Evaluating eDNA and eRNA metabarcoding for aquatic biodiversity assessment: From bacteria to vertebrates.

The monitoring and management of aquatic ecosystems depend on precise estimates of biodiversity. Metabarcoding analyses of environmental nucleic acids (eNAs), including environmental DNA (eDNA) and environmental RNA (eRNA), have garnered attention for their cost-effective and non-invasive biomonitoring capabilities. However, the accuracy of biodiversity estimates obtained through eNAs can vary among different organismal groups. Here we evaluate the performance of eDNA and eRNA metabarcoding across nine organismal groups, ranging from bacteria to terrestrial vertebrates, in three cross-sections of the Yangtze River, China. We observe robust complementarity between eDNA and eRNA data. The relative detectability of eNAs was notably influenced by major taxonomic groups and organismal sizes, with eDNA providing more robust signals for larger organisms. Both eDNA and eRNA exhibited similar cross-sectional and longitudinal patterns. However, the detectability of larger organisms declined in eRNA metabarcoding, possibly due to differential RNA release and decay among different organismal groups or sizes. While underscoring the potential of eDNA and eRNA in large river biomonitoring, we emphasize the need for differential interpretation of eDNA versus eRNA data. This highlights the importance of careful method selection and interpretation in biomonitoring studies.

Prevalence and prognosis of hypoxia-inducible factor-2α (HIF-2α) pathway gene mutations across advanced solid tumors.

INTRODUCTION: Hypoxia-inducible factor-2α (HIF-2α) modulates the hypoxic response pathway in tumors; however, mutations in pathways (including SDHA, SDHB, SDHC, SDHD, FH, and VHL genes) that are suspected to activate HIF-2α are poorly understood, with limited understanding of the prevalence and clinical prognosis. METHODS: This retrospective observational study used a de-identified nationwide (US-based) clinico-genomic database (CGDB) across 15 available tumor types. RESULTS: Among the 9467 adult patients with advanced/metastatic solid tumors included in the analysis, any mutation at the above-mentioned six genes was observed in 1.8% (95% CI: 1.5-2.1) of patients. The mutation prevalence ranged from 0.05% of SDHD to 0.93% of VHL. When further stratified by tumor type, the prevalence of gene mutation in each tumor type was well below 1%, except for VHL with 44% in renal cell carcinomas (RCC). Excluding RCC, the prevalence of any HIF-2α gene mutations in the study population was 0.9% (95% CI: 0.8-1.2). The median overall survival (OS) from 1 and 2 L therapy among patients with any HIF-2α gene mutation was 14.5 (95% CI: 11.5-24.2) and 9.3 (95% CI: 6.0-18.1) months, respectively, compared with 13.4 (95% CI: 12.9-13.9) and 9.8 (95% CI: 9.3-10.4) months among patients without HIF-2α gene mutations. DISCUSSION AND CONCLUSIONS: The prevalence of HIF-2α related gene mutations was generally low (<1%) across the 15 solid tumor types, except for VHL in RCC. No significant association between HIF-2α gene mutation status and OS was identified among patients evaluated in this study.

The therapeutic effectiveness of artificial intelligence-based chatbots in alleviation of depressive and anxiety symptoms in short-course treatments: A systematic review and meta-analysis.

BACKGROUND: The emergence of artificial intelligence-based chatbot has revolutionized the field of clinical psychology and psychotherapy, granting individuals unprecedented access to professional assistance, overcoming time constraints and geographical limitations with cost-effective convenience. However, despite its potential, there has been a noticeable gap in the literature regarding their effectiveness in addressing common mental health issues like depression and anxiety. This meta-analysis aims to evaluate the efficacy of AI-based chatbots in treating these conditions. METHODS: A systematic search was executed across multiple databases, including PubMed, Cochrane Library, Web of Science, PsycINFO, and Embase on April 4th, 2024. The effect size of treatment efficacy was calculated using the standardized mean difference (Hedge's g). Quality assessment measures were implemented to ensure trial's quality. RESULTS: In our analysis of 18 randomized controlled trials involving 3477 participants, we observed noteworthy improvements in depression (g = -0.26, 95 % CI = -0.34, -0.17) and anxiety (g = -0.19, 95 % CI = -0.29, -0.09) symptoms. The most significant benefits were evident after 8 weeks of treatment. However, at the three-month follow-up, no substantial effects were detected for either condition. LIMITATIONS: Several limitations should be considered. These include the lack of diversity in the study populations, variations in chatbot design, and the use of different psychotherapeutic approaches. These factors may limit the generalizability of our findings. CONCLUSION: This meta-analysis highlights the promising role of AI-based chatbot interventions in alleviating depressive and anxiety symptoms among adults. Our results indicate that these interventions can yield substantial improvements over a relatively brief treatment period.

