Retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus: comparison of measurements obtained by retinal thickness analysis and optical coherence tomography

OBJECTIVE: To compare measurements of retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus using 2 different techniques: the retinal thickness analyzer (RTA) and optical coherence tomography (OCT). METHODS: Twenty-eight eyes from 28 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy were classified according to the Wisconsin grading system by 7-field stereoscopic fundus photography. Ten eyes were classified as level 10 (absence of visible lesions) and 18 as level 20 or 35 (minimal retinopathy). All eyes were examined by the RTA and OCT. Healthy populations were used to establish reference maps for the RTA (n = 14; mean age, 48 years; age range, 42-55 years) and OCT (n = 10; mean age, 56 years; age range, 43-68 years). Reference maps were computed using the means + 2 SDs of the values obtained for each location. Increases in thickness were computed as a percentage of increase over these reference maps. RESULTS: The RTA detected increases in thickness in 1 or more locations in 24 of the 28 diabetic eyes examined, whereas OCT detected increases in only 3 eyes. The percentages of increase detected by the RTA ranged from 0.3% to 73.5%, whereas OCT detected percentages of increase of 0.3% to 4.8%. CONCLUSION: Optical coherence tomography is less sensitive than the RTA in detecting localized increases in retinal thickness in the initial stages of diabetic retinal disease

Linking epigenetics and biological conservation: Towards a conservation epigenetics perspective

International audience1. Biodiversity conservation is a global issue where the challenge is to integrate all levels of biodiversity to ensure the long-term evolutionary potential and resilience of biological systems. Genetic approaches have largely contributed to conservation biology by defining "conservation entities" accounting for their evolutionary history and adaptive potential, the so-called evolutionary significant units (ESUs). Yet, these approaches only loosely integrate the short-term ecological history of organisms. 2. Here, we argue that epigenetic variation, and more particularly DNA methylation, represents a molecular component of biodiversity that directly links the genome to the environment. As such, it provides the required information on the ecological background of organisms for an integrative field of conservation biology. 3. We synthesize knowledge about the importance of epigenetic mechanisms in (a) orchestrating fundamental development alternatives in organisms, (b) enabling individuals to respond in real-time to selection pressures and (c) improving ecosystem stability and functioning. 4. Using practical examples in conservation biology, we illustrate the relevance of DNA methylation (a) as biomarkers of past and present environmental stress events as well as biomarkers of physiological conditions of individuals; (b) for documenting the ecological structuring/clustering of wild populations and hence for better integrating ecology into ESUs; (c) for improving conservation transloca-tions; and (d) for studying landscape functional connectivity. 5. We conclude that an epigenetic conservation perspective will provide environmental managers the possibility to refine ESUs, to set conservation plans taking into account the capacity of organisms to rapidly cope with environmental changes, and hence to improve the conservation of wild populations. K E Y W O R D S conservation, DNA methylation, ecological timescales, epigenetic, evolutionary significant unit

Automated detection of proliferative retinopathy in clinical practice

Timely intervention for diabetic retinopathy (DR) lessens the possibility of blindness and can save considerable costs to health systems. To ensure that interventions are timely and effective requires methods of screening and monitoring pathological changes, including assessing outcomes. Fractal analysis, one method that has been studied for assessing DR, is potentially relevant in today’s world of telemedicine because it provides objective indices from digital images of complex patterns such as are seen in retinal vasculature, which is affected in DR. We introduce here a protocol to distinguish between nonproliferative (NPDR) and proliferative (PDR) changes in retinal vasculature using a fractal analysis method known as local connected dimension (Dconn) analysis. The major finding is that compared to other fractal analysis methods, Dconn analysis better differentiates NPDR from PDR (p = 0.05). In addition, we are the first to show that fractal analysis can be used to differentiate between NPDR and PDR using automated vessel identification. Overall, our results suggest this protocol can complement existing methods by including an automated and objective measure obtainable at a lower level of expertise that experts can then use in screening for and monitoring DR

Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates.

