT), and 85.2% of the respondents stated that they continued SCIT for inhalant allergies during the maintenance phase in a regular way (59.1% venom‐SCIT, 90.4% SLIT) in healthy patients without current symptoms indicating an infection with COVID‐19. With regard to tolerability, there was no evidence for increased occurrence of adverse events in patients without current symptoms of COVID‐19 infection during the pandemic.ConclusionsThis retrospective study demonstrated adherence to national and international position papers of AIT during the COVID‐19 pandemic in German‐speaking countries. Besides, the survey has confirmed a good tolerability of AIT for both SCIT and SLIT.     

The Differential Relations Between Empathy and Internalizing and Externalizing Symptoms in Inpatient Adolescents

Impaired empathy is associated with a variety of psychiatric conditions; however, little is known about the differential relations between certain forms of psychopathology and cognitive and affective empathy in adolescent girls and boys. The aim of this study was to examine the relations between externalizing and internalizing disorders and cognitive and affective empathy, respectively, while controlling for covariance among different forms of psychopathology, separately in girls and boys. A total of 507 inpatient adolescents (319 girls and 188 boys) in the age range of 12–17 years completed the Basic Empathy Scale that measures affective and cognitive empathy. The Youth Self-Report Form and Child Behavior Checklist were used to assess the severity of psychopathological symptoms. Results demonstrated that affective and cognitive empathy were negatively associated with conduct problems only in girls, but not in boys. Affective empathy was positively related to internalizing problems observed by parents and youths and self-reported ADHD symptoms in girls and boys. The clinical implications of these differential relationships for externalizing versus internalizing symptoms and empathy are discussed.     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.     

Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State‐of‐the‐art and real‐life current approach

The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life‐threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus‐related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the “State‐of‐the‐art” Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real‐life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge.     

Markers of anaphylaxis – a systematic review

Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patient's life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, histamine and its metabolites.     

Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population

The pathogenesis of age-related macular degeneration (AMD) is thought to be determined by an array of environmental and genetic factors. The association of increased expression of vascular endothelial growth factor (VEGF) with AMD, especially the wet form of AMD, was reported in several studies. The VEGF gene is highly polymorphic and some of its polymorphisms may affect its expression. In our work, we searched for an association between the −460C> (rs833061) and −634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and its dry and wet forms. We have chosen these polymorphisms because they were shown to be significant in other studies and we previously showed their association with diabetic retinopathy. A total of 401 individuals were enrolled in this study: 136 controls, and 88 patients with dry and 177 with wet AMD. The polymorphisms were determined with DNA from peripheral blood lymphocytes by allele-specific and restriction fragment length polymorphism polymerase chain reaction. The significance of the polymorphisms was assessed by multiple logistic regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype of the −460C>T polymorphism. An association (OR 3.77) between the C/T genotype of the −460C>T polymorphism and the occurrence of dry AMD was observed. The T/T genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was associated with the C/C genotype of the −634G>C polymorphism (OR 3.68). Another weak association (OR 2.63) was found between the C/T genotype of the −460C>T polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated with the presence of the combined C/T–G/G genotype of both polymorphisms (OR 2.41), whereas the T/T–G/G and T/T–G/C genotypes exerted a protective effect against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T–G/G and C/T–C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77, respectively), whereas the presence of the T/T–G/G and T/T–G/C genotypes decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the combined genotype C/T–G/G slightly favored the disease (OR 2.61) and the T/T–G/G genotype had a protective effect (OR 0.25). Analysis of haplotypes of both polymorphisms yielded similar results for AMD in general as well as for the dry and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas the TG haplotype protected against both forms of AMD. The results obtained indicate that the −460C>T and −634G>C polymorphisms of the VEGF gene may be associated with the dry and wet forms of AMD in a Polish population.     

Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulation

Recombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements. The mechanisms regulating RAG expression and repression are not clear. Here we identify NWC, a third evolutionarily conserved gene within the RAG locus, and show that it is ubiquitously expressed, with the notable exception of RAG-nonexpressing immature and mature T and B lymphocytes because in lymphocytes it is regulated by the RAG1 promoter and transcribed as RAG1-NWC hybrid mRNA molecules. We also show that in all other cells NWC is controlled by the RAG2 intragenic promoter, which in immature and mature T and B lymphocytes is silent. The possible implications of these findings for understanding the activation and inactivation of RAG genes in lymphocytes and their repression in other cells are discussed.