Ameliorative potential of eriocitrin against cadmium instigated hepatotoxicity in rats via regulating Nrf2/keap1 pathway.

BACKGROUND: Cadmium (Cd) is a hazardous heavy metal that adversely affects the vital body organs particularly liver. Eriocitrin (ERCN) is a plant-based flavonoid that is well-known for its wide range of pharmacological potential. This research trial was aimed to determine the ameliorative potential of ERCN against Cd provoked hepatotoxicity in rats. METHODOLOGY: Twenty-four rats (Rattus norvegicus) were apportioned into control, Cd treated (5 mg/kg), Cd (5 mg/kg) + ERCN (25 mg/kg) and only ERCN (25 mg/kg) administrated group. Expressions of Nrf2/Keap1 pathway and apoptotic markers were assessed through qRT-PCR. The levels of inflammatory and liver function markers were evaluated by using standard ELISA kits. KEY FINDINGS: Cd exposure reduced the expression of Nrf2 and anti-oxidant genes as well as the activity of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione (GSH) contents while escalating the expression of Keap1. Furthermore, Cd intoxication augmented malondialdehyde (MDA) and reactive oxygen species (ROS) levels in hepatic tissues. Exposure to Cd resulted in a notable elevation in the levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Cd administration upregulated nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels as well as cyclooxygenase-2 (COX-2) activity. Furthermore, Cd administration upsurged Bax and Caspase-3 expression while reducing the expression of Bcl-2. Moreover, Cd intoxication disrupted the normal architecture of hepatic tissues. However, supplementation of ERCN significantly (p < 0.05) ameliorated the aforementioned disruptions induced by Cd intoxication. CONCLUSION: ERCN treatment remarkably ameliorated the hepatic tissues owing to its antioxidant, anti-inflammatory, and anti-apoptotic potentials. These findings underscore the therapeutic potential of ERCN to counteract the adverse effects of environmental pollutants on hepatic tissues.

Estimation of population median using bivariate auxiliary information in simple random sampling.

To estimate the unknown population median, several researchers have developed efficient estimators but these estimators are unable to provide efficient results in the existence of outliers. Keeping this point in view, the present work suggests enhanced class of robust estimators to estimate population median under simple random sampling in case of outliers/extreme observations. The suggested estimators are a mixture of bivariate auxiliary information and robust measures with the linear combination of deciles mean, tri-mean and Hodges Lehmann estimator. Mathematical properties associated with the improved class of robust estimators are evaluated in terms of bias and mean squared error. Moreover, the potentiality of our suggested estimators as compared to already available estimators is checked by considering two real-life data sets with outlier(s). In addition, a simulation study is also added in this regard. From theoretical and numerical findings, it is observed that our newly suggested estimators outperforms as compared to its competitors.

The adoption and use of learning analytics tools to improve decision making in higher learning institutions: An extension of technology acceptance model.

Learning Analytics Tools (LATs) can be used for informed decision-making regarding teaching strategies and their continuous enhancement. Therefore, LATs must be adopted in higher learning institutions, but several factors hinder its implementation, primarily due to the lack of an implementation model. Therefore, in this study, the focus is directed towards examining LATs adoption in Higher Learning Institutions (HLIs), with emphasis on the determinants of the adoption process. The study mainly aims to design a model of LAT adoption and use it in the above context to improve the institutions' decision-making and accordingly, the study adopted an extended version of Technology Acceptance Model (TAM) as the underpinning theory. Five experts validated the employed survey instrument, and 500 questionnaire copies were distributed through e-mails, from which 275 copies were retrieved from Saudi employees working at public HLIs. Data gathered was exposed to Partial Least Square-Structural Equation Modeling (PLS-SEM) for analysis and to test the proposed conceptual model. Based on the findings, the perceived usefulness of LAT plays a significant role as a determinant of its adoption. Other variables include top management support, financial support, and the government's role in LATs acceptance and adoption among HLIs. The findings also supported the contribution of LAT adoption and acceptance towards making informed decisions and highlighted the need for big data facility and cloud computing ability towards LATs usefulness. The findings have significant implications towards LATs implementation success among HLIs, providing clear insights into the factors that can enhance its adoption and acceptance. They also lay the basis for future studies in the area to validate further the effect of LATs on decision-making among HLIs institutions. Furthermore, the obtained findings are expected to serve as practical implications for policy makers and educational leaders in their objective to implement LAT using a multi-layered method that considers other aspects in addition to the perceptions of the individual user.

Surface-enhanced Raman spectroscopy of the filtrate portions of the blood serum samples of breast cancer patients obtained by using 30 kDa filtration device.

Raman spectroscopy is reliable tool for analyzing and exploring early disease diagnosis related to body fluids, such as blood serum, which contain low molecular weight fraction (LMWF) and high molecular weight fraction (HMWF) proteins. The disease biomarkers consist of LMWF which are dominated by HMWF hence their analysis is difficult. In this study, in order to overcome this issue, centrifugal filter devices of 30 kDa were used to obtain filtrate and residue portions obtained from whole blood serum samples of control and breast cancer diagnosed patients. The filtrate portions obtained in this way are expected to contain the marker proteins of breast cancer of the size below this filter size. These may include prolactin, Microphage migration inhabitation factor (MIF), γ-Synuclein, BCSG1, Leptin, MUC1, RS/DJ-1 present in the centrifuged blood serum (filtrate portions) which are then analyzed by the SERS technique to recognize the SERS spectral characteristics associated with the progression of breast cancer in the samples of different stages as compared to the healthy ones. The key intention of this study is to achieve early-stage breast cancer diagnosis through the utilization of Surface Enhanced Raman Spectroscopy (SERS) after the centrifugation of healthy and breast cancer serum samples with Amicon ultra-filter devices of 30 kDa. The silver nanoparticles with high plasmon resonance are used as a substrate for SERS analysis. Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) models are utilized as spectral classification tools to assess and predict rapid, reliable, and non-destructive SERS-based analysis. Notably, they were particularly effective in distinguishing between different SERS spectral groups of the cancerous and non-cancerous samples. By comparing all these spectral data sets to each other PLSDA shows the 79 % accuracy, 76 % specificity, and 81 % sensitivity in samples with AUC value of AUC = 0.774 SERS has proven to be a valuable technique for the rapid identification of the SERS spectral features of blood serum and its filtrate fractions from both healthy individuals and those with breast cancer, aiding in disease diagnosis.

Tuning phase separation in DPPDTT/PMMA blend to achieve molecular self-assembly in the conducting polymer for organic field effect transistors.

The semiconductor/insulator blends for organic field-effect transistors are a potential solution to improve the charge transport in the active layer by inducing phase separation in the blends. However, the technique is less investigated for long-chain conducting polymers such as Poly[2,5-(2-octyldodecyl)-3,6-diketopyrrolopyrrole-alt-5,5-(2,5-di(thien-2-yl)thieno [3,2-b]thiophene)] (DPPDTT), and lateral phase separation is generally reported due to the instability during solvent evaporation, which results in degraded device performance. Herein, we report how to tailor the dominant mechanism of phase separation in such blends and the molecular assembly of the polymer. For DPPDTT/PMMA blends, we found that for higher DPPDTT concentrations (more than 75%) where the vertical phase separation mechanism is dominant, PMMA assisted in the self-assembly of DPPDTT to form nanowires and micro-transport channels on top of PMMA. The formation of nanowires yielded 13 times higher mobility as compared to pristine devices. For blend ratios with DPPDTT ≤ 50%, both the competing mechanisms, vertical and lateral phase separation, are taking place. It resulted in somewhat lower charge carrier mobilities. Hence, our results show that by systematic tuning of the blend ratio, PMMA can act as an excellent binding material in long-chain polymers such as DPPDTT and produce vertically stratified and aligned structures to ensure high mobility devices.

