Activity Concentration Research Articles

Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study

Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies.

Assessment of Activity Concentration and Health Hazards of Radiation Exposure in Soil from Mamara Jidda and Waja Tin Mining Sites in Northern Nasarawa State, Nigeria

Natural background radiation exposure is an inevitable occurrence on Earth, and humans are exposed to radiation in their surroundings whether consciously or unconsciously. However, increased artisanal and illegal mining could harm the local environment and increase background radiation levels, affecting the community's overall health. This study assessed the activity concentration of primordial radionuclides (226Ra, 232Th, and 40K) from soil samples obtained from Mamara Jidda and Waja tin mine sites in Nasarawa State, Nigeria, and its risk to human health. The gamma spectroscopy using a Sodium iodide-thallium activated detector was used to measure the activity concentrations of primordial radionuclides in the surface soils/sediments samples. The activity concentrations of 226Ra, 232Th, and 40K for Mamara Jidda and Waja were found to be within the range of 4 - 18 Bq kg-1, 41 - 105 Bq kg-1, and 524 - 717 Bq kg-1; 13 - 40 Bq kg-1, 75 - 134 Bq kg-1, and 591 - 882 Bq kg-1 respectively. The average values show that 40K and 232Th concentrations are above the recommended limit set by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) in Mamara Jidda and Waja mine sites. The annual gonadal dose equivalent (AGDE), annual effective dose rate (AEDE), radium equivalent (Raeq), absorbed dose rate (D), and external hazard index (Hex) for Mamara Jidda and Waja were found to be 0.56 mSv yr-1, 0.10 mSv yr-1, 588.58 Bq kg-1, 78.26 nGy hr-1 and 0.46; 0.73 mSv yr-1, 0.13 mS yr-1, 742.74 Bq kg-1, 103.72 nGy hr-1 and 0.61 respectively. The AEDE and Hex are below the recommended safety limits. However, the high values of AGDE in both mining sites and D in Waja mine demonstrate that with continuous exposure to radiation, a significant genetic impact is eminent to the miners and inhabitants of these areas. Also, the Raeq values for both mines suggest that their soils are unsafe for use as building materials.

Pollen contaminated with a triple-action fungicide induced oxidative stress and reduced longevity though with less impact on lifespan in honey bees from well fed colonies

Experiments were conducted to determine the effects of a triple-action fungicide on bees and whether improved nutrition can ameliorate eventual negative impacts. In cage tests, newly-emerged bees from well fed and from nutritionally-restricted honey bee colonies were fed for five days with pollen from sunflowers that had been sprayed or not with a commercial fungicide containing bixafen, prothioconazole and trifloxystrobin. Bees from well-fed colonies were significantly larger and consumed more uncontaminated pollen. They also exhibited increased glutathione peroxidase activity and higher concentrations of pyridine nucleotides, both of which are involved in antioxidase defense. However, pollen contaminated with fungicide led to an increase in lipoperoxidation, regardless of nutritional status. Bee longevity was reduced by both fungicide contamination of the pollen diet and poor nutritional condition. The fungicide adversely affected bees fed with contaminated pollen, though nutritional supplementation of the bee colonies that reared the bees partially compensated for these effects.

Role of Glutamine Synthetase on Vascular Permeability in Gliomas.

This study aimed to investigate the effect and underlying mechanism of inhibiting glutamine synthetase (GS) on the vascular permeability of gliomas. C6 glioma rat models were randomly divided into control and L-methionine sulfoximine (MSO) treatment groups. MSO was intraperitoneally injected once every other day for a total of three injections in the MSO group. We assessed the effect of MSO on tumor vascular permeability by tail vein injection of Evans blue dye. GS activity, glutamate (Glu) concentration, glutamine (Gln) concentration, and arginine concentration in tumor tissues were measured using the corresponding kits. qPCR experiments were then conducted to examine the effect of glutamate concentration on N-methyl-D-aspartate (NMDA) receptor expression. Finally, the nitric oxide synthase (NOS) assay kit and the nitric oxide (NO) assay kit were employed to detect NOS activity and NO concentration changes, respectively. Increased glioma tumor vascular permeability was observed after intraperitoneal injection of MSO; MSO acted as an inhibitor of GS, leading to a decrease in GS activity; increased glutamate levels caused activation of NMDA receptors and further activation of NOS; additionally, elevated NO levels were detected in association with an increase in arginine and NOS. Inhibiting GS results in increased vascular permeability in gliomas, which is associated with elevated NO levels and the vasodilatory effects of NO.

