Amorphous curcumin-based hydrogels to reduce the incidence of post-surgical intrauterine adhesions.

The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-ß1. To assess the effectiveness of preventing IUAs, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.

Human umbilical cord mesenchymal stem cells combined with porcine small intestinal submucosa promote the healing of full-thickness skin injury in SD rats.

Aim: To assess the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with porcine small intestinal submucosa (SIS) on full-thickness skin injuries in rats. Methods: We established full-thickness skin injury models in Sprague-Dawley rats, dividing them into blank control, SIS, hUCMSCs and hUCMSCs combined with SIS. We monitored wound healing, scores and area, and analyzed inflammatory cells, microvessel density and collagen fibers after 12 days. Results: The blank group showed no healing, forming a scar of 0.6 × 0.5 cm2, while SIS and hUCMSCs groups exhibited incomplete healing with 0.4 × 0.5 cm2 scabs. Wound healing was significantly better in the hUCMSCs combined with the SIS group. Conclusion: Local application of hUCMSCs combined with SIS enhances full-thickness skin injury wound healing in rats.

Our skin protects us from infections and injuries, but severe damage can lead to health problems. In this study, we explored a promising new treatment to enhance skin healing. We used mesenchymal stem cells derived from umbilical cords in combination with a biological material called porcine small intestinal submucosa (SIS) to conduct experiemnts on rats with skin wounds. This treatment led to much better healing in rats with deep skin wounds compared with standard approaches. This approach is promising for treating severe skin injuries, offering hope for quicker recovery and better outcome, including faster recovery, reduced pain and inflammation and less scarring.

Depolymerization and Re/Upcycling of Biodegradable PLA Plastics.

With the escalating utilization of plastic products, global attention has been increasingly drawn to environmental pollution and recycling challenges stemming from plastic waste. Against this backdrop, biodegradable plastics have emerged as viable alternatives owing to their sustainability and capacity for biodegradation. Polylactic acid (PLA) presently commands the largest market share among biodegradable plastics, finding extensive application in products such as thin films, medical materials, and biodegradable straws. However, the widespread adoption of PLA is hindered by challenges such as high cost, low recycling rates, and complete degradation to H2O and CO2 in natural conditions. Therefore, it is imperative and time-sensitive to explore solutions for the depolymerization and re/upcycling of PLA waste plastics. This review comprehensively outlines the current landscape of PLA recycling methods, emphasizing the advantages and significance of chemical re/upcycling. The subsequent exploration encompasses recent breakthroughs and technical obstacles inherent in diverse chemical depolymerization methods. Ultimately, this review accentuates the impediments and forthcoming possibilities in the realm of PLA plastics, emphasizing the pursuit of closed-loop recycling and upcycling.

Enhancing Quantitative Analysis of Xenobiotics in Blood Plasma through Cross-Matrix Calibration and Bayesian Hierarchical Modeling.

This study addresses the challenges of matrix effects and interspecies plasma protein binding (PPB) on measurement variability during method validation across diverse plasma types (human, rat, rabbit, and bovine). Accurate measurements of small molecules in plasma samples often require matrix-matched calibration approaches with the use of specific plasma types, which may have limited availability or affordability. To mitigate the costs associated with human plasma measurements, we explore in this work the potential of cross-matrix-matched calibration using Bayesian hierarchical modeling (BHM) to correct for matrix effects associated with PPB. We initially developed a targeted quantitative approach utilizing biocompatible solid-phase microextraction coupled with liquid chromatography-mass spectrometry for xenobiotic analysis in plasma. The method was evaluated for absolute matrix effects across human, bovine, rat, and rabbit plasma comparing pre- and postmatrix extraction standards. Absolute matrix effects from 96 to 108% for most analytes across plasma sources indicate that the biocompatibility of the extraction phase minimizes interference coextraction. However, the extent of PPB in different media can still affect the accuracy of the measurement when the extraction of small molecules is carried out via free concentration, as in the case of microextraction techniques. In fact, while matrix-matched calibration revealed high accuracy, cross-matrix calibration (e.g., using a calibration curve generated from bovine plasma) proved inadequate for precise measurements in human plasma. A BHM was used to calculate correction factors for each analyte within each plasma type, successfully mitigating the measurement bias resulting from diverse calibration curve types used to quantify human plasma samples. This work contributes to the development of cost-effective, efficient calibration strategies for biofluids. Leveraging easily accessible plasma sources, like bovine plasma, for method optimization and validation prior to analyzing costly plasma (e.g., human plasma) holds substantial advantages applicable to biomonitoring and pharmacokinetic studies.