[Spatial-temporal Distribution and Source Analysis of Polycyclic Aromatic Hydrocarbons in the Sediments of Poyang Lake].

The concentrations, spatial-temporal distribution, and influencing factors of 16 polycyclic aromatic hydrocarbons (PAHs) in the sediments of Poyang Lake were studied, and a quantitative source analysis of PAHs in different areas of the lake was conducted. PAHs were widespread within the sediments. The concentrations of ∑16PAHs in the surface sediments of all sites ranged from 203 to 2 318 µg·kg-1. The concentrations of PAHs in the surface sediments of the lake body were higher than those in the surface sediments of the inlet rivers. The ratio of PAHs in Poyang Lake was 4 rings > 5 rings > 6 rings > 3 rings > 2 rings; the composition of 4-ring PAHs was dominant, and its content accounted for 86.11% of ∑16PAHs. The 2- and 3-ring and some 4-ring PAHs, including Flua and Pyr, were more susceptible to SOM, and the 4 through 6-ring PAHs were more susceptible to ORP and heavy metals and other environmental factors. Spatially, the higher concentration of ∑16PAHs occurred in the area of the lake adjacent to Duchang County and Poyang County, where the terrain was relatively closed, and the water exchange with the surrounding area was less than that in other sections, which was not conducive to the migration, transformation, and degradation of pollutants. In the temporal distribution, the changes in PAHs concentration level and the development of GDP in Jiangxi Province showed high consistency, and the influence of economic development and human activities might have been the main reason for the increasing PAHs concentration level. The main sources of PAHs in surface sediments of Poyang Lake included petroleum pollution and oil and coal and biomass combustion sources, and there were some spatial differences in PAHs sources in different regions. This study can provide a reference for PAHs pollution in surface sediments of Poyang Lake, which is important for the ecological environmental protection and management of Poyang Lake.

Factors Associated With Decision to Use and Dosing of Sugammadex in Children: A Retrospective Cross-Sectional Observational Study.

BACKGROUND: Sugammadex was initially approved for reversal of neuromuscular blockade in adults in the United States in 2015. Limited data suggest sugammadex is widely used in pediatric anesthesia practice however the factors influencing use are not known. We explore patient, surgical, and institutional factors associated with the decision to use sugammadex versus neostigmine or no reversal, and the decision to use 2 mg/kg vs 4 mg/kg dosing. METHODS: Using data from the Multicenter Perioperative Outcomes Group (MPOG) database, an EHR-derived registry, we conducted a retrospective cross-sectional study. Eligible cases were performed between January 1, 2016 and December 31, 2020, for children 0 to 17 years at US hospitals. Cases involved general anesthesia with endotracheal intubation and administration of rocuronium or vecuronium. Using generalized linear mixed models with institution and anesthesiologist-specific random intercepts, we measured the importance of a variety of patient, clinician, institution, anesthetic, and surgical risk factors in the decision to use sugammadex versus neostigmine, and the decision to use a 2 mg/kg vs 4 mg/kg dose. We then used intraclass correlation statistics to evaluate the proportion of variance contributed by institution and anesthesiologist specifically. RESULTS: There were 97,654 eligible anesthetics across 30 institutions. Of these 47.1% received sugammadex, 43.1% received neostigmine, and 9.8% received no reversal agent. Variability in the choice to use sugammadex was attributable primarily to institution (40.4%) and attending anesthesiologist (27.1%). Factors associated with sugammadex use (compared to neostigmine) include time from first institutional use of sugammadex (odds ratio [OR], 1.08, 95% confidence interval [CI], 1.08-1.09, per month, P < .001), younger patient age groups (0-27 days OR, 2.59 [2.00-3.34], P < .001; 28 days-1 year OR, 2.72 [2.16-3.43], P < .001 vs 12-17 years), increased American Society of Anesthesiologists [ASA] physical status (ASA III: OR, 1.32 [1.23-1.42], P < .001 ASA IV OR, 1.71 [1.46-2.00], P < .001 vs ASA I), neuromuscular disease (OR, 1.14 (1.04-1.26], P = .006), cardiac surgery (OR, 1.76 [1.40-2.22], P < .001), dose of neuromuscular blockade within the hour before reversal (>2 ED95s/kg OR, 4.58 (4.14-5.07], P < .001 vs none), and shorter case duration (case duration <60 minutes OR, 2.06 [1.75-2.43], P < .001 vs >300 minutes). CONCLUSIONS: Variation in sugammadex use was primarily explained by institution and attending anesthesiologist. Patient factors associated with the decision to use sugammadex included younger age, higher doses of neuromuscular blocking agents, and increased medical complexity.

Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

BACKGROUND: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. METHODS: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018-2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. RESULTS: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. CONCLUSION: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia.

[Biological Evaluation and Key Stress Factor Diagnosis of Compound Contaminated Soil Based on Environmental DNA].

Healthy biological community composition and diversity are the basis for soil ecosystems to provide complete ecological functions and services. The current technical bottleneck in soil pollution control is the lack of systematic and comprehensive biodiversity indicators. In this study, the compound-polluted soil in an industrial park was taken as the object, and environmental DNA (eDNA)technology was used to monitor and analyze the composition of the biological community in the polluted soil. The environmental DNA-species sensitivity distribution (eDNA-SSD) method was constructed to diagnose the key stress factors and their ecological threshold. The results showed that:① compound pollution did not have a significant impact on the α-diversity of soil organisms in the park but led to changes in the composition of biological communities and dominant species with high relative abundance. The dominant groups in the polluted soil were Proteobacteria (25.54%), Ascomycota (15.65%), Actinobacteria (8.75%), and Chloroflexi (7.64%). ② Environmental factors accounted for 51.27% of the differences in soil biodistribution, and aniline, sulfate, petroleum hydrocarbon, and lead were the key stress factors for soil biomes. Among them, aniline had the most significant effect on the community distribution of bacteria (P=0.030), sulfate on fungi (P=0.025), and metazoans (P=0.032). ③ The ecological risk threshold (hazardous concentration for 5% of species, HC5) of pollutants with 95% species as the protection target showed a gradient decreasing trend of sulfate (470.00 mg·kg-1), petroleum hydrocarbon (17.00 mg·kg-1), lead (13.00 mg·kg-1), arsenic (6.20 mg·kg-1), 4-chloroaniline (0.16 mg·kg-1), and aniline (0.11 mg·kg-1). Nevertheless, the existing soil risk control value was significantly higher than the ecological risk value, indicating that the existing control standards targeting human health were not suitable for protecting soil health. The comprehensive pollution index showed that the soil pollution in the park was mostly mild pollution accompanied by heavy pollution at individual points. The biological evaluation method based on eDNA-SSD could achieve the comprehensive evaluation of composite pollution in the absence of the benchmark value of pollutants and at the same time better distinguish the differences in soil biological community structure and composition under different pollution levels (P=0.053). In conclusion, the environmental DNA soil biomonitoring and assessment method developed in this study has guiding significance and application value for soil ecosystem restoration assessment.

The usefulness of platelet-rich plasma to manage skin wounds: A meta-analysis.

A meta-analysis investigation to measure the usefulness of platelet-rich plasma (PRP) to manage skin wounds (SWs). A comprehensive literature inspection till February 2023 was applied and 1349 interrelated investigations were reviewed. The 22 chosen investigations enclosed animals' SWs were in the chosen investigations' starting point, 3348 of them were treated with PRP, and 2259 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the usefulness of PRP to manage SWs by the dichotomous and continuous approaches and a fixed or random model. PRP significantly higher percent of decreases in open wound area (OWA) (MD, 10.07; 95% CI, 6.55-13.59, P < 0.001), and lower healing time (HT) (MD, -6.31; 95% CI, -10.69 to -1.93, P = 0.005) compared to control in animals' SWs. PRP had a significantly higher percent of decreases in OWA and lower HT compared to control in animals' SWs. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Serum adiponectin concentrations as a risk factor for cardiovascular complications in type 1 diabetes.