Assessment of natural radioactivity levels in polymetallic nodules and potential health risks from deep-sea mining

The activity concentration of U-238, Ra-226, Pb-214, Bi-214, and Pb-210 was measured in samples of polymetallic nodules stored in the repository of the Interoceanmetal Joint Organization (IOM) based in Szczecin, Poland. The nodule samples were collected from the seabed of the Pacific Ocean, within the Clarion-Clipperton Zone, approximately 2,000 kilometres west of Mexico. The activity concentration of U-238 in the studied samples ranged from 9 to 51Bqkg-1. The mean activity concentration of the other radionuclides, Ra-226, Pb-214, Bi-214, and Pb-210, was found to be at comparable levels at 350, 321, 323, and 287Bqkg-1, respectively. Also investigated was the potential radiological hazard to individuals involved in the storing and processing of the nodules, resulting from the radioactive decay of Ra-226 contained in the nodules. It was concluded that the effective dose limit (20mSv) for individuals occupationally exposed to radioactive material can be exceeded in the case of prolonged and close contact with large quantities of nodules. Effective protective measures against the detected radiation include: observing the exposure time, ensuring safe distance from the source of radiation, and selecting suitable shielding where feasible within the operational constraints of the nodule transport or storage system.

Multifractal detrended fluctuation analysis, cross-correlation and clustering of global 7Be activity concentration

Multifractal detrended fluctuation analysis, cross-correlation and clustering of global ⁷<i>Be</i> activity concentration

Quantifying bacterial efflux within subcellular domains of Pseudomonas aeruginosa.

Molecular efflux is a mechanism through which bacteria actively expel undesirable substances. This is a crucial line of defense against toxic chemicals in harsh environments. Understanding how efflux works is critical for designing antimicrobial strategies. Though much is already known about efflux proteins, important details about the mechanisms of efflux (e.g., importance of specific subcellular domains and ejection rates) have yet to be experimentally quantified. Herein, we use the nonlinear optical technique, second harmonic light scattering, to simultaneously measure the efflux rates from the periplasm and cytosol of a Gram-negative bacterium. The influence of efflux on the uptake kinetics of a mild antimicrobial, malachite green (MG), by Pseudomonas aeruginosa was quantified. It is observed that efflux primarily occurs from the periplasm and is two orders of magnitude faster than from the cytosol. Efflux pumps activate to maintain MG concentrations in the periplasm below 1 µM, while efflux from the cytosol maintains MG concentration below 0.1 µM. Efflux pumps are shown to saturate when exogenous MG concentrations are greater than 25 µM, while the cytosol efflux function saturates at >15 µM. Finally, efflux pumps can simultaneously eject different compounds, as proven by experiments with both MG and hexane, a known effluxable compound.IMPORTANCEMolecular efflux pumps are a crucial defense mechanism that protects bacteria from an otherwise unchecked influx of toxic molecules present in the extracellular environment. The efflux functions constitute a significant hindrance to antimicrobial efficacy. While much is now known regarding the structure of these channels, knowledge of the influence of efflux in individual subcellular domains and the associated ejection rates is still lacking. Using the nonlinear optical technique, second-harmonic light scattering, we have measured the threshold concentrations for pump activation, saturation concentrations, and efflux rates from both the periplasm and cytosol in living Gram-negative bacteria. The quantified efflux data in the different subcellular compartments not only provide a clear mechanistic understanding but also are critical for developing antimicrobial strategies.

