Mesopic background lights enhance dark-adapted cone ERG flash responses in the intact mouse retina: a possible role for gap junctional decoupling

The cone-driven flash responses of mouse electroretinogram (ERG) increase as much as twofold over the course of several minutes during adaptation to a rod-compressing background light. The origins of this phenomenon were investigated in the present work by recording preflash-isolated (M-)cone flash responses ex vivo in darkness and during application of various steady background lights. In this protocol, the cone stimulating flash was preceded by a preflash that maintains rods under saturation (hyperpolarized) to allow selective stimulation of the cones at varying background light levels. The light-induced growth was found to represent true enhancement of cone flash responses with respect to their dark-adapted state. It developed within minutes, and its overall magnitude was a graded function of the background light intensity. The threshold intensity of cone response growth was observed with lights in the low mesopic luminance region, at which rod responses are partly compressed. Maximal effect was reached at intensities sufficient to suppress ～ 90% of the rod responses. Light-induced enhancement of the cone photoresponses was not sensitive to antagonists and agonists of glutamatergic transmission. However, applying gap junction blockers to the dark-adapted retina produced qualitatively similar changes in the cone flash responses as did background light and prevented further growth during subsequent light-adaptation. These results are consistent with the idea that cone ERG photoresponses are suppressed in the dark-adapted mouse retina by gap junctional coupling between rods and cones. This coupling would then be gradually and reversibly removed by mesopic background lights, allowing larger functional range for the cone light responses.     

Effort—reward imbalance,heart rate,and heart rate variability: the cardiovascular risk in young finns study

Background: Work stress indicated by effort—reward imbalance is hypothesized to cause autonomic arousal, which, if prolonged or frequent, could contribute to cardiovascular pathology. However, only limited empirical evidence on this mechanism is available. Purpose: This study examined associations between effort-reward imbalance, heart rate (HR), and heart rate variability (HRV). Method: The participants were 457 women and 406 men (mean age 32.3 years) derived from the population-based Young Finns Study. Effort—reward imbalance was defined as the ratio between effort and reward, higher efforts compared to rewards indicating greater imbalance. Results: In age-adjusted regression models, higher effort-reward imbalance was associated with lower HRV, and lower reward was associated with higher HR among women. These associations were not attenuated after additional adjustments for demographic characteristics and coronary risk factors. No significant associations of effort—reward imbalance or its components with HR and HRV were found in men. Conclusion: Our finding of lower HRV and higher HR in young healthy women with high effort—reward imbalance and low rewards provides evidence of a potential mechanism that may link effort-reward imbalance to the development of coronary heart disease (CHD) in women.     

Effects of spatial smoothing on functional brain networks

Graph‐theoretical methods have rapidly become a standard tool in studies of the structure and function of the human brain. Whereas the structural connectome can be fairly straightforwardly mapped onto a complex network, there are more degrees of freedom in constructing networks that represent functional connections between brain areas. For functional magnetic resonance imaging (fMRI) data, such networks are typically built by aggregating the blood‐oxygen‐level dependent signal time series of voxels into larger entities (such as Regions of Interest in some brain atlas) and determining their connection strengths from some measure of time‐series correlations. Although it is evident that the outcome must be affected by how the voxel‐level time series are treated at the preprocessing stage, there is a lack of systematic studies of the effects of preprocessing on network structure. Here, we focus on the effects of spatial smoothing, a standard preprocessing method for fMRI. We apply various levels of spatial smoothing to resting‐state fMRI data and measure the changes induced in functional networks. We show that the level of spatial smoothing clearly affects the degrees and other centrality measures of functional network nodes; these changes are non‐uniform, systematic, and depend on the geometry of the brain. The composition of the largest connected network component is also affected in a way that artificially increases the similarity of the networks of different subjects. Our conclusion is that wherever possible, spatial smoothing should be avoided when preprocessing fMRI data for network analysis.     

