Association between oxytocin receptor gene polymorphisms and self-rated 'empathic concern' in schizophrenia

The nonapeptide oxytocin (OXT) and its receptor (OXTR) have been implicated in social cognition, empathy, emotion and stress regulation in humans. Previous studies reported associations between OXT and OXTR genetic polymorphisms and risk for disorders characterized by impaired socio-emotional functioning, such as schizophrenia and autism. Here we investigate the influence of two single nucleotide polymorphisms (SNPs) within the OXTR gene on a measure of socio-emotional functioning in schizophrenic patients. OXTR SNPs that were previously investigated in other studies were genotyped in 145 patients diagnosed with schizophrenia according to DSM-IV and 145 healthy controls matched for age and gender. The Interpersonal Reactivity Index (IRI) was used to assess cognitive ('perspective taking'), affective ('empathic concern') and self-related ('personal distress') dimensions of empathy. No group differences in genotype frequencies were observed. MANCOVA revealed a significant main (F [1,282] = 10.464; pGG) with 'empathic concern'. Within the schizophrenia group, linear regression analysis determined OXTR rs2254298 genotype, PANSS negative and general symptom score, and age of disease onset as being significantly associated with 'empathic concern'. OXTR rs2254298 significantly impacted PANSS general psychopathology scores. No associations were found for OXTR rs53576, IRI 'perspective taking' or 'personal distress' ratings. Our preliminary findings support hypotheses about an involvement of OXTR rs2254298 in emotional empathy in schizophrenic and healthy individuals, warranting independent replication

Do We Get What We Need from Clinical Acoustic Voice Measurements?

Instrumental acoustic measurements of the human voice have enormous potential to objectively describe pathology and, thereby, to assist clinical treatment decisions. Despite the increasing application and accessibility of technical knowledge and equipment, recent research has highlighted a lack of understanding of physiologic, speech/language-, and culture-related influencing factors. This article presents a critical review of the current state of the art in the clinical application of instrumental acoustic voice quality measurements and points out future directions for improving its applications and dissemination in less privileged populations. The main barriers to this research relate to (a) standardization and reporting of acoustic analysis techniques; (b) understanding of the relation between perceptual and instrumental acoustic results; (c) the necessity to account for natural speech-related covariables, such as differences in speaking voice sound pressure level (SPL) and fundamental frequency f0; (d) the need for a much larger database to understand normal variability within and between voice-disordered and vocally healthy individuals related to age, training, and physiologic factors; and (e) affordable equipment, including mobile communication devices, accessible in various settings. This calls for further research into technical developments and optimal assessment procedures for pathology-specific patient groups

Interaction of Voice Onset Time with Vocal Hyperfunction and Voice Quality

The main aim of the present work was to investigate whether vocal hyperfunction (VH), perceptual voice quality (VQ), gender, and phonetic environment influence Voice Onset Time (VOT). The investigated group consisted of 30 adults, including 19 women (X = 46.1 ± 13.7 years) and 11 men (X = 47.5 ± 11.0 years), who had either phonotraumatic vocal hyperfunction (PVH) and non-phonotraumatic vocal hyperfunction (NPVH). VQ was judged considering the overall severity of dysphonia (OS) and the subcharacteristics of roughness, breathiness, and strain. Phonetic variables such as vowel stress, syllable stress, and mode of speech task were analyzed. Four samples of syllables with [p] plus vowel or diphthong were retrieved from CAPE-V sentences recordings. Acoustic analysis with Praat comprised VOT, mean fundamental frequency (fo), intensity (SPL dB(A)), and coefficient of variation of fundamental frequency (CV_fo %). VOT was significantly influenced by OS (p ≤ 0.001) but not by vocal VH condition (PVH versus NPVH) (p = 0.90). However, CV_fo was affected by the VH condition (p = 0.02). Gender effects were only found for mean fo (p ≤ 0.001) and SPL (p = 0.01). All VQ sub characteristics (OS, roughness, breathiness, and strain) correlated with VOT (p ≤ 0.001) and SPL (p ≤ 0.001) but not with fo. In summary, VOT was affected by voice quality, while it was not affected by vocal hyperfunction conditions. Therefore, VOT has the potential to objectively describe the onset of voicing in voice diagnostics, and may be one underlying objective characteristic of perceptual vocal quality

Relationship Between Laryngeal Signs and Symptoms, Acoustic Measures, and Quality of Life in Finnish Primary and Kindergarten School Teachers

