Improvements in Compassion and Fears of Compassion throughout the COVID-19 Pandemic: A Multinational Study

During large-scale disasters, social support, caring behaviours, and compassion are shown to protect against poor mental health outcomes. This multi-national study aimed to assess the fluctuations in compassion over time during the COVID-19 pandemic. Respondents (Time 1 n = 4156, Time 2 n = 980, Time 3 n = 825) from 23 countries completed online self-report questionnaires measuring the flows of compassion (i.e., Compassionate Engagement and Action Scales) and fears of compassion toward self and others and from others (i.e., Fears of Compassion Scales) and mental health at three time-points during a 10-month period. The results for the flows of compassion showed that self-compassion increased at Time 3. Compassion for others increased at Time 2 and 3 for the general population, but in contrast, it decreased in health professionals, possibly linked to burnout. Compassion from others did not change in Time 2, but it did increase significantly in Time 3. For fears of compassion, fears of self-compassion reduced over time, fears of compassion for others showed more variation, reducing for the general public but increasing for health professionals, whilst fears of compassion from others did not change over time. Health professionals, those with compassion training, older adults, and women showed greater flows of compassion and lower fears of compassion compared with the general population, those without compassion training, younger adults, and men. These findings highlight that, in a period of shared suffering, people from multiple countries and nationalities show a cumulative improvement in compassion and reduction in fears of compassion, suggesting that, when there is intense suffering, people become more compassionate to self and others and less afraid of, and resistant to, compassion

Immunostimulation and Immunoinhibition of Premalignant Lesions

BACKGROUND: The immune reaction may be either stimulatory or inhibitory to tumor growth, depending upon the local ratio of immune reactants to tumor cells. HYPOTHESIS: A tumor-stimulatory immune response may be essential for survival of a neoplasm in vivo and for the biological progression from a premalignant lesion to a malignancy. Neither a positive nor a negative correlation between the magnitude of an immune-cell infiltrate and a cancer's prognosis can reveal whether the infiltrate was stimulating or inhibiting to the tumor's growth unless the position on the nonlinear curve that relates tumor growth to the magnitude of the immune reaction is known. DISCUSSION: This hypothesis is discussed in relation to the development of human malignant melanomas and colorectal cancers

Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease

<p>Abstract</p> <p>Background</p> <p>Mutations in the gene ATP7B cause Wilson disease, a copper storage disorder with a high phenotypic and genetic heterogeneity. We aimed to evaluate whether 'severe' protein-truncating ATP7B mutations (SMs) are associated with low serum ceruloplasmin oxidase activities and an early age of onset when compared to missense mutations (MMs).</p> <p>Methods</p> <p>The clinical phenotype of 59 genetically confirmed WD patients was analyzed retrospectively. Serum ceruloplasmin was measured by its oxidase activity with <it>o</it>-dianisidine dihydrochloride as substrate and immunologically.</p> <p>Results</p> <p>Thirty-nine patients had two MMs, 15 had the genotype SM/MM, and 5 patients had two SMs on their ATP7B alleles. Enzymatic and immunologic serum ceruloplasmin levels differed significantly between the three groups (P < 0.001 and P < 0.01, respectively). The lowest levels were measured in patients with two SMs (0.0 U/L; IQR, 0.0-0.0 U/L and 0.02 g/L; IQR, 0.01-0.02 g/L, respectively) and the highest in patients with two MMs (17.8 U/L; IQR, 5.8-35.1 U/L and 0.11 g/L; IQR,0.10-0.17 g/L, respectively). The age of onset was also significantly different between the three patient groups (P < 0.05), with SM/SM patients showing the earliest onset (13 years; IQR, 9-13 years) and patients with two MMs showing the latest onset (22 years; IQR, 14-27 years). By ROC curve analysis a ceruloplasmin oxidase level ≤ 5 U/L can predict the presence of at least one SM with a sensitivity of 80% and a specificity of 79.5%.</p> <p>Conclusions</p> <p>In our German study cohort truncating ATP7B mutations were associated with lower ceruloplasmin serum oxidase levels and an earlier age of onset when compared to MMs. Measurement of serum ceruloplasmin oxidase might help to predict presence of truncating ATP7B mutations and might facilitate the mutation analysis.</p

Catalogue of BRITE-Constellation targets I. Fields 1 to 14 (November 2013 - April 2016)

The BRIght Target Explorer (BRITE) mission collects photometric time series in two passbands aiming to investigate stellar structure and evolution. Since their launches in the years 2013 and 2014, the constellation of five BRITE nano-satellites has observed a total of more than 700 individual bright stars in 64 fields. Some targets have been observed multiple times. Thus, the total time base of the data sets acquired for those stars can be as long as nine years. Our aim is to provide a complete description of ready-to-use BRITE data, to show the scientific potential of the BRITE-Constellation data by identifying the most interesting targets, and to demonstrate and encourage how scientists can use these data in their research. We apply a decorrelation process to the automatically reduced BRITE-Constellation data to correct for instrumental effects. We perform a statistical analysis of the light curves obtained for the 300 stars observed in the first 14 fields during the first ~2.5 years of the mission. We also perform cross-identification with the International Variable Star Index. We present the data obtained by the BRITE-Constellation mission in the first 14 fields it observed from November 2013 to April 2016. We also describe the properties of the data for these fields and the 300 stars observed in them. Using these data, we detected variability in 64% of the presented sample of stars. Sixty-four stars or 21.3% of the sample have not yet been identified as variable in the literature and their data have not been analysed in detail. They can therefore provide valuable scientific material for further research. All data are made publicly available through the BRITE Public Data Archive and the Canadian Astronomy Data Centre.Comment: accepted by Astronomy & Astrophysics, 13 pages main text, 22 pages of appendi

A clustering of heterozygous missense variants in the crucial chromatin modifier WDR5 defines a new neurodevelopmental disorder

WDR5 is a broadly studied, highly conserved key protein involved in a wide array of biological functions. Among these functions, WDR5 is a part of several protein complexes that affect gene regulation via post-translational modification of histones. We collected data from 11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals, and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (N=11), intellectual disability (N=9), epilepsy (N=7) and autism spectrum disorder (N=4). Additional phenotypic features included abnormal growth parameters (N=7), heart anomalies (N=2) and hearing loss (N=2). Three-dimensional protein structures indicate that all the residues affected by these variants are located at the surface of one side of the WDR5 protein. It is predicted that five out of the six amino acid substitutions disrupt interactions of WDR5 with RbBP5 and/or KMT2A/C, as part of the COMPASS (complex proteins associated with Set1) family complexes. Our experimental approaches in Drosophila melanogaster and human cell lines show normal protein expression, localization and protein-protein interactions for all tested variants. These results, together with the clustering of variants in a specific region of WDR5 and the absence of truncating variants so far, suggest that dominant-negative or gain-of-function mechanisms might be at play. All in all, we define a neurodevelopmental disorder associated with missense variants in WDR5 and a broad range of features. This finding highlights the important role of genes encoding COMPASS family proteins in neurodevelopmental disorders

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems