Search

Objective: The study aims to investigate factors that prevent burnout (BO) and symptoms of posttraumatic stress disorder (PTSD) while facilitating posttraumatic growth (PTG) among nurses combating the coronavirus disease 2019 (COVID-19) pandemic, with the purpose of validating the mediating effects of PTG., Methods: A total of 247 nurses who provided patient care during the COVID-19 pandemic were enrolled, and a questionnaire was used to measure BO, PTSD, and PTG, data on deliberate rumination, emotional expression, adaptive cognitive emotion regulation (CER), maladaptive CER, and social support. The mediation path models for the effects of the predictors on BO and PS through the mediation of PTG were analyzed using the R Lavaan package., Results: The results showed that deliberate rumination, emotional expression, and adaptive CER significantly increased PTG, while PTG significantly reduced BO and PTSD symptoms (PSs). However, maladaptive CER did not have a significant effect on PTG and only had significant direct effects on BO and PS. Bootstrapping confirmed that PTG significantly mediated the effects of all predictors. It partially mediated the effects of deliberate rumination and adaptive CER and completely mediated the effects of emotional expression., Conclusion: Based on the results, it has been supported that deliberate rumination, emotional expression, and adaptive CER should be addressed as important variables in psychological interventions addressing nurses' adversities during the pandemic. These variables can prevent BO and PS by facilitating PTG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sim, Cha and Im.)

Introduction: In the context of the COVID-19 pandemic, which has led to complex psychological problems, it is important to examine the effect of coping flexibility and sense of community, because relying solely on specific coping strategies is ineffective, and the pandemic necessitates social cooperation., Methods: This study was divided into two parts. The first study used a quantitative research method(i.e., structural equation modeling) to test if coping flexibility and sense of community moderated the impact of COVID-19-related concerns on mental health (i.e., depression and anxiety) and posttraumatic growth among Korean college students. The second study used a qualitative research method for an in-depth examination of how Korean college students coped with the COVID-19 pandemic and if they achieved any positive change or growth. Given that the COVID-19 pandemic represents a situation distinct from what people have previously encountered, Study II was designed to examine the experiences of individuals during this exceptional period., Results: In the first study (Study I), coping flexibility was found to increase the impact of COVID-19-related concerns and difficulties on depression and anxiety. Conversely, a sense of community reduced the consequences of these overwhelming worries on depression and anxiety, while also expanding the impact of COVID-19-related disorders on posttraumatic growth. In the second study (Study II), the findings showed that the participants experienced various psychological consequences, including depression and anxiety, and distress in other aspects of their life, including disruptions in interpersonal relationships and college life. Nonetheless, the participants made efforts to cope with such difficulties and overcome the challenges together with the community. In fact, the pandemic improved their coping skills and expanded their value system and worldview., Conclusion: The study findings suggest that given the unique situation presented by the COVID-19 pandemic, a sense of community protected the mental well-being of Korean college students and facilitated their growth. This study emphasizes the necessity of promoting SOC to effectively cope with disaster situations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sim and Im.)

Objective: To determine the molecular basis of a severe neurologic disorder in a large consanguineous family with complete agenesis of the corpus callosum (ACC), pontocerebellar hypoplasia (PCH), and peripheral axonal neuropathy., Methods: Assessment included clinical evaluation, neuroimaging, and nerve conduction studies (NCSs). Linkage analysis used genotypes from 7 family members, and the exome of 3 affected siblings was sequenced. Molecular analyses used Sanger sequencing to perform segregation studies and cohort analysis and Western blot of patient-derived cells., Results: Affected family members presented with postnatal microcephaly and profound developmental delay, with early death in 3. Neuroimaging, including a fetal MRI at 30 weeks, showed complete ACC and PCH. Clinical evaluation showed areflexia, and NCSs revealed a severe axonal neuropathy in the 2 individuals available for electrophysiologic study. A novel homozygous stopgain mutation in adenosine monophosphate deaminase 2 (AMPD2) was identified within the linkage region on chromosome 1. Molecular analyses confirmed that the mutation segregated with disease and resulted in the loss of AMPD2. Subsequent screening of a cohort of 42 unrelated individuals with related imaging phenotypes did not reveal additional AMPD2 mutations., Conclusions: We describe a family with a novel stopgain mutation in AMPD2. We expand the phenotype recently described as PCH type 9 to include progressive postnatal microcephaly, complete ACC, and peripheral axonal neuropathy. Screening of additional individuals with related imaging phenotypes failed to identify mutations in AMPD2, suggesting that AMPD2 mutations are not a common cause of combined callosal and pontocerebellar defects.