Objective This study investigated the relationship between the acoustic measure smoothed cepstral peak prominence (CPPS), teacher's quality of life as measured by the voice activity and participation profile (VAPP), laryngeal signs and symptoms, voice related health problems and laryngoscopic findings in Finnish teachers. The relationship between CPPS and sound pressure level (SPL) was also assessed. Methods Vowel and text samples from 183 healthy Finnish teachers (99 kindergarten teachers [KT] and 84 primary school teachers [PST]) were analyzed for CPPS. Text reading was recorded in conversational loudness by PST, and KT were recorded wearing headphones, while listening to a masking noise of children talking to simulate their classroom voice and environment. CPPS values were correlated with the VAPP, self-reported laryngeal signs and symptoms, voice related health variables, and laryngoscopic findings. Results There was a significant difference between the two groups for CPPS text, PST showed significantly lower CPPS values (10.44) than KT (11.52). There was no difference between the two groups for CPPS vowel phonation. There was a significant correlation between SPL text and CPPS text for KT (P < 0.001, r = 0.43) but not for PST (P < 0.10, r = 0.16). There was a significant correlation between SPL vowel and CPPS vowel for both PST (P < 0.001, r = 0.47) and KT (P < 0.001, r = 0.45). CPPS did not correlate with the VAPP, laryngeal signs and symptoms, health variables or laryngeal findings. Factorial analysis of variance resulted in a significant relationship between the VAPP, laryngeal signs and symptoms, and teacher type. Teacher type and symptoms had a significant effect on VAPP scores. Conclusions In the present work CPPS does not correlate with vocal health indicators of functionally healthy teachers. CPPS was significantly influenced by differences in speaking voice SPL, emphasizing the impact of recording conditions and technique. There was a significant relationship between laryngeal signs and symptoms, teacher type and the VAPP. Laryngeal signs and symptoms and teacher type are important variables and should be included in the clinical evaluation of occupational voice users, and voice problems

Salmonella in reptiles: a review of occurrence, interactions, shedding and risk factors for human infections

Salmonella are considered a part of the normal reptile gut microbiota, but have also been associated with disease in reptiles. Reptile-associated salmonellosis (RAS) can pose a serious health threat to humans, especially children, and an estimated 6% of human sporadic salmonellosis cases have been attributed to direct or indirect contact with reptiles, although the exact number is not known. Two literature searches were conducted for this review. The first evaluated reports of the prevalence of Salmonella in the intestinal tracts of healthy reptiles. Salmonella were most commonly detected in snakes (56.0% overall), followed by lizards (36.9%) and tortoises (34.2%), with lower detection rates reported for turtles (18.6%) and crocodilians (9%). Reptiles in captivity were significantly more likely to shed Salmonella than those sampled in the wild. The majority of Salmonella strains described in reptiles belonged to subspecies I (70.3%), followed by subspecies IIIb (29.7%) and subspecies II (19.6%). The second literature search focused on reports of RAS, revealing that the highest number of cases was associated with contact with turtles (35.3%), followed by lizards (27.1%) and snakes (20.0%). Reptiles associated with RAS therefore did not directly reflect prevalence of Salmonella reported in healthy representatives of a given reptile group. Clinical symptoms associated with RAS predominantly involved the gastrointestinal tract, but also included fever, central nervous symptoms, problems with circulation, respiratory symptoms and others. Disease caused by Salmonella in reptiles appears to be dependent on additional factors, including stress, inadequate husbandry and hygiene, and other infectious agents. While it has been suggested that reptile serovars may cause more severe disease than human-derived strains, and some data is available on invasiveness of individual strains in cell culture, limited information is available on potential mechanisms influencing invasiveness and immune evasion in reptiles and in RAS. Strategies to mitigate the spread of Salmonella through reptiles and to reduce RAS focus mostly on education and hygiene, and have often been met with some success, but additional efforts are needed. Many aspects regarding Salmonella in reptiles remain poorly understood, including the mechanisms by which Salmonella persist in reptile hosts without causing disease

Dietary fiber and its role in performance, welfare, and health of pigs

Dietary fiber (DF) is receiving increasing attention, and its importance in pig nutrition is now acknowledged. Although DF for pigs was frowned upon for a long time because of reductions in energy intake and digestibility of other nutrients, it has become clear that feeding DF to pigs can affect their well-being and health. This review aims to summarize the state of knowledge of studies on DF in pigs, with an emphasis on the underlying mode of action, by considering research using DF in sows as well as suckling and weaned piglets, and fattening pigs. These studies indicate that DF can benefit the digestive tracts and the health of pigs, if certain conditions or restrictions are considered, such as concentration in the feed and fermentability. Besides the chemical composition and the impact on energy and nutrient digestibility, it is also necessary to evaluate the possible physical and physiologic effects on intestinal function and intestinal microbiota, to better understand the relation of DF to animal health and welfare. Future research should be designed to provide a better mechanistic understanding of the physiologic effects of DF in pigs

Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism

Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration

IL-10 Receptor Signaling Is Essential for T R 1 Cell Function In Vivo

Interleukin-10 (IL-10) is essential to maintain intestinal homeostasis. CD4+ T regulatory type 1 (TR1) cells produce large amounts of this cytokine and being therefore currently examined in clinical trials as T-cell therapy in patients with inflammatory bowel disease (IBD). However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified in order to optimize the efficiency and to ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome

Background Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases.Methods While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in similar to 550 European patients with JS and compared them with controls (&gt;15 000 Italian plus gnomAD), and with an independent cohort of similar to 600 JS probands from the USA.Results All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G&gt;T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T&gt;G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes. Two recurrent variants (MKS1 c.1476T&gt;G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T&gt;G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote.Conclusion This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants

Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone marrow molecular profile in myelodysplastic syndromes

Altres ajuts: José Carreras Leukämie-Stiftung, Award/Grant number: project AR 14/34