Higher gait variability is associated with decreased parietal gray matter volume among healthy older adults

The objectives of this study were to examine the association of stride time variability (STV) with gray and white matter volumes in healthy older adults, and to determine the specific location of any parenchymal loss associated with higher STV. A total of 71 participants (mean age 69.0 +/- 0.8 years; 59.7 % female) were included in this study. All participants had a 1.0 Tesla 3D T1-weighted MRI of the brain to measure gray and white matter volumes. STV was measured at steady-state self-selected walking speed using an electronic footswitch system. We found an association between higher STV and lower gray matter volume in the right parietal lobe (e.g., angular gyrus, Brodmann area 39, cluster corrected pFWE = 0.035). There were no significant associations between STV and higher gray matter volume or change in white matter volume. To the best of our knowledge this study is the first to identify a significant association of higher STV with lower right parietal gray matter volume in healthy older adults

Individual Fluorouracil Dose Adjustment in FOLFOX Based on Pharmacokinetic Follow-Up Compared With Conventional Body-Area-Surface Dosing: A Phase II, Proof-of-Concept Study

BackgroundTo compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). Patients And Methods A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FUODPM Protocol). Results The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Conclusions Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC

Association between ambulatory 24-hour blood pressure levels and brain volume reduction: a cross-sectional elderly population-based study

Previous literature has shown mixed results regarding the association between blood pressure levels and brain volume reduction. The objectives of this study were to determine whether high blood pressure levels were associated with focal brain volume reduction and whether high blood pressure-related focal brain volume reduction was associated with a decline in executive function performance. On the basis of a cross-sectional design, 24-hour ambulatory blood pressure measurements, as well as brain morphology from 3-dimensional magnetic resonance images, were assessed among 183 participants (mean, 65 +/- 0.6 years; 62.4% women). Average levels of systolic and diastolic blood pressures, as well as dip, pulse pressure, and mean arterial blood pressure, were used as outcomes. Cortical gray and white matter volumes were determined by automatic calculation using Statistical Parametric Mapping segmentation. Folstein\u27s Mini-Mental State Examination, digit span, part B of Trail Making, and Stroop tests were used to assess executive function performance. Sex, use of antihypertensive drugs, duration of hypertension, leukoaraiosis, body mass index, education level, and total brain matter volume were used as potential confounders. A significant blood pressure-related decrease in gray matter volume of the left supplementary motor areas (Brodmann area 6) and of the left superior and middle frontal gyrus (Brodmann area 8) was shown. No significant decrease was found with white matter volume. Blood pressure-related decreases in gray matter volume were significantly associated with a decline in executive function performance. The association of high blood pressure with brain volume reduction may in part explain blood pressure-related cognitive decline leading to dementia

Three-grating monolithic phase-mask for the single-order writing of large-period gratings

A new type of achromatic high-efficiency monolithic phase mask is presented. The mask comprises three submicron period diffraction gratings at a single substrate side that create a purely single spatial frequency interferogram of large period. The optical scheme is that of an integrated Mach-Zehnder interferometer where all light circulation functions are performed by diffraction gratings. The paper describes the operation principle of the phase mask, the fabrication process, and its utilization in a write-on-the-fly scheme for the writing of a long, 2 µm-period grating

Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments

Production of considerable amounts of reactive oxygen species (ROS) eventually leads to oxidative stress. A key role of oxidative stress is evident in the pathologic mechanisms of endothelial dysfunction and associated cardiovascular diseases. Vascular enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase are involved in the production of ROS. The question remains whether pharmacologic approaches can effectively combat the excessive ROS production in the vasculature. Interestingly, existing registered cardiovascular drugs can directly or indirectly act as antioxidants, thereby preventing the damaging effects of ROS. Moreover, new compounds targeting NADPH oxidases have been developed. Finally, food-derived compounds appear to be effective inhibitors of oxidative stress and preserve vascular function

The great melting pot. Common sole population connectivity assessed by otolith and water fingerprints

Quantifying the scale and importance of individual dispersion between populations and life stages is a key challenge in marine ecology. The common sole (Solea solea), an important commercial flatfish in the North Sea, Atlantic Ocean and the Mediterranean Sea, has a marine pelagic larval stage, a benthic juvenile stage in coastal nurseries (lagoons, estuaries or shallow marine areas) and a benthic adult stage in deeper marine waters on the continental shelf. To date, the ecological connectivity among these life stages has been little assessed in the Mediterranean. Here, such an assessment is provided for the first time for the Gulf of Lions, NW Mediterranean, based on a dataset on otolith microchemistry and stable isotopic composition as indicators of the water masses inhabited by individual fish. Specifically, otolith Ba/Ca and Sr/Ca profiles, and delta C-13 and delta O-18 values of adults collected in four areas of the Gulf of Lions were compared with those of young-of-the-year collected in different coastal nurseries. Results showed that a high proportion of adults (>46%) were influenced by river inputs during their larval stage. Furthermore Sr/Ca ratios and the otolith length at one year of age revealed that most adults (similar to 70%) spent their juvenile stage in nurseries with high salinity, whereas the remainder used brackish environments. In total, data were consistent with the use of six nursery types, three with high salinity (marine areas and two types of highly saline lagoons) and three brackish (coastal areas near river mouths, and two types of brackish environments), all of which contributed to the replenishment of adult populations. These finding implicated panmixia in sole population in the Gulf of Lions and claimed for a habitat integrated management of fisherie