Absence Of Changes Research Articles

Long-term changes in riparian connectivity and groundwater chemistry in an urban watershed.

Hydrologic alterations associated with urbanization can weaken connections between riparian zones, streams, and uplands, leading to negative effects on the ability of riparian zones to intercept pollutants carried by surface water runoff and groundwater flow such as nitrate (NO3 -) and phosphate (PO4 3-). We analyzed the monthly water table as an indicator of riparian connectivity, along with groundwater NO3 - and PO4 3- concentrations, at four riparian sites within and near the Gwynns Falls Watershed in Baltimore, MD, from 1998 to 2018. The sites included one forested reference site (Oregon Ridge), two suburban riparian sites (Glyndon and Gwynnbrook), and one urban riparian site (Cahill) with at least two locations and four monitoring wells, located 5m from the center of the stream, at each site. Results show an increase in connectivity as indicated by shallower water tables at two of the four sites studied: Glyndon and Cahill. This change in connectivity was associated with decreases in NO3 - at Glyndon and increases in PO4 3- at Glyndon, Gwynnbrook, and Cahill. These changes are consistent with previous studies showing that shallower water table depths increase anaerobic conditions, which increase NO3 - consumption by denitrification and decrease PO4 3- retention. The absence of change in the forested reference site, where climate would be expected to be the key driver, suggests that other drivers, including best management practices and stream restoration projects, could be affecting riparian water tables at the two suburban sites and the one urban site. Further research into the mechanisms behind these changes and site-specific dynamics is needed.

The Burden of Gastric Cancer in Northern Central America.

Gastric cancer is the fourth leading cause of cancer-related death worldwide, with nearly one million new cases diagnosed in 2020. There is marked variation in gastric cancer incidence globally, with highest incidence rates reported in the United Nations regions of Eastern Asia, Eastern Europe, and Latin America. Although the United States is considered a low-incidence country, gastric cancer presents an important cancer disparity, with higher incidence in minoritized populations, including immigrants from high-incidence regions. The Northern Central America nations are low- and middle-income countries with a high gastric cancer incidence and large US immigrant populations. These countries lack comprehensive cancer registries, but recent GLOBOCAN-imputed gastric cancer estimates are in the range of 8 to 12/100,000 age-standardized incidence rates. Three epidemiologic studies carried out in El Salvador, Nicaragua, and Honduras demonstrate a higher than predicted burden of gastric cancer with low 5-year survival (<10%). The gastric cancer burden is projected to increase in the absence of changes to national and regional cancer control plans. Twelve evidence-based recommendations to reduce gastric cancer mortality in the Americas have recently been proposed, ranging from the "test-and-treat" Helicobacter pylori eradication strategy to endoscopic screening and surveillance programs. Translating these recommendations into a practical plan for this resource-limited setting could address the disproportionate gastric cancer burden. See related article by Peña-Galo et al., p. 1564 See related article by Ruiz de Campos et al., p. 1571 See related article by Dominguez et al., p. 1578.

Exploring the effects of erythropoietin treatment on cortical thickness and hippocampal volume in patients with mood disorders undergoing electroconvulsive therapy: A randomized, placebo-controlled trial.

Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its utilization is limited to the most severely ill patients due to stigma, healthcare provider unfamiliarity, and concerns regarding cognitive side effects. Erythropoietin (EPO) is a promising add-on treatment during ECT due to its potential to increase neuroplasticity and cognition. To explore the effects of EPO administration on cortical thickness and hippocampal volumes. In a randomized, double-blinded, placebo-controlled trial, we previously investigated the impact of EPO (40,000 IU) versus placebo (saline) infusions on cognitive side effects of unipolar or bipolar depression patients undergoing eight ECT sessions over 2.5 weeks. This cross-sectional magnetic resonance imaging study explores the effect of EPO on cortical thickness and hippocampal volumes 3 days post-ECT in 37 of the EPO trial patients (EPO n = 21; placebo n = 16). Compared to the placebo group, EPO-treated patients displayed thicker cortex in distributed regions of the right hemisphere, predominantly in the parietal and occipital areas. There were no significant group differences in the hippocampal volumes or prefrontal cortex thickness. EPO treatment may produce a selective increase in the right-side occipito-parietal cortical thickness. In contrast, the thickness of other cognition-relevant structures was not significantly affected. This aligns with our previously reported finding that EPO has a selective effect on autobiographical memory and associated right-side parietal activity in the absence of changes in global cognition. It remains to be investigated whether longer EPO treatment and follow-up assessment may be necessary for overt structural changes in cognition-relevant brain networks.

