Detecting white spot lesions on post-orthodontic oral photographs using deep learning based on the YOLOv5x algorithm: a pilot study.

BACKGROUND: Deep learning model trained on a large image dataset, can be used to detect and discriminate targets with similar but not identical appearances. The aim of this study is to evaluate the post-training performance of the CNN-based YOLOv5x algorithm in the detection of white spot lesions in post-orthodontic oral photographs using the limited data available and to make a preliminary study for fully automated models that can be clinically integrated in the future. METHODS: A total of 435 images in JPG format were uploaded into the CranioCatch labeling software and labeled white spot lesions. The labeled images were resized to 640 × 320 while maintaining their aspect ratio before model training. The labeled images were randomly divided into three groups (Training:349 images (1589 labels), Validation:43 images (181 labels), Test:43 images (215 labels)). YOLOv5x algorithm was used to perform deep learning. The segmentation performance of the tested model was visualized and analyzed using ROC analysis and a confusion matrix. True Positive (TP), False Positive (FP), and False Negative (FN) values were determined. RESULTS: Among the test group images, there were 133 TPs, 36 FPs, and 82 FNs. The model's performance metrics include precision, recall, and F1 score values of detecting white spot lesions were 0.786, 0.618, and 0.692. The AUC value obtained from the ROC analysis was 0.712. The mAP value obtained from the Precision-Recall curve graph was 0.425. CONCLUSIONS: The model's accuracy and sensitivity in detecting white spot lesions remained lower than expected for practical application, but is a promising and acceptable detection rate compared to previous study. The current study provides a preliminary insight to further improved by increasing the dataset for training, and applying modifications to the deep learning algorithm. CLINICAL REVELANCE: Deep learning systems can help clinicians to distinguish white spot lesions that may be missed during visual inspection.

First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Fostering innovation and sustainable thinking in surgery: an evaluation of a surgical hackathon.

INTRODUCTION: Surgery represents a major source of carbon emissions, with numerous initiatives promoting more sustainable practices. Healthcare innovation and the development of a digitally capable workforce are fundamental in leveraging technologies to tackle challenges, including sustainability in surgery. METHODS: A surgical hackathon was organised with three major themes: (1) how to make surgery greener, (2) the future of plastic surgery in 10 years, and (3) improving healthcare outcomes using machine learning. Lectures were given on sustainability and innovation using the problem, innovation, market size, strategy and team (PIMST) framework to support their presentations, as well as technological support to translate ideas into simulations or minimum viable products. Pre- and post-event questionnaires were circulated to participants. RESULTS: Most attendees were medical students (65%), although doctors and engineers were also present. There was a significant increase in delegates' confidence in approaching innovation in surgery (+20%, p < 0.001). Reducing waste packaging (70%), promoting recyclable material usage (56%) and the social media dimension of public perceptions towards plastic surgery (40%) were reported as the most important issues arising from the hackathon. The top three prizes went to initiatives promoting an artificial intelligence-enhanced operative pathway, instrument sterilisation and an educational platform to teach students research and innovation skills. CONCLUSIONS: Surgical hackathons can result in significant improvements in confidence in approaching innovation, as well as raising awareness of important healthcare challenges. Future innovation events may build on this to continue to empower the future workforce to leverage technologies to tackle healthcare challenges such as sustainability.

Identification of potential antiviral compounds from Egyptian sea stars against MERS-CoV with the in vitro and in silico experiments.

Recently, the world faced many epidemics which were caused by viral respiratory pathogens. Marine creatures including Asteroidea class have been one of the recent research topics due to their diverse and complex secondary metabolites. Some of these constituents exhibit antiviral activities. The present study aimed to extract and identify the potential antiviral compounds from Pentaceraster cumingi, Astropecten polyacanthus and Pentaceraster mammillatus. The results showed that promising activity of the methanolic extract of P. cumingi with 50% inhibitory concentration (IC50) of 3.21 mg/ml against MERS-CoV with a selective index (SI) of 13.975. The biochemical components of the extracts were identified by GC/MS analysis. The Molecular docking study highlighted the virtual mechanism of binding the identified compounds towards three PDB codes of MERS-CoV non-structural protein 10/16. Interestingly, 2-mono Linolein showed promising binding energy of -14.75 Kcal/mol with the second PDB code (5YNI) and -15.22 Kcal/mol with the third PDB code (5YNQ).

Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .

Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2.

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.

Treatment with onion bulb extract both prevents and reverses allergic inflammation in a murine model of asthma.

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.

Identification of some variable parameters in serum of COVID-19 patients in comparison with control group.

The study intended to determine the correlation among coronavirus disease 2019 (COVID-19) infection and variable abnormalities in liver function test, lipids, and thyroid hormones. The study included 160 infected COVID-19 patients (80 females and 80 male) and 100 subjects as a control group (50 females and 50 males), attended the Al-Sader Medical City in Al-Najaf, Iraq during the period between January 2021 to October 2021. The patients' age ranged from 16-80 years old. Liver enzymes, lipid profile and thyroid hormone were tested. The results revealed a significant increase in liver function levels including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and Albumin (p < 0.05). Also, there was an increase in lipids levels including total cholesterol, low-density lipoprotein, and triglycerides. The result showed significant difference in levels of thyroid hormones triiodothyronine, thyroxine and thyroid stimulating hormone between COVID-19 infected patients and the control group. As well the antithyroid antibodies (thyroglobulin antibody, thyroid peroxidase antibody and thyrotropin receptor antibodies) were increased. There was a correlation between increasing thyroid hormones and their antibodies with infection by COVID-19. This study concluded that COVID-19 infection can induce disturbances in liver and thyroid function tests and changes in the lipid metabolism.

Identification of potential antiviral compounds from Egyptian sea stars against seasonal influenza A/H1N1 virus.

BACKGROUND: One of the most dangerous problems that the world faced recently is viral respiratory pathogens. Marine creatures, including Echinodermata, specially Asteroidea class (starfish) have been extensively studied due to their miscellaneous bioactivities, excellent pharmacological properties, and complex secondary metabolites, including steroids, steroidal glycosides, anthraquinones, alkaloids, phospholipids, peptides, and fatty acids. These chemical constituents show antiviral activities against a wide range of viruses, including respiratory viruses. RESULTS: The present study aimed at the identification of potential antiviral compounds from some starfish species. The bioactive compounds from Pentaceraster cumingi, Astropecten polyacanthus, and Pentaceraster mammillatus were extracted using two different solvents (ethyl acetate and methanol). The antiviral activity against influenza A/H1N1 virus showed that ethyl acetate extract from Pentaceraster cumingi has the highest activity, where the selective index was 150.8. The bioactive compounds of this extract were identified by GC/MS analysis. The molecular docking study highlighted the virtual mechanism of binding of the identified compounds towards polymerase basic protein 2 and neuraminidase for H1N1 virus. Interestingly, linoleic acid showed promising binding energy of -10.12 Kcal/mol and -24.20 Kcal/mol for the selected two targets, respectively, and it formed good interactive modes with the key amino acids inside both proteins. CONCLUSION: The molecular docking analysis showed that linoleic acid was the most active antiviral compound from P. cumingi. Further studies are recommended for in-vitro and in-vivo evaluation of this compound against influenza A/H1N1 virus.

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-ß, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-ß-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

Biochar influences nitrogen and phosphorus dynamics in two texturally different soils.