Phlebosclerosis: An overlooked complication of varicose veins that affects clinical outcome: A case report.

BACKGROUND: Phlebosclerosis is a common age-related fibrotic degeneration of the venous wall. It is a disorder rather than a disease, which may cause venous dysfunction and even venous thrombosis. It is rarely reported in patients with varicose veins. CASE SUMMARY: The present report describes the case of a 70-year-old man with varicose veins, vitiligo, and phlebosclerosis. Venous angiography revealed blood reflux in the superficial and deep veins. The patient underwent surgery to remove the saphenous veins. During the operation, a calcified vein resembling a wooden stick was found, which was surprisingly extracted from the thickened venous wall. A cross-section of this wooden stick-like vein revealed venous fibrosis and calcification, obvious thickening of the venous wall, extensive collagen deposition on the venous wall, hyaline degeneration, and venous sclerosis causing closure of the venous lumen. CONCLUSION: This is probably the first report of a wooden stick-like structure being found in the venous wall in patients with varicose veins and venous ulcers. Phlebosclerosis can be observed in the late stage of varicose veins complicated by frequent infections and worse clinical outcomes. Therefore, it is important to be aware of this condition and address it rather than overlook it.

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites.

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4'-trihydroxy-isoflavonoid; (Sm7)7,4'-dihydroxy-isoflavonoid; (Sm9)7,8,4'-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4'-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4'-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor.

Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis.

Background: The impact of lipid-lowering medications on sepsis is still not well defined. A Mendelian randomization (MR) study was carried out to probe the causal connections between genetically determined lipids, lipid-reducing drugs, and the risk of sepsis. Materials and methods: Data on total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and triglycerides (TG) were retrieved from the MR-Base platform and the Global Lipids Genetics Consortium in 2021 (GLGC2021). Our study categorized sepsis into two groups: total sepsis and 28-day mortality of sepsis patients (sepsis28). The inverse-variance weighted (IVW) method was the primary method used in MR analysis. Cochran's Q test and the MR-Egger intercept method were used to assess the heterogeneity and pleiotropy. Results: In the MR analysis, we found that ApoA-I played a suggestively positive role in protecting against both total sepsis (OR, 0.863 per SD increase in ApoA-I; 95% CI, 0.780-0.955; P = 0.004) and sepsis28 (OR, 0.759; 95% CI, 0.598-0.963; P = 0.023). HDL-C levels were also found to suggestively reduce the incidence of total sepsis (OR, 0.891 per SD increase in HDL-C; 95% CI, 0.802-0.990; P = 0.031). Reverse-MR showed that sepsis28 led to a decrease in HDL-C level and an increase in TG level. In drug-target MR, we found that HMGCR inhibitors positively protected against total sepsis (1OR, 0.719 per SD reduction in LDL-C; 95% CI, 0.540-0.958; P = 0.024). LDL-C and HDL-C proxied CETP inhibitors were found to have a protective effect on total sepsis, with only LDL-C proxied CETP inhibitors showing a suggestively protective effect on sepsis28. In Mediated-MR, BMI exhibited a negative indirect effect in HMGCR inhibitors curing sepsis. The indirect impact of ApoA-I explained over 50% of the curative effects of CETP inhibitors in sepsis. Conclusions: Our MR study suggested that ApoA-I and HDL-C protected against sepsis, while HMGCR and CETP inhibitors showed therapeutic potential beyond lipid-lowering effects. ApoA-I explained the effects of CETP inhibitors. Our study illuminates how lipids affect sepsis patients and the effectiveness of new drugs, opening new avenues for sepsis treatment.