Effect of a thiazole derivative on the activity of antioxidant enzymes in murine lymphoma cells

Previous in vitro studies have demonstrated a pronounced cytotoxic effect of the thiazole derivative N-(5-Benzyl-13-thiazole-2-yl)-35-dimethyl-1-benzofuran-2-carboxami­de (BF1) on tumor cells. Additionally, it has been determined that scavengers of reactive Oxygen species (ROS) significantly reduce the cytotoxic effect of BF1. In this study, the influence of BF1 on the activity of superoxide dismutase (SOD) and catalase (CAT), both normally and in the presence of ascorbic acid, in mouse Nemeth-Kellner lymphoma (NK/Ly) cells has been studied to evaluate the possible role of antioxidant activity during the action of this substance. The experiments were performed using nonlinear male mice weighing 20–30 g. Intraperitoneal inoculation of 10–15 million cancer cells into the mice induced the ascites form of lymphoma. The thiazole derivative (BF1) was dissolved in dimethyl sulfoxide and added to the test samples at 1, 10, and 50 μM final concentrations. Superoxide dismutase (SOD) and catalase (CAT) activities were determined spectrophotometrically in a homogenate of the lymphoma cells after incubation with the drug for 30 minutes. The baseline level of SOD in the lymphoma of the mice was 0.33±0.02 activity units/min×mg protein. BF1 significantly increased the enzyme activity by 35 % and 29 % at concentrations of 10 (p&lt;0.01) and 50 μM (p&lt;0.05), respectively. The baseline level of CAT activity was 4.61±0.17 nmoles H2O2/min×mg protein, and this significantly decreased by 15 % (p&lt;0.05) and 20 % (p&lt;0.01) following the action of the thiazole derivative at a concentration of 10 and 20 μM, respectively. The increase of SOD activity, coupled with a decrease or absence of changes in CAT activity, may be cytotoxic to cancer cells. Simultaneously, upon the addition of ascorbic acid as a scavenger of ROS to the environment, the activities of SOD and CAT did not change under the action of BF1 at any of the investigated concentrations. Therefore, the effect of the thiazole derivative BF1 has been canceled in the presence of ROS scavengers in the environment. This may indicate the dependence of the cytotoxic effect of BF1 on the presence of ROS in tumor cells.

Investigating the role of an orphan nuclear receptor NR4A1 in atrial fibrillation

Abstract Introduction Atrial fibrosis is a major remodelling process in atrial fibrillation (AF). The lack of clinically effective drug targets, due to insufficient understanding of the mechanisms of cardiac fibrosis, hampers the treatment of AF. Orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is linked to fibrotic disease in multiple organs, however, its role in cardiac fibrosis and AF is yet to be demonstrated. Recent transcriptomic profiling revealed that NR4A1 expression is downregulated in human atrial cardiac fibroblasts (ACFs) in the presence of persistent AF. However, its mechanistic role in atrial fibrogenesis and AF is unknown. Purpose To investigate the expression profile and function of NR4A1 in human ACFs and provide insights into the role of NR4A1 in the context of persistent AF. Methods Human ACFs were isolated (enzymatic digestion) from right and left atrial appendages of 24 patients with persistent AF and controls in sinus rhythm (SR), who had elective heart surgery. NR4A1 knockdown in ACFs was achieved using NR4A1-siRNA. Gene and protein expression were determined by qPCR and western blot respectively, while BrdU assay and scratch assay were used to evaluate cell proliferation and migration. Atrial fibroblasts subpopulations were identified by single-nucleus RNA-sequencing. Subcellular localisation of NR4A1 was assessed by immunostaining, analysed by ImageJ. Results Validation of RNA-sequencing data confirmed a reduction of NR4A1 gene expression in human ACFs in persistent AF by 25% (p=0.029, Fig. 1A) and the NR4A1 predominant abundance in one of three identified subclusters of human ACFs (NR4A1+NAMPT+). The siRNA-mediated knockdown of NR4A1 in ACFs suppressed gene and protein expression of important component of extracellular matrix collagen-1 (Fig. 1B and Fig. 1C) and fibronectin protein (but not mRNA). The NR4A1-deficient cells also had decreased alpha-smooth muscle actin (αSMA) protein and gene expression (Fig. 1D and Fig. 1E), reduced periostin gene expression in the absence of changes in its protein. Furthermore, the NR4A1-deficiency reduced proliferation (by 18%, p=0.005, Fig. 1F) and accelerated migration (p=0.019, Fig. 1G) of human ACFs. These effects were independent of TGF-β1 stimulation, unlike reported in rat neonatal cardiac and dermal fibroblasts. Despite decreased NR4A1 gene expression, patients with AF had doubled NR4A1 protein levels compared to SR-ACFs (p=0.049, Fig. 2A). This was associated with abnormal 1.8-fold increase in the receptor subcellular localisation (p=0.032, Fig. 2B and Fig. 2C), as opposed to the physiological nuclear localisation observed in ACFs in the absence of AF. Conclusion While under physiological conditions, NR4A1 potently activates profibrotic processes in human ACFs, persistent AF patients have increased but abnormally distributed NR4A1 protein in atrial fibroblasts, whose consequences are yet to be determined in order to develop new therapies for AF.Figure 1Figure 2

