Grazing management impacts on ecosystem services under contrasting climatic conditions in Texas and North Dakota.

Grazing management is an important factor affecting the delivery of ecosystem services at the watershed scale. Moreover, characterizing the impacts of climate variation on water resources is essential in managing rangelands. In this study, the effects of alternative grazing management scenarios on provisioning, regulating, and supporting services were assessed in two watersheds with contrasting climates; the Lower Prairie Dog Town Fork Red River (LPDTFR) Watershed in North Texas and the Apple Watershed in South Dakota. The impacts of heavy stocking continuous grazing, light stocking continuous grazing, Adaptive Multi-Paddock (AMP) grazing, and an ungrazed exclosure were compared using the Soil and Water Assessment Tool (SWAT) model. Our results indicate that the quantity of snow and timing of snow melt substantially influenced grazing management effects on ecosystem services in the Apple Watershed. In contrast, precipitation was the main factor influencing these effects in the LPDTFR Watershed because it highly affected the variation in water cycling, streamflow, sediment, and nutrient controls. Simulated results indicated that AMP grazing was the optimal grazing management approach for enhancing water conservation and ecosystem services in both watersheds regardless of climatic conditions. The Apple Watershed, which is a snow-dominated watershed, exhibited greater ecosystem service improvements under AMP grazing (50.6%, 58.7%, 74.4%, 61.5% and 72.6% reduction in surface runoff, streamflow, and sediment, total nitrogen (TN) and total phosphorus (TP) losses, respectively as compared to HC grazing) than the LPDTFR Watershed (46.0%, 22.8%, 34.1%, 18.9% and 38.4% reduction in surface runoff, streamflow, and sediment, TN and TP losses, respectively). Our results suggest that improved grazing management practices enhance ecosystem services and water catchment functions in rangeland-dominated areas, especially in colder climates.

Improving nitrate load simulation of the SWAT model in an extensively tile-drained watershed.

Subsurface drainage systems are effective management practices employed to remove excess soil water, thereby improving soil aeration and crop productivity. However, these systems can also contribute to water quality issues by enhancing nitrate leaching and loads from agricultural fields. The Soil and Water Assessment Tool (SWAT) is commonly used to assess nitrate loads and long-term water quality impacts from agricultural watersheds. However, the current SWAT model oversimplifies nitrate transport processes by assuming a linear relationship between nitrate concentrations in tile flow and soil nitrate content. It also neglects the time lag between nitrate loading and transport with the flow. This study aimed to enhance the accuracy of nitrate load prediction by revising the subsurface drainage routine in the SWAT model. The revised routine was tested using flow and nitrate load measurements from a typical tile-drained watershed in east-central Illinois, U.S. The results demonstrated that the revised SWAT nitrate routine outperformed the current one in simulating nitrate transport at field and watershed scales. The revised routine improved the nitrate load prediction from an "unacceptable" to a "satisfactory" or "good" rating on the field scale. A sensitivity analysis conducted using the revised nitrate module showed the parameters directly associated with transpiration, groundwater discharge to the reach, the lag time of tile flow, and channel flow hydraulics were the most sensitive in nitrate load simulation. In addition, different tile depth scenarios were modeled to evaluate variation in the amount of surface runoff, tile flow, and nitrate loads by the surface flow and tile flow. The results of tile configuration scenarios agreed with understanding the tile flow process. The test results demonstrated the potential of the revised SWAT nitrate module as a tool to accurately evaluate the effects of tile drainage systems on water quality.

Effects of Long-acting Injectable 3-Monthly Paliperidone Palmitate on the Clinical and Social Performance of Patients with Schizophrenia.

Objective: To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. Methods: This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. Results: The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p < 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71-100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p < 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p < 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p < 0.001; McNemar-Bowker test). Conclusion: Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Suicidal motivations among opioid overdose survivors: Replication and extension.

BACKGROUND: Several studies suggest suicidal motivation may contribute to opioid overdose fatalities in people with opioid use disorder. In this study, we sought to replicate and extend prior findings suggesting that a desire to die is common prior to nonfatal opioid overdose in people with opioid use disorder. METHODS: Adults receiving inpatient detoxification and stabilization who reported a history of opioid overdose (N = 60) completed questions about suicidal cognition prior to their most recent overdose. RESULTS: Approximately 45% reported some desire to die prior to their most recent overdose, with 20% reporting they had some intention to die. The correlation between these ratings was of a moderate magnitude (ρ = 0.58). Almost 40% of the sample perceived no risk of overdose prior to their most recent overdose event, suggesting a significant underestimation of risk in this population. CONCLUSIONS: Desire to die was common in adults with opioid use disorder prior to nonfatal opioid overdose events, and 1 in 5 people with a history of opioid overdose reported intention to die prior to their most recent opioid overdose. Careful assessment of suicidal cognition in this population may improve prevention of opioid overdose deaths.