Seasonal Variation of Polyphenols and Pigments in Ginkgo (Ginkgo biloba L.) Leaves: Focus on 3′,8″-Biflavones

Ginkgo (Ginkgo biloba L.) is a widely recognized medicinal plant, often grown as an ornamental species in parks around the world. Its leaves change color from green in spring to yellow in autumn. In this study, we collected ginkgo leaves at seven developmental stages from May to November and measured chlorophylls, carotenoids, flavonoids, and antioxidant activity. The total polyphenol content showed a significant increase from May to November, rising from 15.15 ± 0.14 mg GAE g−1 dw to 45.18 ± 0.42 mg GAE g−1 dw. The total flavonoid content reached its peak in August at 5.87 ± 0.18 mg GAE g−1 dw. In contrast, the highest concentrations of total polyphenolic acids (4.13 ± 0.16 mg CAE g−1 dw) and antioxidant activity (306.95 ± 3.47 µmol TE g−1) were recorded in May. We specifically focused on a less-studied group of dimeric flavonoids or biflavonoids—3′,8″-biflavones. We identified five 3′,8″-biflavones (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) throughout all developmental stages. Sciadopitysin was the most abundant biflavonoid, with its concentration rising from 614.71 ± 5.49 µg g−1 dw in May to 2642.82 ± 47.47 µg g−1 dw in November. Alongside sciadopitysin, the content of other biflavonoids (excluding amentoflavone) generally increased over the same period. This trend is further highlighted by the total biflavonoid content, which grew from 1448.97 ± 6.63 µg g−1 dw in May to 6071.67 ± 97.15 µg g−1 dw in November. We observed a negative correlation between biflavonoid and chlorophyll content, which may indicate their involvement in leaf senescence. However, this hypothesis warrants further investigation.

Correlation Between Physical Activity and Learning Concentration, Self-Management, and Interpersonal Skills Among Korean Adolescents

This study aimed to investigate the association between physical activity participation and key developmental competencies—learning concentration, self-management, and interpersonal skills—among Korean adolescents. Data were drawn from the 2021 Study on the State of Play Culture of Children and Adolescents and Measures to Support Growth, conducted by the Korea Adolescent Policy Institute. The study participants included elementary, middle, and high school students in Korea, consisting of 1507 males (53.3%) and 1322 females (46.7%), totaling 2829. We analyzed the data using frequency distribution, chi-square test, and multivariate logistic regression. The results revealed a significant sex difference in the duration of physical activity, with boys spending more time engaging in physical activity than girls. In addition, time spent on physical activities decreased as the school grade level increased. Notably, the more time Korean adolescents spent engaging in daily physical activity, the higher they rated their learning concentration, self-management, and interpersonal skills. These findings suggest the need to promote greater physical activity among adolescents—particularly among girls—which can help improve learning concentration, self-management, and interpersonal skills.

Assessment of natural radioactivity in the Higher and Tethys Himalayan Rocks along Manali-Leh Highway, India.

The Higher and Tethys Himalayan region of NW-Himalaya is less explored from the natural radioactivity mapping assessment, though geologically and tectonically, this region is still active. The concentration of primordial radionuclides (226Ra, 232Th, and 40K) in rock samples of the Manali-Leh Highway region of the Himalayas is determined in the present study using the HPGe detector. The radiological hazard parameters are also estimated in terms of radium equivalent activity (Raeq), annual effective dose (Ein and Eout), hazard indices (Hin, Hex, Hα, and Hγ), and gamma absorbed dose rate. SEM-EDS analysis was used to understand the mineralogical composition of the rocks. The activity concentration of 226Ra, 232Th, and 40K radionuclides varies from 1.4 ± 0.9 to 25.3 ± 1.2, 0.7 ± 0.5 to 59.6 ± 1.6, and BDL (below detection limit) to 830.3 ± 45.7Bqkg-1, with an average value of 13.0 ± 1.0, 21.7 ± 1.0, and 243.7 ± 25.2Bqkg-1, respectively. The average of Raeq in the study region lies within the safe limit of 370Bqkg-1. The hazard indices have values < 1, indicating no radiological hazards to the population from the rocks. The annual effective dose also has values less than the global average value. This study revealed that the rocks of the Higher Himalayan region have a higher concentration of natural radioactivity, while the Tethys Himalayan rocks have lower concentrations of 226Ra, 232Th, and 40K radionuclides. The origin of rocks from different lithologies may be the reason for the natural radioactivity variation. The average concentrations of primordial radionuclides in the region are within the world average indicating that the rocks of the region are safe to be used for different purposes.