Nutrient reduction mitigated the expansion of cyanobacterial blooms caused by climate change in Lake Taihu according to Bayesian network models.

Although nutrient reduction has been used for lake eutrophication mitigation worldwide, the use of this practice alone has been shown to be less effective in combatting cyanobacterial blooms, primarily because of climate change. In addition, quantifying the climate change contribution to cyanobacterial blooms is difficult, further complicating efforts to set nutrient reduction goals for mitigating blooms in freshwater lakes. This study employed a continuous variable Bayesian modeling framework to develop a model to predict spring cyanobacterial bloom areas and frequencies (the responses) using nutrient levels and climatic factors as predictors. Our results suggested that both spring climatic factors (e.g., increasing temperature and decreasing wind speed) and nutrients (e.g., total phosphorus) played vital roles in spring blooms in Lake Taihu, with climatic factors being the primary drivers for both bloom areas and frequencies. Climate change in spring had a 90% probability of increasing the bloom area from 35 km2 to 180 km2 during our study period, while nutrient reduction limited the bloom area to 170 km2, which helped mitigate expansion of cyanobacterial blooms. For lake management, to ensure a 90% probability of the mean spring bloom areas remaining under 154 km2 (the 75th percentile of the bloom areas in spring), the total phosphorus should be maintained below 0.073 mg·L-1 under current climatic conditions, which is a 46.3% reduction from the current level. Our modeling approach is an effective method for deriving dynamic nutrient thresholds for lake management under different climatic scenarios and management goals.

DECREASE IN THE PLATELET-TO-LYMPHOCYTE RATIO IN DAYS AFTER ADMISSION FOR SEPSIS CORRELATES WITH IN-HOSPITAL MORTALITY.

ABSTRACT: Background: A previous study has linked an increase in platelet-to-lymphocyte ratio (PLR) to a poor prognosis; however, the relationship between early change in PLR and outcomes in sepsis patients is unclear. Methods : The Medical Information Mart for Intensive Care IV database was for this retrospective cohort analysis on patients meeting the Sepsis-3 criteria. All the patients meet the Sepsis-3 criteria. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count. We collected all PLR measurements that were available within 3 days of admission for analysis of longitudinal changes over time. Multivariable logistic regression analysis was used to determine the relationship between the baseline PLR and in-hospital mortality. After correcting for possible confounders, the generalized additive mixed model was used to examine the trends in PLR over time among survivors and nonsurvivors. Results: Finally, 3,303 patients were enrolled, and both low and high PLR levels were significantly associated with higher in-hospital mortality in the multiple logistic regression analysis (tertile 1: odds ratio, 1.240; 95% confidence interval, 0.981-1.568 and tertile 3: odds ratio, 1.410; 95% confidence interval, 1.120-1.776, respectively). The generalized additive mixed model results revealed that the PLR of the nonsurvival group declined faster than that of the survival group within 3 days after intensive care unit admission. After controlling for confounders, the difference between the two groups steadily decreased and increased by an average of 37.38 daily. Conclusions : There was a U-shaped relationship between the baseline PLR and in-hospital mortality of sepsis patients, and there was a significant difference between the nonsurvival and survival groups in the change in PLR over time. The early decrease in PLR was related to an increase in in-hospital mortality.

Strategies and challenges in treatment of varicose veins and venous insufficiency.