Natural COA water inhibits mitochondrial ROS-mediated apoptosis through Plk3 downregulation under STZ diabetic stress in pancreatic ß-cell lines.

Diabetes from pancreatic ß cell death and insulin resistance is a serious metabolic disease in the world. Although the overproduction of mitochondrial reactive oxygen species (ROS) plays an important role in the pathogenesis of diabetes, its specific molecular mechanism remains unclear. Here, we show that the natural Charisma of Aqua (COA) water plays a role in Streptozotocin (STZ) diabetic stress-induced cell death inhibition. STZ induces mitochondrial ROS by increasing Polo-like kinase 3 (Plk3), a major mitotic regulator, in both Beta TC-6 and Beta TC-tet mouse islet cells and leads to apoptosis. Overexpression of Plk3 regulates an increase in mitochondrial ROS as well as cell death, also these events were inhibited by Plk3 gene knockdown in STZ diabetic stimulated-Beta TC-6 cells. Interestingly, we found that natural COA water blocks mitochondrial ROS generation through the reduction of Plk3 and prevents apoptosis in STZ-treated beta cells. Furthermore, using the 3D organoid (ex vivo) system, we confirmed that the insulin secretion of the supernatant medium under STZ treated pancreatic ß-cells is protected by the natural COA water. These findings demonstrate that the natural water COA has a beneficial role in maintaining ß cell function through the inhibition of mitochondrial ROS-mediated cell death, and it might be introduced as a potential insulin stabilizer.

Development of the Korea-Polyenvironmental Risk Score for Psychosis.

OBJECTIVE: Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). METHODS: We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the "population proportion" (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). RESULTS: We first constructed the "K-PERS-I," comprising five factors based on the PPS, and then the "K-PERS-II" comprising six factors based on the ERS. The instruments accurately predicted participants' status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. CONCLUSION: The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

Fast dissolving nanofiber mat for the local antimicrobial application of roxithromycin in oral cavity.

Fast disintegrating and dissolving nanofiber (NF) mat was devised to deliver roxithromycin for the treatment of the respiratory tract infection. NF membrane was made by an electrospinning process with poly(vinyl alcohol) (PVA), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and d-α-tocopheryl polyethylene glycol succinate (TPGS) for local application of roxithromycin. Roxithromycin has a poor water solubility thus HP-ß-CD is introduced for enhancing drug solubility by forming an inclusion complex in this study. The addition of TPGS provided multiple roles such as accelerating wetting, disintegration, and dissolution speed and overcoming bacterial resistance. Roxithromycin was successfully entrapped in NF structure and drug amorphization occurred during the electrospinning process. PVA/HP-ß-CD/TPGS/roxithromycin (PHTR) NF exhibited faster wetting, disintegration, and dissolution speed rather than the other NF mats. PHTR NF displayed higher antibacterial potentials in Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) compared to other NF mat formulations. The administration of PHTR NF to oral cavity in pneumococcal disease mouse model provided the most efficient therapeutic potentials in lung tissue. Designed multiple phase-based NF mat may be one of powerful local drug delivery systems for the therapy of respiratory tract infection.

Exploring Hidden Issues in the Use of Antipsychotic Polypharmacy in the Treatment of Schizophrenia.

The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first- and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore anti-psychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice.

Assessing the impacts of irrigation termination periods on cotton productivity under strategic deficit irrigation regimes.

Determining optimum irrigation termination periods for cotton (Gossypium hirsutum L.) is crucial for efficient utilization and conservation of finite groundwater resources of the Ogallala Aquifer in the Texas High Plains (THP) region. The goal of this study was to suggest optimum irrigation termination periods for different Evapotranspiration (ET) replacement-based irrigation strategies to optimize cotton yield and irrigation water use efficiency (IWUE) using the CROPGRO-Cotton model. We re-evaluated a previously evaluated CROPGRO-Cotton model using updated yield and in-season physiological data from 2017 to 2019 growing seasons from an IWUE experiment at Halfway, TX. The re-evaluated model was then used to study the effects of combinations of irrigation termination periods (between August 15 and September 30) and deficit/excess irrigation strategies (55%-115% ET-replacement) under dry, normal and wet years using weather data from 1978 to 2019. The 85% ET-replacement strategy was found ideal for optimizing irrigation water use and cotton yield, and the optimum irrigation termination period for this strategy was found to be the first week of September during dry and normal years, and the last week of August during wet years. Irrigation termination periods suggested in this study are useful for optimizing cotton production and IWUE under different levels of irrigation water availability.