BACKGROUND: T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. OBJECTIVE: To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. MATERIALS AND METHODS: Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. RESULTS: No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. CONCLUSION: High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information

How the 'plates' of a health system can shift, change and adjust during economic recessions: A qualitative interview study of public and private health providers in Brazil's Sao Paulo and Maranhao states

Background: Economic recessions carry an impact on population health and access to care; less is known on how health systems adapt to the conditions brought by a downturn. This particularly matters now that the COVID-19 epidemic is putting health systems under stress. Brazil is one of the world’s most affected countries, and its health system was already experiencing the aftermath of the 2015 recession. Methods: Between 2018 and 2019 we conducted 46 semi-structured interviews with health practitioners, managers and policy-makers to explore the impact of the 2015 recession on public and private providers in prosperous (São Paulo) and impoverished (Maranhão) states in Brazil. Thematic analysis was employed to identify drivers and consequences of system adaptation and coping strategies. Nvivo software was used to aid data collection and analysis. We followed the Standards for Reporting Qualitative Research to provide an account of the findings. Results: We found the concept of ‘health sector crisis’ to be politically charged among healthcare providers in São Paulo and Maranhão. Contrary to expectations, the public sector was reported to have found ways to compensate for diminishing federal funding, having outsourced services and adopted flexible–if insecure–working arrangements. Following a drop in employment and health plans, private health insurance companies have streamlined their offer, at times at the expenses of coverage. Low-cost walk-in clinics were hit hard by the recession, but were also credited for having moved to cater for higher-income customers in Maranhão. Conclusions: The ‘plates’ of a health system may shift and adjust in unexpected ways in response to recessions, and some of these changes might outlast the crisis. As low-income countries enter post-COVID economic recessions, it will be important to monitor the adjustments taking place in health systems, to ensure that past gains in access to care and job security are not eroded

The dynamics of apparent horizons in Robinson-Trautman spacetimes

We present an alternative scheme of finding apparent horizons based on spectral methods applied to Robinson-Trautman spacetimes. We have considered distinct initial data such as representing the spheroids of matter and the head-on collision of two non-rotating black holes. The evolution of the apparent horizon is presented. We have obtained in some cases a mass gap between the final Bondi and apparent horizon masses, whose implications were briefly commented in the light of the thermodynamics of black holes.Comment: 9 pages, 7 figure

Resolving the Sources of Plasma Glucose Excursions following a Glucose Tolerance Test in the Rat with Deuterated Water and [U-13C]Glucose

Sources of plasma glucose excursions (PGE) following a glucose tolerance test enriched with [U-13C]glucose and deuterated water were directly resolved by 13C and 2H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose and water enrichments in rat. Plasma water 2H-enrichment attained isotopic steady-state within 2–4 minutes following the load. The fraction of PGE derived from endogenous sources was determined from the ratio of plasma glucose position 2 and plasma water 2H-enrichments. The fractional gluconeogenic contributions to PGE were obtained from plasma glucose positions 2 and 5 2H-positional enrichment ratios and load contributions were estimated from plasma [U-13C]glucose enrichments. At 15 minutes, the load contributed 26±5% of PGE while 14±2% originated from gluconeogenesis in healthy control rats. Between 15 and 120 minutes, the load contribution fell whereas the gluconeogenic contribution remained constant. High-fat fed animals had significant higher 120-minute blood glucose (173±6 mg/dL vs. 139±10 mg/dL, p<0.05) and gluconeogenic contributions to PGE (59±5 mg/dL vs. 38±3 mg/dL, p<0.01) relative to standard chow-fed controls. In summary, the endogenous and load components of PGE can be resolved during a glucose tolerance test and these measurements revealed that plasma glucose synthesis via gluconeogenesis remained active during the period immediately following a glucose load. In rats that were placed on high-fat diet, the development of glucose intolerance was associated with a significantly higher gluconeogenic contribution to plasma glucose levels after the load

Conservation Patterns of HIV-1 RT Connection and RNase H Domains: Identification of New Mutations in NRTI-Treated Patients

Background: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions

Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade