Concomitant Effects Research Articles

Bone Morphogenetic Protein Signaling Agonist SB4 (BMPSB4) Inhibits Corticotroph Pituitary Neuroendocrine Tumors by Activation of Autophagy via a BMP4/SMADs-Dependent Pathway.

Corticotroph pituitary neuroendocrine tumors (PitNETs), associated with Cushing's disease (CD), have limited treatment options other than surgical resection. Bone morphogenetic protein 4 (BMP4), a potential therapeutic target, is decreased in patients with CD. Previous studies have identified BMPSB4 as a potent agonist of the BMP4 signaling pathway. Here, we investigated the effect of BMPSB4 on the corticotroph PitNET cell line AtT20/D16v-F2 and explored the underlying mechanisms and therapeutic potential. We verified the low expression patterns of BMP4 and downstream p-SMAD1/5/9 in CD samples at the transcriptional and protein levels. In addition, BMPSB4 activated SMAD1/5/9 in a time- and concentration-dependent manner, with concomitant inhibitory effects on AtT20/D16v-F2 cells. Further RNA sequencing, transmission electron microscopy (TEM), and transfection with the mRFP-EGFP-LC3 adenoviral vector revealed that BMPSB4 induced cellular autophagy, which was the basis for the inhibitory effect of BMPSB4. Moreover, we demonstrated that autophagy induced by BMPSB4 was achieved through the SMADs-dependent pathway. In vivo, BMPSB4 inhibited tumor growth and significantly reduced adrenocorticotrophin (ACTH) and corticosterone (CORT) secretion, thereby alleviating the CD phenotype. In conclusion, this study identified BMPSB4 as an effective therapeutic agent for CD. BMPSB4 activates autophagy through a SMADs-dependent pathway, which in turn promotes autophagy-mediated cell death. Our work further elucidates the mechanism of the BMP4 signaling pathway in CD and suggests broad prospects for the development and application of BMPSB4 in CD therapy.

Apples and oranges: PTSD patients and healthy individuals are not comparable in their subjective and physiological responding to emotion induction and bilateral stimulation.

Bilateral stimulation is a core element of Eye Movement Desensitization and Reprocessing Therapy, a psychotherapeutic intervention for the treatment of Posttraumatic Stress Disorder (PTSD). Promising previous findings showed measurable physiological effects of bilateral stimulation in healthy individuals, but studies that replicated these findings in PTSD patients are sparse. 23 patients with PTSD and 30 healthy controls were confronted with affective standard scripts (pleasant, neutral, unpleasant) while bilateral tactile stimulation was applied. Monolateral and no stimulation served as control conditions. Noise-induced startle reflex response (valence measure) and galvanic skin response (arousal measure) were used for physiological responses and the valence and arousal scale of the Self-Assessment-Manikin for subjective responses. Both groups showed a subjective distress reduction for unpleasant scripts and a subjective attention increase for positive scripts under bilateral stimulation. In healthy individuals, this was also for physiological measures, and a general startle-reducing effect of bilateral stimulation in the absence of affective stimuli was found. In PTSD patients, however, the effects were restricted on the subjective level, and no concomitant physiological effects were observed. The findings indicate, that generalizing the effects of BLS in healthy individuals to PTSD patients may be problematic. The herein-reported group differences can be explained by PTSD-specific peculiarities in emotion processing and cognitive processing style.

Pregnancy, delivery, and neonatal outcomes among women with PCOS and endometriosis: a population database cohort.

PCOS and endometriosis are independent risk factors for perinatal outcomes. Little research has evaluated the concomitant effects of these conditions, nor have studies been conducted on a population database. We sought to identify the pregnancy, delivery, and neonatal outcomes in women with polycystic ovary syndrome (PCOS) and endometriosis vs. PCOS without endometriosis. A retrospective population-based cohort study was performed extracting data using ICD-9 codes from the HCUP-NIS Database from 2004 to 2014. Endometriosis in women with PCOS represented the study group (n = 163), and the remaining PCOS, non-endometriosis patients constituted the reference group (n = 14,719). Subjects were included once per delivery. Demographics were compared using chi-squared tests. Confounding effects in pregnancy outcomes were controlled using binary logistic regression analysis. Concomitant endometriosis and PCOS patients were more likely to be white (88.5% vs.71.0%, p < 0.001), with BMI < 30kg/m2 (87.1% vs.77.8%, p < 0.004) and from lower income quartiles (27.1% vs.17.1%, p < 0.017) when compared to PCOS without endometriosis. Comparing pregnancy complication rates, placental abruption (p < 0.018, aOR 3.01, 95% CI 1.21-7.50), Cesarean section (p < 0.003, aOR 1.75, 95% CI 1.21-2.53), deep venous thromboses (p < 0.002, aOR 74.31, 95% CI 4.57-1209.21), and venous thromboembolic events (p < 0.031, aOR 10.40, 95% CI 1.24-87.37), were increased in the study group compared to the reference group. Women with PCOS and endometriosis were more likely to be white, of lower socioeconomic status, lean, and experience abruptio-placenta, cesarean deliveries, and venous thromboembolisms. Since little was previously known about the combined outcomes of PCOS and endometriosis, it is difficult to counsel patients on risks. Our findings can help clinicians manage pregnant PCOS patients with endometriosis to minimize complications such as abruptio placenta and VTE.

Changes in pCO2 and climate paced by grand orbital cycles in the late Cenozoic

As one of the most important greenhouse gases, CO2 is considered a major controlling factor of Earth's climate over geological timescales. However, the origins of quasi-periodic fluctuations in pCO2 on a million-year timescale remain unclear. Here, we used published datasets of atmospheric pCO2, oxygen isotopes of benthic foraminifera (δ18Obenthic) and global mean sea-level (GMSL) from 23 Ma to the present to explore the pacing of pCO2 changes and concomitant climatic effects using multiple time series analysis approaches. Our results indicate that the evolution of late Cenozoic pCO2 and climate was paced by the grand orbital cycles, in particular the ∼4.5 Myr and ∼2.4 Myr eccentricity cycles, and ∼1.3 Myr obliquity cycle. Periodic occurrence of cold conditions was associated with low climate seasonality during the minima of ∼4.5 Myr and ∼2.4 Myr eccentricity cycles. We suggest that cooler conditions are associated with decreased atmospheric pCO2 as a result of higher organic carbon burial due to lower metabolic rate of heterotrophic bacteria and more organic carbon export to the deep ocean. Furthermore, the buildup of glaciers during the minima of grand eccentricity cycles might lower pCO2 via increased ice cover and enhanced dust fluxes. In contrast, high seasonal climate may lead to an opposite effect on atmospheric pCO2 during the maxima of the grand eccentricity cycles. Moreover, we found a distinct shift in the dominant signal from eccentricity to obliquity cycles recorded in the pCO2, δ18Obenthic and GMSL datasets at ∼13 Ma, a time when perennial sea ice occurred in the Arctic and significant ice growth shown in Antarctica. We suggest that the change in the type and distribution of the ice sheets would shift glacial response to orbital forcing and hence mediated global climate and pCO2. Our analysis reveals a clear synchrony among atmospheric pCO2, climate change, and the grand orbital cycles in the late Cenozoic.

Woody plant encroachment drives population declines in 20% of common open ecosystem bird species.

Grassy ecosystems cover more than 40% of the world's terrestrial surface, supporting crucial ecosystem services and unique biodiversity. These ecosystems have experienced major losses from conversion to agriculture with the remaining fragments threatened by global change. Woody plant encroachment, the increase in woody cover threatening grassy ecosystems, is a major global change symptom, shifting the composition, structure, and function of plant communities with concomitant effects on all biodiversity. To identify generalisable impacts of encroachment on biodiversity, we urgently need broad-scale studies on how species respond to woody cover change. Here, we make use of bird atlas, woody cover change data (between 2007 and 2016) and species traits, to assess: (1) population trends and woody cover responses using dynamic occupancy models; (2) how outcomes relate to habitat, diet and nesting traits; and (3) predictions of future occupancy trends, for 191 abundant, southern African bird species. We found that: (1) 63% (121) of species showed a decline in occupancy, with 18% (34) of species' declines correlated with increasing woody cover (i.e. losers). Only 2% (4) of species showed increasing population trends linked with increased woody cover (i.e. winners); (2) Open habitat specialist, invertivorous, ground nesting birds were the most frequent losers, however, we found no definitive evidence that the selected traits could predict outcomes; and (3) We predict open habitat loser species will take on average 52 years to experience 50% population declines with current rates of encroachment. Our results bring attention to concerning region-wide declining bird population trends and highlight woody plant encroachment as an important driver of bird population dynamics. Importantly, these findings should encourage improved management and restoration of our remaining grassy ecosystems. Furthermore, our findings show the importance of lands beyond protected areas for biodiversity, and the urgent need to mitigate the impacts of woody plant encroachment on bird biodiversity.

Persistent and lagged effects of fire on stream solutes linked to intermittent precipitation in arid lands

Increased occurrence, size, and intensity of fire result in significant but variable changes to hydrology and material retention in watersheds with concomitant effects on stream biogeochemistry. In arid regions, seasonal and episodic precipitation results in intermittency in flows connecting watersheds to recipient streams that can delay the effects of fire on stream chemistry. We investigated how the spatial extent of fire within watersheds interacts with variability in amount and timing of precipitation to influence stream chemistry of three forested, montane watersheds in a monsoonal climate and four coastal, chaparral watersheds in a Mediterranean climate. We applied state-space models to estimate effects of precipitation, fire, and their interaction on stream chemistry up to five years following fire using 15 + years of monthly observations. Precipitation alone diluted specific conductance and flushed nitrate and phosphate to Mediterranean streams. Fire had positive and negative effects on specific conductance in both climates, whereas ammonium and nitrate concentrations increased following fire in Mediterranean streams. Fire and precipitation had positive interactive effects on specific conductance in monsoonal streams and on ammonium in Mediterranean streams. In most cases, the effects of fire and its interaction with precipitation persisted or were lagged 2–5 years. These results suggest that precipitation influences the timing and intensity of the effects of fire on stream solute dynamics in aridland watersheds, but these responses vary by climate, solute, and watershed characteristics. Time series models were applied to data from long-term monitoring that included observations before and after fire, yielding estimated effects of fire on aridland stream chemistry. This statistical approach captured effects of local-scale temporal variation, including delayed responses to fire, and may be used to reduce uncertainty in predicted responses of water quality under changing fire and precipitation regimes of arid lands.

Loss of protein phosphatase 2A regulatory subunit PPP2R5A is associated with increased incidence of stress-induced proarrhythmia.

Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme that controls Ca2+ homeostasis and contractility of the heart via dephosphorylation of regulatory proteins. In some genetically modified mouse models with increased arrhythmogenicity, a reduced expression of the regulatory subunit B56α of PP2A was found as a concomitant effect. Whether there is a general correlation between the abundance of B56α and the promotion of cardiac arrhythmogenesis remains unclear. The aim of this study was therefore to investigate the role of PP2A-B56α in the propensity for arrhythmic activity in the heart. The experimental analysis of this question has been addressed by using a mouse model with deletion of the PP2A-B56α gene, PPP2R5A (KO), in comparison to wild-type animals (WT). Evidence for arrhythmogenicity was investigated in whole animal, isolated heart and cardiomyocytes by ECG, recording of monophasic action potential (MAP) induced by programmed electrical stimulation (PES), measurement of Ca2+ transients under increased pacing frequencies and determination of total K+ channel currents (I K). ECG measurements showed a prolongation of QT time in KO vs. WT. KO mice exhibited a higher rate of premature ventricular contractions in the ECG. MAP measurements in Langendorff-perfused KO hearts showed increased episodes of ventricular tachyarrhythmia induced by PES. However, the KO hearts showed values for MAP duration that were similar to those in WT hearts. In contrast, KO showed more myocardial cells with spontaneous arrhythmogenic Ca2+ transient events compared to WT. The whole-cell patch-clamp technique applied to ventricular cardiomyocytes revealed comparable peak potassium channel current densities between KO and WT. These findings support the assumption that a decrease or even the loss of PP2A-B56α leads to an increased propensity of triggered arrhythmias. This could be based on the increased spontaneous Ca2+ tansients observed.

Abstract 3133: Selective Vulnerability Of Coronary Arteries To Hypercholesterolemia And Angiotensin II-induced Hypertension

Hypercholesterolemia and hypertension are major risk factors for cardiovascular disease. We aimed to determine their concomitant effects on coronary atherogenesis. An SR-BI (an HDL receptor) suppression and doxycycline-inducible angiotensin II (AngII) cassette was inserted downstream of the ApoE promoter to ablate ApoE expression and overproduce AngII. The resulting mutants (ApoE SA/SA ) exhibited mild coronary atherosclerosis after Western diet feeding. Doxycycline induced AngII-induced hypertension and drastically accelerated coronary atherosclerosis, with lesions exhibiting endothelial erosion, myeloid cell infiltration, and plaque rupture, resulting in myocardial infarction, heart failure, and male-propensity of sudden death. AngII, but not norepinephrine-induced hypertension, led to severe coronary atherogenesis under hypercholesterolemia, which was abolished by losartan. Notably, norepinephrine constricted femoral arteries, but it dilated coronary arteries. In contrast to coronary arteries, femoral arteries did not develop atherosclerosis. Proteomic analyses revealed distinctive differences between the two vascular beds. Coronary vasodilation to acetylcholine was highly susceptible to the risk factors, compared to femoral artery, and was markedly attenuated by AngII exposure and prostaglandin inhibition. Interestingly, coronary prostaglandin synthesis was suppressed in atherogenesis, and elevated coronary capacity to produce prostaglandins following methotrexate administration was associated with ameliorated early coronary endothelial dysfunction and improved cardiovascular survival, featuring markedly reduced lesional myeloid cells. Coronary arteries from patients with hypertension and hypercholesterolemia showed substantially impaired endothelium-dependent vasodilation, compared to internal mammary arteries of similar risk exposure, whereas their endothelium-independent vasodilation was intact. Thus, the combination of hypercholesterolemia and AngII-induced hypertension drastically promoted coronary atherosclerosis with spontaneous lesion rupture, which confers a selective vulnerability of coronary vasodilation to prostaglandin inhibition and AngII exposure.

African Academics in Norway: Experiences of Inclusion and Exclusion and Impact on Mental Wellbeing

This study explored the experiences of inclusion and exclusion of African academics in Norway in various sectors of the society and their participation in these sectors. Using a mixed method research approach, 166 African academics completed a 20-item questionnaire entitled Perceived Exclusion Scale (PES) and two open-ended questions about their mental effects and coping mechanisms of exclusion. Descriptive statistics and qualitative analysis procedures were used to analyze the data. The results showed that the participants experienced exclusion in almost all the sectors of the Norwegian society with concomitant effects of depression and insomnia for most of the participants. Participants mentioned acceptance, confrontational strategy, avoidance strategy, theological group discussion and positive attitudes as key coping mechanisms to exclusion and discrimination. This study could be used as a baseline for future research on the psychological and mental health effects of discrimination of Africans and African- Norwegians. The study is a pointer to the public discourses on the positive sides of immigration in general and the role of migrants’ contribution to the Norwegian society. Keywords: Norway, African academics, inclusion and exclusion, mental wellbeing, minorities

Effect of isoflurane anaesthetic time on ocular a-scan ultrasonography measures and their relationship to age and OCT measures in the Guinea pig

A-scan ultrasonography enables precise measurement of internal ocular structures. Historically, its use has underpinned fundamental studies of eye development and aberrant eye growth in animal models of myopia; however, the procedure typically requires anaesthesia. Since anaesthesia affects intra-ocular pressure (IOP), we investigated changes in internal ocular structures with isoflurane exposure and compared measurements with those taken in awake animals using optical coherence tomography (OCT). Continuous A-scan ultrasonography was undertaken in tri-coloured guinea pigs aged 21 (n = 5), 90 (n = 5) or 160 (n = 5) days while anaesthetised (up to 36 min) with isoflurane (5% in 1.5L/min O2). Peaks were selected from ultrasound traces corresponding to the boundaries of the cornea, crystalline lens, retina, choroid and sclera. OCT scans (Zeiss Cirrus Photo 800) of the posterior eye layers were taken in 28-day-old animals (n = 19) and compared with ultrasound traces, with choroid and scleral thickness adjusted for the duration of anaesthesia based on the changes modelled in 21-day-old animals. Ultrasound traces recorded sequentially in left and right eyes in 14-day-old animals (n = 30) were compared, with each adjusted for anaesthesia duration. The thickness of the cornea was measured in enucleated eyes (n = 5) using OCT following the application of ultrasound gel (up to 20 min). Retinal thickness was the only ultrasound internal measure unaffected by anaesthesia. All other internal distances rapidly changed and were well fitted by exponential functions (either rise-to-max or decay). After 10 and 20 min of anaesthesia, the thickness of the cornea, crystalline lens and sclera increased by 17.1% and 23.3%, 0.4% and 0.6%, and 5.2% and 6.5% respectively, whilst the anterior chamber, vitreous chamber and choroid decreased by 4.4% and 6.1%, 0.7% and 1.1%, and 10.7% and 11.8% respectively. In enucleated eyes, prolonged contact of the cornea with ultrasound gel resulted in an increase in thickness of 9.3% after 10 min, accounting for approximately half of the expansion observed in live animals. At the back of the eye, ultrasound measurements of the thickness of the retina, choroid and sclera were highly correlated with those from posterior segment OCT images (R2 = 0.92, p = 1.2 × 10−13, R2 = 0.55, p = 4.0 × 10−4, R2 = 0.72, p = 5.0 × 10−6 respectively). Furthermore, ultrasound measures for all ocular components were highly correlated in left and right eyes measured sequentially, when each was adjusted for anaesthetic depth. This study shows that the depth of ocular components can change dramatically with anaesthesia. Researchers should therefore be wary of these concomitant effects and should employ adjustments to better render ‘true’ values.

Crystallographic texture evolution in hot-press sintered tungsten heavy alloy with the effect of niobium (Nb) addition

This study examines the impact of niobium on the crystallographic texture evolution and grain boundary distribution of hot press sintered tungsten heavy alloy (W-4.9Ni-2.1Cu). EBSD analysis was used to examine the evolution of crystallographic texture and grain boundary character distribution in sintered compacts. The important findings of this study depict that cubic texture component {001} <111> were evolved in niobium unalloyed compacts due to the solidification of atoms aligned in a specified preferred orientation. Besides, it reveals the weakness in the cubic texture in niobium alloyed compacts due to the recrystallization followed by sub structural recovery occurrence during sintering. In addition, an increase in CSL fraction in niobium alloyed compacts illustrates the dominance of surface diffusion during sintering caused by the grain refinement attributed from the niobium enrichment at the tungsten-binder interface. Metallographic studies showed that the niobium concentration increment in WHAs has concomitant effect with sintered compacts' properties. A W-4.9Ni-2.1Cu-1 Nb alloy achieved the highest values for micro-hardness (432 HV0.5), electrical conductivity (23.74 % of IACS), and relative density (99.90 %).

Exploring the burden on family caregivers in providing care for their mentally ill relatives in the Upper East Region of Ghana.

Caring for the mentally ill involves numerous challenges, including financial difficulties, stigma, and psychosocial issues, among others. Unpaid family caregivers must endure these challenges as they continue their care for their relatives with mental illness. Despite these burdens and their concomitant effects on both the patients and their caregivers, there is no evidence of this burden in the Bolgatanga municipality. This study explored the burden on family caregivers providing care for mentally ill relatives in the Bolgatanga Municipality of the Upper East Region of Ghana. The study employed a phenomenological research design. Fifteen family caregivers were purposively sampled from two secondary-level health facilities. In-depth interviews were conducted, audio-recorded, and transcribed verbatim. NVivo 12 pro software was used for data analysis. Thematic analysis was conducted following Braun and Clarke's approach. The study identified three themes including social, physical, and psychological burdens. Under social burden, financial challenges and stigma were identified, weight loss was identified as a physical burden, and poor concentration as a psychological burden. These themes represent the challenges encountered by the family caregivers as they provided care for their mentally ill relatives. There is a need to provide support for family caregivers including respite, formation of support groups, and financial support to alleviate family caregivers of the burdens they endure. Additionally, it is imperative to integrate mental health services into the national health insurance scheme to alleviate the financial burden on family caregivers.

Tree growth and survival are more sensitive to high rainfall than drought in an aseasonal forest in Malaysia

Global change research has largely focused on the effects of drought on forest dynamics while the importance of excessive rainfall that can cause waterlogged soils has largely been assessed in riparian zones or seasonally flooded sites. However, increased rainfall may also cause decreased growth and survival of tree species in lowland aseasonal tropical forests due to increased risk from potentially more extensive and frequent waterlogged soils. We used a Bayesian modelling approach on a tree dynamics dataset from 2004 to 2017 to test the concomitant effects of rainfall excess and deficit and dry period length on tree growth and survival across a network of experimentally planted trees in a primary aseasonal forest in Malaysia. Growth declined in 48% of the species and survival decreased in 92% of the species during periods of high rainfall while as little as 4% of species had decreased growth or survival with drought and long dry periods. Climate change is projected to cause more frequent and severe rainfall deficit and excess, and our results suggest increased rainfall may have stronger negative effects on aseasonal tropical forests than that of severe drought.

Differential modulation of resting-state functional connectivity between amygdala and precuneus after acute physical exertion of varying intensity: indications for a role in affective regulation.

Physical activity influences psychological well-being. This study aimed to determine the impact of exercise intensity on psychological well-being and alterations in emotion-related brain functional connectivity (FC). Twenty young, healthy, trained athletes performed a low- and high-intensity interval exercise (LIIE and HIIE) as well as a control condition in a within-subject crossover design. Before and after each condition, Positive And Negative Affect Scale (PANAS) was assessed as well as resting-state functional MRI (rs-fMRI). Voxel-wise FC was examined for bilateral amygdala seed region to whole-brain and emotion-related anatomical regions (e.g., insula, temporal pole, precuneus). Data analyses were performed using linear mixed-effect models with fixed factors condition and time. The PANAS Positive Affect scale showed a significant increase after LIIE and HIIE and a significant reduction in Negative Affect after the control condition. In rs-fMRI, no significant condition-by-time interactions were observed between the amygdala and whole brain. Amygdala-precuneus FC analysis showed an interaction effect, suggesting reduced post-exercise anticorrelation after the control condition, but stable, or even slightly enhanced anticorrelation for the exercise conditions, especially HIIE. In conclusion, both LIIE and HIIE had positive effects on mood and concomitant effects on amygdala-precuneus FC, particularly after HIIE. Although no significant correlations were found between amygdala-precuneus FC and PANAS, results should be discussed in the context of affective disorders in whom abnormal amygdala-precuneus FC has been observed.

Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout)

Objectives: The objectives of this study were to observe the Efficacy of unani pharmacopoeial formulation Boozidan (Pyrethrum indicum) for the management of Niqris Muzmin (Chronic gout) and to observe any concomitant and adverse effects of formulation.&#x0D; Methods: This single blind, randomized and standard control clinical study was conducted between April 2021 to October 2021 for a period of 28 days. 60 patients diagnosed with chronic gout were divided into two groups, 30 Test group and 30 Control group. The test group was administered with 5g boozidaan in powder form once daily with water and the patients of control group were given tablet febuxostat 80mg once daily. Patients were followed up and improvements in subjective parameters were assessed weekly at 7th, 14th, 21st, and 29th day. Objective parameters were assessed at the baseline and at 29th day. The data obtained was subjected to statistical analysis.&#x0D; Results: Both the test and control drug were effective in reducing Serum uric acid level, ESR and CRP levels. A significant improvement in subjective and objective parameters was observed in both test and control groups and no adverse effects were observed during and after the study.&#x0D; However, the test drug had superior efficacy in reducing the objective parameters and it was statistically significant (p-value&lt;0.0001).&#x0D; Conclusion: Both Boozidaan and Febuxostat were safe and significantly effective in resolving the symptoms and signs of gouty arthritis and both have significant effect on reducing serum uric acid level.&#x0D; Keywords: Boozidaan, Chronic gout, Niqris, Febuxostat, serum uric acid, unani medicine

