Cyclic Deposition of Calcium Salts During Growth of Cholesterol Gallstones

Some cholesterol gallstones contain darkly pigmented centers or peripheral concentric pigmented bands. We examined the cross-sectional surface of three cholesterol gallstones which contained both central and peripheral pigmented areas with electron-probe microanalysis (EPM) and energy dispersive x-ray microanalysis (EDXA) to determine the elemental composition of the pigmented regions. Linear EPM across the cross-sectional surface of the stones demonstrated that most of the pigmented regions of all three stones had high Ca and P signals; the nonpigmented intervening areas had markedly lower or no detectable Ca and P signals. In two of the three stones, high O signals coincided with the high Ca and P signals suggesting that both calcium bilirubinate and calcium phosphate were present in these pigmented areas. EDXA of the central and peripheral pigmented areas of each stone confirmed the presence of a high Ca signal. Our results demonstrate that in some cholesterol gallstones there is cyclic deposition of calcium bilirubinate and other calcium salts

Prosocial video game as an intimate partner violence prevention tool among youth: A randomised controlled trial

Evidence demonstrates that exposure to prosocial video games can increase players’ prosocial behaviour, prosocial thoughts, and empathic responses. Prosocial gaming has also been used to reduce gender-based violence among young people, but the use of video games to this end as well as evaluations of their effectiveness are rare. The objective of this study was to assess the effectiveness of a context-specific, prosocial video game, Jesse, in increasing affective and cognitive responsiveness (empathy) towards victims of intimate partner violence (IPV) among children and adolescents (N = 172, age range 9 – 17 years, M = 12.27, SD = 2.26). A randomised controlled trial was conducted in seven schools in Barbados. Participants were randomly assigned to an experimental (prosocial video game) or control (standard school curriculum) condition. Experimental and control group enrolled 86 participants each. Girls and boys in the experimental condition, but not their counterparts in the control condition, recorded a significant increase in affective responsiveness after intervention. This change was sustained one week after game exposure. No significant effects were recorded for cognitive responsiveness. Findings suggest that Jesse is a promising new IPV prevention tool among girls and boys, which can be used in educational settings

Immune response to COVID‐19 vaccination in patients with Waldenström macroglobulinaemia who pause their BTKi therapy

Patients with Waldenström macroglobulinaemia (WM) are at increased risk of severe COVID-19 infection and have poor immune responses to COVID-19 vaccination. This study assessed whether a closely monitored pause in Bruton's Tyrosine Kinase inhibitor (BTKi) therapy might result in an improved humoral response to a 3rd COVID-19 vaccine dose. Improved response was observed in WM patients who paused their BTKi, compared to a group who did not pause their BTKi. However, the response was attenuated after BTKi recommencement. This data contributes to our understanding of vaccination strategies in this patient group and may help inform consensus approaches in the future

Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output

Growth factor receptor levels are aberrantly high in diverse cancers, driving the proliferation and survival of tumor cells. Understanding the molecular basis for this aberrant elevation has profound clinical implications. Here we show that the pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) suppresses receptor tyrosine kinase (RTK) signaling output by a previously unidentified epigenetic mechanism unrelated to its previously described function as the hydrophobic motif phosphatase for the protein kinase AKT, protein kinase C, and S6 kinase. Specifically, we show that nuclear-localized PHLPP suppresses histone phosphorylation and acetylation, in turn suppressing the transcription of diverse growth factor receptors, including the EGF receptor. These data uncover a much broader role for PHLPP in regulation of growth factor signaling beyond its direct inactivation of AKT: By suppressing RTK levels, PHLPP dampens the downstream signaling output of two major oncogenic pathways, the PI3 kinase/AKT and the Rat sarcoma (RAS)/ERK pathways. Our data are consistent with a model in which PHLPP modifies the histone code to control the transcription of RTKs

Updated Safety And Efficacy Data In The Phase 1 Trial Of Patients With Mantle Cell Lymphoma (Mcl) Treated With Bruton Tyrosine Kinase (Btk) Inhibitor Zanubrutinib (Bgb‐3111)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149513/1/hon55_2630.pd

A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management

In a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS-HGNET-MN1 cases. Whole genome sequencing however identified a novel MN1-GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1-PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours

Stress exposure and sensitivity in the clinical high-risk syndrome: Initial findings from the North American Prodrome Longitudinal Study (NAPLS)

There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with age, (3) baseline self-reported stress is associated with follow-up clinical status, and (4) there is a sensitization effect of LE on the response to DH. In contrast to some previous research, the present findings indicate that the CHR group (N = 314) reported exposure to more LE when compared to the HC group (N= 162). As predicted, CHR participants rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted. There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current DH as more stressful. The results indicate that the prodromal phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors. (C) 2014 Elsevier B.V. All rights reserved