The Effect of Short- and Long-Term Cryopreservation on Chicken Primordial Germ Cells.

Primordial germ cells (PGCs) are the precursors of functional gametes and the only cell type capable of transmitting genetic and epigenetic information from generation to generation. These cells offer valuable starting material for cell-based genetic engineering and genetic preservation, as well as epigenetic studies. While chicken PGCs have demonstrated resilience in maintaining their germness characteristics during both culturing and cryopreservation, their handling remains a complex challenge requiring further refinement. Herein, the study aimed to compare the effects of different conditions (freezing-thawing and in vitro cultivation) on the expression of PGC-specific marker genes. Embryonic blood containing circulating PGCs was isolated from purebred Green-legged Partridgelike chicken embryos at 14-16 Hamburger-Hamilton (HH) embryonic development stage. The blood was pooled separately for males and females following sex determination. The conditions applied to the blood containing PGCs were as follows: (1) fresh isolation; (2) cryopreservation for a short term (2 days); and (3) in vitro culture (3 months) with long-term cryopreservation of purified PGCs (~2 years). To characterize PGCs, RNA isolation was carried out, followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of specific germ cell markers (SSEA1, CVH, and DAZL), as well as pluripotency markers (OCT4 and NANOG). The investigated genes exhibited consistent expression among PGCs maintained under diverse conditions, with no discernible differences observed between males and females. Notably, the analyzed markers demonstrated higher expression levels in PGCs when subjected to freezing than in their freshly isolated counterparts.

ABCA4-related retinopathies in Lebanon.

Variants in ATP-binding cassette transporter type A4 (ABCA4) have been linked to several forms of inherited retinal diseases (IRDs) besides the classically defined Stargardt disease (STGD), known collectively as ABCA4 retinopathies. ABCA4 is a sizable locus harboring 50 exons; thus, its analysis has revealed over 2,400 variants described, of which more than 2,000 are causal. Due to the clinical and genetic heterogeneity, diagnosing ABCA4 retinopathies is challenging. To date, no ABCA4-related retinopathy has been detected in Lebanon. Using next-generation sequencing, we analyzed our IRDs' cohort retrospectively (61 families) and identified five with ABCA4-related retinopathies, making it a relatively abundant cause of IRDs (about 8 %). Three families were diagnosed with rod-cone dystrophy (RCD), two with STGD, and one with cone-rod dystrophy (CRD). In conclusion, our study showed the presence of ABCA4 variants with a high degree of heterogeneity in Lebanon.

Persistent Paradoxical Reaction to Midazolam despite General Anesthesia with Dexmedetomidine.

Midazolam is a widely used benzodiazepine due to its rapid onset of action and relatively safe side effect profile. It is used for sedation, anxiolysis, and induction of general anesthesia. However, in <1% of instances, it may cause a paradoxical excitement: agitation, restlessness, myoclonus, stiffening of the limbs, and aggression. We report a case report in which preoperative administration of midazolam caused onset of the aforementioned symptoms that were not attenuated by general anesthesia with dexmedetomidine. This case report aims to create awareness about the rare adverse reactions of midazolam and prepare clinicians to manage these situations.

The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK-GABA-CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK-GABA-CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK-GABA-CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK-GABA combination and AMK-GABA-CSNPs on the renal tissue, 42 healthy Sprague-Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK-GABA-CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK-GABA-CSNPs (30 mg/kg/day; i.p.). The results showed that AMK-GABA-CSNPs formulation is superior to unloaded AMK-GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK-GABA-CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

The Pharmacokinetics of CPZEN-45, a Novel Anti-Tuberculosis Drug, in Guinea Pigs.