Potential hepatoprotective properties of synthetic derivatives of thiourea — 2-aminobenzothiazole and IEM-2320

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

Comparative Evaluation of Lipid Profile, C-Reactive Protein and Paraoxonase-1 Activity in Dogs with Inflammatory Protein-Losing Enteropathy and Healthy Dogs

Chronic inflammation alters lipoprotein metabolism and causes changes in the serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme that may act as a local detoxifier, antioxidant, and immunomodulator in the gastrointestinal tract. Scarce information is available in dogs with protein-losing enteropathy secondary to chronic enteropathy (iPLE). The first aim was to describe and compare the lipid profiles, CRP concentrations and PON-1 activities in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides and lipoprotein classes. Serum concentrations of albumin, total protein, cholesterol, PON-1 activity, and high-density and very-low-density lipoproteins were lower in iPLE dogs compared to healthy controls, while those of triglycerides, low-density lipoproteins, chylomicrons and CRP were higher. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. High-density and low-density lipoproteins correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. The results need to be confirmed in further studies.

Increased circulating levels of standardized inflammatory and endothelial dysfunction biomarkers in patients with myocardial infarction with nonobstructive coronary arteries

Abstract Introduction Around 10% of patients with acute myocardial infarction (AMI) present with nonobstructive coronary arteries (MINOCA), for which the underlying pathophysiology is often uncertain. Our aim was to evaluate inflammatory burden and endothelial dysfunction in MINOCA patients by assessing biomarkers in both acute and stable phases. Methods An analytical and observational study at a University Hospital involving 166 MI patients admitted over the past 3years. Following ESC guidelines, patients were categorized into MINOCA or myocardial infarction with significant coronary artery disease (MI-CAD) groups. Circulating levels of inflammatory biomarkers (interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and high-sensitivity C-reactive protein(hs-CRP)) and of endothelial dysfunction (asymmetric dimethylarginine (ADMA)) were measured in 44 MINOCA patients and 122 MI-CAD patients at acute phase (admission and discharge) and stable phase (2months after MI). As biomarker levels may vary with MI size, each value was standardized by dividing it by the peak troponin, resulting in a biomarker/troponinT ratio. We evaluated the effects of standardized (SB) and non-standardized (NSB) biomarker values using a multivariate regression model adjusted for age and sex. Results We analyzed 166 patients (median age:68 years, 70% males). MI-CAD patients had higher peak high-sensitive troponinT (hs-TnT) levels upon admission compared to those with MINOCA (1491ng/L vs 247ng/L,p&amp;lt;0.001),likely due to larger infarctions generating higher levels of inflammation. When examining the association between infarct size, as measured by peak hs-TnT values, and biomarker levels, we observed a significant dose-response relationship for hs-CRP at admission (βcoefficient 0.16 [95%CI,0.02-0.29],p0.02) and IL-6 at admission (βcoefficient 0.15 [95%CI,0.04-0.27],p0.01). Significant positive associations were found between MINOCA and all SBs, both during the acute phase and in follow-up. During the acute phase ORs ranged from 1.35to2.7 (p&amp;lt;0.05) for inflammatory biomarkers and from 2.34 to 2.76 (p&amp;lt;0.01) for ADMA. In the stable phase ORs ranged from 1.49to3.06 (p&amp;lt;0.05) for inflammatory biomarkers, and OR was 2.79(p&amp;lt;0.01) for ADMA (Figure 1). In contrast, none of the NSBs were associated with MINOCA. Regarding temporal biomarker changes, during the acute phase of MI and 2 months post-event, both MINOCA and MI-CAD patients showed similar trends. However, MINOCA patients consistently maintained elevated inflammatory activity and ADMA concentrations only when biomarkers were standardized by infarct size (Figure 2). Conclusions Higher levels of SBs were consistently associated with MINOCA, both during the acute phase of the event and in follow-up, compared to MI-CAD. Consequently, this study suggests that the inflammatory burden, measured by heightened levels of standardized inflammatory biomarkers, and endothelial dysfunction, as measured by ADMA, may play a role in the pathophysiology of MINOCA.Boxplots for SBs at three time points.Temporal changes in biomarker levels.