Nitrogen (N) and phosphorus (P) are vital for crop growth. However, most agricultural systems have limited inherent ability to supply N and P to crops. Biochars (BCs) are strongly advocated in agrosystems and are known to improve the availability of N and P in crops through different chemical transformations. Herein, a soil-biochar incubation experiment was carried out to investigate the transformations of N and P in two different textured soils, namely clay loam and loamy sand, on mixing with rice straw biochar (RSB) and acacia wood biochar (ACB) at each level (0, 0.5, and 1.0% w/w). Ammonium N (NH4-N) decreased continuously with the increasing incubation period. The ammonium N content disappeared rapidly in both the soils incubated with biochars compared to the unamended soil. RSB increased the nitrate N (NO3-N) content significantly compared to ACB for the entire study period in both texturally divergent soils. The nitrate N content increased with the enhanced biochar addition rate in clay loam soil until 15 days after incubation; however, it was reduced for the biochar addition rate of 1% compared to 0.5% at 30 and 60 days after incubation in loamy sand soil. With ACB, the net increase in nitrate N content with the biochar addition rate of 1% remained higher than the 0.5% rate for 60 days in clay loam and 30 days in loamy sand soil. The phosphorus content remained consistently higher in both the soils amended with two types of biochars till the completion of the experiment.

A unified exponential-H family for modeling real-life data: Properties and inference.

The exponential distribution is one of the most widely used statistical distribution for reliability issues. In this paper, we introduce a novel family based on the exponential model, called the new exponential-H (NEx-H) family. The sub-models of the NEx-H family are capable of accommodating variable failure rates, as well as unimodal, bimodal, left-skewed, symmetric, right-skewed, and J-shape densities. The mathematical features of the NEx-H family are derived. The parameters of the NEx-Weibull distribution are estimated by using seven estimation methods. Detailed numerical simulations are presented. Based on our study, the maximum likelihood is the best estimation method for estimating the NEx-Weibull parameters. Three real-life data sets are fitted using the NEx-Weibull distribution. The NEx-Weibull model provides better fit as compared to some competing Weibull models.

Cobalt-modulated dual emission carbon dots for ratiometric fluorescent vancomycin detection.

This work presents a simple yet selective fluorometric protocol for the quantification of vancomycin, an important antibiotic for treating infections caused by Gram-positive bacteria. A novel ratiometric fluorometric method for the determination of vancomycin is developed based on dual emissive carbon dots (DECDs) with emission at 382 nm and 570 nm in combination with Co2+ ions. Upon addition of Co2+ions, the fluorescence at 382 nm of DECDs is enhanced while emission at 570 nm remains constant. In the presence of vancomycin, it complexes with Co2+ leading to quenching of the 382 nm fluorescence due to strong binding with Co2+ in the Co@DECDs system. The DECDs are fully characterized by TEM and different spectroscopic techniques. The proposed ratiometric method is based on measuring fluorescence ratio (F570/F382) against vancomycin concentration and the method exhibits a good linearity range from 0.0 to 120.0 ng mL-1 with a low limit of detection (S/N = 3) of 0.31 ng mL-1. The method shows good selectivity with minimal interference from potential interfering species. This ratiometric fluorometric approach provides a promising tool for sensitive and specific vancomycin detection in clinical applications.

Impact of neuromyelitis optica spectrum disorder on employment and income in the United States.

BACKGROUND AND OBJECTIVES: We aim to characterize the sociodemographic and clinical factors associated with loss of jobs, income, and work hours in people with neuromyelitis optica spectrum disorder (NMOSD) in the United States. METHODS: A REDCap-based survey was administered to working-age NMOSD patients (18-70 years old) querying demographic information, symptoms, immunosuppression, work hours, income, and caregiver work (11/2022-07/2023). Regression models were developed using MATLAB. RESULTS: Of 127 participants (97 female; 55% AQP4-antibody, 19% MOG antibody; 69% Caucasian, 7% Hispanic), with an average diagnosis age of 38.7 years, average disease duration of 6.4 years, mean 3.1 attacks, and 94% of whom were treated with immune system-directed therapy (53% rituximab, 8% satralizumab, 7% eculizumab, 6% mycophenolate mofetil, 4% inebilizumab, 2% azathioprine, 10% IVIg, 10% other), 56% lost a job due to NMOSD. Employment decreased 12% (80% pre- to 68% post-diagnosis). Thirty-six percent of participants said they no longer worked outside the home. Significant predictors for post-NMOSD diagnosis employment status included younger age, lower pain level, no walking aids, and having a job prediagnosis. Sixty-eight percent of those employed prediagnosis reduced their work hours, dropping an average of 18.4 h per month since being diagnosed (±10.1 h). Average annual income grew slowly at $1998 during the average 6.4 years of disease duration (14% of the value predicted by the U.S. Bureau of Labor Statistics). Sixty percent of participants had a regular unpaid caregiver; 34% of caregivers changed their work hours or job to help manage NMOSD. DISCUSSION: We provide a structured analysis of the impact of NMOSD on employment, work hours, and income in the United States, demonstrating its major effect on the livelihoods of patients and their caregivers.