CPZEN-45 is a novel compound with activity against drug-susceptible and drug-resistant tuberculosis (TB). The present study was undertaken to determine the best dose and dosing regimen of inhalable CPZEN-45 powders to use in efficacy studies with TB-infected guinea pigs. The disposition of CPZEN-45 after intravenous, subcutaneous (SC), and direct pulmonary administration (INS) was first determined to obtain their basal pharmacokinetic (PK) parameters. Then, the disposition of CPZEN-45 powders after passive inhalation using consecutive and sequential doses was evaluated. Plasma concentration versus time curves and PK parameters indicated that the absorption of CPZEN-45 after INS was faster than after SC administration (Ka = 12.94 ± 5.66 h-1 and 1.23 ± 0.55 h-1, respectively), had a longer half-life (2.06 ± 1.01 h versus 0.76 ± 0.22 h) and had higher bioavailability (67.78% and 47.73%, respectively). The plasma concentration versus time profiles and the lung tissue concentration at the end of the study period were not proportional to the dose size after one, two, and three consecutive passive inhalation doses. Three sequential passive inhalation doses maintained therapeutic concentration levels in plasma and lung tissue for a longer time than three consecutive doses (10 h vs. 3 h, respectively). Future studies to evaluate the efficacy of inhaled CPZEN-45 powders should employ sequential doses of the powder, with one nominal dose administered to animals three times per day.

Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma.

External beam radiation therapy (EBRT) has increasingly been utilized in the treatment of hepatocellular carcinoma (HCC) due to technological advances with positive clinical outcomes. Innovations in EBRT include improved image guidance, motion management, treatment planning, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Moreover, proton beam therapy (PBT) and magnetic resonance image-guided radiation therapy (MRgRT) have expanded the capabilities of EBRT. PBT offers the advantage of minimizing low- and moderate-dose radiation to the surrounding normal tissue, thereby preserving uninvolved liver and allowing for dose escalation. MRgRT provides the advantage of improved soft tissue delineation compared to computerized tomography (CT) guidance. Additionally, MRgRT with online adaptive therapy is particularly useful for addressing motion not otherwise managed and reducing high-dose radiation to the normal tissue such as the stomach and bowel. PBT and online adaptive MRgRT are emerging technological advancements in EBRT that may provide a significant clinical benefit for patients with HCC.

Eobania vermiculata whole-body muscle extract-loaded chitosan nanoparticles enhanced skin regeneration and decreased pro-inflammatory cytokines in vivo.

BACKGROUND: Usually, wounds recover in four to six weeks. Wounds that take longer time than this to heal are referred to as chronic wounds. Impaired healing can be caused by several circumstances like hypoxia, microbial colonization, deficiency of blood flow, reperfusion damage, abnormal cellular reaction and deficiencies in collagen production. Treatment of wounds can be enhanced through systemic injection of the antibacterial drugs and/or other topical applications of medications. However, there are a number of disadvantages to these techniques, including the limited or insufficient medication penetration into the underlying skin tissue and the development of bacterial resistance with repeated antibiotic treatment. One of the more recent treatment options may involve using nanotherapeutics in combination with naturally occurring biological components, such as snail extracts (SE). In this investigation, chitosan nanoparticles (CS NPs) were loaded with an Eobania vermiculata whole-body muscle extract. The safety of the synthesized NPs was investigated in vitro to determine if these NPs might be utilized to treat full-skin induced wounds in vivo. RESULTS: SEM and TEM images showed uniformly distributed, spherical, smooth prepared CS NPs and snail extract-loaded chitosan nanoparticles (SE-CS NPs) with size ranges of 76-81 and 91-95 nm, respectively. The zeta potential of the synthesized SE-CS NPs was - 24.5 mV, while that of the CS NPs was 25 mV. SE-CS NPs showed a remarkable, in vitro, antioxidant, anti-inflammatory and antimicrobial activities. Successfully, SE-CS NPs (50 mg/kg) reduced the oxidative stress marker (malondialdehyde), reduced inflammation, increased the levels of the antioxidant enzymes (superoxide dismutase and glutathione), and assisted the healing of induced wounds. SE-CS NPs (50 mg/kg) can be recommended to treat induced wounds safely. SE was composed of a collection of several wound healing bioactive components [fatty acids, amino acids, minerals and vitamins) that were loaded on CS NPs. CONCLUSIONS: The nanostructure enabled bioactive SE components to pass through cell membranes and exhibit their antioxidant and anti-inflammatory actions, accelerating the healing process of wounds. Finally, it is advised to treat rats' wounds with SE-CS NPs.

The trapeziometacarpal screw home torque mechanism as a clinical indicator of the posterior joint ligament complex integrity: A cadaveric investigation.