Temporal Trends in Obesity-Related Mortality Rates: An Analysis of Gender, Race/Ethnicity, and Geographic Disparities in the United States.

Obesity is a global public health concern linked to premature death and an increased burden of noncommunicable diseases. This study aims to assess obesity-related mortality rates and temporal trends in the United States. We investigate variations by gender, ethnicity, and state-level demographics using data from the Centers for Disease Control and Prevention WONDER database spanning 1999 to 2021. We identified 124,076 obesity-related deaths, with a mean age-adjusted mortality rate (AAMR) of 2.7 per 100,000 population. AAMRs increased over time, with the highest rises observed in non-Hispanic Black/African American and American Indian/Alaska Native populations, and among males. Certain states showed higher AAMRs. These findings underscore racial disparities in obesity-related mortality and the need for further research to address these disparities.

Role of time-dependent foreign molecules bonding in the degradation mechanism of polymer field-effect transistors in ambient conditions.

Long-standing research efforts have enabled the widespread introduction of organic field-effect transistors (OFETs) in next-generation technologies. Concurrently, environmental and operational stability is the major bottleneck in commercializing OFETs. The underpinning mechanism behind these instabilities is still elusive. Here we demonstrate the effect of ambient air on the performance of p-type polymer field-effect transistors. After exposure to ambient air, the device showed significant variations in performance parameters for around 30 days, and then relatively stable behaviour was observed. Two competing mechanisms influencing environmental stability are the diffusion of moisture and oxygen in the metal-organic interface and the active organic layer of the OFET. We measured the time-dependent contact and channel resistances to probe which mechanism is dominant. We found that the dominant role in the degradation of the device stability is the channel resistance rather than the contact resistance. Through time-dependent Fourier transform infrared (FTIR) analysis, we systematically prove that moisture and oxygen cause performance variation in OFETs. FTIR spectra revealed that water and oxygen interact with the polymer chain and perturb its conjugation, thus resulting in degraded performance of the device upon prolonged exposure to ambient air. Our results are important in addressing the environmental instability of organic devices.

Polypill Therapy in Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials.

The effectiveness of polypill therapy in the prevention and treatment of cardiovascular disorders is still unclear. This meta-analysis aimed to assess the efficacy of polypill therapy in reducing cardiovascular risk factors. We conducted a systematic search of PubMed, Cochrane CENTRAL, SCOPUS, and Google Scholar for randomized controlled trials (RCTs) that evaluated polypill therapy for cardiovascular diseases, hypertension, or dyslipidemia. We included 18 RCTs with a total of 20,463 participants in our analysis. Pooled effect estimates were reported as Odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Polypill therapy was associated with a statistically significant reduction in systolic blood pressure (SBP) (OR: -0.33, 95% CI [-0.64, -0.03]; P-value = 0.03), diastolic blood pressure (DBP) (OR: -0.70, 95% CI [-1.20, -0.21]; P-value = 0.005), and total cholesterol level (OR: -1.25, 95% CI [-1.82, -0.68]; P-value < 0.0001). Polypill therapy also showed improved adherence (OR 2.18, 95% CI [1.47, 3.24]; P-value = 0.0001). However, there was no statistically significant benefit in the reduction of all-cause mortality, major cardiovascular events, and LDL-c levels. The use of polypill therapy is associated with a statistically significant reduction in SBP, DBP, and total cholesterol levels, as well as improved adherence. Further research is needed to determine its impact on hard clinical outcomes such as mortality and major cardiovascular events.

Vaccine Adjuvants: Selection Criteria, Mechanism of Action Associated with Immune Responses and Future Directions.