High-density lipoprotein cholesterol and longevity

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were studied in three groups: (1) 85 healthy subjects aged 85-89 years, (2) 62 patients without coronary artery disease aged 38-62 years, and (3) 323 patients aged 32-69 years with triple-vessel disease diagnosed by coronary angiography. The mean values for total cholesterol were significantly higher in patients with triple-vessel disease than in those without coronary artery disease and in the elderly. Total cholesterol was over 6.5 mmol/l in 32% of the elderly, in 31% of patients without coronary artery disease and in 42% of patients with triple-vessel disease, but these differences were not significant. HDL-cholesterol and the ratio of HDL/total cholesterol were significantly higher in the elderly than in the patients without coronary artery disease and patients with triple-vessel disease. Serum HDL-cholesterol was over 1.0 mmol/l in 92% of the elderly, in 69% of patients without coronary artery disease and in 46% of patients with triple-vessel disease, the differences being significant between all groups.     

Adult Hirschsprung's disease

To assess the clinical features and long-term functional outcome after surgery, eight patients operated on for adult Hirschsprung's disease during the 20-year period, 1968–1988, were re-examined. There were six men and two women with a mean age of 40±3 years at the time of survey. The mean age of the patients at the time of diagnosis was 23.8 years (range, 16 to 41 years). Results were compared with eight consecutive patients operated on for Hirschsprung's disease during the neonatal period. The Duhamel operation was performed initially on seven patients in the adult group and on all patients in the neonatal group. Anterior resection was performed on one adult patient initially but this was converted subsequently to Soave's pullthrough operation. None of the patients had constipation after definitive surgery. The mean defecation frequency was two in both groups. Three patients in the adult group and two patients in the neonatal group were completely continent, others had occasional soiling. The mean anal sphincter pressures were lower in the neonatal group than in the adult group and in each group lower than in normal controls. Adult Hirschsprung's disease must always be suspected in the context of chronic constipation. Functional results after surgery in adult patients are similar to those achieved in children.     

Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention

Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants ( n =160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [–1.1%, 95% confidence interval (CI) –0.1% to –2.1% and –1.6%, 95% CI –0.4% to –2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (–7.7%, 95% CI –9.7% to –5.6% vs. –2.9%, 95% CI –5.3 to –0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P =0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.There was no conflict of interest.     

Dentin enhances the effectiveness of bioactive glass S53P4 against a strain of Enterococcus faecalis.

OBJECTIVE: The aim of the current study was to test the impact of dentin powder on the antimicrobial efficacy of bioactive glass S53P4 (BAG). STUDY DESIGN: BAG was suspended (preincubated) in saline at 37 degrees C for different time periods with or without human dentin powder, hydroxylapatite, or decalcified dentin. Subsequently, Enterococcus faecalis ATCC 29212 cells were added to these suspensions and bacterial recovery measured with and without the use of gentle sonication. Furthermore, survival of bacteria in test and control suspensions was assessed over time. Supernatants of suspensions were analyzed for their element contents using atomic absorption spectrophotometry. The effects of pH, silica, and osmolarity on E faecalis viability were assessed using specifically prepared solutions. RESULTS: BAG preincubated with dentin powder caused a significant (P < .05) decrease in viability compared to pure BAG suspensions. This was not based on adherence of bacteria to solid particles or agglutination of the cells, because sonication did not increase bacterial yields. Hydroxylapatite and decalcified dentin did not increase BAG killing efficacy. The additive effect of BAG + dentin powder was dose dependent, occurred only with solids in suspension, and increased with suspension time. An augmented dissolution of glass components, especially silicon, was measured in BAG + dentin powder compared to pure BAG suspensions or counterparts containing hydroxylapatite or decalcified dentin. High osmolarity per se did not affect E faecalis viability, whereas high pH and silica levels did. CONCLUSION: The observed phenomenon was related to an increased BAG dissolution triggered by dentin powder, causing elevated local pH and silica levels.     

Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2–4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.