Subregional Hippocampal Thickness Abnormalities in Older Adults with a History of Heavy Cannabis Use.

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology. Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB- group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use. Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p<0.0001], and in the entire HC averaged over all subregions [F(1,42)=8.49, p=0.006]. Conclusions: Negative effects of chronic adolescent CB use on hippocampal structure are maintained well into late life. Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage. Clinical Trial Registration: ClinicalTrials.gov # NCT01874886

Physical Activity and Hippocampal Sub-Region Structure in Older Adults with Memory Complaints.

BackgroundPhysical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited.ObjectiveTo examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints.MethodsTwenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with >4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups.ResultsTwenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (n = 13) had thicker fusiform gyrus (median difference = 0.11 mm, effect size (ES) = 1.43, p = 0.001) and parahippocampal cortex (median difference = 0.12 mm, ES = 0.93, p = 0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median difference = 0.90, ES = 1.61, p = 0.003) and executive functioning (median difference = 0.97, ES = 1.24, p = 0.05). Memory recall was not significantly different between the two groups.ConclusionOlder non-demented individuals complaining of memory loss who walked >4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy

The Mixing Rate of the Arterial Blood Pressure Waveform Markov Chain is Correlated with Shock Index during Hemorrhage in Anesthetized Swine

Identifying the need for interventions during hemorrhage is complicated due to physiological compensation mechanisms that can stabilize vital signs until a significant amount of blood loss. Physiological systems providing compensation during hemorrhage affect the arterial blood pressure waveform through changes in dynamics and waveform morphology. We investigated the use of Markov chain analysis of the arterial blood pressure waveform to monitor physiological systems changes during hemorrhage. Continuous arterial blood pressure recordings were made on anesthetized swine (N=7) during a 5 min baseline period and during a slow hemorrhage (10 ml/kg over 30 min). Markov chain analysis was applied to 20 sec arterial blood pressure waveform segments with a sliding window. 20 ranges of arterial blood pressure were defined as states and empirical transition probability matrices were determined for each 20 sec segment. The mixing rate (2nd largest eigenvalue of the transition probability matrix) was determined for all segments. A change in the mixing rate from baseline estimates was identified during hemorrhage for each animal (median time of 13 min, ~10% estimated blood volume, with minimum and maximum times of 2 and 33 min, respectively). The mixing rate was found to have an inverse correlation with shock index for all 7 animals (median correlation coefficient of -0.95 with minimum and maximum of -0.98 and -0.58, respectively). The Markov chain mixing rate of arterial blood pressure recordings is a novel potential biomarker for monitoring and understanding physiological systems during hemorrhage

Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

<p>Abstract</p> <p>Background</p> <p>During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy.</p> <p>Methods</p> <p>We evaluated the effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV). CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM) or Ang-(1-7) (1 nM and 1 microM). The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH), and human placenta lactogen (HPL) was measured by ELISA.</p> <p>Results</p> <p>The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM) and Ang-(1-7) (1 nM and 1 microM). There was a time-dependent increase in HPL indicating that the CV were functioning normally.</p> <p>Conclusions</p> <p>Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.</p

Titanium Nitride Films for Ultrasensitive Microresonator Detectors

Titanium nitride (TiNx) films are ideal for use in superconducting microresonator detectors because: a) the critical temperature varies with composition (0 < Tc < 5 K); b) the normal-state resistivity is large, \rho_n ~ 100 $\mu$Ohm cm, facilitating efficient photon absorption and providing a large kinetic inductance and detector responsivity; and c) TiN films are very hard and mechanically robust. Resonators using reactively sputtered TiN films show remarkably low loss (Q_i > 10^7) and have noise properties similar to resonators made using other materials, while the quasiparticle lifetimes are reasonably long, 10-200 $\mu$s. TiN microresonators should therefore reach sensitivities well below 10^-19 WHz^(-1/2).Comment: to be published in AP

Understanding Schools and Schooling. (Book Review)

A review of a book written by Clive Chitty (2002 with a useful focus on issues of equity and social justice, including prejudice, discrimination and bullying in secondary schools. Education policy makers need to explore the extent to which it is important to produce interested, motivated and socially balanced young adults. It is well researched and documented