Beneficial effects of the SGLT2 inhibition on oxidative skeletal muscle in infarcted rats

Abstract Introduction Metabolic, morphological, and biochemical changes in skeletal muscle are common in chronic heart failure patients. Despite the cardioprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition in heart failure, the impact of this drug on skeletal muscle remains poorly understood. This study investigated the effects of SGLT2 inhibitor empagliflozin (EMPA) on the soleus muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction, male Wistar rats were divided into Sham (n=10), Sham+EMPA (n=12), MI (n=10) and MI+EMPA (n=09) groups. EMPA was added to rat chow (5 mg/kg/day) for 12 weeks. Cardiac remodeling was evaluated by echocardiogram. Enzymatic activity and oxidative stress marker concentrations were assessed by spectrophotometry; protein expression was evaluated by Western blotting. After histological analysis of the left ventricle (LV), only rats with MI greater than 35% of total LV area were included in the study. Statistical analysis: ANOVA and Tukey or Kruskal–Wallis and Dunn and t test; p&amp;lt;0.05. Results Infarction size did not differ between groups. Infarcted groups had larger LV systolic and diastolic diameters, LV diastolic area (Sham 47±7.1; Sham+EMPA 48±4.5; MI 100±16.1*; MI+EMPA 85±10.1#† mm2; p&amp;lt;0.05: * vs Sham; # vs Sham+EMPA; † vs MI), and left atrial diameter (Sham 5.62±0.2; Sham+EMPA 5.65±0.3; MI 7.69±1.3*; MI+EMPA 6.85±0.9#† mm; p&amp;lt;0.05: * vs Sham; # vs Sham+EMPA; † vs MI); and lower LV posterior wall shortening velocity and ejection fraction than control groups. Echocardiographic changes were attenuated in MI+EMPA compared to MI. Other results are shown in Picture 1. Conclusion SGLT2 inhibitor empagliflozin attenuates infarction-induced cardiac remodeling in rats. Empagliflozin prevents increase in oxidative stress, modulates protein turnover by IGF-1 pathway, and attenuates morphological and biochemical changes in the soleus muscle of infarcted rats.

The effect of spironolactone versus eplerenone on blood pressure targets in resistant hypertension patients

Abstract Objective to evaluate different effects on blood pressure (BP) control in two treatment options spironolactone (SPIR) versus eplerenone (EPL) as an add-on therapy in resistant hypertensive (RAH) patients. Design and methods: We studied 208 patients with true RAH confirmed by the office and ambulatory BP monitoring (ABPM) despite the use of 3 antihypertensive medications including a calcium channel blocker, a blocker of the renin-angiotensin system, and a thiazide diuretic with maximally tolerated doses for at least 3 months. Patients were randomized into 2 groups throughout 12 weeks of once-daily treatment with SPIR (25–50 mg) or EPL (25-50 mg) in addition to their baseline triple-combination and then rotated with drugs. BP was measured in the office and by ABPM. Changes in laboratory tests were also studied. The predictive values of plasma aldosterone, active renin concentration (ARC), aldosterone-renin ratio (ARR), and serum potassium were analyzed to determine the antihypertensive response. Results There were no significant differences in the reduction of average office BP, average systolic 24-h, daytime, and nighttime BP by SPIR and EPL. SPIR reduced average diastolic 24-h BP by 7.3 mm Hg, diastolic daytime BP by 7.2 mm Hg, and diastolic nighttime BP by 7.5 mm Hg compared with a reduction of 5.6 mm Hg (P = 0.01), 5.6 mm Hg (P = 0.03) and 4.2 mm Hg (P = 0.0001) with EPL, respectively. Overall, 40.7 % RAH patients achieved targets of clinical BP and 24-h ABPM levels on SPIR and 33.3 % on EPL (Р = 0.002). After 12 weeks of treatment mean plasma potassium concentrations increased by 7.1 (P = 0.0001) on SPIR and by 5.0 % (Р = 0.0001) on EPL, but eGFR did not significantly change on the two drugs. Plasma aldosterone (β = 0.498, Р = 0.02) and ARC (β= -0.374, Р = 0.04) were predictors of the BP-lowering effect of SPIR and plasma aldosterone (β = 0.453, Р = 0.04) was a predictor of reduction BP for EPL in multivariate modeling. Breast pain or tenderness, changes in sex drive, and irregular menstrual cycles or spotting were more often by SPIR than by EPL (5.2 % vs 1.9 %, respectively, P = 0.04). Conclusions The greater antihypertensive effect of SPIR is related to aldosterone status, ARS level in resistant hypertension. EPL may be recommended for RAH patients who have high serum potassium levels that cannot tolerate spironolactone and for people with systolic resistant hypertension.

