Charcot-Marie-Tooth disease type 2A (CMT2A), the most common form of CMT2, is caused by mutations in the mitofusin 2 gene (MFN2), a nuclear encoded gene essential for mitochondrial fusion and ...tethering the endoplasmic reticulum to mitochondria. Published CMT2A phenotypes have differed widely in severity.
To determine the prevalence and phenotypes of CMT2A within our clinics we performed genetic testing on 99 patients with CMT2 evaluated at Wayne State University in Detroit and on 27 patients with CMT2 evaluated in the National Hospital for Neurology and Neurosurgery in London. We then preformed a cross-sectional analysis on our patients with CMT2A.
Twenty-one percent of patients had MFN2 mutations. Most of 27 patients evaluated with CMT2A had an earlier onset and more severe impairment than patients without CMT2A. CMT2A accounted for 91% of all our severely impaired patients with CMT2 but only 11% of mildly or moderately impaired patients. Twenty-three of 27 patients with CMT2A were nonambulatory prior to age 20 whereas just one of 78 non-CMT2A patients was nonambulatory after this age. Eleven patients with CMT2A had a pure motor neuropathy while another 5 also had profound proprioception loss. MFN2 mutations were in the GTPase domain, the coiled-coil domains, or the highly conserved R3 domain of the protein.
We find MFN2 mutations particularly likely to cause severe neuropathy that may be primarily motor or motor accompanied by prominent proprioception loss. Disruption of functional domains of the protein was particularly likely to cause neuropathy.
Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not ...elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed. Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids.
Abstract Purpose An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This ...article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). Methods Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. Results Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. Conclusion Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life.
Summary
Type 2 diabetes (T2D) is a risk factor for cataract development. With T2D prevalence increasing, the burden of cataract‐associated vision loss will also increase. We aimed to characterise ...cataract diabetes‐specific risk factors to assist prevention and management strategies. As part of a systematic review, two investigators independently searched online electronic databases according to a predetermined protocol for relevant published data to end‐March 2018. Studies were included if they were longitudinal with ≥100 participants, diabetes was defined, a description of cataract assessment was provided, data were from humans, and the reports were in English. Study quality was assessed using the Newcastle Ottawa Scale and GRADE. Of 5255 publications identified, 19 from 13 study populations were included. The overall risk of bias was low. There was between‐study variability. Age and glycaemic control were consistently associated with cataract development in T2D, but blood pressure, diabetes duration, sex, and aspirin use were not. Serum lipids and smoking remain possible risk factors, but available data are inconclusive. Glycaemia is the only consistent modifiable risk factor amongst a range of candidate variables. Due to the lack of consistency of the available evidence, and since mortality associated with T2D is declining with the likelihood of increased cataract‐associated vision loss, additional well‐conducted longitudinal studies are needed to identify modifiable risk factors that could prevent or delay cataract formation.
Abstract
We describe the Dark Energy Survey (DES) photometric data set assembled from the first three years of science operations to support DES Year 3 cosmologic analyses, and provide usage notes ...aimed at the broad astrophysics community.
Y3
GOLD
improves on previous releases from DES,
Y1
GOLD
, and Data Release 1 (DES DR1), presenting an expanded and curated data set that incorporates algorithmic developments in image detrending and processing, photometric calibration, and object classification.
Y3
GOLD
comprises nearly 5000 deg
2
of
grizY
imaging in the south Galactic cap, including nearly 390 million objects, with depth reaching a signal-to-noise ratio ∼10 for extended objects up to
i
AB
∼ 23.0, and top-of-the-atmosphere photometric uniformity <3 mmag. Compared to DR1, photometric residuals with respect to Gaia are reduced by 50%, and per-object chromatic corrections are introduced.
Y3
GOLD
augments DES DR1 with simultaneous fits to multi-epoch photometry for more robust galactic color measurements and corresponding photometric redshift estimates.
Y3
GOLD
features improved morphological star–galaxy classification with efficiency >98% and purity >99% for galaxies with 19 <
i
AB
< 22.5. Additionally, it includes per-object quality information, and accompanying maps of the footprint coverage, masked regions, imaging depth, survey conditions, and astrophysical foregrounds that are used to select the cosmologic analysis samples.
There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of ...established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials.
Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters.
The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6-17.9 years) and glycated hemoglobin 7.3% (6.6-8.4%) 56 mmol/mol (49-68 mmol/mol). Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval CI 32.7-36.8) and 31.8% (95% CI 29.7-33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively.
In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).
Cohort Profile: The Fremantle Diabetes Study DAVIS, Timothy M. E; BRUCE, David G; DAVIS, Wendy A
International journal of epidemiology,
04/2013, Letnik:
42, Številka:
2
Journal Article
Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time ...with outcomes would help to guide implementation.
To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage.
Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites.
Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment.
The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation.
Among all 1287 patients (endovascular thrombectomy + medical therapy n = 634; medical therapy alone n = 653) enrolled in the 5 trials (mean age, 66.5 years SD, 13.1; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 95% CI, 0.76 to 0.93; ARD, -6.7%) and less functional independence (OR, 0.81 95% CI, 0.71 to 0.92, ARD, -5.2% 95% CI, -8.3% to -2.1%), but no change in mortality (OR, 1.12 95% CI, 0.93 to 1.34; ARD, 1.5% 95% CI, -0.9% to 4.2%).
In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
Ice cores from low latitudes can provide a wealth of unique information about past climate in the tropics, but they are difficult to recover and few exist. Here, we report annually resolved ice core ...records from the Quelccaya ice cap (5670 meters above sea level) in Peru that extend back ~1800 years and provide a high-resolution record of climate variability there. Oxygen isotopic ratios (δ¹⁸O) are linked to sea surface temperatures in the tropical eastern Pacific, whereas concentrations of ammonium and nitrate document the dominant role played by the migration of the Intertropical Convergence Zone in the region of the tropical Andes. Quelccaya continues to retreat and thin. Radiocarbon dates on wetland plants exposed along its retreating margins indicate that it has not been smaller for at least six millennia.
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