Ventilatory response to head-down-tilt in healthy human subjects.

Postural fluid shifts may directly affect respiratory control via a complex interaction of baro- and chemo-reflexes, and cerebral blood flow. Few data exist concerning the steady state ventilatory responses during head-down tilt. We examined the cardiorespiratory responses during acute 50° head-down tilt (HDT) in 18 healthy subjects (mean [SD] age 27 [10] years). Protocol 1 (n=8, two female) was 50° HDT from 60° head-up posture sustained for 10min, while exposed to normoxia, normoxic hypercapnia (5% CO2), hypoxia (12% inspired O2) or hyperoxic hypercapnia (95% O2, 5% CO2). Protocol 2 (n=10, four female) was 50° HDT from supine, sustained for 10min, while breathing either medical air or normoxic hypercapnic (5% CO2) gas. Ventilation ( , pneumotachograph), end-tidal O2 and CO2 concentration and blood pressure (Finapres) were measured continuously throughout each protocol. Middle cerebral artery blood flow velocity (MCAv; transcranial Doppler) was also measured during protocol 2. Ventilation increased significantly (P<0.05) compared to baseline during HDT in both hyperoxic hypercapnia (protocol 1 by mean [SD] 139 [26]%) and normoxic hypercapnia (protocol 1 by mean [SD] 131 [21]% and protocol 2 by 129 [23]%), despite no change in or from baseline. No change in was observed during HDT with medical air or hypoxia, and there was no significant change in MCAv during HDT compared to baseline. The absence of change in cerebral blood flow leads us to postulate that the augmented ventilatory response during steep HDT may involve mechanisms related to cerebral venous pressure and venous outflow.

Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice.

Fibroblast growth factor 23 (FGF23) is a bone-secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about the nonskeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with a high-fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the adiponectin-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio and increased brown fat Ucp1 expression in knockout mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.

Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.

Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Here, we test the hypothesis that loss of PKP2 expression leads to pro-arrhythmic changes in atrial cardiomyocytes. Atrial cells/tissue were obtained from a cardiac-specific, tamoxifen-activated model of PKP2 deficiency (PKP2cKO). By contrast to PKP2cKO ventricular myocytes, PKP2cKO atrial cardiomyocytes presented no significant differences in intracellular calcium (Ca2+ i) transient dynamics, sarcoplasmic reticulum load or action potential morphology. PKP2cKO atrial cardiomyocytes showed elevated reactive oxygen species levels, increased frequency and amplitude of Ca2+ sparks, and increased diastolic [Ca2+]i compared to control; the latter two parameters were further increased by isoproterenol exposure and reversed by exposure to ryanodine receptor blocker dantrolene. We speculate that these isoproterenol-dependent effects may impact on the exercise-related atrial arrhythmia risk in ARVC patients. Despite absence of changes in Ca2+ i transient dynamics, PKP2cKO atrial cardiomyocytes showed enhanced sarcomere shortening and impaired sarcomere relaxation. Orthogonal transcriptomic analysis of human(GTEx) and PKP2cKO atrial tissue led to identification of 41 transcripts depending on PKP2 expression. Biochemical follow-up confirmed reduced abundance of sarcomeric protein myosin binding protein C, potentially playing a role in cellular shortening and relaxation changes observed. Our findings provide novel insights into the role of PKP2 in atrial myocardium with potential implications to therapeutic management of atrial fibrillation in patients with PKP2-related ARVC. KEY POINTS: Atrial arrhythmias occur in a large group of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a cardiac disease mostly caused by pathogenic variants in the desmosomal gene plakophilin-2 (PKP2). Exercise is considered to be an independent risk factor for arrhythmias consequent to PKP2 deficiency. Weshow that loss of PKP2 expression affects cellular calcium handling and electrophysiology differently in left atrial vs. ventricular myocardium and causes extensive atrial fibrosis. PKP2-deficient atrial cardiomyocytes present increased spontaneous sarcoplasmic reticulum calcium release events, furtherenhancedby isoproterenol exposure and reversiblebya ryanodine receptor blocker(dantrolene). In addition, PKP2-deficient atrial myocytes exhibit impaired relaxation and enhanced sarcomere shortening, most probably related to reduced abundance of myosin binding protein C. We speculate that cellular effects reported upon isoproterenol impact on the exercise-related atrial arrhythmia risk in ARVC patients. We further propose that therapeutic approaches aimed at mitigating ventricular damage may be effective to treat the atrial disease in ARVC.