BACKGROUND: To date, no clinical test provides specific objective information on the integrity of key ligamentous support of the trapeziometacarpal (TMC) joint. PURPOSE: To examine the potential of the TMC joint screw home torque mechanism (SHTM) in estimating the integrity of the posterior ligament complex in older adult population. STUDY DESIGN: Cross-sectional laboratory-based study. METHODS: Twenty cadaver hands presenting with various degrees of TMC joint degradation ranging from none to severe osteoarthritis (OA) were radiographed in multiple positions to establish their degeneration status, joint mobility, and amount of dorsal subluxation at rest and with the application of the SHTM. Comparisons and correlations between degeneration status, joint mobility, subluxation reduction and ligament status obtained from dissection were calculated. RESULTS: No significant statistical correlation was demonstrated with the subluxation reduction ratio of the SHTM and the combined ligament complex value however, a moderate negative correlation was found with dorsal central ligament injury at 21 Nm (τb = -0.46, p < 0.05) and 34 Nm (τb = -0.45, p < 0.05). A statistically significant reduction of radial subluxation of the TMC joint was observed between the subluxation at rest (M = 5.2, SD = 1.9) and subluxation with SHTM of 21 Nm (M = 4.4, SD = 2.4), t (19) = 3.2, p = 0.01, 95% CI [0.3, 1.4] and subluxation with SHTM of 34 Nm (M = 4.3, SD = 2.6), t (19) = 2.6, p = 0.02, 95% CI [0.2, 1.5]. CONCLUSION: Our results did not support the SHTM as indicator of the TMC posterior ligament complex integrity however, it demonstrated 100% stabilization effect with non-arthritic TMC population.

The genetic landscape of inherited retinal dystrophies in Arabs.

Inherited retinal dystrophies (IRDs) are a major cause of vision loss. Altogether are highly heterogeneous genotypically and phenotypically, exhibiting substantial differences worldwide. To shed more light on these conditions, we investigated the genetic and phenotypic landscape of IRDs in the Arabs globally and per country.We analyzed 1,621 affected individuals from 16 Arabic countries reported in 198 articles. At the phenotypic level, rod-cone dystrophy (RCD) and Usher syndrome were the most prevalent conditions among non-syndromic and syndromic IRDs. At the gene level, TULP1, ABCA4, RP1, CRB1, MYO7A, RPE65, KCNV2, and IMPG2 were the most mutated genes. Interestingly, all except CRB1 were highly prevalent because they harbored founder mutations, implying that consanguinity is a major determinant in Arab countries. Of note, ~ 93% of the investigated individuals carried homozygous mutations. The country analysis for the IRDs conditions and their associated genotypes revealed that whereas Leber Congenital Amaurosis, RCD, and USHER syndrome were widely distributed, bestrophinopathies and non-syndromic hearing loss were restricted to specific countries (till now).This study could be a starting point for initiating suitable health policies towards IRDs in the Arab world. The high degree of homozygosity urges the need for genetic counsellors to provide personalized information and support the affected individuals.

Mechanism of Insoluble Aggregate Formation in a Reconstituted Solution of Spray-Dried Protein Powder.

BACKGROUND: Spray-drying is considered a promising alternative drying method to lyophilization (freeze-drying) for therapeutic proteins. Particle counts in reconstituted solutions of dried solid dosage forms of biologic drug products are closely monitored to ensure product quality. We found that high levels of particles formed after reconstitution of protein powders that had been spray-dried under suboptimal conditions. METHODS: Visible and subvisible particles were evaluated. Soluble proteins in solution before spray-drying and in the reconstituted solution of spray-dried powder were analyzed for their monomer content levels and melting temperatures. Insoluble particles were collected and analyzed by Fourier transform infrared microscopy (FTIR), and further analyzed with hydrogen-deuterium exchange (HDX). RESULTS: Particles observed after reconstitution were shown not to be undissolved excipients. FTIR confirmed their identity as proteinaceous in nature. These particles were therefore considered to be insoluble protein aggregates, and HDX was applied to investigate the mechanism underlying aggregate formation. Heavy-chain complementarity-determining region 1 (CDR-1) in the aggregates showed significant protection by HDX, suggesting CDR-1 was critical for aggregate formation. In contrast, various regions became more conformationally dynamic globally, suggesting the aggregates have lost protein structural integrity and partially unfolded after spray-drying. DISCUSSION: The spray-drying process could have disrupted the higher-order structure of proteins and exposed the hydrophobic residues in CDR-1 of the heavy chain, contributing to the formation of aggregate through hydrophobic interactions upon reconstitution of spray-dried powder. These results can contribute to efforts to design spray-dry resilient protein constructs and improve the robustness of the spray-drying process.