Improving Biocompatibility of Polyurethanes Apply in Medicine Using Oxygen Plasma and Its Negative Effect on Increased Bacterial Adhesion.

Polyurethanes (PUs) are versatile polymers used in medical applications due to their high flexibility and fatigue resistance. PUs are widely used for synthetic blood vessels, wound dressings, cannulas, and urinary and cardiovascular catheters. Many scientific reports indicate that surface wettability is crucial for biocompatibility and bacterial adhesion. The use of oxygen plasma to modify PUs is advantageous because of its effectiveness in introducing oxygen-containing functional groups, thereby altering surface wettability. The purpose of this study was to investigate the effect of the modification of the oxygen plasma of polyurethane on its biocompatibility with lung tissue (A549 cell line) and the adhesion of Gram-positive bacteria (S. aureus and S. epidermidis). The results showed that the modification of polyurethane by oxygen plasma allowed the introduction of functional groups containing oxygen (-OH and -COOH), which significantly increased its hydrophilicity (change from 105° ± 2° to 9° ± 2°) of PUs. Surface analysis by atomic force microscopy (AFM) showed changes in PU topography (change in maximum height from ∼110.3 nm to ∼32.1 nm). Moreover, biocompatibility studies on A549 cells showed that on the PU-modified surface, the cells exhibited altered morphology (increases in cell surface area and length, and thus reduced circularity) without concomitant effects on cell viability. However, serial dilution and plate count and microscopic methods confirmed that plasma modification significantly increased the adhesion of S. aureus and S. epidermidis bacteria. This study indicate the important role of surface hydrophilicity in biocompatibility and bacterial adhesion, which is important in the design of new medical biomaterials.

Climatic variables are more effective on the spatial distribution of oak forests than land use change across their historical range.

The current research is conducted to model the effect of climate change and land use change (LUC) on the geographical distribution of Quercus brantii Lindl. (QB) forests across their historical range. Forecasting was done based on six general circulation models under RCP 2.6 and RCP 8.5 future climate change scenarios for the future years 2050 and 2070. In order to model the species distribution, different modeling methods were used. The results indicated that, in general, climatic variables had a higher influence on the distribution of QB than land use-related attributes. The mean diurnal range (bio2), the precipitation seasonality (bio15), and the mean temperature of the driest quarter (bio9) were the main predictors in the distribution of QB forests, while land use variables were less important in oak species distribution. The GBM, MaxEnt, and RF had higher accuracy and performance in modeling species distribution. The outputs also showed that in the current climate circumstances, 97,608.81 km2 of the studied area has high desirability for the presence of QB, and by 2070, under the pessimistic scenario, 96.29% of these habitats will be lost under the concomitant effect of LUC and climate change. By using the results of this research, it is possible to predict and identify the effective factors in changing the habitat of this oak species with more certainty. Based on the insights obtained from the results of such studies, the protection and restoration planning of the habitat of this key species, which supports diverse species, will be provided more efficiently.

Identifying Brexit voting patterns in the British house of commons: an analysis based on Bayesian mixture models with flexible concomitant covariate effects

Abstract The results of some divisions related to Brexit held in the House of Commons are investigated. In particular, a new class of mixture models with concomitant covariates is developed to identify groups of members of parliament with similar voting behaviour. The methodological novelty lies in the flexibility introduced by the use of smooth functions to model the effect of concomitant covariates on the component weights of the mixture. Results show this approach allows to quantify the effect of the age of members of parliament, as well as preferences and competitiveness in the constituencies they represent, on their position towards Brexit.

