Trauma and PTSD symptoms: Does spiritual struggle mediate the link?

Because exposure to potentially traumatic events is common (Kessler, Sonnega, Bromet, & Hughes, 1995), the mechanisms through which posttraumatic stress disorder (PTSD) symptoms develop is a critical area of investigation (Ozer, Best, Lipsey, & Weiss, 2003). Among the mechanisms that may predict PTSD symptoms is spiritual struggle, a set of negative religious cognitions related to understanding or responding to stressful events. Although prominent theories emphasize cognitive factors in the development and maintenance of PTSD symptoms, they have not explicitly addressed spiritual struggle. The present prospective study tested the role of spiritual struggle in the development and maintenance of PTSD symptoms following trauma. We assessed exposure to trauma and nontrauma events during the first year of college, spiritual struggle due to the most stressful event, and PTSD symptoms resulting from the index event. Spiritual struggle partially mediated the relationship between trauma and PTSD symptoms. We found interesting that some individual subscales of spiritual struggle (specifically, Punishing God Reappraisal, Reappraisal of God's Powers, and Spiritual Discontent) partially mediated the relationship between trauma and PTSD symptoms; however, reappraisal of the event to evil forces did not relate to PTSD symptoms. These results suggest that spiritual struggle is an important cognitive mechanism for many trauma victims and may have relevance for cognitive therapy for PTSD

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Is it better to Struggle and Resolve than to never Struggle at All? The Course and Consequences of Resolving Spiritual Struggles

Extensive psychological research has associated spiritual struggle with negative outcomes, including depression, post-traumatic distress, suicidality, and mortality. Yet other research has linked it with positive outcomes, such as personal and spiritual growth, less prejudice, greater compassion, and increased religious tolerance. Furthermore, religious and developmental theorists posit that spiritual struggle is essential to value development and life adjustment, as rigid systems are replaced by flexible ones. The paradox of struggle being associated with negative outcomes but linked to spiritual and personal growth raises the question: what distinguishes healthy or productive spiritual struggle from maladaptive struggle? The current study hypothesizes that struggle can be beneficial if it is resolved over time: by integrating benevolent views of a higher power, increasing psychological closure, and finding meaning in questioning. It is this productive struggle that exercises a “spiritual muscle,” developing psychosocial resources and forging a stronger and more flexible spirituality. The study empirically tests correlates of spiritual struggle and outcomes of resolution of struggle over time in response to a writing paradigm (versus a control condition). Spiritual struggle was assessed with multiple measures to capture the multidimensionality of this construct. At baseline, participants were asked to identify an open, negative event, respond to questionnaires, and write over three days. At the first follow-up resolution of struggle and event-related closure were assessed. At the final follow-up, extent of resilient response to a subsequent stressor was assessed in terms of distress response, use of positive coping methods, meaning violations, and spiritual struggle. Additional general, non-event-specific outcomes were measured as well. Repeated-measures analysis of variance was used to assess changes in spiritual struggle and outcomes, and structural equation modeling of latent growth curves was used to analyze the trajectory of struggle and the relationships between resolution and outcomes. Results indicated that measures of struggle, except quest, were cross-sectionally associated with negative outcomes, particularly at follow-ups. Spiritual struggle decreased over time and closure increased for both the struggle intervention and control groups. Finally, resolved spiritual struggle, although largely unrelated to outcomes, predicted some aspects of resilient response to a subsequent stressor and greater meaning in life

Table to accompany Religion/Spirituality and Change in Meaning after Bereavement: Qualitative Evidence for the Meaning Making Model

This table accompanies the manuscript entitled Religion/Spirituality and Change in Meaning after Bereavement: Qualitative Evidence for the Meaning Making Model by Wortmann & Park (2009). The table summarizes the sample characteristics for published, qualitative studies that describe the involvement of religion/spirituality in adjustment after bereavement. Fields include author(s)\u27s last name, publication year, population characteristics and sample size, study design, age of the bereaved, type or cause of death, and time post-loss

Table to accompany Religion and Spirituality in Adjustment Following Bereavement: An Integrative Review

This table accompanies the article entitled Religion and Spirituality in Adjustment Following Bereavement: An Integrative Review, (Wortmann & Park, 2008). The table summarizes the results of published studies that contain a quantitative assessment of religion and an adjustment outcome in bereaved participants. Fields include author(s)\u27s last name, publication year, sample characteristics, independent religious/spiritual variable, adjustment variable, results, and study design

FGFR inhibition in endometrial cancer induces caspase-independent cell death that can be augmented with ABT-737

Endometrial cancer (EC) is the most commonly diagnosed malignancy of the female reproductive tract. Unfortunately, 15-20% of women demonstrate persistent or recurrent tumors that are refractory to current chemotherapies with an associated poor prognosis. Our laboratory identified activating mutations in Fibroblast Growth Factor Receptor 2 (FGFR2) in 12% (stage I/II) to 17% (stage III/IV) endometrioid endometrial tumors and have since shown in a large (n=970) multi-institutional cohort they are associated with shorter progression free and cancer specific survival. Although FGFR inhibitors are in clinical trials in several cancer types, no detailed study of the mechanism of cell death has been published. We now show that treatment with BGJ398, AZD4547 and PD173074 leads to the induction of mitochondrial depolarization and changes in metabolic flux in two endometrial cancer cell lines (JHUEM2 and AN3CA) carrying activating mutations (C383R and N550K respectively). Despite this mitochondrial dysfunction, we have convincingly shown that the cell death following FGFR inhibition was caspase-independent, as evidenced by the lack of caspase-3, -7, and -9 activation, absence of PARP cleavage, and the inability of the broad-spectrum caspase inhibitor, Z-VAD-FMK, to prevent cell death. Knockdown of EndoG and AIF, common mediators of caspase-independent death, had no effect. Detailed quantification of LC3 positive puncta shows an increase in autophagy in JHUEM2 and AN3CA cells treated with all FGFR inhibitors. Knockdown of ATG3, ATG7 and ATG12 resulted in a slight increase in Annexin positive cell death indicating that the autophagy was cytoprotective in this context. We have now confirmed this novel caspase-independent cell death is mitochondrial dependent as it can be blocked by overexpression of Bcl-2 and/or Bcl-XL. Importantly we have shown that the combination of FGFR inhibitors with the BH3 mimetic ABT737 can markedly augment this caspase-independent cell death which may have implications for the design of more effective clinical trials

Debunking the myth of wool allergy:Reviewing the evidence for immune and non-immune cutaneous reactions

Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30–32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.Full Tex