Hyperosmosis enhances radiation and hydroxyurea resistance of Schizosaccharomyces pombe checkpoint mutants through the spindle checkpoint and delayed cytokinesis

The DNA damage and stress response pathways interact to regulate cellular responses to genotoxins and environmental stresses. How these pathways interact in Schizosaccharomyces pombe is not well understood. We demonstrate that osmotic stress suppresses the DNA damage sensitivity of checkpoint mutants, and that this occurs through three distinct cell cycle delays. A delay in G2/M is dependent on Srk1. Progression through mitosis is halted by the Mad2‐dependent spindle checkpoint. Finally, cytokinesis is impaired by modulating Cdc25 expression. These three delays, imposed by osmotic stress, together compensate for the loss of checkpoint signalling.     

Internet and Computer-Based Cognitive Behavioral Therapy for Anxiety and Depression in Youth: A Meta-Analysis of Randomized Controlled Outcome Trials

Background

Anxiety and depression in children and adolescents are undertreated. Computer- and Internet-based cognitive behavioral treatments (cCBT) may be an attractive treatment alternative to regular face-to-face treatment.This meta-analysis aims to evaluate whether cCBT is effective for treating symptoms of anxiety and depression in youth.

Methods and Findings

We conducted systematic searches in bibliographical databases (Pubmed, Cochrane controlled trial register, PsychInfo) up to December 4, 2013. Only randomized controlled trials in which a computer-, Internet- or mobile-based cognitive behavioral intervention targeting either depression, anxiety or both in children or adolescents up to the age of 25 were compared to a control condition were selected. We employed a random-effects pooling model in overall effect analyses and a mixed effect model for sub-group analyses. Searches resulted in identifying 13 randomized trials, including 796 children and adolescents that met inclusion criteria. Seven studies were directed at treating anxiety, four studies at depression, and two were of a transdiagnostic nature, targeting both anxiety and depression. The overall mean effect size (Hedges’ g) of cCBT on symptoms of anxiety or depression at post-test was g=0.72 (95% CI:0.55-0.90, numbers needed to be treated (NNT)=2.56). Heterogeneity was low (I²=20.14%, 95% CI: 0-58%). The superiority of cCBT over controls was evident for interventions targeting anxiety (g=0.68; 95% CI: 0.45-0.92; p < .001; NNT=2.70) and for interventions targeting depression (g=0.76; 95% CI: 0.41-0.12; p < .001; NNT=2.44) as well as for transdiagnostic interventions (g=0.94; 95% CI: 0.23-2.66; p < .001; NNT=2.60).

Conclusions

Results provide evidence for the efficacy of cCBT in the treatment of anxiety and depressive symptoms in youth. Hence, such interventions may be a promising treatment alternative when evidence based face-to-face treatment is not feasible. Future studies should examine long-term effects of treatments and should focus on obtaining patient-level data from existing studies, to perform an individual patient data meta-analysis.     

Association between Perivascular Spaces and Progression of White Matter Hyperintensities in Lacunar Stroke Patients

Objectives

Perivascular spaces are associated with MRI markers of cerebral small vessel disease, including white matter hyperintensities. Although perivascular spaces are considered to be an early MRI marker of cerebral small vessel disease, it is unknown whether they are associated with further progression of MRI markers, especially white matter hyperintensities. We determined the association between perivascular spaces and progression of white matter hyperintensities after 2-year follow-up in lacunar stroke patients.

Methods

In 118 lacunar stroke patients we obtained brain MRI and 24-hour ambulatory blood pressure measurements at baseline, and a follow-up brain MRI 2 years later. We visually graded perivascular spaces and white matter hyperintensities at baseline. Progression of white matter hyperintensities was assessed using a visual white matter hyperintensity change scale. Associations with white matter hyperintensity progression were tested with binary logistic regression analysis.

