To prospectively determine the relationship of OCT angiography (OCTA) metrics to diabetic retinopathy (DR) progression and development of diabetic macular edema (DME).
Prospective, observational ...study.
A total of 205 eyes from 129 patients with diabetes mellitus followed up for at least 2 years.
All participants underwent OCTA with a swept-source OCT device (DRI-OCT Triton, Topcon, Inc, Tokyo, Japan). Individual OCTA images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were generated by IMAGEnet6 (Basic License 10). After a quality check, automated measurements of foveal avascular zone (FAZ) area, FAZ circularity, vessel density (VD), and fractal dimension (FD) of both SCP and DCP were then obtained.
Progression of DR and development of DME.
Over a median follow-up of 27.14 months (interquartile range, 24.16-30.41 months), 28 of the 205 eyes (13.66%) developed DR progression. Of the 194 eyes without DME at baseline, 17 (8.76%) developed DME. Larger FAZ area (hazard ratio HR, 1.829 per SD increase; 95% confidence interval CI, 1.332-2.512), lower VD (HR, 1.908 per SD decrease; 95% CI, 1.303-2.793), and lower FD (HR, 4.464 per SD decrease; 95% CI, 1.337-14.903) of DCP were significantly associated with DR progression after adjusting for established risk factors (DR severity, glycated hemoglobin, duration of diabetes, age, and mean arterial blood pressure at baseline). Lower VD of SCP (HR, 1.789 per SD decrease; 95% CI, 1.027-4.512) was associated with DME development. Compared with the model with established risk factors alone, the addition of OCTA metrics improved the predictive discrimination of DR progression (FAZ area of DCP, C-statistics 0.723 vs. 0.677, P < 0.001; VD of DCP, C-statistics 0.727 vs. 0.677, P = 0.001; FD of DCP, C-statistics 0.738 vs. 0.677, P < 0.001) and DME development (VD of SCP, C-statistics 0.904 vs. 0.875, P = 0.036).
The FAZ area, VD, and FD of DCP predict DR progression, whereas VD of SCP predicts DME development. Our findings provide evidence to support that OCTA metrics improve the evaluation of risk of DR progression and DME development beyond traditional risk factors.
Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. ...This study aims to characterize the gut virome alterations in obese subjects with or without T2DM.
There were 128 obese subjects (body mass index ≥28 kg/m2) and 101 lean controls (body mass index ≥18.5 and <23 kg/m2) recruited from 2 regions in China (Hong Kong and Kunming). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome, and viral-bacterial correlations were compared between obese subjects and lean controls.
Obese subjects, especially those with T2DM (ObT2), had a decreased gut viral richness and diversity compared with lean controls in the Hong Kong cohort (P < .05), while no significant differences were observed in the Kunming cohort. Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, 17 differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecologic analysis revealed that intensive transkingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (P < .001).
Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Obesity accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that the gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.
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Obese individuals have a dysbiotic gut virome, and type 2 diabetes mellitus further aggravates such dysbiosis.
Background
Postoperative nausea and vomiting (PONV) are common complications following surgery and anaesthesia. Antiemetic drugs are only partially effective in preventing PONV. An alternative ...approach is to stimulate the PC6 acupoint on the wrist. This is an update of a Cochrane review first published in 2004, updated in 2009 and now in 2015.
Objectives
To determine the effectiveness and safety of PC6 acupoint stimulation with or without antiemetic drug versus sham or antiemetic drug for the prevention of PONV in people undergoing surgery.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 12, 2014), MEDLINE (January 2008 to December 2014), EMBASE (January 2008 to December 2014), ISI Web of Science (January 2008 to December 2014), World Health Organization Clinical Trials Registry, ClinicalTrials.gov, and reference lists of articles to identify additional studies. We applied no language restrictions.
Selection criteria
All randomized trials of techniques that stimulated the PC6 acupoint compared with sham treatment or drug therapy, or combined PC6 acupoint and drug therapy compared to drug therapy, for the prevention of PONV. Interventions used in these trials included acupuncture, electro‐acupuncture, transcutaneous electrical acupoint stimulation, transcutaneous nerve stimulation, laser stimulation, capsicum plaster, acu‐stimulation device, and acupressure in people undergoing surgery. Primary outcomes were the incidences of nausea and vomiting after surgery. Secondary outcomes were the need for rescue antiemetic therapy and adverse effects.