Characteristics of Occupational Environmental Heat Injuries/Illnesses: Survey of Occupational Injuries and Illnesses, 2011 to 2019.

OBJECTIVE: This study describes the characteristics of workers experiencing occupational heat-related injuries/illnesses in the United States and explores the associations between states' average annual temperatures and heat-related injury/illness rates. METHODS: The number and rate of occupational environmental heat injuries/illnesses were calculated according to age group, gender, race/ethnicity, occupation group, and state from 2011 to 2019. RESULTS: Injury/illness rates were higher among Black and Hispanic workers. Workers in farming, fishing, and forestry; installation, maintenance, and repair; and construction/extraction occupations had the highest rates. There was a positive correlation between states' average annual temperatures and heat-related injury/illness rates. DISCUSSION: There are demographic and occupational disparities in occupational environmental heat-related injuries/illnesses in the United States and a correlation between these injuries/illnesses and state average annual temperatures. There is a need for policies and other interventions to protect workers from occupational environmental heat injuries/illnesses.

Security Analysis of Cyber-Physical Systems Using Reinforcement Learning.

Future engineering systems with new capabilities that far exceed today's levels of autonomy, functionality, usability, dependability, and cyber security are predicted to be designed and developed using cyber-physical systems (CPSs). In this paper, the security of CPSs is investigated through a case study of a smart grid by using a reinforcement learning (RL) augmented attack graph to effectively highlight the subsystems' weaknesses. In particular, the state action reward state action (SARSA) RL technique is used, in which the agent is taken to be the attacker, and an attack graph created for the system is built to resemble the environment. SARSA uses rewards and penalties to identify the worst-case attack scenario; with the most cumulative reward, an attacker may carry out the most harm to the system with the fewest available actions. Results showed successfully the worst-case attack scenario with a total reward of 26.9 and identified the most severely damaged subsystems.

Protein Aggregates in Inhaled Biologics: Challenges and Considerations.

Pulmonary delivery is the main route of administration for treatment of local lung diseases. Recently, the interest in delivery of proteins through the pulmonary route for treatment of lung diseases has significantly increased, especially after Covid-19 pandemic. The development of an inhalable protein combines the challenges of inhaled as well as biologic products since protein stability may be compromised during manufacture or delivery. For instance, spray drying is the most common technology for manufacture of inhalable biological particles, however, it imposes shear and thermal stresses which may cause protein unfolding and aggregation post drying. Therefore, protein aggregation should be evaluated for inhaled biologics as it could impact the safety and/or efficacy of the product. While there is extensive knowledge and regulatory guidance on acceptable limits of particles, which inherently include insoluble protein aggregates, in injectable proteins, there is no comparable knowledge for inhaled ones. Moreover, the poor correlation between in vitro setup for analytical testing and the in vivo lung environment limits the predictability of protein aggregation post inhalation. Thus, the purpose of this article is to highlight the major challenges facing the development of inhaled proteins compared to parenteral ones, and to share future thoughts to resolve them.

Dispositional Active Coping Predicts Patterns of Adolescents' Cortisol Responsivity in the Context of School-related Stressors.