The effect of inhibiting hindbrain A2 noradrenergic neurons by 6-Hydroxydopamine on lipopolysaccharide-treated male rats autistic animal model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

Increased healthcare utilization in the year before multiple sclerosis diagnosis.

BACKGROUND: Studies have suggested possible multiple sclerosis (MS) prodrome with non-routine healthcare utilization as an indicator. The objective of this project was to compare utilization in the four years (years -1, -2, -3, -4) before clinically definite diagnosis and examine demographic associations. METHODS: i2B2 database search at the Medical College of Wisconsin Comprehensive MS center yielded 613 patients between 07/01/2018 and 07/01/2022. Patients with established MS diagnosis, MS mimicker diagnoses, and pediatric-onset MS were excluded; 108 met the criteria for adult patients ≥ 18 years of age newly diagnosed with clinically definite MS after manual chart review. Utilization score for each of the four years before diagnosis was calculated; demographic variables were also collected. Adjusted repeated measures mixed model and Pearson correlation analysis were performed; P value was set at <0.05 for statistical significance. RESULTS: Utilization was greatest for year -1 compared to years -2, -3, and -4 after demographics adjustment (p < 0.001). Utilization was greater (p < 0.05) for older age and unmarried, patients. CONCLUSIONS: Utilization increased a year before formal MS diagnosis, suggestive of prodromal presentation.

Selective fluorescence turn-on detection of combination cisplatin-etoposide chemotherapy based on N-CDs/GSH-CuNCs nanoprobe.

Cisplatin (CIS) and etoposide (ETP) combination therapy is highly effective for treating various cancers. However, the potential for pharmacokinetic interactions between these drugs necessitates selective sensing methods to quantitate both CIS and ETP levels in patient's plasma. This work develops a dual fluorescence probe strategy using glutathione-capped copper nanoclusters (GSH-CuNCs) and nitrogen-doped carbon dots (N-CDs) for the simultaneous analysis of CIS and ETP. The fluorescence signal of GSH-CuNCs at 615 nm increased linearly with CIS concentration while the N-CD emission at 480 nm remained unaffected. Conversely, the N-CD fluorescence was selectively enhanced by ETP with no interference with the CuNC fluorescence. Extensive materials characterization including UV-vis, fluorescence spectroscopy, XRD, and TEM confirmed the synthesis of the nanoprobes. The sensor showed high sensitivity with limits of detection of 6.95 ng mL-1 for CIS and 7.63 ng mL-1 for ETP along with excellent selectivity against potential interferences in rabbit plasma. Method feasibility was demonstrated with application to real rabbit plasma samples. The method was further applied to estimate the pharmacokinetic parameters of CIS before and after ETP coadministration. The dual nanoprobe sensing strategy enables rapid and selective quantitation of CIS and ETP levels to facilitate therapeutic drug monitoring and optimization of combination chemotherapy regimens.

Interactive effects of long-term management of crop residue and phosphorus fertilization on wheat productivity and soil health in the rice-wheat.