Data collection and analysis
Two review authors independently extracted the data and assessed the risk of bias domains for each trial. We used a random‐effects model and reported risk ratio (RR) with associated 95% confidence interval (95% CI). We used trial sequential analyses to help provide information on when we had reached firm evidence in cumulative meta‐analyses of the primary outcomes, based on a 30% risk ratio reduction in PONV.
Main results
We included 59 trials involving 7667 participants. We rated two trials at low risk of bias in all domains (selection, attrition, reporting, blinding and other). We rated 25 trials at high risk in one or more risk‐of‐bias domains. Compared with sham treatment, PC6 acupoint stimulation significantly reduced the incidence of nausea (RR 0.68, 95% CI 0.60 to 0.77; 40 trials, 4742 participants), vomiting (RR 0.60, 95% CI 0.51 to 0.71; 45 trials, 5147 participants) and the need for rescue antiemetics (RR 0.64, 95% CI 0.55 to 0.73; 39 trials, 4622 participants). As heterogeneity among trials was substantial and there were study limitations, we rated the quality of evidence as low. Using trial sequential analysis, the required information size and boundary for benefit were reached for both primary outcomes.
PC6 acupoint stimulation was compared with six different types of antiemetic drugs (metoclopramide, cyclizine, prochlorperazine, droperidol. ondansetron and dexamethasone). There was no difference between PC6 acupoint stimulation and antiemetic drugs in the incidence of nausea (RR 0.91, 95% CI 0.75 to 1.10; 14 trials, 1332 participants), vomiting (RR 0.93, 95% CI 0.74 to 1.17; 19 trials, 1708 participants), or the need for rescue antiemetics (RR 0.87, 95% CI 0.65 to 1.16; 9 trials, 895 participants). We rated the quality of evidence as moderate, due to the study limitations. Using trial sequential analyses, the futility boundary was crossed before the required information size was surpassed for both primary outcomes.
Compared to antiemetic drugs, the combination of PC6 acupoint stimulation and antiemetic therapy reduced the incidence of vomiting (RR 0.56, 95% CI 0.35 to 0.91; 9 trials, 687 participants) but not nausea (RR 0.79, 95% CI 0.55 to 1.13; 8 trials, 642 participants). We rated the quality of evidence as very low, due to substantial heterogeneity among trials, study limitations and imprecision. Using trial sequential analysis, none of the boundaries for benefit, harm or futility were crossed for PONV. The need for rescue antiemetic was lower in the combination PC6 acupoint stimulation and antiemetic group than the antiemetic group (RR 0.61, 95% CI 0.44 to 0.86; 5 trials, 419 participants).
The side effects associated with PC6 acupoint stimulation were minor, transient and self‐limiting (e.g. skin irritation, blistering, redness and pain) in 14 trials. Publication bias was not apparent in the contour‐enhanced funnel plots.
Authors' conclusions
There is low‐quality evidence supporting the use of PC6 acupoint stimulation over sham. Compared to the last update in 2009, no further sham comparison trials are needed. We found that there is moderate‐quality evidence showing no difference between PC6 acupoint stimulation and antiemetic drugs to prevent PONV. Further PC6 acupoint stimulation versus antiemetic trials are futile in showing a significant difference, which is a new finding in this update. There is inconclusive evidence supporting the use of a combined strategy of PC6 acupoint stimulation and antiemetic drug over drug prophylaxis, and further high‐quality trials are needed.
The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification ...could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).
In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.
Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in
and
compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).
Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.
NCT03127696.
