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Age and Long-Term Hormone Treatment Effects on the Ultrastructural Morphology of the Median Eminence of Female Rhesus Macaques. - Neuroendocrinology
The median eminence (ME) of the hypothalamus comprises the hypothalamic nerve terminals, glia (especially tanycytes) and the portal capillary vasculature that transports hypothalamic neurohormones to the anterior pituitary gland. The ultrastructure of the ME is dynamically regulated by hormones and undergoes organizational changes during development and reproductive cycles in adult females, but relatively little is known about the ME during aging, especially in non-human primates. Therefore, we used a novel transmission scanning electron microscopy (tSEM) technique to examine the cytoarchitecture of the ME of young and aged female rhesus macaques in a preclinical monkey model of menopausal hormone treatments. Rhesus macaques were ovariectomized and treated for 2 years with vehicle, estradiol, or estradiol + progesterone (E2 + P4). While the overall cytoarchitecture of the ME underwent relatively few changes with age and hormones, changes to some features of neural and glial components near the portal capillaries were observed. Specifically, large neuroterminal size was greater in aged compared to young adult animals, an effect that was mitigated or reversed by E2 alone but not E2 + P4 treatment. Overall glial size, and the density and tissue fraction of the largest subset of glia, were greater in aged monkeys, and in some cases reversed by E2 treatment. Mitochondrial size was decreased by E2, but not E2 + P4, only in aged macaques. These results contrast substantially with work in rodents, suggesting that the ME of aging macaques is less vulnerable to age-related disorganization, and that estradiol's effects in the monkey ME are age-specific.Â© 2015 S. Karger AG, Basel.
Integration of Cyanine, Merocyanine and Styryl Dye Motifs with Synthetic Bacteriochlorins. - Photochemistry and photobiology
Understanding the effects of substituents on spectral properties is essential for the rational design of tailored bacteriochlorins for light-harvesting and other applications. Towards this goal, three new bacteriochlorins containing previously unexplored conjugating substituents have been prepared and characterized. The conjugating substituents include two positively charged species, 2-(N-ethyl 2-quinolinium)vinyl- (B-1) and 2-(N-ethyl 4-pyridinium)vinyl- (B-2), and a neutral group, acroleinyl- (B-3); the charged species resemble cyanine (or styryl) dye motifs whereas the neutral unit resembles a merocyanine dye motif. The three bacteriochlorins are examined by static and time-resolved absorption and emission spectroscopy and density functional theoretical calculations. B-1 and B-2 have Qy absorption bathochromically shifted well into the NIR region (822 and 852 nm), farther than B-3 (793 nm) and other 3,13-disubstituted bacteriochlorins studied previously. B-1 and B-2 have broad Qy absorption and fluorescence features with large peak separation (Stokes shift), low fluorescence yields, and shortened S1 (Qy ) excited-state lifetimes (~700 ps and ~100 ps). More typical spectra and S1 lifetime (~2.3 ns) are found for B-3. The combined photophysical and molecular-orbital characteristics suggest the altered spectra and enhanced nonradiative S1 decay of B-1 and B-2 derive from excited-state configurations in which electron density is shifted between the macrocycle and the substituents. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Variable impact of late-Quaternary megafaunal extinction in causing ecological state shifts in North and South America. - Proceedings of the National Academy of Sciences of the United States of America
Loss of megafauna, an aspect of defaunation, can precipitate many ecological changes over short time scales. We examine whether megafauna loss can also explain features of lasting ecological state shifts that occurred as the Pleistocene gave way to the Holocene. We compare ecological impacts of late-Quaternary megafauna extinction in five American regions: southwestern Patagonia, the Pampas, northeastern United States, northwestern United States, and Beringia. We find that major ecological state shifts were consistent with expectations of defaunation in North American sites but not in South American ones. The differential responses highlight two factors necessary for defaunation to trigger lasting ecological state shifts discernable in the fossil record: (i) lost megafauna need to have been effective ecosystem engineers, like proboscideans; and (ii) historical contingencies must have provided the ecosystem with plant species likely to respond to megafaunal loss. These findings help in identifying modern ecosystems that are most at risk for disappearing should current pressures on the ecosystems' large animals continue and highlight the critical role of both individual species ecologies and ecosystem context in predicting the lasting impacts of defaunation currently underway.
Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers. - European heart journal
Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding in genotype-phenotype correlations in HCM, particularly the contribution of an MYL2 founder mutation and risk factors to left ventricular hypertrophic remodelling.We analysed 14 HCM families of whom 38 family members share the MYL2 c.64G > A [p.(Glu22Lys)] mutation and a common founder haplotype. In this unique cohort, we investigated factors influencing phenotypic outcome in addition to the primary mutation. The mutation alone showed benign disease manifestation with low penetrance. The co-presence of additional risk factors for hypertrophy such as hypertension, obesity, or other sarcomeric gene mutation increased disease penetrance substantially and caused HCM in 89% of MYL2 mutation carriers (P = 0.0005). The most prominent risk factor was hypertension, observed in 71% of mutation carriers with HCM and an additional risk factor.The MYL2 mutation c.64G > A on its own is incapable of triggering clinical HCM in most carriers. However, the presence of an additional risk factor for hypertrophy, particularly hypertension, adds to the development of HCM. Early diagnosis of risk factors is important for early treatment of MYL2 mutation carriers and close monitoring should be guaranteed in this case. Our findings also suggest that the presence of hypertension or another risk factor for hypertrophy should not be an exclusion criterion for genetic studies.Published on behalf of the European Society of Cardiology. All rights reserved. Â© The Author 2015. For permissions please email: firstname.lastname@example.org.
Variability in Fluoroscopic Image Acquisition During Operative Fixation of Ankle Fractures. - Orthopedics
The goal of this study was to determine whether injury, level of surgeon training, and patient factors are associated with increased use of fluoroscopy during open reduction and internal fixation of ankle fractures. These relationships are not well defined. The study was a retrospective chart review of patients treated at an academic institution with primary open reduction and internal fixation of an ankle. Patient demographics, including sex, age, and body mass index, were collected, as was surgeon year of training (residency and fellowship). Image acquisition data included total number of images, total imaging time, and cumulative dose. Ankle fractures were classified according to the Weber and Lauge-Hansen classifications and the number of fixation points. Bivariate analysis and multiple regression models were used to predict increasing fluoroscopic image acquisition. Alpha was set at 0.05. Of 158 patients identified, 58 were excluded. After bivariate analysis, fracture complexity and year of training showed a significant correlation with increasing image acquisition. After multiple regression analysis, fracture complexity and year of training remained clinically significant and were independent predictors of increased image acquisition. Increasing fracture complexity resulted in 20 additional images, 16 additional seconds, and an increase in radiation of 0.7 mGy. Increasing year of training resulted in an additional 6 images and an increase of 0.35 mGy in cumulative dose. The findings suggest that protocols to educate trainee surgeons in minimizing the use of fluoroscopy would be beneficial at all levels of training and should target multiple fracture patterns. [Orthopedics. 2015; 38(10):e864-e868.].Copyright 2015, SLACK Incorporated.
Genome Sequence of a Urease-Positive Campylobacter lari Strain. - Genome announcements
Campylobacter lari is frequently isolated from shore birds and can cause illness in humans. Here, we report the draft whole-genome sequence of a urease-positive strain of C.Â lari that was isolated in estuarial water on the coast of Delaware, USA.Copyright Â© 2015 Meinersmann et al.