A Role for Non-Covalent SUMO Interaction Motifs in Pc2/CBX4 E3 Activity

Background: Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins, which can increase the efficiency and specificity of the sumoylation process. In addition to covalent attachment of SUMO to target proteins, specific non-covalent SUMO interaction motifs (SIMs) that are generally short hydrophobic peptide motifs have been identified. Methodology/Principal Findings: Intriguingly, consensus SIMs are present in most SUMO E3s, including the polycomb protein, Pc2/Cbx4. However, a role for SIMs in SUMO E3 activity remains to be shown. We show that Pc2 contains two functional SIMs, both of which contribute to full E3 activity in mammalian cells, and are also required for sumoylation of Pc2 itself. Pc2 forms distinct sub-nuclear foci, termed polycomb bodies, and can recruit partner proteins, such as the corepressor CtBP. We demonstrate that mutation of the SIMs in Pc2 prevents Pc2-dependent CtBP sumoylation, and decreases enrichment of SUMO1 and SUMO2 at polycomb foci. Furthermore, mutational analysis of both SUMO1 and SUMO2 reveals that the SIM-interacting residues of both SUMO isoforms are required for Pc2-mediated sumoylation and localization to polycomb foci

Chorus song of the indri (Indri indri: Primates, Lemuridae): Group differences and analysis of within-group vocal interactions

Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) applies.The loud chorus songs of the group-living lemur Indri indri are a striking feature of rainforest areas of eastern Madagascar. Despite some research on the conspicuous vocal display of the indri, two hypotheses have not been addressed: do groups differ in the acoustic properties of their songs, and is there evidence of coordinated singing between individuals within groups. We recorded and analyzed the songs of three indri groups to examine these two questions. To answer the first question, we made quantitative spectral measures on songs of the three groups and performed multivariate analyses of the acoustic features of the notes constituting the songs. Our results showed songs of the three groups differed significantly, although there was overlap between groups. To answer the second question, we classified note types and quantified their occurrence as overlapping and abutting pairs. We found non-random associations between sequential note types in all three indri groups. These associations were consistent among groups, suggesting that individuals follow consistent answering rules when contributing to choruses. Whether indris use acoustic group identifiers in management of behavioral strategies and how within-group coordinated note production might function remain unknown. We compare our results to a number of taxonomically diverse species that live in groups and broadcast chorus and duet vocal signals.Ye

Effects of Antihypertensive Medications on Quality of Life in Elderly Hypertensive Women

The impact of antihypertensive medications on the quality of life of elderly hypertensive women has rarely been systematically evaluated in large clinical trials using drugs from the new generations of pharmaceutic preparations. We carried out a multicenter, randomized double-blind clinical trial with 309 hypertensive women aged 60 to 80 years to assess effects of atenolol, enalapril, and isradipine on measures of quality of life over a 22-week period. The patients had mild to moderate hypertension. Hydrochlorothiazide was added to treatment if monotherapy was inadequate in lowering blood pressure. At the conclusion of the trial the three drug groups did not differ in degree of reduction of diastolic blood pressure or in supplementation with hydrochlorothiazide. Over the 22-week trial, linear trend analysis showed no differences between the treatment groups in change from baseline on quality of life measures of well-being, physical status, emotional status, cognitive functioning, and social role participation. Regarding each of 33 physical side effects over the 22 weeks, we found no general difference between atenolol, enalapril, and isradipine groups on measures of change in distress over symptoms except for enalapril patients who worsened in distress over cough (P = .001) and atenolol patients who worsened in distress over dry mouth (P = .014). Centering on three medications that are relatively new additions to the armamentarium for blood pressure control, the findings underline the increasing opportunities for the physician to select drugs that can control blood pressure while maintaining the quality of life of elderly hypertensive women

Demonstration of integrated microscale optics in surface-electrode ion traps

In ion trap quantum information processing, efficient fluorescence collection is critical for fast, high-fidelity qubit detection and ion-photon entanglement. The expected size of future many-ion processors require scalable light collection systems. We report on the development and testing of a microfabricated surface-electrode ion trap with an integrated high numerical aperture (NA) micromirror for fluorescence collection. When coupled to a low NA lens, the optical system is inherently scalable to large arrays of mirrors in a single device. We demonstrate stable trapping and transport of 40Ca+ ions over a 0.63 NA micromirror and observe a factor of 1.9 enhancement in photon collection compared to the planar region of the trap.Comment: 15 pages, 8 figure