Associations between retinal microvascular structure and the severity and extent of coronary artery disease

Objective

Microvascular mechanisms are increasingly recognized as being involved in a significant proportion of coronary artery disease (CAD) cases, but their exact contribution or role is unclear. We aimed to define the association between retinal microvascular signs and both CAD extent and severity.

Methods

1120 participants of the Australian Heart Eye Study were included. Retinal vessel caliber was measured from digital retinal images. Extent and severity of CAD was assessed using several approaches. First, a simple scoring classifying participants as having one-vessel, two-vessel, and three-vessel disease was used. Gensini and Extent scores were calculated using angiography findings.

Results

After multivariable adjustment, significantly narrower retinal arteriolar caliber in women (comparing lowest versus highest quartile or reference) and wider venular caliber in men (comparing highest versus lowest quartile or reference) were associated with 2-fold and 54% higher odds of having at least one stenosis ≥50% in the epicardial coronary arteries, respectively. Women in the third versus first tertile of retinal venular caliber had 92% and ∼2-fold higher likelihood of having higher Gensini and Extent scores, respectively. Women in the lowest versus highest tertile of retinal arteriolar caliber had greater odds of having higher Extent scores, OR 2.99 (95% CI 1.45–6.16). In men, non-significant associations were observed between retinal vascular caliber and Gensini and Extent scores.

Conclusions

An unhealthy retinal microvascular profile, namely, narrower retinal arterioles and wider venules was associated with more diffuse and severe CAD among women.     

Artificial selection for structural color on butterfly wings and comparison with natural evolution