Patients with varicose veins can be treated with conservative or surgical approaches based on the clinical conditions and patient preferences. In the recent decade, the recommendations for managing symptomatic varicose veins have changed dramatically due to the rise of minimally invasive endovascular techniques. The literature was systematically searched on Medline without language restrictions. All papers on the treatment of varicose veins and venous insufficiency with different procedures were included and reviewed. Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) both are same safe and effective in terms of occlusion rate, and time to return to normal activity. In comparison with RFA or EVLT, Cure conservatrice et Hemodynamique de l'Insufficience Veineuse en Ambulatoire (CHIVA) may cause more bruising and make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury, or hematoma. In terms of recurrence of varicose veins, there is little or no difference between CHIVA and stripping, RFA, or EVLT. Great saphenous vein recanalization is highest in the ultrasound-guided foam sclerotherapy (FS) group (51%) during 1 year of follow-up. The 2013 National Institute for Health and Care Excellence clinical guidelines recommend surgery as a third-line therapeutic option after EVLA or RFA and sclerotherapy. Although the mechanochemical endovenous ablation (MOCA) is a non-thermal, non-tumescent option and appears to be of similar efficacy to stab avulsion with no potential risk of nerve damage, the overall success rate of MOCA is lower than those of other procedures such as EVLA, RFA, or high ligation and stripping. EVLA is the most cost-effective therapeutic option, with RFA being a close second for the treatment of patients with varicose veins. Endovenous thermal ablation (EVLA or RFA) is recommended as a first-line treatment for varicose veins and has substituted the high ligation of saphenofemoral junctional reflux and stripping of varicose veins. Ultrasound-guided FS is associated with a high recurrence rate and can be used in conjunction with other procedures. MOCA and cyanoacrylate embolization appear promising, but evidence of their effectiveness is required.

Large-scale patterns of understory biomass and its allocation across China's forests.

Plant biomass storage and its allocation reflect the ecosystem productivity and adaptation to different environments. Understory vegetation is a significant component of any forest ecosystem and plays a vital role in biodiversity maintenance and the ecosystem's carbon cycle. Although many studies have addressed the relationships of climate, stand structure and resource availability with understory biomass and its allocation at local scales, the large-scale variation of understory biomass and allocation and their underlying mechanisms remain unclear. We compiled a large database of understory biomass at the community level across China's forests to explore the large-scale patterns of understory biomass and R/S ratio, and to quantify the relative importance of drivers. Understory biomass and R/S ratio varied largely with forest types, and decreased with increasing longitude, but increased with elevation. Understory biomass increased with increasing latitude, mean annual temperature (MAT), and mean annual precipitation (MAP), while the R/S ratio decreased with latitude, MAT, and MAP. Stand structure had a strong effect on the variations in understory biomass. MAP was the most important driver in determining R/S ratio. This synthesis provides a first assessment of the large-scale patterns of understory biomass and allocation and sheds new light on the mechanisms underlying the variations in understory biomass and its allocation over a broad geographic scale. These findings will improve predictions of understory community dynamics in response to climate change and aid in further optimizing ecosystem process models.

Association of FIB-4 index and clinical outcomes in critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and clinical outcomes in patients with acute kidney injury (AKI) is unclear. We aimed to investigate the association between FIB-4 index and all-cause mortality in critically ill patients with AKI. METHODS: We used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). The FIB-4 score was calculated using the existing formulas. logistic regression model, and Cox proportional hazards model were used to assessed the relationship between the FIB-4 index and in-hospital,28-day and 90-day mortality, respectively. RESULTS: A total of 3592 patients with AKI included in the data analysis. 395 (10.99%) patients died during hospitalization and 458 (12.74%) patients died in 28-day. During the 90-day follow-up, 893 (22.54%) patients were dead. An elevated FIB-4 value was significantly associated with increased in-hospital mortality when used as a continuous variable (odds ratio [OR] 1.183, 95% confidence interval [CI] 1.072-1.305, P = 0.002) and as a quartile variable (OR of Q2 to Q4 1.216-1.744, with Q1 as reference). FIB-4 was positively associated with 28-day mortality of AKI patients with hazard ratio (HR) of 1.097 (95% CI 1.008, 1.194) and 1.098 (95% 1.032, 1.167) for 90-day mortality, respectively. CONCLUSION: This study demonstrated the FIB-4 index is associated with clinical outcomes in critically ill patients with acute kidney injury.