Mutations in the gene encoding AT-rich interactive domain-containing protein 1B (ARID1B) were recently associated with multiple syndromes characterized by developmental delay and intellectual disability, in addition to nonsyndromic intellectual disability. While the majority of ARID1B mutations identified to date are predicted to result in haploinsufficiency, the underlying pathogenic mechanisms have yet to be fully understood. ARID1B is a DNA-binding subunit of the Brahma-associated factor chromatin remodelling complexes, which play a key role in the regulation of gene activity. The function of remodelling complexes can be regulated by their subunit composition, and there is some evidence that ARID1B is a component of the neuron-specific chromatin remodelling complex. This complex is involved in the regulation of stem/progenitor cells exiting the cell cycle and differentiating into postmitotic neurons. Recent research has indicated that alterations in the cell cycle contribute to the underlying pathogenesis of syndromes associated with ARID1B haploinsufficiency in fibroblasts derived from affected individuals. This review describes studies linking ARID1B to neurodevelopmental disorders and it summarizes the function of ARID1B to provide insights into the pathogenic mechanisms underlying ARID1B-mediated disorders. In conclusion, ARID1B is likely to play a key role in neurodevelopment and reduced levels of wild-type protein compromise normal brain development. Additional studies are required to determine the mechanisms by which impaired neural development contributes to the intellectual disability and speech impairment that are consistently observed in individuals with ARID1B haploinsufficiency.

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders., (Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism., Methods/results: High density microarray analysis of the patient demonstrated a heterozygous deletion at 6q25.3, which resulted in the loss of four genes including AT Rich Interactive Domain 1B (ARID1B). Subsequent quantitative real-time PCR analysis revealed ARID1B haploinsufficiency in the patient. Analysis of both patient-derived and ARID1B knockdown fibroblasts after serum starvation demonstrated delayed cell cycle re-entry associated with reduced cell number in the S1 phase. Based on the patient's distinctive phenotype, we ascertained four additional patients and identified heterozygous de novo ARID1B frameshift or nonsense mutations in all of them., Conclusions: This study broadens the spectrum of ARID1B associated phenotypes by describing a distinctive phenotype including plantar fat pads but lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris syndrome. We present the first direct evidence in patient-derived cells that alterations in cell cycle contribute to the underlying pathogenesis of syndromes associated with ARID1B haploinsufficiency.

Cadmium is known to exert toxic effects on multiple organs, including the testes. To determine if alpha-tocopherol, an antioxidant, could protect testicular tissues and spermatogenesis from the toxic effects of cadmium, six-week old male Sprague-Dawley rats were randomized to receive cadmium at doses of 0 (control), 1, 2, 4 or 8 mg/kg by the intraperitoneal route (Group A) or alpha-tocopherol for 5 days before being challenged with cadmium (Group B) in an identical dose-dependent manner. When both groups received cadmium at 1 mg/kg, there were no changes in testicular histology relative to controls. When Group A received cadmium at 2 mg/kg, undifferentiated spermatids and dead Sertoli cells increased in the seminiferous tubules while interstitial cells decreased and inflammatory cells increased in the interstitial tissues. On flow cytometric analysis, the numbers of elongated spermatids (M1) and round spermatids (M2) decreased while 2c stage cells (M3, diploid) increased. In contrast, when Group B received cadmium at 2 mg/kg, the histological insults were reduced and the distribution of the germ cell population remained comparable to controls. However, alpha-tocopherol had no protective effects with higher cadmium doses of 4 and 8 mg/kg. These findings indicate that alpha-tocopherol treatment can protect testicular tissue and preserve spermatogenesis from the detrimental effects of cadmium but its effectiveness is dependent on the dose of cadmium exposed.