Assessment of radioactive nuclides and heavy metals in soil and drink water in Lahij city, Yemen

This study was conducted in Lahij city, Yemen, to evaluate the concentrations and potential health risks of natural radioactive nuclides and heavy metals in soil and drinking water. A total of 21 soil samples and 17 water samples were collected from various locations. A high-purity germanium gamma detector HPGe was used to measure the concentrations of 40K, 232Th, and 226Ra in all samples, along with the concentrations of heavy metals. In soil samples, the average concentrations of 40K, 232Th, and 226Ra were 731.5, 30.7, and 28.16 Bq kg−1, respectively. While some samples showed higher than permissible levels for 226Ra and 232Th, the overall average remained within acceptable limits. However, 40K levels were almost twice the recommended global limits. In water samples, the average concentrations of these nuclides were 5.38, 0.73, and 0.66 Bq L−1, all within the global safety limits. Radiological risk assessments for soil indicated an average radium equivalent activity (Raeq) of 124.4 Bq kg−1, absorbed dose rate in air of 59.9 nGy h−1, annual effective dose rate of 0.07 mSv y−1, outdoor excess lifetime cancer risk (ELCR) of 0.26 × 10−3, and annual gonad equivalent dose (AGED) of 336.6 mSv y−1. Risk indices, including the activity concentration index (Iγ), external hazard index (Hex), and internal hazard index (Hin), averaged 0.48, 0.34, and 0.41, respectively, all below global limits except for AGED, which slightly exceeded the recommended level. For drinking water, the total ingestion dose was calculated for different age groups. The average doses for infants, children, and adults were 0.15, 0.27, and 0.19 mSv y−1, respectively. The doses for children and adults exceeded the permissible limits, while those for infants were within safe levels. Heavy metal concentrations were measured in all samples, and the Hazard Quotient (HQ) was calculated. In soil samples, HQ values for all metals >1, indicating potential health risks. In water samples, HQ values were also >1 for all metals except vanadium (V) and iron (Fe). To reduce the dangers associated with radioactive nuclides and heavy metals, regular monitoring and cleanup are crucial, and further research is needed to understand contamination sources and long-term health impacts.

Subsurface basement structures of the Usangu basin, East African rift system, with implications for basin structural configuration and hydrocarbon potential