AIM: By analyzing data from DCCT/EDIC study, we investigated the associations of serum adiponectin concentrations with macrovascular complications and cardiovascular events in T1D. MATERIALS AND METHODS: Adiponectin concentrations were measured in EDIC year 8. The participants (n = 1040) were divided into four groups by quartiles of adiponectin concentrations. The association of macrovascular complications and cardiovascular events were analyzed by using multivariable regression and Cox proportional hazards models. RESULTS: High adiponectin concentrations were associated with decreased risk of peripheral artery disease represented by ankle brachial index (ORs (95% CI): 0.22 (0.07-0.72), 0.48 (0.18-1.25), and 0.38 (0.14-0.99) in fourth, third, and second quartiles compared with first quartile), with reduced carotid intima-media thickness, and with increased LVEDV index. Moreover, high adiponectin concentrations were also associated with increased risk of any cardiovascular events (HRs (95% CI): 2.59 (1.10-6.06), 2.03 (0.90-4.59), and 1.22 (0.52-2.85)) and major atherosclerotic cardiovascular events (HRs (95% CI): 11.37 (2.04-63.43), 5.68 (1.04-31.07), and 3.76 (0.65-21.77) in fourth, third, and second quartiles compared with first quartile), however, after adjustments with LVEDV index, these associations were diminished. CONCLUSIONS: Adiponectin may protect carotid atherosclerosis and peripheral artery disease in T1D. It may be associated with increased cardiovascular events, depending on cardiac structural changes.

Environmental DNA metabarcoding revealed the impacts of anthropogenic activities on phytoplankton diversity in Dianchi Lake and its three inflow rivers.

Phytoplankton diversity is closely related to environmental variables and has been widely used in ecological health assessment of rivers and lakes. Combining advantages of DNA-based identification and high-throughput sequencing technology, environmental DNA (eDNA) metabarcoding permits a new measurement for biodiversity monitoring in aquatic ecosystems. However, it had rarely been used to explore the variability and similarity of phytoplankton diversity between lake and its inflow rivers and the effects of environmental variables on phytoplankton. This study utilized eDNA metabarcoding to investigate the spatial distribution of phytoplankton and the impacts of environmental variables on the phytoplankton diversity in Dianchi Lake (one of the most polluted urban lakes in China) and its main inflow rivers (Panlong River, Baoxiang River, and Chai River). A total of 243 distinct phytoplankton taxa were detected, covering 9 phyla, 30 classes, 84 orders, and 132 families, and the taxonomic richness of rivers was higher than that of Dianchi Lake. Distinct biodiversity patterns (e.g., community structure, dominant taxon, ɑ-diversity) were exhibited among Dianchi Lake and its three inflow rivers, but similar biodiversity patterns were also observed in Dianchi Lake and the estuarine sites. The patterns of phytoplankton diversity were closely related to environmental variables, which were associated with pollution sources from different anthropogenic activities (e.g., urbanization, water diversion, industrial and agricultural activities). The primary environmental variables correlated with phytoplankton diversity varied in different habitats. The total phosphorus (TP) and chemical oxygen demand (COD) positively correlated with the phytoplankton community structures in Dianchi Lake, whereas negatively correlated in Panlong River and Baoxiang River. The total nitrogen (TN) positively correlated with the phytoplankton community structures in Baoxiang River and Chai River but negatively correlated in Dianchi Lake. Overall, this study provides insights on the phytoplankton diversity monitoring and the conservation of its diversity and healthy management of Dianchi Lake.

Contribution of Comorbid Conditions to the Diagnosis of Insomnia: A Database Study in a Commercially Insured Population.

