Unresolved grief and its consequences. A nationwide follow-up of teenage loss of a parent to cancer 6-9 years earlier.

PURPOSE: The early loss of a parent is a tragedy and a serious life event. This study investigated grief resolution and morbidity in cancer-bereaved teenagers 6 to 9 years after the loss of a parent to cancer. METHODS: In a nationwide population-based study of 622 of 851 (73 %) youths who as teenagers 6 to 9 years earlier had lost a parent to cancer, we explored the magnitude of unresolved grief and its association with psychological and physiological morbidity. Participants answered a study-specific anonymous questionnaire including questions about if they had worked through their grief and about their current health. RESULTS: Six to nine years post-loss 49 % reported unresolved grief (8 % no and 41 % a little grief resolution). They had, in comparison with youths reporting resolved grief, statistically significantly elevated risks, e.g. for insomnia (sons' relative risk (RR) 2.3, 95 % CI 1.3-4.0; daughters' RR 1.7, 95 % CI 1.1-2.7), fatigue (sons' RR 1.8, 95 % CI 1.3-2.5; daughters' RR 1.4, 95 % CI 1.1-1.7) and moderate to severe depression, i.e. score >9, PHQ-9 (sons' RR 3.6, 95 % CI 1.4-8.8; daughters' RR 1.8, 95 % CI 1.1-3.1). Associations remained for insomnia in sons, exhaustion in daughters and fatigue in both sons and daughters when depression, negative intrusive thoughts and avoiding reminders of the parents' disease or death were included in a model. CONCLUSIONS: Approximately half of cancer-bereaved youth report no or little grief resolution 6 to 9 years post-loss, which is associated with fatigue, sleeping problems and depressive symptoms

Model of brain maintenance reveals specific change-change association between medial-temporal lobe integrity and episodic memory

Brain maintenance has been identified as a major determinant of successful memory aging. However, the extent to which brain maintenance in support of successful memory aging is specific to memory-related brain regions or forms part of a brain-wide phenomenon is unresolved. Here, we used longitudinal brain-wide gray matter MRI volumes in 262 healthy participants aged 55 to 80 years at baseline to investigate separable dimensions of brain atrophy, and explored the links of these dimensions to different dimensions of cognitive change. We statistically adjusted for common causes of change in both brain and cognition to reveal a potentially unique signature of brain maintenance related to successful memory aging. Critically, medial temporal lobe (MTL)/hippocampal change and episodic memory change were characterized by unique, residual variance beyond general factors of change in brain and cognition, and a reliable association between these two residualized variables was established (r = 0.36, p < 0.01). The present study is the first to provide solid evidence for a specific association between changes in (MTL)/hippocampus and episodic memory in normal human aging. We conclude that hippocampus-specific brain maintenance relates to the specific preservation of episodic memory in old age, in line with the notion that brain maintenance operates at both general and domain-specific levels

Longitudinal dopamine D2 receptor changes and cerebrovascular health in aging

BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis

Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. CFS were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.Comment: 18 pages, accepted for publication in BMC Bioinformatic

A multidisciplinary, multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture

INTRODUCTION: This study evaluates whether a postoperative multidisciplinary, intervention program, including systematic assessment and treatment of fall risk factors, active prevention, detection, and treatment of postoperative complications, could reduce inpatient falls and fall-related injuries after a femoral neck fracture. METHODS: A randomized, controlled trial at the orthopedic and geriatric departments at Umeå University Hospital, Sweden, included 199 patients with femoral neck fracture, aged  ≥70 years. RESULTS: Twelve patients fell 18 times in the intervention group compared with 26 patients suffering 60 falls in the control group. Only one patient with dementia fell in the intervention group compared with 11 in the control group. The crude postoperative fall incidence rate was 6.29/1,000 days in the intervention group vs 16.28/1,000 days in the control group. The incidence rate ratio was 0.38 [95% confidence interval (CI): 0.20 – 0.76, p = 0.006] for the total sample and 0.07 (95% CI: 0.01–0.57, p=0.013) among patients with dementia. There were no new fractures in the intervention group but four in the control group. CONCLUSION: A team applying comprehensive geriatric assessment and rehabilitation, including prevention, detection, and treatment of fall risk factors, can successfully prevent inpatient falls and injuries, even in patients with dementia

Individual Exposure to NO2 in Relation to Spatial and Temporal Exposure Indices in Stockholm, Sweden: The INDEX Study

Epidemiology studies of health effects from air pollution, as well as impact assessments, typically rely on ambient monitoring data or modelled residential levels. The relationship between these and personal exposure is not clear. To investigate personal exposure to NO2 and its relationship with other exposure metrics and time-activity patterns in a randomly selected sample of healthy working adults (20–59 years) living and working in Stockholm. Personal exposure to NO2 was measured with diffusive samplers in sample of 247 individuals. The 7-day average personal exposure was 14.3 µg/m3 and 12.5 µg/m3 for the study population and the inhabitants of Stockholm County, respectively. The personal exposure was significantly lower than the urban background level (20.3 µg/m3). In the univariate analyses the most influential determinants of individual exposure were long-term high-resolution dispersion-modelled levels of NO2 outdoors at home and work, and concurrent NO2 levels measured at a rural location, difference between those measured at an urban background and rural location and difference between those measured in busy street and at an urban background location, explaining 20, 16, 1, 2 and 4% (R2) of the 7-day personal NO2 variation, respectively. A regression model including these variables explained 38% of the variation in personal NO2 exposure. We found a small improvement by adding time-activity variables to the latter model (R2 = 0.44). The results adds credibility primarily to long-term epidemiology studies that utilise long-term indices of NO2 exposure at home or work, but also indicates that such studies may still suffer from exposure misclassification and dilution of any true effects. In contrast, urban background levels of NO2 are poorly related to individual exposure

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

PurposeThe two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.MethodsIn total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.ResultsTumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.ConclusionTumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.</div