Brilliant animal colors often are produced from light interacting with intricate nano-morphologies present in biological materials such as butterfly wing scales. Surveys across widely divergent butterfly species have identified multiple mechanisms of structural color production; however, little is known about how these colors evolved. Here, we examine how closely related species and populations of Bicyclus butterflies have evolved violet structural color from brown-pigmented ancestors with UV structural color. We used artificial selection on a laboratory model butterfly, B. anynana, to evolve violet scales from UV brown scales and compared the mechanism of violet color production with that of two other Bicyclus species, Bicyclus sambulos and Bicyclus medontias, which have evolved violet/blue scales independently via natural selection. The UV reflectance peak of B. anynana brown scales shifted to violet over six generations of artificial selection (i.e., in less than 1 y) as the result of an increase in the thickness of the lower lamina in ground scales. Similar scale structures and the same mechanism for producing violet/blue structural colors were found in the other Bicyclus species. This work shows that populations harbor large amounts of standing genetic variation that can lead to rapid evolution of scales’ structural color via slight modifications to the scales’ physical dimensions.Organisms produce colors in two basic ways: by synthesizing pigments that selectively absorb light of certain spectral bands so that only light outside the absorption bands is backscattered (chemical color) or by developing nanomorphologies that enhance the reflection of light of certain wavelengths by interference (physical color or structural color). Structural colors play major roles in natural and sexual selection in many species (1) and have a broad range of applications in color display, paint, cosmetics, and textile industries (2). Structural color surveys across widely divergent species have revealed a large diversity of color-producing mechanisms (3–9). However, there has been a lack of systematic study and comparison of how different colors from closely related species or within populations of a single species evolve, even though these colors can vary dramatically. By examining how these species/populations evolve different colors, it is possible to identify the minimal amount of morphological change that results in significant color variation. Furthermore, this research may serve as an inspiration for future application of similar evolutionary principles to the design of photonic devices for color tuning, light trapping, or beam steering (2, 10–20). From an evolutionary biology point of view, we are curious to examine how structural colors respond to selection pressure and whether there is sufficient standing genetic variation in natural populations to allow the rapid evolution of novel colors. Here we focus on determining the morphological changes and the physical mechanisms that cause the evolution of violet structural color in populations of a single species and also across different species within a single genus of butterflies.We focus on the genus Bicyclus (Lepidoptera: Nymphalidae), composed of more than 80 species that predominantly exhibit brown color along with marginal eyespots. Some Bicyclus species, however, have independently evolved transverse bands of bright violet/blue structural color on the dorsal surface of the forewings (black asterisks in Fig. 1A) (21, 22). One species, Bicyclus anynana, has become a model species amenable to laboratory rearing, and multiple aspects of its marginal eyespots (size, relative width of the color rings, shape) have been altered by artificial selection (23–27). However, change of color (hue), either pigmentary or structural, via artificial selection has not been reported. B. anynana does not exhibit bright violet coloration on its wings and therefore provides an excellent opportunity for investigating whether there is genetic potential to produce violet color upon directed selection. We investigated this potential by performing an artificial selection experiment in B. anynana that targeted the color of the specific dorsal wing region that evolved violet/blue coloration in other members of the genus (Fig. 1 B–G).Open in a separate windowFig. 1.Structural color in Bicyclus butterflies and basic wing scale morphology. (A) A phylogenetic estimate of Bicyclus butterfly relationships (modified from ref. 41) illustrating the evolution of color in the genus. The black asterisks mark two clades that evolved violet/blue color independently, represented here by B. sambulos and B. medontias. (B–D) Dorsal wing images of B. sambulos, B. anynana (the region used for artificial selection is marked by white asterisk), and B. medontias. (E–G) Graphs of reflectance spectra of the blue/violet wing band showing reflectance peaks in the 400–450 nm range and in the brown-colored homologous region in B. anynana with a UV reflectance peak centered at 300 nm (colored arrows). (H) 3D illustration of the wing and scales in the selected wing area of B. anynana. (I) Magnified view of the ripped region in H showing how cover (c; brown) and ground (g; green) scales are attached to the wing membrane (m, pink) and alternate along rows. Scales on the other (ventral) side of the wing membrane are visible also. (J) Cross-sectional view of a single scale showing the trabeculae (T) connecting the lower lamina (LL) to the upper lamina that includes ridges (R), microribs (Mr), and crossribs (Cr). Windows (W) are the spaces between the ridges and crossribs. Cover and ground scales have the same basic morphology. [llustrations in H–J courtesy of Katerina Evangelou (Central Saint Martin’s College, London).]B. anynana, like other butterflies, has two types of scales, cover and ground, which alternate within a row with cover scales partially covering the ground scales and the point where both scales attach to the wing membrane (Fig. 1 H and I and Fig. S1) (28). Both cover and ground scales contain a lower lamina with a continuous smooth surface below a region composed of longitudinal ridges and crossribs, collectively referred to as the “upper lamina” and connected to the lower lamina via pillars called “trabeculae” (Fig. 1J and Fig. S1) (6). Previous studies on butterflies showed that structural color can be produced by interference with light reflected from the overlapping lamella that build the longitudinal ridges, from microribs protruding from the sides of the longitudinal ridges, or from the lower lamina, which can vary in thickness and patterning (Fig. 1J) (29, 30). However, it is not clear how the violet/blue color is produced in members of the two Bicyclus clades that separately evolved this color, whether B. anynana can be made to evolve the same violet/blue color via artificial selection, and whether it will generate the color in the same way as the other species. To answer these questions, we conducted detailed optical characterization and structural analysis of butterfly wing scales from three separate species and artificially evolved populations of Bicyclus to illustrate how color is generated and how it has evolved.     

Corrigendum

Introduction

In the mid-1990s, Cambodia faced one of the fastest growing HIV epidemics in Asia. For its achievement in reversing this trend, and achieving universal access to HIV treatment, the country received a United Nations millennium development goal award in 2010. This article reviews Cambodia’s response to HIV over the past two decades and discusses its current efforts towards elimination of new HIV infections.

Methods

A literature review of published and unpublished documents, including programme data and presentations, was conducted.