The most effective method to minimize the prevalence of infectious diseases is vaccination. Vaccines enhance immunity and provide protection against different kinds of infections. Subunit vaccines are safe and less toxic, but due to their lower immunogenicity, they need adjuvants to boost the immune system. Adjuvants are small particles/molecules integrated into a vaccine to enhance the immunogenic feedback of antigens. They play a significant role to enhance the potency and efficiency of vaccines. There are several types of adjuvants with different mechanisms of action; therefore, improved knowledge of their immunogenicity will help develop a new generation of adjuvants. Many trials have been designed using different kinds of vaccine adjuvants to examine their safety and efficacy, but in practice, only a few have entered in animal and human clinical trials. However, for the development of safe and effective vaccines, it is important to have adequate knowledge of the side effects and toxicity of different adjuvants. The current review discussed the adjuvants which are available for producing modern vaccines as well as some new classes of adjuvants in clinical trials.

Approaching Bulk Mobility in PbSe Colloidal Quantum Dots 3D Superlattices.

3D superlattices made of colloidal quantum dots are a promising candidate for the next generation of optoelectronic devices as they are expected to exhibit a unique combination of tunable optical properties and coherent electrical transport through minibands. While most of the previous work was performed on 2D arrays, the control over the formation of these systems is lacking, where limited long-range order and energetical disorder have so far hindered the potential of these metamaterials, giving rise to disappointing transport properties. Here, it is reported that nanoscale-level controlled ordering of colloidal quantum dots in 3D and over large areas allows the achievement of outstanding transport properties. The measured electron mobilities are the highest ever reported for a self-assembled solid of fully quantum-confined objects. This ultimately demonstrates that optoelectronic metamaterials with highly tunable optical properties (in this case in the short-wavelength infrared spectral range) and charge mobilities approaching that of bulk semiconductor can be obtained. This finding paves the way toward a new generation of optoelectronic devices.

The effects of bariatric surgery on male and female fertility: A systematic review and meta-analysis.

•Currently natural lifestyle modification is recommended over bariatric surgery in the management of infertility in obese men and women, despite natural weight loss often being an ineffective method to both lose and maintain weight loss in these individuals.•Through this meta-analysis and systematic review, we provide evidence that bariatric surgery effectively improves fertility outcomes for men and women by measurements of hormone levels and improvements in sexual function index scores.•This study demonstrates the importance and even cruciality of bariatric surgery in obese men and women who struggle with reproductive health, especially when finding it difficult to lose and maintain weight. It also proves that it is vital to continue to create and expand our knowledge with evidence-based medicine to help this cohort of patients.

Evaluation of the combination therapy of hydroxyurea and thalidomide in ß-thalassemia.

Transfusion-related complications and lack of resources in low-to-middle-income countries have led to a search for novel therapies to reduce the need for blood transfusions in patients with ß-thalassemia. Hydroxyurea (HU) has demonstrated promising outcomes; additionally, thalidomide has also shown improvement in hemoglobin (Hb) levels for patients with ß-thalassemia in some studies. This study presents the findings of a single-arm nonrandomized trial to evaluate the efficacy of combination therapy of HU and thalidomide in children with ß-thalassemia. A total of 135 patients (median age, 6 [interquartile range, 3-10] years), 77 (57%) males and 58 (43%) females, were followed first using HU alone, for 6 months, and then using the combination of HU and thalidomide for another 6 months. The primary outcome was a response to therapy, as measured by the number of transfusions required and Hb levels, for patients while receiving HU alone and then while using the combination therapy. Study findings showed a significant decline in blood transfusion volume (P < .001) and a significant increase in median Hb levels within 3 and 6 months of the combination therapy (P < .001). Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were nonresponders, whereas the responders had variable genetic mutations. A total of 38 adverse events were reported that resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with ß-thalassemia. This trial was registered at www.clinicaltrials.gov as #NCT05132270.

A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among ß-Thalassemia Major Patients in Pakistan.