Results

Extensive basal ganglia perivascular spaces were associated with progression of white matter hyperintensities (OR 4.29; 95% CI: 1.28–14.32; p<0.05), after adjustment for age, gender, 24-hour blood pressure and vascular risk factors. This association lost significance after additional adjustment for baseline white matter hyperintensities. Centrum semiovale perivascular spaces were not associated with progression of white matter hyperintensities.

Conclusions

Our study shows that extensive basal ganglia perivascular spaces are associated with progression of white matter hyperintensities in cerebral small vessel disease. However, this association was not independent of baseline white matter hyperintensities. Therefore, presence of white matter hyperintensities at baseline remains an important determinant of further progression of white matter hyperintensities in cerebral small vessel disease.     

Effectiveness of an Internet Intervention for Family Caregivers of People with Dementia: Results of a Randomized Controlled Trial

BackgroundThe World Health Organization stresses the importance of accessible and (cost)effective caregiver support, given the expected increase in the number of people with dementia and the detrimental impact on the mental health of family caregivers.MethodsThis study assessed the effectiveness of the Internet intervention ‘Mastery over Dementia’. In a RCT, 251 caregivers, of whom six were lost at baseline, were randomly assigned to two groups. Caregivers in the experimental group (N = 149) were compared to caregivers who received a minimal intervention consisting of e-bulletins (N = 96). Outcomes were symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (Hospital Anxiety and Depression Scale: HADS-A). All data were collected via the Internet, and an intention-to-treat analysis was carried out.ResultsAlmost all caregivers were spouses or children (in-law). They were predominantly female and lived with the care recipient in the same household. Age of the caregivers varied from 26 to 87 years. Level of education varied from primary school to university, with almost half of them holding a bachelor’s degree or higher. Regression analyses showed that caregivers in the experimental group showed significantly lower symptoms of depression (p = .034) and anxiety (p = .007) post intervention after adjustment for baseline differences in the primary outcome scores and the functional status of the patients with dementia. Effect sizes were moderate for symptoms of anxiety (.48) and small for depressive symptoms (.26).ConclusionsThe Internet course ‘Mastery over Dementia’ offers an effective treatment for family caregivers of people with dementia reducing symptoms of depression and anxiety. The results of this study justify further development of Internet interventions for family caregivers of people with dementia and suggest that such interventions are promising for keeping support for family caregivers accessible and affordable. The findings are even more promising because future generations of family caregivers will be more familiar with the Internet.

Trial Registration

Dutch Trial Register NTR-2051 www.trialregister.nl/trialreg/admin/rctview.asp?TC=2051     

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.     

Pretransplant HRCT Characteristics Are Associated with Worse Outcome of Lung Transplantation for Cystic Fibrosis Patients

Objectives

Peri- and postoperative complications diminish the outcome of lung transplantation (LTx) in patients with cystic fibrosis (CF). We hypothesized that the degree of pathological findings on pre-LTx high resolution computed tomography (HRCT) is associated with higher morbidity and mortality in CF.

Methods

All our CF patients undergoing LTx between 2001 and 2011 were included. HRCT examinations were evaluated according to a scoring system for pulmonary disease in CF patients, the Severe Advanced Lung Disease (SALD) score and for pleural involvement.

Results

Fifty-three patients were included. Dominant infectious/inflammatory disease according to the SALD score was observed in 10 patients (19%). Five (50%) of those patients died within one week after LTx, compared to 2 (5%) patients without dominant infectious/inflammatory disease (p<0.001). This difference in survival percentage remained also significant in multivariate analysis. Patients with infectious/inflammatory disease received more packed red blood cells; 26 versus 8 in the first week (p<0.001). Pleural thickening was associated with higher requirement (10 units) for blood transfusion during LTx, compared to patients with normal pleura (4 units).

Conclusions

The analysis of HRCT in CF patients according to the SALD score showed that dominant infectious/inflammatory disease is associated with a higher mortality after LTx. If confirmed in other studies, HRCT might aid estimation of surgical risk in some adult CF patients.