Endoscopically assisted extralevator abdominoperineal excision. - Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland
Extralevator abdominoperineal excision (ELAPE) has been advocated to optimize clearance of lower third rectal cancers with an involved or threatened circumferential resection margin. ELAPE could reduce positive margins and specimen perforation compared with standard APE. ELAPE can, however, be difficult particularly in identifying the anterior plane in the male. Usually, the dissection is performed in the prone position, which can be hazardous particularly in obese patients, where wound problems are commonly encountered. We describe an endoscopically assisted approach for ELAPE in the lithotomy position.Three male patients with a rectal tumour located at the anorectal junction underwent an endoscopically assisted ELAPE in the lithotomy position after preoperative radiotherapy.All the procedures were performed successfully with operation times of 180, 390 and 420 minutes. There was no instance of intra-operative perforation or other complications. One patient developed postoperative intestinal obstruction which resolved on conservative management. There were no wound complications. Histopathological examination demonstrated clear margins and intact mesorectal planes in each patient.We report a good outcome in three patients after endoscopically assisted ELAPE. The approach allows the patient to be operated in the lithotomy position giving excellent views of the anterior dissection. This is the first paper describing an endoscopically assisted ELAPE, including a step-by-step accounts and a video recording. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes aegypti: Extent and Duration of Protection. - PLoS neglected tropical diseases
Dengue transmission by the mosquito vector, Aedes aegypti, occurs indoors and outdoors during the day. Personal protection of individuals, particularly when outside, is challenging. Here we assess the efficacy and durability of different types of insecticide-treated clothing on laboratory-reared Ae. aegypti.Standardised World Health Organisation Pesticide Evaluation Scheme (WHOPES) cone tests and arm-in-cage assays were used to assess knockdown (KD) and mortality of Ae. aegypti tested against factory-treated fabric, home-dipped fabric and microencapsulated fabric. Based on the testing of these three different treatment types, the most protective was selected for further analysis using arm-in cage assays with the effect of washing, ultra-violet light, and ironing investigated using high pressure liquid chromatography.Efficacy varied between the microencapsulated and factory dipped fabrics in cone testing. Factory-dipped clothing showed the greatest effect on KD (3 min 38.1%; 1 hour 96.5%) and mortality (97.1%) with no significant difference between this and the factory dipped school uniforms. Factory-dipped clothing was therefore selected for further testing. Factory dipped clothing provided 59% (95% CI = 49.2%- 66.9%) reduction in landing and a 100% reduction in biting in arm-in-cage tests. Washing duration and technique had a significant effect, with insecticidal longevity shown to be greater with machine washing (LW50 = 33.4) compared to simulated hand washing (LW50 = 17.6). Ironing significantly reduced permethrin content after 1 week of simulated use, with a 96.7% decrease after 3 months although UV exposure did not reduce permethrin content within clothing significantly after 3 months simulated use.Permethrin-treated clothing may be a promising intervention in reducing dengue transmission. However, our findings also suggest that clothing may provide only short-term protection due to the effect of washing and ironing, highlighting the need for improved fabric treatment techniques.
Holding-time and method comparisons for the analysis of fecal-indicator bacteria in groundwater. - Environmental monitoring and assessment
As part of the US Geological Survey National Water-Quality Assessment Program, groundwater samples from domestic- and public-supply wells were collected and analyzed for fecal-indicator bacteria. A holding time comparison for total coliforms, Escherichia coli, and enterococci was done by analyzing samples within 8Â h using presence/absence methods and within 18-30Â h using quantitative methods. The data indicate that results obtained within 18-30Â h were not significantly different from those obtained within 8Â h for total coliforms and enterococci, by ColilertÂ® and EnterolertÂ® methods (IDEXX Laboratories Inc., Westbrook, ME), respectively. Quantitative laboratory methods for samples analyzed within 18-30Â h showed a statistically significant higher detection frequency when compared to presence/absence methods done within 8Â h for the following methods, E. coli by Colilert and enterococci by membrane filtration on mEI agar. Additionally, a comparison of methods for the enumeration of enterococci was done. Using non-parametric statistical analyses, results from the two methods were statistically different. In this study, the membrane filtration method on mEI agar was more sensitive, resulted in more detections of enterococci, and results were easier to interpret than with the quantitative Enterolert method. The quantitative Enterolert method produced varying levels of fluorescence, which required additional verification steps to eliminate false-positive results. It may be more advantageous to analyze untreated groundwater for enterococci using the membrane filtration method on mEI agar.
Small Molecules that Protect Mitochondrial Function from Metabolic Stress Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models. - Advances in experimental medicine and biology
One feature common to many of the pathways implicated in retinal degeneration is increased metabolic stress leading to impaired mitochondrial function. We found that exposure of cells to calcium ionophores or oxidants as metabolic stressors diminish maximal mitochondrial capacity. A library of 50,000 structurally diverse "drug-like" molecules was screened for protection against loss of calcium-induced loss of mitochondrial capacity in 661W rod-derived cells and C6 glioblastomas. Initial protective hits were then tested for protection against IBMX-induced loss of mitochondrial capacity as measured via respirometry. Molecules that protected mitochondria were then evaluated for protection of rod photoreceptor cells in retinal explants from rd1 mice. Two of the molecules attenuated loss of photoreceptor cells in the rd1 model. In the 661W cells, exposure to calcium ionophore or tert-butylhydroperoxide caused mitochondrial fragmentation that was blocked with the both compounds. Our studies have identified molecules that protect mitochondria and attenuate loss of photoreceptors in models of retinal degeneration suggesting that they could be good leads for development of therapeutic drugs for treatment of a wide variety of retinal dystrophies.
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