Fibroblast growth factor 21 associating with serotonin and dopamine in the cerebrospinal fluid predicts impulsivity in healthy subjects.

BACKGROUND: Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects. METHODS: A total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits. RESULTS: Negative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity. CONCLUSIONS: FGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Evaluating the impact of watershed development and climate change on stream ecosystems: A Bayesian network modeling approach.

A continuous-variable Bayesian network (cBN) model is used to link watershed development and climate change to stream ecosystem indicators. A graphical model, reflecting our understanding of the connections between climate change, weather condition, loss of natural land cover, stream flow characteristics, and stream ecosystem indicators is used as the basis for selecting flow metrics for predicting macroinvertebrate-based indicators. Selected flow metrics were then linked to variables representing watershed development and climate change. We fit the model to data from two river basins in southeast US and the resulting model was used to simulate future stream ecological conditions using projected future climate and development scenarios. The three climate models predicted varying ecological condition trajectories, but similar worst-case ecological conditions. The established modeling approach couples mechanistic understanding with field data to develop predictions of management-relevant variables across a heterogeneous landscape. We discussed the transferability of the modeling approach.

The association between triglyceride glucose index and depression: data from NHANES 2005-2018.

BACKGROUND: The association between triglyceride glucose (TyG) index and depression is unclear. We conducted this analysis to explore whether higher TyG index is associated with a higher odd of depression. METHODS: This was an observational study using data from the National Health and Nutrition Examination Survey (2005-2018), a cross-sectional and nationally representative database. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). TyG index was calculated based on the equation as follows: ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2], and participants were divided into quartiles based on TyG index. Weighted multivariable logistic regression models were used to explore the relationship between the TyG index and depression. RESULTS: A total of 13,350 patients were included, involving 1001 (7.50%) individuals with depression. Higher TyG index is significantly associated with elevated depressive symptoms in U.S. adults. Multivariate-adjusted HRs for patients in the TyG index 4th quartile were higher for depression (OR = 1.46; 95% confidence interval (CI) 1.30, 1.64) compared with the 1st quartile of TyG index. Similar results were seen in men and women, across age groups, and baseline comorbidities. CONCLUSION: In this large cross-sectional study, our result suggests that population with higher TyG index are significantly more likely to have depressive symptoms in U.S. adults.

Improving the reliability of eDNA data interpretation.

Global declines in biodiversity highlight the need to effectively monitor the density and distribution of threatened species. In recent years, molecular survey methods detecting DNA released by target-species into their environment (eDNA) have been rapidly on the rise. Despite providing new, cost-effective tools for conservation, eDNA-based methods are prone to errors. Best field and laboratory practices can mitigate some, but the risks of errors cannot be eliminated and need to be accounted for. Here, we synthesize recent advances in data processing tools that increase the reliability of interpretations drawn from eDNA data. We review advances in occupancy models to consider spatial data-structures and simultaneously assess rates of false positive and negative results. Further, we introduce process-based models and the integration of metabarcoding data as complementing approaches to increase the reliability of target-species assessments. These tools will be most effective when capitalizing on multi-source data sets collating eDNA with classical survey and citizen-science approaches, paving the way for more robust decision-making processes in conservation planning.

Seasonal overturn and stratification changes drive deep-water warming in one of Earth's largest lakes.

Most of Earth's fresh surface water is consolidated in just a few of its largest lakes, and because of their unique response to environmental conditions, lakes have been identified as climate change sentinels. While the response of lake surface water temperatures to climate change is well documented from satellite and summer in situ measurements, our understanding of how water temperatures in large lakes are responding at depth is limited, as few large lakes have detailed long-term subsurface observations. We present an analysis of three decades of high frequency (3-hourly and hourly) subsurface water temperature data from Lake Michigan. This unique data set reveals that deep water temperatures are rising in the winter and provides precise measurements of the timing of fall overturn, the point of minimum temperature, and the duration of the winter cooling period. Relationships from the data show a shortened winter season results in higher subsurface temperatures and earlier onset of summer stratification. Shifts in the thermal regimes of large lakes will have profound impacts on the ecosystems of the world's surface freshwater.