Effects of Long-Acting Injectable Paliperidone Palmitate on Clinical and Functional Outcomes in Patients With Schizophrenia Based on Illness Duration.

OBJECTIVE: This study aimed to examine the degree of clinical and functional improvement after paliperidone long-acting injectable (LAI) administration according to the duration of illness. METHODS: Patients with schizophrenia diagnosed by ICD-10 criteria who were planned to start once-monthly paliperidone LAI were recruited from 2010 to 2017. Clinical and functional changes were measured every 4 weeks using the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Personal and Social Performance scale (PSP), respectively, for 6 months after paliperidone LAI initiation. Improvements after starting paliperidone LAI were compared among patients with duration of illness < 3 years, ≥ 3 and < 10 years, and ≥ 10 years. RESULTS: A total of 1,166 participants (duration of illness < 3 years, n = 240; 3 ≤ duration of illness < 10 years, n = 442; duration of illness ≥ 10 years, n = 484) were enrolled. The total olanzapine-equivalent doses of antipsychotics and the LAI monotherapy proportion at the final visit were significantly different among the 3 duration of illness groups (dose: F2,1163 = 18.41, P < .001; monotherapy: χ²2 = 11.73, P = .003). The changes in CGI-S score were significantly different according to the duration of illness, and those with duration of illness < 3 years showed the best improvement (group × week: χ²12 = 25.33, P = .013). All 3 groups showed significantly improved PSP scores (week: χ²6 = 294.2, P < .001). CONCLUSIONS: Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.

Extracellular matrix stiffness determines DNA repair efficiency and cellular sensitivity to genotoxic agents.

DNA double-strand breaks (DSBs) are highly toxic lesions that can drive genetic instability. These lesions also contribute to the efficacy of radiotherapy and many cancer chemotherapeutics. DNA repair efficiency is regulated by both intracellular and extracellular chemical signals. However, it is largely unknown whether this process is regulated by physical stimuli such as extracellular mechanical signals. Here, we report that DSB repair is regulated by extracellular mechanical signals. Low extracellular matrix (ECM) stiffness impairs DSB repair and renders cells sensitive to genotoxic agents. Mechanistically, we found that the MAP4K4/6/7 kinases are activated and phosphorylate ubiquitin in cells at low stiffness. Phosphorylated ubiquitin impairs RNF8-mediated ubiquitin signaling at DSB sites, leading to DSB repair deficiency. Our results thus demonstrate that ECM stiffness regulates DSB repair efficiency and genotoxic sensitivity through MAP4K4/6/7 kinase-mediated ubiquitin phosphorylation, providing a previously unidentified regulation in DSB-induced ubiquitin signaling.

Telmisartan Inhibits TNFα-Induced Leukocyte Adhesion by Blocking ICAM-1 Expression in Astroglial Cells but Not in Endothelial Cells.

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α- induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

Structural Alterations in Large-scale Brain Networks and Their Relationship with Sleep Disturbances in the Adolescent Population.

Although sleep disturbances are highly prevalent in adolescents, neuroimaging evidence on the effects of sleep disturbances on their developing brains remains limited. Therefore, we explored gray matter volumes (GMVs) at the whole-brain level and investigated their relationship to sleep disturbances in a sample of Korean adolescents in the general population. We recruited participants from one middle school and high school. All participants and their legal guardians gave informed consent before participating in our study. We used component 5 of the Pittsburgh Sleep Quality Index to measure sleep disturbances and conducted a voxel-based morphometry-DARTEL procedure to measure GMVs. We performed partial correlation analyses to examine whether the GMVs were associated with sleep disturbances. A total of 56 adolescents participated in this study. Our results revealed that GMVs in multiple global regions were negatively correlated with sleep disturbances. Moreover, most of these identified regions belong to large-scale brain networks categorized by functional neuroimaging studies. We found an association between regional GMVs in multiple global regions involved in large-scale networks and the severity of sleep disturbances in the adolescent population. Based on this evidence and previous neuroimaging evidence, we suggest that structural alterations in the networks may be linked to sleep disturbances.

Suicidal motivations reported by opioid overdose survivors: A cross-sectional study of adults with opioid use disorder.