Polarized Raman scattering and magnetic ordering in Mn lightly doped van der Waals Cr1−xMnxGeTe3 crystals

A layered van der Waals ferromagnet CrGeTe3 has attracted considerable interest due to the great potential for exploring low-power functional spintronic devices. However, research on the incorporation of chemical substitution in CrGeTe3 to tune the lattice vibrations and magnetic interactions is still lacking. In this work, an understanding of the phonon property and magnetic orders in Mn lightly doped Cr1−xMnxGeTe3 single crystals has been reported. It is found that the phonon symmetries are preserved over the studied Mn substitution content, as confirmed by angle-resolved polarized Raman spectroscopy and first-principles calculations. Furthermore, clear signatures of improved ferromagnetic Curie–Weiss temperature and magnetic moment are observed by detailed magnetic measurements. The higher magnetic moment of Mn ions, the variation of Mn–Te–Cr angle, Mn-induced hole doping, and the concomitant strain effect may all contribute to the enhanced ferromagnetism. Overall, our results demonstrate that chemical substitution is an effective pathway to engineering the lattice and magnetism of CrGeTe3.

Amiloride Reduces Urokinase/Plasminogen-Driven Intratubular Complement Activation in Glomerular Proteinuria.

Proteinuria predicts accelerated decline in kidney function in CKD. The pathologic mechanisms are not well known, but aberrantly filtered proteins with enzymatic activity might be involved. The urokinase-type plasminogen activator (uPA)-plasminogen cascade activates complement and generates C3a and C5a in vitro / ex vivo in urine from healthy persons when exogenous, inactive, plasminogen, and complement factors are added. Amiloride inhibits uPA and attenuates complement activation in vitro and in vivo . In conditional podocin knockout (KO) mice with severe proteinuria, blocking of uPA with monoclonal antibodies significantly reduces the urine excretion of C3a and C5a and lowers tissue NLRP3-inflammasome protein without major changes in early fibrosis markers. This mechanism provides a link to proinflammatory signaling in proteinuria with possible long-term consequences for kidney function. Persistent proteinuria is associated with tubular interstitial inflammation and predicts progressive kidney injury. In proteinuria, plasminogen is aberrantly filtered and activated by urokinase-type plasminogen activator (uPA), which promotes kidney fibrosis. We hypothesized that plasmin activates filtered complement factors C3 and C5 directly in tubular fluid, generating anaphylatoxins, and that this is attenuated by amiloride, an off-target uPA inhibitor. Purified C3, C5, plasminogen, urokinase, and urine from healthy humans were used for in vitro / ex vivo studies. Complement activation was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and ELISA. Urine and plasma from patients with diabetic nephropathy treated with high-dose amiloride and from mice with proteinuria (podocin knockout [KO]) treated with amiloride or inhibitory anti-uPA antibodies were analyzed. The combination of uPA and plasminogen generated anaphylatoxins C3a and C5a from intact C3 and C5 and was inhibited by amiloride. Addition of exogenous plasminogen was sufficient for urine from healthy humans to activate complement. Conditional podocin KO in mice led to severe proteinuria and C3a and C5a urine excretion, which was attenuated reversibly by amiloride treatment for 4 days and reduced by >50% by inhibitory anti-uPA antibodies without altering proteinuria. NOD-, LRR- and pyrin domain-containing protein 3-inflammasome protein was reduced with no concomitant effect on fibrosis. In patients with diabetic nephropathy, amiloride reduced urinary excretion of C3dg and sC5b-9 significantly. In conditions with proteinuria, uPA-plasmin generates anaphylatoxins in tubular fluid and promotes downstream complement activation sensitive to amiloride. This mechanism links proteinuria to intratubular proinflammatory signaling. In perspective, amiloride could exert reno-protective effects beyond natriuresis and BP reduction. Increased Activity of a Renal Salt Transporter (ENaC) in Diabetic Kidney Disease, NCT01918488 and Increased Activity of ENaC in Proteinuric Kidney Transplant Recipients, NCT03036748 .