Maternal microchimerism in the livers of patients with Biliary atresia

BACKGROUND: Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA. METHODS: Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM. RESULTS: By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2–4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1–142 copies of maternal DNA per 25,000 copies of patients DNA was found. CONCLUSIONS: Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA

The Nature of Attachment Relationships and Grief Responses in Older Adults: An Attachment Path Model of Grief

BACKGROUND: Various researchers have theorized that bereaved adults who report non-secure attachment are at higher risk of pathological grief. Yet past findings on avoidant attachment representations and grief have yielded limited and contradictory outcomes. Little research has been conducted with older adults to identify the psychological processes that mediate between self-reported attachment representations and the patterns of grief. OBJECTIVE: To examine the impacts of avoidant attachment and anxious attachment dimensions on emotion and non-acceptance, in response to the loss of a conjugal partner, and the mediating effect of yearning thoughts. DESIGN: Men (N = 21) and women (N = 68) aged 60 years and above who had lost a partner within the last 12 to 72 months were invited to participate. Participants rated their levels of yearning thoughts about the deceased, emotions and non-acceptance on the Texas Revised Inventory of Grief (TRIG-Present), and their type and level of general romantic attachment on the Experiences In Close Relationship questionnaire (ECR). RESULTS: Structural equation modelling (SEM) indicated that individuals who reported higher levels of avoidant attachment reported less emotional responses and less non-acceptance. SEM also showed that individuals who reported higher levels of anxious attachment reported greater emotional responses and greater non-acceptance. SEM further indicated that these relationships were mediated by yearning thoughts. CONCLUSION: People adopt different grief coping patterns according to their self-reported attachment representations, with the nature of their yearning thoughts influencing the process. Grief therapy may be organized according to individual differences in attachment representations

Systematic review of surgical interventions for Crohn's anal fistula

Background Anal fistula occurs in approximately one in three patients with Crohn's disease and is typically managed through a multimodal approach. The optimal surgical therapy is not yet clear. The aim of this systematic review was to identify and assess the literature on surgical treatments of Crohn's anal fistula. Methods A systematic review was conducted that analysed studies relating to surgical treatment of Crohn's anal fistula published on MEDLINE, Embase and Cochrane databases between January 1995 and March 2016. Studies reporting specific outcomes of patients treated for Crohn's anal fistula were included. The primary outcome was fistula healing rate. Bias was assessed using the Cochrane ROBINS‐I and ROB tool as appropriate. Results A total of 1628 citations were reviewed. Sixty‐three studies comprising 1584 patients were ultimately selected in the analyses. There was extensive reporting on the use of setons, advancement flaps and fistula plugs. Randomized trials were available only for stem cells and fistula plugs. There was inconsistency in outcome measures across studies, and a high degree of bias was noted. Conclusion Data describing surgical intervention for Crohn's anal fistula are heterogeneous with a high degree of bias. There is a clear need for standardization of outcomes and description of study cohorts for better understanding of treatment options

HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing

Mammals have evolved many antiviral factors impacting different steps of the viral life cycle. Associated with chromatin-modifying enzymes, the cellular cofactor CTIP2 contributes to HIV-1 gene silencing in latently infected reservoirs that constitute the major block toward an HIV cure. We report, for the first time, that the virus has developed a strategy to overcome this major transcriptional block. Productive HIV-1 infection results in a Vpr-mediated depletion of CTIP2 in microglial cells and CD4+ T cells, two of the major viral reservoirs. Associated to the Cul4A-DDB1-DCAF1 ubiquitin ligase complex, Vpr promotes CTIP2 degradation via the proteasome pathway in the nuclei of target cells and notably at the latent HIV-1 promoter. Importantly, Vpr targets CTIP2 associated with heterochromatin-promoting enzymes dedicated to HIV-1 gene silencing. Thereby, Vpr reactivates HIV-1 expression in a microglial model of HIV-1 latency. Altogether our results suggest that HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Electrochemical deposition of zeolitic imidazolate framework electrode coatings for supercapacitor electrodes

Zn and Co electrodes have been successfully coated with five different zeolitic imidazolate frameworks ZIFs (ZIF-4, ZIF-7, ZIF-8, ZIF-14 and ZIF-67) via the anodic dissolution method. Careful control of the reaction conditions allows for electrode coating growth; in contrast to previous reports of electrochemical ZIF growth, which have not succeeded in obtaining ZIF electrode coatings. Coating crystallinity is also shown to be heavily dependent upon reaction conditions, with amorphous rather than crystalline material generated at shorter reaction times and lower linker concentrations. Electrochemical applications for ZIF-coated electrodes are highlighted with the observation of an areal capacitance of 10.45 mF cm−2 at 0.01 V s−1 for additive-free ZIF-67 coated Co electrodes. This is superior to many reported metal organic framework (MOF)/graphene composites and to capacitance values previously reported for additive-free MOFs

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Butyrate Attenuates Lipopolysaccharide-Induced Inflammation in Intestinal Cells and Crohn's Mucosa through Modulation of Antioxidant Defense Machinery

Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CrD). High levels of Reactive Oxygen Species (ROS) induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB), which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia Coli (EC-LPS) in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2) mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa

Psychological well-being in Europe after the outbreak of war in Ukraine

The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences

A global experience-sampling method study of well-being during times of crisis : The CoCo project

We present a global experience-sampling method (ESM) study aimed at describing, predicting, and understanding individual differences in well-being during times of crisis such as the COVID-19 pandemic. This international ESM study is a collaborative effort of over 60 interdisciplinary researchers from around the world in the “Coping with Corona” (CoCo) project. The study comprises trait-, state-, and daily-level data of 7490 participants from over 20 countries (total ESM measurements = 207,263; total daily measurements = 73,295) collected between October 2021 and August 2022. We provide a brief overview of the theoretical background and aims of the study, present the applied methods (including a description of the study design, data collection procedures, data cleaning, and final sample), and discuss exemplary research questions to which these data can be applied. We end by inviting collaborations on the CoCo dataset