Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Improving question formulation for use in evidence appraisal in a tertiary care setting: a randomised controlled trial [ISRCTN66375463]

BACKGROUND: The specificity of clinical questions is gauged by explicit descriptions of four dimensions: subjects, interventions, comparators and outcomes of interest. This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the submitted question compared to using a standard form without instructions and examples. METHODS: A randomised controlled trial was conducted in an evidence-search and appraisal service. New participants were invited to reformulate clinical queries. The Control Group was given no instructions. The Intervention Group was given a brief explanation of proper formulation, written instructions, and diagrammatic examples. The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity. RESULTS: Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up. The remaining 17 Intervention Group and 22 Control Group participants were analysed. Baseline characteristics were comparable. Overall, 20% of initially submitted questions from both groups were properly specified (defined as an explicit statement describing all dimensions of specificity). On follow-up, 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up (p = 0.008) while the Control Group did not show any changes from baseline. Participants in the Intervention Group were also more likely to explicitly describe patients (p = 0.028), comparisons (p = 0.014), and outcomes (p = 0.008). CONCLUSIONS: This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries. The evaluation of the long-term impact of such changes is an area of continued research

Activity of Bdellovibrio Hit Locus Proteins, Bd0108 and Bd0109, Links Type IVa Pilus Extrusion/Retraction Status to Prey-Independent Growth Signalling

Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction) locus on the Bdellovibrio genome were associated with the transition to preyindependent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall), and that the presence (and possibly retraction state) of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation background

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Follow-up Observations of the Neptune Mass Transiting Extrasolar Planet HAT-P-11b

We have confirmed the existence of the transiting super Neptune extrasolar planet HAT-P-11b. On May 1, 2009 UT the transit of HAT-P-11b was detected at the University of Arizona's 1.55m Kuiper Telescope with 1.7 millimag rms accuracy. We find a central transit time of T_c = 2454952.92534+/-0.00060 BJD; this transit occurred 80+/-73 seconds sooner than previous measurements (71 orbits in the past) would have predicted. Hence, our transit timing rules out the presence of any large (>200 s) deviations from the ephemeris of Bakos et al. (2009). We obtain a slightly more accurate period of P=4.8878045+/-0.0000043 days. We measure a slightly larger planetary radius of R_p=0.452+/-0.020 R_J (5.07+/-0.22 R_earth) compared to Bakos and co-workers' value of 0.422+/-0.014 R_J (4.73+/-0.16 R_earth). Our values confirm that HAT-P-11b is very similar to GJ 436b (the only other known transiting super Neptune) in radius and other bulk properties.Comment: accepted to ApJ Letters, 11 pages, 2 figures (see Dittmann et al. 2009 ApJ 699 L48-L51

Chinese Medicinal Herbs in Relieving Perimenopausal Depression: A Randomized, Controlled Trial

Abstract Objective: To explore the effects of GengNianLe (GNL, also called perimenopausal depression relieving formula), a defined formula of Chinese medicinal herbs in relieving perimenopausal depression in Chinese women. Methods : Between September 2004 and April 2008, 47 Chinese women were randomized into a GNL group (n ϭ 21) and a control group which received tibolone (n ϭ 26) using a randomization chart. Depression was rated with the 24-item Hamilton Depression Scale (HAMD). The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E 2 ) were detected before and after the treatment. Results: After 12 weeks of treatment, HAMD scores in both groups decreased significantly (p Ͻ 0.05) with no significant difference between the groups (p Ͼ 0.05). The levels of FSH decreased significantly and the level of E 2 increased significantly in both groups, and they changed more in the control group. No side-effect of treatment was reported in either group during treatment. Conclusions: The Chinese medicinal formula GNL showed promise in relieving perimenopausal depression and merits further study. 9

Use of antihypertensive medications in pregnancy and the risk of adverse perinatal outcomes: McMaster Outcome Study of Hypertension In Pregnancy 2 (MOS HIP 2)

BACKGROUND: Uncertainty remains about the potential harmful effects of antihypertensive therapy on the developing fetus, especially for beta-blockers (βb). METHODS: We prospectively enrolled all singleton women with a blood pressure ≥ 140/90 mm Hg during pregnancy. The main analysis included 1948 women with all forms of hypertension and compared the use of βb drugs, non-βb drugs or a combination of both, to no treatment. The primary study outcome was a composite of the diseases of prematurity, need for assisted ventilation for greater than 1 day, or perinatal death. A sub-group analysis evaluated the four treatment options among 583 singleton women with chronic hypertension before 20 weeks gestation. RESULTS: In the main analysis, no association was observed between βb use and the primary composite outcome [adjusted odds ratio (OR) 1.4, 95% CI 0.9–2.2], while an association was seen with non-βb therapy (OR 5.0, 95% CI 2.6–9.6) and combination therapy (OR 2.9, 95% CI 1.8–4.7). In the sub-group of 583 women with hypertension before 20 weeks, use of a non-βb drug (OR 4.9, 95% CI 1.7–14.2) or combination therapy (OR 2.9. 95% CI 1.1–7.7) was significantly associated with the primary composite outcome, while βb monotherapy was not (OR 1.4, 95% CI 0.6–3.4). CONCLUSIONS: Maternal use of antihypertensive medications other than βbs was associated with both major perinatal morbidity and mortality, while βb monotherapy was not. The combined use of βb and non-βb medications demonstrated the strongest association. Before definitive conclusions can be drawn, a large multicentre randomized controlled trial is needed to address the issues of both maternal efficacy and fetal safety with the use of one or more antihypertensive agents in pregnancy

Zeta-carotene isomerase (Z-ISO) is required for light-independent carotenoid biosynthesis in the cyanobacterium Synechocystis sp. PCC 6803

Carotenoids are crucial photosynthetic pigments utilized for light harvesting, energy transfer, and photoprotection. Although most of the enzymes involved in carotenoid biosynthesis in chlorophototrophs are known, some are yet to be identified or fully characterized in certain organisms. A recently characterized enzyme in oxygenic phototrophs is 15-cis-zeta(ζ)-carotene isomerase (Z-ISO), which catalyzes the cis-to-trans isomerization of the central 15–15′ cis double bond in 9,15,9′-tri-cis-ζ-carotene to produce 9,9′-di-cis-ζ-carotene during the four-step conversion of phytoene to lycopene. Z-ISO is a heme B-containing enzyme best studied in angiosperms. Homologs of Z-ISO are present in organisms that use the multi-enzyme poly-cis phytoene desaturation pathway, including algae and cyanobacteria, but appear to be absent in green bacteria. Here we confirm the identity of Z-ISO in the model unicellular cyanobacterium Synechocystis sp. PCC 6803 by showing that the protein encoded by the slr1599 open reading frame has ζ-carotene isomerase activity when produced in Escherichia coli. A Synechocystis Δslr1599 mutant synthesizes a normal quota of carotenoids when grown under illumination, where the photolabile 15–15′ cis double bond of 9,15,9′-tri-cis-ζ-carotene is isomerized by light, but accumulates this intermediate and fails to produce ‘mature’ carotenoid species during light-activated heterotrophic growth, demonstrating the requirement of Z-ISO for carotenoid biosynthesis during periods of darkness. In the absence of a structure of Z-ISO, we analyze AlphaFold models of the Synechocystis, Zea mays (maize), and Arabidopsis thaliana enzymes, identifying putative protein ligands for the heme B cofactor and the substrate-binding site