Dynamic Bayesian Networks to Assess Anthropogenic and Climatic Drivers of Saltwater Intrusion: A Decision Support Tool Toward Improved Management.

Saltwater intrusion (SWI) is a global coastal problem caused by aquifer overpumping, land-use change, and climate change impacts. Given the complex pathways that lead to SWI, coastal urban areas with poorly monitored aquifers are in need of probabilistic-based decision support tools that can assist in better understanding and predicting SWI, while exploring effective means for sustainable aquifer management. In this study, we develop a Bayesian Belief Network (BBN) to account for the complex interactions of climatic and anthropogenic processes leading to SWI, while relating the severity of SWI to associated socioeconomic impacts and possible adaptation strategies. The BBN is further expanded into a Dynamic Bayesian Network (DBN) to assess the temporal progression of SWI and account for the compounding uncertainties over time. The proposed DBN is then tested at a pilot coastal aquifer underlying a highly urbanized water-stressed metropolitan area along the Eastern Mediterranean coastline (Beirut, Lebanon). The results show that the future impacts of climate change are largely secondary when compared to the persistent water deficits. While both supply and demand management could halt the progression of salinity, the potential for reducing or reversing SWI is not evident. The indirect socioeconomic burden associated with aquifer salinity was observed to improve, albeit heterogeneously, with the application of various adaptation strategies; however, this was at a cost associated with the implementation and operation of these strategies. The proposed DBN acts as an effective decision support tool that can promote sustainable aquifer management in coastal regions through its robust representation of the main drivers of SWI and linking them to expected socioeconomic burdens and management options. Integr Environ Assess Manag 2021;17:202-220. © 2020 SETAC.

Clinical Characteristics and Outcomes of Severe and Critical Patients With 2019 Novel Coronavirus Disease (COVID-19) in Wenzhou: A Retrospective Study.

Information about severe cases of 2019 novel coronavirus disease (COVID-19) infection is scarce. The aim of this study was to report the clinical characteristics and outcomes of severe and critical patients with confirmed COVID-19 infection in Wenzhou city. In this single-centered, retrospective cohort study, we consecutively enrolled 37 RT-PCR confirmed positive severe or critical patients from January 28 to February 16, 2020 in a tertiary hospital. Outcomes were followed up until 28-day mortality. Fifteen severe and 22 critical adult patients with the COVID-19 infection were included. Twenty-six (68.4%) were men. Echocardiography data results suggest that normal or increased cardiac output and diastolic dysfunction are the most common manifestations. Compared with severe patients, critical patients were older, more likely to exhibit low platelet counts and high blood urea nitrogen, and were in hospital for longer. Most patients had organ dysfunction during hospitalization, including 11 (29.7%) with ARDS, 8 (21.6%) with acute kidney injury, 17 (45.9%) with acute cardiac injury, and 33 (89.2%) with acute liver dysfunction. Eighteen (48.6%) patients were treated with high-flow ventilation, 9 (13.8%) with non-invasive ventilation, 10 (15.4%) with invasive mechanical ventilation, 7 (18.9%) with prone position ventilation, 6 (16.2%) with extracorporeal membrane oxygenation (ECMO), and 3 (8.1%) with renal replacement therapy. Only 1 (2.7%) patient had died in the 28-day follow up in our study. All patients had bilateral infiltrates on their chest CT scan. Twenty-one (32.3%) patients presented ground glass opacity (GGO) with critical patients more localized in the periphery and the center. The mortality of critical patients with the COVID-19 infection is low in our study. Cardiac function was enhanced in the early stage and less likely to develop into acute cardiac injury, but most patients suffered with acute liver injury. The CT imaging presentations of COVID-19 in critical patients were more likely with consolidation and bilateral lung involvement.