BACKGROUND: Prior studies in heroin use disorder reported low rates (10%) of suicidal intention with non-fatal opioid overdose but did not assess dimensional ratings of suicidal ideation. This study aims to quantify the frequency and intensity of ratings of desire to die and perceived overdose risk proximal to the most recent opioid overdose event among individuals admitted for opioid use disorder detoxification/stabilization. METHODS: Cross-sectional study (June 2017-July 2018) assessing patterns of opioid use and variables related to overdose history was conducted in a not-for-profit psychiatric hospital. Adults (>18 years) with opioid use disorder were eligible and 120 of 122 participants completed all measures. Forty-one percent were women and 85% self-identified as white. Participants' perceptions of the likelihood of overdose and their suicidal motivations (defined as desire to die) prior to most recent opioid overdose was self-rated on a scale of 0 (no desire to die/no risk of death) to 10 (I definitely wanted to die/I definitely thought I would die). RESULTS: Most (92%) surviving opioid overdose used heroin/fentanyl; over half reported some desire to die prior to their most recent overdose, with 36% reporting strong (>7/10) desire to die and 21% reporting 10/10 "I definitely wanted to die." Perceptions of overdose risk were also variable, with 30% reporting no (0/10) likelihood of overdose and 13% reporting a high (10/10) likelihood. CONCLUSIONS: Suicidal motivation prior to opioid overdose is common and falls along a continuum of severity. Longitudinal studies are needed to determine if suicide prevention interventions may reduce opioid overdose in those at risk.

USP20 positively regulates tumorigenesis and chemoresistance through ß-catenin stabilization.

ß-catenin is a major transcriptional activator of the canonical Wnt/ß-catenin signaling pathway. It is important for a series of biological processes including tissue homeostasis, and embryonic development and is involved in various human diseases. Elevated oncogenic activity of ß-catenin is frequently observed in cancers, which contributes to survival, metastasis and chemo-resistance of cancer cells. However, the mechanism of ß-catenin overexpression in cancers is not well defined. Here we demonstrate that the deubiquitination enzyme USP20 is a new regulator of the Wnt/ß-catenin signaling pathway. Mechanistically, USP20 regulates the deubiquitination of ß-catenin to control its stability, thereby inducing proliferation, invasion and migration of cancer cells. High expression of USP20 correlates with increased ß-catenin protein level in multiple cancer cell lines and patient samples. Moreover, knockdown of USP20 increases ß-catenin polyubiquitination, which enhances ß-catenin turnover and cell sensitivity to chemotherapy. Collectively, our results establish the USP20-ß-catenin axis as a critical regulatory mechanism of canonical Wnt/ß-catenin signaling pathway with an important role in tumorigenesis and chemo response in human cancers.

Dissolution of studtite [UO2(O2)(H2O)4] in various geochemical conditions.

This study determined the dissolution rate of studtite, (UO2)O2(H2O)4, which can be formed by reaction between H2O2 and UO22+ that leaks from spent nuclear fuel (SNF) in deep geological repositories. The batch dissolution experiments were conducted using synthesized studtite under different solution conditions with varying pHs and concentrations of HCO3- and [H2O2] in synthetic groundwater. The experimental results suggested that carbonate ligand and H2O2 in groundwater accelerated the dissolution of studtite and uranium (U) release. Above 10-5 M of H2O2 initial concentration, the released uranium concentration in solution decreased, possibly as a result of reprecipitation of studtite due to reaction between uranium and H2O2. The results will be useful to assess the comprehensive transport of uranium from both nuclear waste and SNF stored in deep geological repositories.

Polydopamine-coated nanocomposites of Angelica gigas Nakai extract and their therapeutic potential for triple-negative breast cancer cells.

Polydopamine (PD)-coated nanocomposites (NCs) based on the ethanol extract of Angelica gigas Nakai (AGN EtOH ext) were fabricated and evaluated for breast cancer therapy. AGN NCs were prepared using a modified emulsification-solvent evaporation method and were further incubated in dopamine solution (at pH 8.6) to be covered with the PD layer. PD-AGN NCs with a 213-nm mean diameter, narrow size distribution, and negative zeta potential values were fabricated in this study. Less negative (close to zero) zeta potential value of PD-AGN NCs than that of AGN NCs implied the existence of the PD layer in the outer surface of NCs. The PD layer in PD-AGN NCs was also identified by X-ray photoelectron spectroscopy (XPS) and ultraviolet (UV)/visible absorption analyses. The sustained release of decursin (D) and decursinol angelate (DA), as major active pharmacological components of AGN, was observed in both AGN NCs and PD-AGN NCs. Enhanced cellular binding property of PD-AGN NCs, compared to AGN NCs, in MDA-MB-231 (human breast adenocarcinoma; triple-negative breast cancer) cells was observed. Improved anticancer activities of PD-AGN NCs compared with those of AGN EtOH ext and AGN NCs were also shown in MDA-MB-231 cells. The developed PD-AGN NCs may be used as remarkable platform nanocarriers for efficient breast cancer therapy.