In the context of degradation of soil health, environmental pollution, and yield stagnation in the rice-wheat system in the Indo-Gangetic Plains of South Asia, an experiment was established in split plot design to assess the long-term effect of crop residue management on productivity and phosphorus requirement of wheat in rice-wheat system. The experiment comprised of six crop residue management practices as the main treatment factor with three levels (0, 30 and 60 kg P2O5 ha-1) of phosphorus fertilizer as sub-treatments. Significant improvement in soil aggregation, bulk density, and infiltration rate was observed under residue management (retention/incorporation) treatments compared to residue removal or residue burning. Soil organic carbon (SOC), available nutrient content (N, P, and K), microbial count, and enzyme activities were also significantly higher in conservation tillage and residue-treated plots than without residue/burning treatments. The residue derived from both crops when was either retained/incorporated improved the soil organic carbon (0.80%) and resulted in a significant increase in SOC (73.9%) in the topsoil layer as compared to the conventional practice. The mean effect studies revealed that crop residue management practices and phosphorus levels significantly influenced wheat yield attributes and productivity. The higher grain yield of wheat was recorded in two treatments, i.e. the basal application of 60 kg P2O5 ha-1 without residue incorporation and the other with half the P-fertilizer (30 kg P2O5 ha-1) with rice residue only. The grain yield of wheat where the rice and wheat residue were either retained/incorporated without phosphorus application was at par with 30 and 60 kg P2O5ha-1. Phosphorus levels also significantly affected wheat productivity and available P content in the soil. Therefore, results suggested that crop residue retention following the conservation tillage approach improved the yield of wheat cultivated in the rice-wheat cropping system.

Worsening of imiquimod-induced psoriasiform inflammation in mice by environmental pollutant, di-(2-ethylhexyl) phthalate through dysregulation in IL-17A and Nrf2/iNOS signaling in peripheral myeloid and CD4 + T cells.

Psoriasis is a devastating autoimmune illness resulting from excessive keratinocyte growth and leukocyte infiltration into the dermis/epidermis. In the pathogenesis of psoriasis, different immune cells such as myeloid cells and CD4 + T cells play a key role. Th17/Th1 immune responses and oxidant-antioxidant responses are critical in regulation of psoriatic inflammation. Di-2-ethylhexyl phthalate (DEHP) is one of the well-known plasticizers and has widespread use worldwide. DEHP exposure through ingestion may produce harmful effects on the skin through systemic inflammation and oxidative stress, which may modify psoriatic inflammation. However, the effect of oral DEHP exposure on inflammatory cytokines and Nrf2/iNOS signaling in myeloid cells and CD4 + T cells in the context of psoriatic inflammation has not been investigated earlier. Therefore, this study explored the effect of DEHP on systemic inflammation in myeloid cells (IL-6, IL-17A, IL-23), Th17 (p-STAT3, IL-17A, IL-23R, TNF-α), Th1 (IFN-γ), Treg (Foxp3, IL-10), and Nrf2/iNOS signaling in imiquimod (IMQ)-induced mouse model of psoriasis-like inflammation. Our study showed increased Th17 signaling in imiquimod model which was further aggravated by DEHP exposure. Further, Nrf2 and iNOS signaling were also elevated in IMQ model where DEHP exposure further increased iNOS expression but did not modify the Nrf2 expression. Most importantly, IL-17A levels were also elevated in myeloid cells along with IL-6 which were further elevated by DEHP exposure. Overall, this study shows that IL-17A signaling is upregulated, whereas there is deficiency of Nrf2/HO-1 signaling by DEHP exposure in mice with psoriasiform inflammation. These observations suggest that DEHP aggravates IL-17A-mediated signaling both in CD4 + T cells as well as myeloid cells which is linked to exacerbation of IMQ-induced psoriatic inflammation in mice. Strategies that counteract the effect of DEHP exposure in the context of psoriatic inflammation through downregulation of IL-17A may be fruitful.

Time to involve the multiple sclerosis expert community at large when revising the McDonald diagnostic criteria.

Prof. Kurtzke once said, "Multiple sclerosis is what a good clinician would call multiple sclerosis." Recent McDonald's diagnostic criteria revisions have allowed for earlier diagnoses over the past decades. Revisions often allowed increasing sensitivity but at the expense of lowering specificity. In this correspondence, I suggest that the multiple sclerosis expert community worldwide should be given the opportunity to comment and provide feedback on the proposed revisions of the diagnostic criteria before their publication via providing a duration where open commentaries are welcomed to allow for the expert panel to incorporate diverse feedback to improve the final product.