The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications

Diabetic retinopathy is one of the most common complications of diabetes mellitus and the leading cause of low vision and blindness worldwide. Mounting evidence demonstrates that inflammation is a key mechanism driving diabetes-associated retinal disturbance, yet the pathophysiological process and molecular mechanisms of inflammation underlying diabetic retinopathy are not fully understood. Cytokines, chemokines, and adhesion molecules interact with each other to form a complex molecular network that propagates the inflammatory and pathological cascade of diabetic retinopathy. Therefore, it is important to understand and elucidate inflammation-related mechanisms behind diabetic retinopathy progression. Here, we review the current understanding of the pathology and pathogenesis of inflammation in diabetic retinopathy. In addition, we also summarize the relevant clinical trials to further suggest inflammation-targeted therapeutics for prevention and management of diabetic retinopathy

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acutely decompensated cirrhosis

BACKGROUND AND AIMS: Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in cirrhosis patients with acute decompensation (AD), focusing on NHVs and related the findings to clinical outcomes. METHODS: Plasma mNGS was performed in 129 cirrhosis patients with AD in study cohort. Ten healthy volunteers and 20, 39, and 81 patients with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation in a validation cohort (n = 58) were performed and exploratory treatment instituted. RESULTS: In study cohort, 188 microorganisms were detected in 74.4% (96/129) patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). Patients with AD had an NHV signature, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure (ACLF), and 90-day mortality. The NHV signature in ACLF patients was similar to patients with sepsis and hematological malignancies. The treatable NHV, CMV was detected in 24.1% (14/58) patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, 9 were further validated by DNA RT-PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in exploratory manner with clinical resolutions. CONCLUSIONS: The results of this study suggests that NHVs may have a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated in the routine management of AD patients. IMPACT AND IMPLICATIONS: ●Cirrhosis patients with acute decompensation have a non-hepatotropic virus (NHV) signature, which is similar to that in sepsis and hematological malignancies patients. ●The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. ●The treatable NHV, CMV reactivation may be involved in the clinical outcomes of decompensated cirrhosis. ●Routine screening for NHVs, especially CMV, may be useful for the management of patients with acutely decompensated cirrhosis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Clinical and laboratory characteristics of severe fever with thrombocytopenia syndrome in Chinese patients

Severe fever with thrombocytopenia syndrome (SFTS) associated with severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging infectious disease. 12 patients with severe fever with thrombocytopenia syndrome in our study were presented mainly with fever and severe malaise. The clinical manifestations typically became worse on the 6th or 7th day. The average fever time is 9.11 ± 1.54 days. Most of them had multiorgan dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of white blood cells (WBC), platelets (PLT) and serum Ca++, while increase of aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). CD3+CD4+ were significantly decreased, while CD3-CD56+ were significantly increased, whereas CD3+CD8+ were constantly elevated throughout the disease course. Ten to 14 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities. These results indicate that severe fever with thrombocytopenia syndrome has an acute onset and self-limited course. It is a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests is consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to better understand this disease and guide the clinical treatment

Redox-dependent effects of phosphate on arsenic speciation in paddy soils

Capsule: Contrasting effects of phosphate on As speciation were observed. In suboxic soils, phosphate inhibited Fe and As reduction, but in anoxic soils, phosphate stimulated Fe and As reduction.</p

Understanding major NOM properties controlling its interactions with phosphorus and arsenic at goethite-water interface

Among natural organic matter (NOM), oxyanions and metal (hydr)oxides, a complicated interaction exists in natural aquatic and terrestrial systems and in waste waters. Effects of seven types of NOM (four humic acids (HA), three fulvic acids (FA)) that vary in properties on the adsorption of oxyanions, including phosphate, arsenate and arsenite, at goethite-water interface were quantitatively studied. Results show that the adsorption of oxyanions to goethite is decreased by the presence of NOM, especially for phosphate and arsenate at low pH. In general, the effects of the three FA are similar, which are more effective than HA in reducing oxyanion adsorption at low pH (<6). Differences were observed between the four HA in their competition with oxyanions. The adsorption of phosphate, arsenate and arsenite in the presence of NOM are well described with both the NOM-CD (CD: Charge Distribution) and LCD (Ligand and Charge Distribution) model. The NOM-CD model is relatively simple to use, whereas the LCD model can better reveal different factors in the interaction, including the spatial distribution of adsorbed NOM on oxide surface. According to these two models: site density of carboxylic groups, protonation constant of carboxylic groups, and particle size of NOM are major properties of NOM determining its effect on oxyanion adsorption to oxides. At relatively low loadings, morphological change of adsorbed NOM takes place, and the degree of morphological change of adsorbed NOM depends on the particle size, site density of carboxylic groups and aromaticity of NOM. The influence of particle size on the interaction becomes more important at higher NOM loadings. The results suggested that the fixation or removal efficiency of phosphate, arsenate and arsenite with iron oxides (e.g. goethite) can be significantly decreased by the presence of NOM, especially when NOM rich in acidic and aromatic groups.</p

Comparison of the effects of large-grained and nano-sized biochar, ferrihydrite, and complexes thereof on Cd and As in a contaminated soil–plant system

Cd and As are difficult to co-remediate in co-contaminated soils. In this study, remediation materials comprising large-grained and nano-sized biochar (BC), ferrihydrite (FH), and complexes thereof were added to Cd- and As-contaminated soil. The uptake of Cd and As by pak choi (Brassica chinensis L.) was then evaluated using a pot experiment and the Cd and As concentrations of the soil pore water and leaching water were measured. The Cd and As concentrations of the pore and leaching water were slightly increased with the addition of BC, and decreased with addition of FH and the biochar–ferrihydrite complex (BC-FH). However, nano-sized BC (BCN), FH (FHN), and BC-FH (BC–FHN) had little influence on the decreases in Cd and As of the two monitored water types. Large-grained remediation materials, rather than nanomaterials, decreased the Cd and As concentrations of the two monitored water types. Nonetheless, nanomaterial treatments more effectively decreased the Cd and As concentrations in plants by an average of >10% relative to the large-grained treatments. The DLVO theory analysis suggested that BCN, FHN, and BC-FHN, immobilized in the topsoil, adsorbed heavy metals in the rhizosphere soil. The remainder of the nano-sized materials was dispersed in the rhizosphere soil pores, shielding the uptake of Cd and As by the roots. Although the doses of nanomaterials used in this study were less than one-fortieth of those of the large-grained materials, changes in the plant rhizosphere microenvironment caused by the nanomaterials decreased the risk of toxicity transfer from the soil to the plants.</p