The Usangu basin is a rift basin developed along the Eastern arm of the East African rift system trending in the NE-SW direction. Although the general structures of the basin have been well studied, the structural configuration of the basin and the spatial and depth variations of sediment thickness are still not well known. This study investigates the structures related basement configuration and the variation of sediment thickness within the basin using the Shuttle Radar Topography Mission (SRTM) Digital Elevation Model (DEM), aeromagnetic and gravity data. Results from DEM data indicate a few lineaments on the basin flanks representing the Usangu and Chimala border faults with no structures in the central part of the basin. The aeromagnetic and gravity data highlight three sets of normal and strike-slip faults, most of which trend NE-SW and others NNE-SSW, while a few trends WNW-ESE or NW-SE. Structures on the southwest of the basin reveal complex patterns attributed to the concentration of important tectonic and seismic activities in the study area. The Euler deconvolution and gravity models used to calculate the depth to the basement show that the basement is shallow in the north and south to southwest, and the basin deepens in the northeastern, northwestern and western parts. The findings also reveal that the basin has two grabens, troughs, depression and intrabasinal basement trending in the same direction as the basin configuration. The general thickness of sediments filling the basin ranges from 3 to 4.5 km, with the maximum accumulation of sediments reaching up to 4.8 km in the two depocenters at the south and southwest of the basin. The depth range of the sediments obtained implies that the basin has potential for hydrocarbon exploration with the possibility of natural gas occurrence.

Monitoring of urinary nickel and chromium in metal industries workers in Alborz, Iran

Heavy metal contamination from occupational sources is a cause for concern due to its potential accumulation in the environment and the body of living organisms, which leads to long-term toxic effects. There is limited evidence on the concentration of heavy metals in the body fluids of welding workers. This study aimed to measure the concentration of nickel (Ni) and chromium (Cr) as two main toxic heavy metals in the urine samples of welders and determine the potential relationship of various environmental factors on their concentration levels. This study was conducted in Iran in 2022–2023. Eighty-five urine samples were collected from the studied welding workers. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to measure the concentration of Ni and Cr. Data related to socio-demographic characteristics (education level, income, work experience, age, and body mass index (BMI)), lifestyle profile (consumption of seafood and canned food, smoking, physical activity), type of ventilation and preventive devices at work, and suffering from underlying diseases (cardiovascular and high blood pressure) were collected using valid questionnaires. Ni and Cr were present in 100% of urine samples with mean concentrations of (1.09 ± 0.294) and (11.45 ± 16.751) µg/g creatinine, respectively. A significant correlation was observed between the mean concentration of Ni and Cr with the level of education, income, work experience, age, consumption of seafood and canned food, smoking, type of ventilation and preventive devices, and underlying diseases (p-value < 0.05). Also, there was no significant difference between Ni concentration and physical activity and Cr concentration with BMI. Lifestyle determinants and not using preventive devices are important predictors of urinary heavy metals in welding workers. Therefore, more research is required to determine the adverse effects of long-term exposure to these heavy metals.

Assessment of background dose rate on non-human biota in a Mediterranean terrestrial ecosystem.

The assessment of radiological impact to the environment is usually carried out by the dose rate estimation to hypothetical entities named Reference Animals and Plants (RAPs). There are many codes to carry out this assessment, which requires the definition of a scenario and using site-specific transfer parameters when possible. Transfer parameters present a geographical bias, as they are mostly derived from temperate and arctic climate datasets, but there is a scarcity of data for Mediterranean climates. In this study, a terrestrial Mediterranean scenario was defined using the distribution of activity concentrations of anthropogenic (90Sr, 137Cs) and naturally occurring radionuclides (40K, 210Pb, 210Po, 226,228Ra, 235,238U, 232Th) in Cáceres province (Spain). Site-specific transfer factors, CRwo-media, defined as the ratio between the concentration in the whole organism and the medium (soil in this case) were considered. Dose rate assessments for terrestrial RAPs were carried out using Tier 3 in ERICA Tool, ranging 0.23-3.73µGy/h which is below the screening level of 10µGy/h. Therefore, no harmful effects are expected to occur. Internal dose rate predominates over external one because the main contributors are naturally occurring radionuclides (in most cases 40K, 226,228Ra, 210Pb, 210Po), which are mostly α-emitting radionuclides. These results can be used for the evaluation of other radiological and nuclear installations in Mediterranean climates, as they set the background dose rate.

Efficacy and Safety of Rivaroxaban, Apixaban, and Edoxaban for Nonvalvular Atrial Fibrillation Based on Blood Coagulation Activity and Drug Plasma Concentration: SETtsu and North Osaka Multicenter Direct Oral AntiCoagulant (SET DOAC) Registry

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (&lt;6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p &lt; 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.