Although Q fever has been widely reported in the rural areas of China, there is a paucity of data on the epidemiology and clinical characteristics of this disease in large metropolitan cities. In ...this study, we profile the epidemiology and clinical manifestations of Q fever from a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city with a large immigrant population from other parts of China. A total of 14 patients were confirmed to have Q fever during a nine-year-and-six-month period, five of whom were retrospectively diagnosed during case review or incidentally picked up because of another research project on unexplained fever without localizing features. Some patients had the typical exposure histories and clinical features, while a few other patients had rare manifestations of Q fever, including one with heart failure and diffuse intracapillary proliferative glomerulonephritis, a patient presenting with a spontaneous bacterial peritonitis-like syndrome, and another one with concomitant Q fever and brucellosis. Using a combination of clinical manifestation, inflammatory marker levels, echocardiographic findings and serological or molecular test results, nine, three and two patients were diagnosed to have acute, chronic and convalescent Q fever, respectively. Seven, five and two patients were diagnosed to have Q fever by serological test, nested real-time PCR and next-generation sequencing respectively. Diverse and atypical manifestations are associated with Q fever. The incidence of Q fever is likely to be underestimated. Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections, particularly those that the physicians fail to recognize clinically, such as Q fever.
Lepidoptera (butterflies and moths) is one of the most geographically widespread insect orders in the world, and its species play important and diverse ecological and applied roles. Climate change is ...one of the biggest challenges to biodiversity this century, and lepidopterans are vulnerable to climate change. Temperature-dependent gene expression differences are of relevance under the ongoing climate crisis. However, little is known about how climate affects gene expression in lepidopterans and the ecological consequences of this, particularly with respect to genes with biased expression in one of the sexes. The common yellow butterfly, Eurema hecabe (Family Pieridae), is one of the most geographically widespread lepidopterans that can be found in Asia, Africa, and Australia. Nevertheless, what temperature-dependent effects there may be and whether the effects differ between the sexes remain largely unexplored. Here, we generated high-quality genomic resources for E. hecabe along with transcriptomes from eight developmental stages. Male and female butterflies were subjected to varying temperatures to assess sex-specific gene expression responses through mRNA and microRNA transcriptomics. We find that there are more temperature-dependent sex-biased genes in females than males, including genes that are involved in a range of biologically important functions, highlighting potential ecological impacts of increased temperatures. Further, by considering available butterfly data on sex-biased gene expression in a comparative genomic framework, we find that the pattern of sex-biased gene expression identified in E. hecabe is highly species-specific, rather than conserved across butterfly species, suggesting that sex-biased gene expression responses to climate change are complex in butterflies. Our study lays the foundation for further understanding of differential responses to environmental stress in a widespread lepidopteran model and demonstrates the potential complexity of sex-specific responses of lepidopterans to climate change.
To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong.
Array CGH was performed on 220 samples recruited prospectively as the ...first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays.
Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population.
Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.
BACKGROUND: The mountain pine beetle, Dendroctonus ponderosae Hopkins, is the most serious insect pest of western North American pine forests. A recent outbreak destroyed more than 15 million ...hectares of pine forests, with major environmental effects on forest health, and economic effects on the forest industry. The outbreak has in part been driven by climate change, and will contribute to increased carbon emissions through decaying forests. RESULTS: We developed a genome sequence resource for the mountain pine beetle to better understand the unique aspects of this insect's biology. A draft de novo genome sequence was assembled from paired-end, short-read sequences from an individual field-collected male pupa, and scaffolded using mate-paired, short-read genomic sequences from pooled field-collected pupae, paired-end short-insert whole-transcriptome shotgun sequencing reads of mRNA from adult beetle tissues, and paired-end Sanger EST sequences from various life stages. We describe the cytochrome P450, glutathione S-transferase, and plant cell wall-degrading enzyme gene families important to the survival of the mountain pine beetle in its harsh and nutrient-poor host environment, and examine genome-wide single-nucleotide polymorphism variation. A horizontally transferred bacterial sucrose-6-phosphate hydrolase was evident in the genome, and its tissue-specific transcription suggests a functional role for this beetle. CONCLUSIONS: Despite Coleoptera being the largest insect order with over 400,000 described species, including many agricultural and forest pest species, this is only the second genome sequence reported in Coleoptera, and will provide an important resource for the Curculionoidea and other insects.
To determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema ...(DMO) treated with antivascular endothelial growth factors (VEGF) injections.
This is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.
The presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.
Baseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation ...(Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.
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