ABSTRACT: Insomnia is a common sleep disorder characterized as dissatisfaction with sleep quantity or quality resulting in distress or impairment of social, occupational, or other daily functioning. It is unknown if there are medical conditions that have strong associations with insomnia but are unrecognized in previous literature. In this cross-sectional study based on IBM Marketscan Research Databases, we measured insomnia and 78 medical conditions in patients with 2-year continuous enrollment during 2018-2019. We selected important comorbidities associated with insomnia for eight age-sex groups and built logistic regression models to measure the associations. The prevalence of diagnosed insomnia increased with age, from <0.4% in the age group 0-17 to 4%-5% in the age group ≥65. Females had a higher prevalence of insomnia than males. Anxiety and depression were two important comorbidities across all age-sex subgroups. Most odds ratios of comorbidities remained significant after adjusting for other comorbidities in regression models. We did not find any new medical conditions that had strong associations with insomnia but were unrecognized in previous literature. The findings can help physicians use comorbidities to identify patients with high risk of insomnia.

Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of CRISPR/dCas9-SAM system.

Aim: Hepatic fibrosis is one of the most common conditions worldwide, and yet no effective antifibrotic therapy is available. This study aimed to reverse hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system. Materials & methods: The authors constructed a modified-exosome delivery system targeting hepatic stellate cells (HSCs), and constructed the CRISPR/dCas9-SAM system inducing HSCs convert into hepatocyte-like cells in vitro and in vivo. Results: RBP4-modified exosomes could efficiently load and deliver the CRISPR/dCas9 system to HSCs. The in vitro CRISPR/dCas9 system induced the conversion from HSCs to hepatocyte-like cells via targeted activation of HNF4α/HGF1/FOXA2 genes. Importantly, in vivo targeted delivery of this system significantly attenuated CCl4-induced hepatic fibrosis. Conclusion: Targeted activation of HNF4α/HGF1/FOXA2 reverses hepatic fibrosis via exosome-mediated delivery of the CRISPR/dCas9-SAM system, which provides a feasible antifibrotic strategy.

CRISPR/dCas9 for hepatic fibrosis therapy: implications and challenges.

Hepatic fibrosis is a pathological reaction of tissue damage and repair caused by various pathogenic factors acting on liver. At present, there is no effective anti-fibrotic specific therapy. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system is a new generation of gene editing technology. The CRISPR/dCas9 system provides a platform for studying site-specific transcriptional regulation, which has high efficiency in gene transcriptional activation for achieving robust. This system holds promise for hepatic fibrosis therapy via acting on liver fibrosis effector cells. However, there are some challenges associated with this novel technology, such as large structural variants at on-target, off-target sites, and targeted delivery efficiency. In this review, we present the potential implications and describe the challenges of CRISPR/dCas9 system that might be encountered in hepatic fibrosis therapy.

HbA1c Variability as an Independent Risk Factor for Microvascular Complications in Type 1 Diabetes.

BACKGROUND: There are few studies on the role of long-term glycemic variability in complications of type 1 diabetes (T1D). This study was aimed to investigate the associations of HbA1c variability represented by the coefficient of variation of HbA1c with incident microvascular complications in T1D by analyzing the data set from the DCCT/EDIC study. METHODS: Patients (n = 1240) were divided into four groups by HbA1c variability quartiles. Incident microvascular complications were assessed for a duration of an average of 20.5 years. Multivariable models were performed to examine the associations between HbA1c variability and incident microvascular complications. RESULTS: All incident microvascular complications were higher in the fourth quartile of the HbA1c variability group. After adjusting for clinical risk factors, HbA1c variability was positively associated with a higher risk of all diabetic microvascular complications (P < .05). Specifically, it had 1.125 (1.082-1.170), 1.114 (1.074-1.154), 1.061 (1.024-1.099), or 1.088 (1.052-1.125) times higher odds (95% confidence interval [CI]) of having retinopathy, nephropathy, clinical neuropathy, or autonomic neuropathy, independent of mean HbA1c values (P < .05). Furthermore, there were higher incident microvascular complications with higher HbA1c variability when HbA1c value was above the group median of 7.9%, while only higher incident autonomic neuropathy with higher HbA1c variability when HbA1c was below the group median. CONCLUSIONS: Our results showed a significant independent association between HbA1c variability and the risk of microvascular complications in T1D. HbA1c variability might be a supplemental risk stratification tool to mean HbA1c for microvascular complications in T1D.

Holistic Impact Evaluation of Human Activities on the Coastal Fish Biodiversity in the Chinese Coastal Environment.