Dietary salt, vascular dysfunction, and cognitive impairment.

Excessive salt consumption is a major health problem worldwide leading to serious cardiovascular events including hypertension, heart disease and stroke. Additionally, high salt diet has been increasingly associated with cognitive impairment in animal models and late-life dementia in humans. High salt consumption is harmful for the cerebral vasculature, disrupts blood supply to the brain and could contribute to Alzheimer's disease pathology. Although animal models have advanced our understanding of the cellular and molecular mechanisms, additional studies are needed to further elucidate the effects of salt on brain function. Furthermore, the association between excessive salt intake and cognitive impairment will have to be more thoroughly investigated in humans. Since the harmful effects of salt on the brain are independent by its effect on blood pressure, in this review, I will specifically discuss the evidence, available in experimental models and humans, on the effects of salt on vascular and cognitive function in the absence of changes in blood pressure. Given the strong effects of salt on the function of immune cells, I will also discuss the evidence linking salt consumption to gut immunity dysregulation with particular attention to the ability of salt to disrupt T-helper 17 (Th17) cells homeostasis. Lastly, I will briefly discuss the data implicating IL-17A, the major cytokine produced by Th17 cells, in vascular dysfunction and cognitive impairment.

Dietary biogenic selenium nanoparticles improve growth and immune-antioxidant indices without inducing inflammatory responses in Nile tilapia

The present study evaluated the use of green-synthesized selenium nanoparticles (SeNPs), using the microalgae Pediastrum boryanum as a diet additive in aquaculture to improve the growth performance, health, and immune response of Nile tilapia. Nile tilapia were fed different concentrations of green SeNPs (79.26 nm) as follows: 0, 0.75, and 1.5 mg/kg of SeNPs for 8 weeks. Following the trial, growth performance, biochemical indices, antioxidant and pro-inflammatory cytokine-related genes, and tissue histological examinations were performed. The study showed that SeNPs significantly improved (P < 0.05) growth performance and innate immune parameters (P < 0.001, IgM, and lysozyme) at both supplemented doses compared with the control. The protein profile and liver function enzymes were normal compared with those in the control group (P > 0.05). Serum malondialdehyde and superoxide dismutase levels were not significantly changed, while reduced glutathione and catalase were significantly enhanced (P < 0.01, P < 0.05) in the SeNPs 1.5 mg/kg compared to the control group. No inflammatory response was detected upon SeNP supplementation, as indicated by the absence of changes in the expression of pro-inflammatory cytokine genes. The earlier assays’ results were histopathologically evidenced, where hepatic and splenic tissue architectures in SeNPs groups did not reveal any deviation from the control group. Our findings indicate that green selenium nanoparticles can potentially improve the growth and immunological response of Nile tilapia, offering opportunities for incorporating health benefits into functional foods and nutraceuticals, which corresponds to the increasing consumer interest in eco-friendly, environmentally sustainable dietary supplements.

Factors influencing quality of processing in EMDR therapy.