Despite high prevalence and incidence of ß-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani ß-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and ß-globin mutations with HU response in ß-thalassemia major (BTM). Of 272 patients treated with HU, 98 were complete responders, 55 partial responders, and 119 nonresponders. Our analysis shows that HU response was significantly associated with patients having IVSI-1 or CD 30 mutation (P<0.001), age at first transfusion >1 year (P<0.001), and with the presence of XmnI polymorphism (P<0.001). The single-nucleotide polymorphisms of BCL11A were more prevalent among responders, but could not show significant association with HU response (P>0.05). Cumulative effect of all 5 predicting factors through simple binary scoring indicates that the likelihood of HU response increases with the number of primary and secondary genetic modifiers (P<0.001). Predictors scoring is a pragmatic tool to foresee HU response in patients with BTM. The authors recommend a score of ≥2 for starting HU therapy in Pakistani patients with BTM.

Prenatal diagnosis of maternal serum from mothers carrying ß-thalassemic fetus.

BACKGROUND: This study focuses on the discovery of protein biomarkers from the maternal serum of ß-thalassemic trait mothers carrying the normal fetus and ß-thalassemic major fetus. METHODS: Serum samples from ß-thalassemic trait mothers carrying major (N = 5) and normal fetuses (N = 5) were studied. The IVS1-5 thalassemia mutation was common among ß-thalassemic trait mothers who were carrying a homozygous ß-thalassemic fetus (IVS1-5/ IVS1-5 mutation) or a normal fetus (no mutation). We employed two-dimensional gel electrophoresis and mass spectrometry analysis to explore differentially expressed maternal serum proteins from thalassemia carrier couples with the same ß-thalassemia mutation. Western blotting was performed for one of the identified proteins to validate our data. RESULTS: Ten proteins were identified in the maternal serum of ß-thalassemic trait mothers carrying the ß-thalassemic major fetus and normal fetus. Among these, serotransferrin, haptoglobin, α-1 anti-trypsin, apo-lipoprotein A1, and the fibrinogen-ß chain were found to be upregulated in mothers carrying major fetuses and are known to be associated with pregnancy-related disorders. The expression of α-1 anti-trypsin was validated through western blotting. CONCLUSIONS: Proteins identified in the current study from maternal serum are reported to contribute to hereditary disorders. We suggest that these can serve as putative screening markers for non-invasive prenatal diagnosis in ß-thalassemic pregnancies.

A Rare and Challenging Case of Neck Infection - Thyroid Abscess.

Acute suppurative thyroiditis (AST) is serious and rare infection of the thyroid gland, often it can progress to thyroid abscess. Both anatomical defects and underlying thyroid disorders are attributed to etiopathogenesis of the disease. Bacteria usually reach the gland either by lymphatic spread or via hematogenous routes. If untreated it has fatal outcome and had serious complications. The mainstay of treatment is usually a combination of intravenous antibiotics and drainage, and sometimes surgery.

Pleural Effusion: A Rare Presentation of Mature Teratoma in a Young Patient.

Mediastinal masses always present a diagnostic challenge to clinicians and radiologists. There are wide varieties of pathologies ranging from benign to malignant conditions. Teratomas are one of the rare causes of mediastinal tumors. In this case, we report a young male who presented to the emergency room with acute pleuritic chest pain. The chest X-ray showed massive right-sided pleural effusion. Subsequently, bedside chest ultrasound ruled out septations and helped drain the fluid. The pleural fluid analysis demonstrated transudate chemistry. A computerized tomography (CT) of the chest was performed, revealing a complex anterior mediastinal mass suspected of Mature Teratoma. The tumor was surgically removed in its entirety, and pathology confirmed it a mature teratoma. The patient remained asymptomatic on postoperative follow-up.

Antioxidant Activity and Oxidative Stress Status in Maternal Serum of ß-thalassemic Mothers Carrying ß-thalassemic Major and Normal Fetuses.