Results and discussion

Cambodia classifies its response to one of the most serious HIV epidemics in Asia into three phases. In Phase I (1991–2000), when adult HIV prevalence peaked at 1.7% and incidence exceeded 20,000 cases, a nationwide HIV prevention programme targeted brothel-based sex work. Voluntary confidential counselling and testing and home-based care were introduced, and peer support groups of people living with HIV emerged. Phase II (2001–2011) observed a steady decline in adult prevalence to 0.8% and incidence to 1600 cases by 2011, and was characterized by: expanding antiretroviral treatment (coverage reaching more than 80%) and continuum of care; linking with tuberculosis and maternal and child health services; accelerated prevention among key populations, including entertainment establishment-based sex workers, men having sex with men, transgender persons, and people who inject drugs; engagement of health workers to deliver quality services; and strengthening health service delivery systems. The third phase (2012–2020) aims to attain zero new infections by 2020 through: sharpening responses to key populations at higher risk; maximizing access to community and facility-based testing and retention in prevention and care; and accelerating the transition from vertical approaches to linked/integrated approaches.

Conclusions

Cambodia has tailored its prevention strategy to its own epidemic, established systematic linkages across different services and communities, and achieved nearly universal coverage of HIV services nationwide. Still, the programme must continually (re)prioritize the most effective and efficient interventions, strengthen synergies between programmes, contribute to health system strengthening, and increase domestic funding so that the gains of the previous two decades are sustained, and the goal of zero new infections is reached.     

Ciliated muconodular papillary tumor of the lung: A newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: A case report and review of literature

We report the case of a 68‐year‐old man with a newly defined rare entity of a peripheral pulmonary tumor, consisting of a nodular papillary lesion with papillary structures containing ciliated columnar and goblet cells, as well as floating tumor cells in the mucin pool. The conspicuous mucin pool was observed to be mimicking colloid adenocarcinoma in a low‐power view, particularly in a frozen section slide. We originally reported it as an adenocarcinoma during intraoperative consultation. Immunohistochemically, the tumor cells exhibited a similar immunophenotype to pulmonary adenocarcinoma, except for the presence of focal ciliated and basaloid cells, which we found using CK5/6 and P63 immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge resection, the patient remained free of tumors. Although the malignant potential of CMPT cannot be ignored, a wedge resection with a safe margin might be a treatment option for CMPT patients.     

低热量营养支持对肝癌术后营养和免疫功能的影响

目的:比较低热量肠内、外营养支持对肝癌术后营养和免疫功能的影响.方法:将49例可切除肝癌的病人随机分为两组,术后第2 d始分别接受低热量肠内营养(HEN组)和低热量肠外营养(HPN组),比较两组术后的免疫和营养指标.结果:HEN组术后前清蛋白、转铁蛋白、IgA、IgG、IgM下降幅度小,CD3和CD4/CD8易恢复至术前水平,与HPN组比较,差异有显著性意义(P＜0.05).结论:HEN支持有利于肝癌术后营养和免疫功能的改善.     

Novel method of intraoperative liver tumour localisation with indocyanine green and near-infrared imaging

INTRODUCTIONFluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection.METHODSFrom 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0–3 or Day 4–7.RESULTSAmong 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0−3 and Day 4−7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events.CONCLUSIONICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis.     

An essential review of Singapore’s response to out-of-hospital cardiac arrests: improvements over a ten-year period

Care for patients who experience out-of-hospital cardiac arrest (OHCA) has rapidly evolved in the past decade. Increased sophistication of care in the community, emergency medical services (EMS) and hospital setting is associated with improved patient-centred outcomes. Notably, Utstein survival doubled from 11.6% to 23.1% between 2011 and 2016. These achievements involved collaboration between policymakers, clinicians and researchers, and were made possible by a strategic interplay of policy, research and implementation. We review the development and current state of OHCA in Singapore using primary population-based data from the Pan-Asian Resuscitation Outcomes Study and an unstructured search of research databases. We discuss the roles of important milestones in policy, community, dispatch, EMS and hospital interventions. Finally, we relate these interventions to relevant processes and outcomes, such as the relationship between the strategic implementation of bystander cardiopulmonary resuscitation and placement of automated external defibrillator with return of spontaneous circulation, survival to discharge and survival with favourable neurological outcomes.     

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTIONChest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.METHODSThis is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.RESULTSIn total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.CONCLUSIONIn a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.