This study presents a preliminary analysis of a new instrument oriented at the analysis of processes in EMDR trauma therapy, the Processing Difficulties Scale (PDS). This scale includes 17 items described by experienced EMDR consultants and practitioners as indicative of problems during memory reprocessing. The proposed factorial solution based on four factors explains a total variance explained of 55% and an adequate goodness of fit, based on the proposed indices: RMSEA = 0.07; TLI = 0.91; CFI = 0.95. Table 1 shows the factorial loads for each of the items. The first factor includes 5 items (7, 8, 9, 10, 11), the second factor includes 6 items (13, 14, 25, 27, 28, 31), the third factor includes 3 items (3, 16, 22) and the fourth factor includes 3 items (19, 23, 24). Confirmatory analysis confirms the factorial solution proposed in the exploratory analysis factor and based on four factors with 17 items. The analysis of internal consistency from Cronbach's alpha and the Omega index shows good internal consistency: Factor 1 (good processing; α = 0.92; ω = 0.94), Factor 2 (lack of generalization and/or absence of changes; α = 0.87; ω = 0.90), Factor 3 (poor emotional processing; α = 0.83; ω = 0.85) an Factor 4 (loss of dual attention; α = 0.82; ω = 0.83). In the case of the total scale, both coefficients exceeded 0.90, with an alpha of 0.92 and an Omega of 0.94. The convergent and discriminant validity criteria were estimated by calculating correlations, exploring the relationship between the factors resulting from the final result, the global severity index (GSI) of the SCL-90 and the level of improvement (NGS). These statistical analyses showed good levels of convergent and discriminant validity for all final factors. The PDS may offer a different perspective to analyze the controversy between clinicians and researchers about the need of a preparation phase in patients with complex early traumatization, dissociative symptoms and/or emotion dysregulation, and the different results in specific research around this topic. Exploring the problems in processing in a transdiagnostic way, in a preliminary analysis, we found that the number of early traumatic events measured with the ACE correlates positively with indicators of a loss of dual attention, while emotional dysregulation measured with the DERS does not predict poor processing. Finally, the dissociation measured with the DES seems to correlate positively with the indicators of a loss of dual attention during processing, not seeming to predict poor processing but did show a negative correlation with the indicators of good general processing. These results partially support the findings of some authors on the involvement of certain variables in the processing of traumatic memories, and it may be interesting to evaluate processing styles and their relationship with various indicators, to develop specific interventions in phase 2 of EMDR therapy, thus improving clinical interventions.

Age-related features of some plasminogen activation system components content and activity in the blood of benign and malignant uterine body tumors

Purpose of the study. Is to determine the features in the content and activity of some components of the plasminogen activation system in the blood of patients of different ages with leiomyomas (LM) and uterine corpus endometrial cancer (UCEC). Patients and methods. The study was carried out in patients with LM (n = 35) and UCEC T1a-2N0M0 (n = 56) of reproductive, perimenopausal and postmenopausal ages. Using ELISA methods, the content and activity of urokinase (u-PA), tissue plasminogen activator (t-PA), their inhibitor PAI-1, as well as the content of the soluble form of the u-PA receptor (su-PAR) were determined in the blood of patients. The Student´s test was used for statistical processing. Results. Regardless of the nature of the uterus tumor, it has been noted a significant increase in the activity and blood level of PAI-1 (up to 8 times, p &lt; 0.01), especially pronounced in patients with UCEC of reproductive age. It was combined with the absence of changes or with a decreasing in blood level of su-PAR by more than 40 % (p &lt; 0.05). We observed a rise of u-PA blood level without changes in one´s activity in patients with LM of perimenopausal age. And in patients with LM and UCEC of postmenopausal age an increase in u-PA blood level as well as elevation of u-PA activity (up to 3.9 times, p &lt; 0.01–0.05) were noted. There was an increase in the calculated t-PA index (activity per unit mass) by 1.4–2.8 times (p &lt; 0.05) in the most patients. The indicators of LM patients were characterized by the minimum value of the ratio “t-PA activity/u-PA activity in the blood” among all studied subgroups of patients. Age-related features of the researched parameters were observed more often in the cases of LM than in the cases of UCEC. The most pronounced differences between LM and UCEC were observed in patients of reproductive and postmenopausal age, characterized by stable hormonal levels. Conclusion. The participation of the plasminogen activation system in the pathogenesis of tumor lesions of the uterine body has been shown. The system’s “response” to the development of tumors in the uterus has both general characteristics and features that depend on the nature of the tumors and on the age-specific hormonal regulation of the body, which are most pronounced in postmenopausal women. The results obtained can be used in research aimed at clarifying the targets of targeted therapy for LM and UCEC in accordance with the age of patients.