Ecological qualities and resources in coasts are threatened by various human activities, such as pollution and fishery. Impact evaluation of environmental stressors over a wide coastal stretch has been limited due to lack of efficient and standardizable biodiversity monitoring and assessment tools. Integrating environmental DNA (eDNA) and ecological traits, a holistic approach was developed to assess the impact of pollution and aquaculture on fish biodiversity in Chinese coastal areas. Taking the Yalujiang Estuary (YLJK) from the Yellow Sea and the Nan'ao Island Area (NAO) from the South China Sea as cases, the performance of the eDNA biomonitoring workflow was validated. First, the eDNA results of 22 sampling sites reached more than 85% of the asymptotes of species or ASVs in each area. A total of 115 fish species in both areas were detected and NAO was 1.8 times richer than YLJK using eDNA and the fish eDNA composition was consistent with the historical data. eDNA recovered distinct variations of fish sequence, taxonomic and functional diversity, and the corresponding trends following the offshore distance between the two areas. Fish sequence diversity was decreased primarily by estuarine pollution factors (chemical oxygen demand and zinc) in the YLJK. Compared with no breeding areas, lower fish sequence diversity was in breeding areas in the NAO. By integrating ecological traits, the eDNA approach offers promising opportunities for future fish biodiversity monitoring and assessment in national and global coastal environments.

Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River.

Since a large number of contaminants are detected in source waters (SWs) and tap waters (TWs), it is important to perform a comprehensive effect evaluation and key contributor identification. A reduced human transcriptome (RHT)-based effect-directed analysis, which consisted of a concentration-dependent RHT to reveal the comprehensive effects and noteworthy pathways and systematic identification of key contributors based on the interactions between compounds and pathway effects, was developed and applied to typical SWs and TWs along the Yangtze River. By RHT, 42% more differentially expressed genes and 33% more pathways were identified in the middle and lower reaches, indicating heavier pollution. Hormone and immune pathways were prioritized based on the detection frequency, sensitivity, and removal efficiency, among which the estrogen receptor pathway was the most noteworthy. Consistent with RHT, estrogenic effects were widespread along the Yangtze River based on in vitro evaluations. Furthermore, 38 of 100 targets, 39 pathway-related suspects, and 16 estrogenic nontargets were systematically identified. Among them, diethylstilbestrol was the dominant contributor, with the estradiol equivalent (EEQ) significantly correlated with EEQwater. In addition, zearalenone and niclosamide explained up to 54% of the EEQwater. The RHT-based EDA method could support the effect evaluation, contributor identification, and risk management of micropolluted waters.

Changes of insulin resistance status and development of complications in type 1 diabetes mellitus: Analysis of DCCT/EDIC study.

AIM: There is no longitudinal study regarding the changes of insulin resistance (IR) status and the development of complications in type 1 diabetes (T1D). By analyzing data sets from DCCT/EDIC study, we investigated the associations of IR status changes and diabetic complications in T1D. MATERIALS AND METHODS: Estimated glucose disposal rate (eGDR) was calculated at entry of DCCT and in EDIC year 12 (average 18.5 years later) to represent IR. The participants (n = 957) were divided into four groups based on IR changes from baseline: RR group (stayed resistant; n = 49), RS group (became sensitive; n = 42), SR group (became resistant; n = 197), and SS group (stayed sensitive; n = 669). The association of diabetic complications were analyzed by using multivariable logistic regression models. RESULTS: The improved IR decreased the risk of peripheral neuropathy, whereas the deteriorated IR increased the risk of diabetic complications including hypertension, peripheral artery disease, coronary artery calcification, retinopathy, albuminuria, peripheral neuropathy, and cardiac autonomic neuropathy (P < 0.05). Moreover, RR group (HR = 3.59, 95% CI (2.05-6.32)), RS group (HR = 2.27, 95% CI (1.11-4.64)) and SR group (HR = 1.90, 95% CI (1.24-2.92)) had higher risk of cardiovascular events compared to SS group (P < 0.05). CONCLUSIONS: This study highlights the importance of IR changes represented by eGDR in the development of diabetic complications. Patients with T1D and IR may require intensive therapy.