Objectiveß-thalassemia is a genetic disorder characterized by reduction or absence of ß-globin chain with mutations in both copies (ß-thalassemia major) or in one copy (ß-thalassemia minor). Pregnancies in ß- thalassemic carrier women are considered symptom free but have risk of inheriting ß-thalassemic fetuses. Current study was designed to compare oxidative stress and antioxidants status in maternal serum from ß-thalassemic minor mothers having ß-thalassemic major and normal fetuses. Method: We investigated paraoxonase (PON1) and arylesterase (ARE) activities along with malondialdehyde (MDA) and reactive oxygen species (ROS) in maternal serum of ß-thalassemic carrier women. Results: PON1 and ARE activities were found to be significantly decreased, whereas the concentration of MDA and ROS were significantly increased in ß-thalassemic minor mothers with ß-thalassemic major fetuses. Conclusion: The study concludes that redox imbalance in ß-thalassemic trait mothers carrying thalassemic fetuses is higher than in mothers carrying normal fetuses.

Satellite-based global-scale irrigation water use and its contemporary trends.

Irrigated agriculture is important for satisfying the increasing world food demand, but it interrupts the natural hydrological cycle by applying additional water to crops. Accurate information regarding irrigation water use (IWU) is a prerequisite to exploit land surface modeling and to quantify the uncertainty of climate projections. In this study, the global IWU was estimated for 2000-2015 by combining satellite-based soil moisture (SM) observations from the European Space Agency's Climate Change Initiative (ESA CCI) and the model estimated SM from European ReAnalysis-5 (ERA5). Considering irrigation as an unmodeled hydrological process in ERA5 and the ability of ESA CCI SM to capture the irrigation patterns, the global IWU was estimated by solving the water balance equations for ESA CCI and ERA5 SM. Owing to the global absence of ground-truth data for IWU, the IWU estimates were compared with the reported irrigation water withdrawals (IWWs) provided by Food and Agriculture Organization. The results indicated that satellite-based SM observations have the potential to identify global irrigation. All three ESA CCI products (active, passive, and merged) discerned the global irrigated areas satisfactorily, and the estimated IWU captured the pattern of the country-level IWWs (R = 0.77, 0.72, and 0.81 for active, passive, and merged products, respectively). However, the estimated IWU substantially underestimated the reported IWWs (bias of -76.55, -76.01, and -73.93 km3 for active, passive, and merged products, respectively) due to the coarse spatial resolution (0.25° × 0.25°) of the microwave remote sensing products and the inclusion of supplemental water in the IWWs, which was lost during distribution to crops. Trend analysis of the IWU indicated an increasing trend of the IWU in the first decade of the 21st century. However, in recent years the trend has reversed due to advances in agriculture technology and the adoption of water-efficient irrigation methods.

Detecting global irrigated areas by using satellite and reanalysis products.

Despite the importance of irrigation in meeting the world's food demand and as an essential human modification to water and energy cycles, the reliable extent and distribution of the global irrigated areas remain undefined. In this study, an intuitive method is proposed, based on the aftereffects of irrigation, to detect global irrigated areas by combining satellite and reanalysis datasets. The proposed methodology assumes that irrigation is an unmodeled land surface process, while satellite observations can effectively detect irrigation signals in near real-time. The spatial extents of irrigation were derived by calculating the difference between the remotely sensed and reanalysis datasets. To detect the irrigated areas, three irrigation-dependent variables, soil moisture (SM), land surface temperature (LST), and surface albedo (AL), were used. In the absence of reliable ground truths, the proposed irrigation map was compared to the commonly used global irrigation maps, namely Global Map of Irrigated areas, Global Irrigated Area Map, and recently developed Global Irrigated Areas by Meier et al. (2018). Individual detection by SM, LST, and AL has discrepancies in detecting irrigation signals in highly irrigated, urbanized, and semi-arid regions. However, by combining the individual detection maps, the proposed method showed reasonable agreement with the reference irrigated maps overlapping with approximately 70% of the irrigated areas. We believe that the proposed method, as stand-alone or in combination with the existing irrigation maps, will benefit the studies regarding water and energy balance closure in near-real time for large-scale land surface models by minimizing the uncertainties in model parameterization.