Enhanced nitrous oxide emission factors due to climate change increase the mitigation challenge in the agricultural sector.

Effective nitrogen fertilizer management is crucial for reducing nitrous oxide (N2O) emissions while ensuring food security within planetary boundaries. However, climate change might also interact with management practices to alter N2O emission and emission factors (EFs), adding further uncertainties to estimating mitigation potentials. Here, we developed a new hybrid modeling framework that integrates a machine learning model with an ensemble of eight process-based models to project EFs under different climate and nitrogen policy scenarios. Our findings reveal that EFs are dynamically modulated by environmental changes, including climate, soil properties, and nitrogen management practices. Under low-ambition nitrogen regulation policies, EF would increase from 1.18%-1.22% in 2010 to 1.27%-1.34% by 2050, representing a relative increase of 4.4%-11.4% and exceeding the IPCC tier-1 EF of 1%. This trend is particularly pronounced in tropical and subtropical regions with high nitrogen inputs, where EFs could increase by 0.14%-0.35% (relative increase of 11.9%-17%). In contrast, high-ambition policies have the potential to mitigate the increases in EF caused by climate change, possibly leading to slight decreases in EFs. Furthermore, our results demonstrate that global EFs are expected to continue rising due to warming and regional drying-wetting cycles, even in the absence of changes in nitrogen management practices. This asymmetrical influence of nitrogen fertilizers on EFs, driven by climate change, underscores the urgent need for immediate N2O emission reductions and further assessments of mitigation potentials. This hybrid modeling framework offers a computationally efficient approach to projecting future N2O emissions across various climate, soil, and nitrogen management scenarios, facilitating socio-economic assessments and policy-making efforts.

Deciphering how promoting land consolidation for village revitalization in rural China: A comparison study

As an efficient toolkit to relieve and resolve rural issues, land consolidation (LC) has been suggested as a promising policy instrument for sustainable rural development. Villages are the most basic units of rural planning and development. However, few studies have examined and compared the relationships between LC and rural revitalization at the village level. Given the sophisticated experience of Eastern China in LC practices, this study, based on theoretical analysis of the relationship between land use and village revitalization, compared two Chinese villages in this region with distinct spatial locations from neighboring cities to analyze and reveal the mechanisms of LC in promoting local revitalization. The results show that under the combined effect of internal and external factors, LC programs have been successfully implemented in the two case villages, during which the interactive mechanism between various aspects, mainly involving industry, habitat, and governance, has been created to promote local revitalization. In the absence of changes in resource endowments, policy support and the efforts of local elites are the key factors for the success of LC in the two villages. However, due to different economic and socio-cultural conditions between the two villages, there are also differences in their revitalization mechanisms. Parts of the lessons learned from the case villages can be useful for villages with similar situations in plain areas. These findings can advance the understanding of how to promote LC for village development and serve as a reference point for other developing countries and regions with similar socio-cultural backgrounds eradicating poverty and revitalizing localities through LC.

Analysis of opinions of medical workers and patients on the activities of the clinical diagnostic service

Everyday medical practice convinces us of the need for well-thought-out management functions in the organization of any business. Laboratory work is no exception. Gradually,there comes an awareness of the need to master and use scientific methods of management and organization of the laboratory service, i.e. what is commonly referred to as «management» throughout the world. Target. To study the existing system of organization, activity and management of the clinical diagnostic service in the conditions of the SBHI of the Samara Region «Tolyatti City Clinical Polyclinic No. 3». Results. The opinion of the medical personnel of the clinical diagnostic laboratory (CDL) was analyzed: laboratory doctors, laboratory paramedics on the organization of the laboratory service; The results of a survey of medical doctors on the organization of the clinical diagnostic service were examined; the opinion of patients on the organization of the laboratory service was studied; an analysis of the management style of the laboratory service of a medical organization was conducted. Conclusion. Clinical laboratory tests are diagnostic tests undertaken to obtain objectively substantiated information about the presence or absence of changes in the composition of the internal environment of the patient’s body. When treating or preventing a disease, the end consumer of the medical service is the patient, and when prescribing clinical diagnostic tests, it is the attending physician, since it is he who interprets, supplements and monitors the patient’s clinical laboratory tests. In this regard, the quality of the services provided for the former and the working conditions for the latter become important for both patients and medical personnel of the clinical laboratory.

Progerin Can Induce DNA Damage in the Absence of Global Changes in Replication or Cell Proliferation.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin." Progerin is also expressed at low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs) and alterations in the nature of DSB repair. The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In this work, we used a model system involving immortalized human cell lines to investigate progerin-induced genomic damage. Using an immunofluorescence approach to visualize phosphorylated histone H2AX foci which mark sites of genomic damage, we report that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Genomic damage was enhanced and persistent in progerin-expressing cells treated with hydroxyurea. Overexpression of wild-type lamin A did not elicit the outcomes associated with progerin expression. Our results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation.

Predominance of CD4+ T cells in metastatic cervical lymph nodes in papillary thyroid carcinoma.

Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is essential, as well as understanding the mechanisms of tumor progression and the conditions that indicate a worse prognosis. Assessment of the tumor microenvironment can allow us understand how the immune system organizes itself to contain neoplastic progression. We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and lymph nodes in two groups, with and without lymph node metastatic involvement. Of the 400 cases followed up at a thyroid cancer reference service, 32 were selected, of which, 13 cases did not present lymph node metastasis (N0 group) and 19 had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for markers CD4, CD8, FoxP3, CD25, and CD20 in lymph nodes and peritumoral infiltrate. We found that the N1 group had larger tumor sizes, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free times, and higher expression of CD4+ T lymphocytes in lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocyte distribution in the lymph node. In cervical lymph nodes, the higher frequency of CD4+ T lymphocytes is related to the presence of metastasis. However, there were no differences in lymphocytic subpopulations in the thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.

Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients using 18F-FDG positron emission tomography.

Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma. 1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m2/biweekly IV, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT. In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses. In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.

High glucose-induced downregulation of PTEN-Long is sufficient for proximal tubular cell injury in diabetic kidney disease

During the progression of diabetic kidney disease, proximal tubular epithelial cells respond to high glucose to induce hypertrophy and matrix expansion leading to renal fibrosis. Recently, a non-canonical PTEN has been shown to be translated from an upstream initiation codon CUG (leucine) to produce a longer protein called PTEN-Long (PTEN-L). Interestingly, the extended sequence present in PTEN-L contains cell secretion/penetration signal. Role of this non-canonical PTEN-L in diabetic renal tubular injury is not known. We show that high glucose decreases expression of PTEN-L. As a mechanism of its function, we find that reduced PTEN-L activates Akt-2, which phosphorylates and inactivate tuberin and PRAS40, resulting in activation of mTORC1 in tubular cells. Antibacterial agent acriflavine and antiviral agent ATA regulate translation from CUG codon. Acriflavine and ATA, respectively, decreased and increased expression of PTEN-L to altering Akt-2 and mTORC1 activation in the absence of change in expression of canonical PTEN. Consequently, acriflavine and ATA modulated high glucose-induced tubular cell hypertrophy and lamininγ1 expression. Importantly, expression of PTEN-L inhibited high glucose-stimulated Akt/mTORC1 activity to abrogate these processes. Since PTEN-L contains secretion/penetration signals, addition of conditioned medium containing PTEN-L blocked Akt-2/mTORC1 activity. Notably, in renal cortex of diabetic mice, we found reduced PTEN-L concomitant with Akt-2/mTORC1 activation, leading to renal hypertrophy and lamininγ1 expression. These results present first evidence for involvement of PTEN-L in diabetic kidney disease.

Atopic Dermatitis, Sleep, and the COVID-19 Pandemic

Abstract Objective To investigate sleep disorders among children with atopic dermatitis (AD), before and during the coronavirus disease 2019 (COVID-19) pandemic. Materials and Methods The present longitudinal, prospective study included 26 patients with AD, and the Sleep Disturbance Scale for Children (SDSC) questionnaire and questions about sleep hygiene were used. The severity of AD was determined by the Patient-Oriented Eczema Measure (POEM). The first evaluation was conducted before the pandemic (in 2019) and the second, during the pandemic, from September to December 2020. Results Sleep disorder was present in 17 (65.38%) patients in the 1st evaluation, and in 11 (42.30%) in the 2nd (p = 0.04). In the 1st evaluation, disorders of initiating and maintaining sleep (DIMSs) were more frequent in patients with moderate-to-severe AD (83.33%). During the pandemic, 6 patients (23.07%) reported improvement in sleep quality. Conclusion Sleep quality was negatively influenced by the severity of AD. During the COVID-19 pandemic, there was improvement in sleep quality, despite the absence of changes in disease severity.