OBJECTIVE: The goal of this study was to examine the direct and conditional effects of active coping and prior exposure to school-related stressors on cortisol reactivity and recovery in response to an academically salient, social stress task. METHOD: Participants included N= 758 adolescents (50% male; M age = 12.03 years, SD = .49) enrolled in the 7th grade in Title 1 middle schools. Adolescents were predominantly ethnic minorities (62% Hispanic, 12% non-Hispanic White, 11% non-Hispanic Black, 7% Native American, and 8% "other"). Youth completed self-reported assessments of their dispositional use of active coping strategies, prior exposure to school hassles, pubertal status, medication use, and relevant demographic information. In addition, youth engaged in an academically salient group public speaking task adapted for adolescents and provided salivary cortisol sample pre-task, immediately post-task, 15-, and 30-minutes post-task. RESULTS: Results from piecewise latent growth curve modeling revealed that active coping independently predicted lower cortisol reactivity to the stress task. Furthermore, active coping was associated with slower cortisol recovery when adolescents reported not having experienced any school hassles in the past three months and faster recovery when having experienced several school hassles in the past three months. Results from multinomial logistic regressions revealed that greater use of active coping strategies was less likely to predict a hyper-reactive pattern of cortisol responding compared to other patterns. CONCLUSION: Findings provide support for active coping as a way to promote adaptive physiological responding to school-related stressors among ethnically diverse youth residing in low-income communities.

Postharvest physiology and biochemistry of Valencia orange after coatings with chitosan nanoparticles as edible for green mold protection under room storage conditions.

Because of their unique features, nanomaterials have been proposed and have gained acceptance in postharvest applications in fruit. Increasing the storage life and improving the quality of Valencia oranges was investigated using nano-chitosan. A chitosan nanoparticle was prepared by using high-energy ball milling. Chitosan nanoparticles were characterized by Dynamic light scattering, FTIR spectroscopy and Surface morphology by transmission electron microscopy. Fully mature Valencia oranges were harvested and then coated with one of these concentrations (0.2, 0.4, and 0.8% nano-chitosan) and control. The fruits were stored under room storage conditions for 75 days. The quality parameters (fruit weight losses, fruit decay percentage, fruit firmness, total acidity, total soluble solids percentage and T.S.S./acid ratio, ascorbic acid content) were taken in biweekly intervals after 0, 15, 30, 45, 60, and 75 days. Beside the in vitro testing of antifungal activity of chitosan nanoparticles. According to the findings of the two succeeding seasons, the nano-chitosan 0.8% treatment showed the best effects and had the lowest rate of fruit weight loss, fruit deterioration, and T.S.S./acid ratio in comparison to the other treatments in both seasons. Furthermore, the 0.8% nano-chitosan reveled the highest levels of fruit hardness and fruit pulp firmness. Fruit weight loss, fruit deterioration, TSS, and TSS/acid ratio, as well as other metrics, were steadily elevated prior to the storage time. The best results were obtained when Valencia oranges fruits were treated with 0.8% nano-chitosan for 75 days at room temperature.

Alleviate the Drought Stress on Triticum aestivum L. Using the Algal Extracts of Sargassum latifolium and Corallina elongate Versus the Commercial Algal Products.

Herein, two seaweed extracts (Sargassum latifolium and Corallina elongate), and two commercial seaweed products (Canada power and Oligo-X) with a concentration of 5% were used to alleviate the drought stress on wheat plants. The extract of C. elongate had the highest capacity to ameliorate the deleterious effects of water scarcity followed by S. latifolium and the commercial products. The drought stress reduced wheat shoots length and the contents of pigments (chlorophyll and carotenoids), carbohydrates, and proteins. While the highest increment in the total carbohydrates and protein contents of the wheat shoot after two stages, 37-and 67-days-old, were noted in drought-stressed plants treated with C. elongate extract with values of (34.6% and 22.8%) and (51.9% and 39.5%), respectively, compared to unstressed plants. Decreasing the activity of antioxidant enzymes, peroxidase, superoxidase dismutase, and polyphenol oxidase in drought-stressed plants treated with algal extracts indicated amelioration of the response actions. Analysis of phytohormones in wheat plants exhibited increasing GA3 and IAA contents with percentages of (20.3-13.8%) and (72.7-25%), respectively. Interestingly, all morphological and metabolic characteristics of yield were improved due to the algal treatments compared with untreated drought-stressed plants. Overall, the algal extracts, especially those from seaweed of C. elongate, could represent a sustainable candidate to overcome the damage effects of water deficiency in the wheat plant.

Hydrogel Improved Growth and Productive Performance of Mango Trees under Semi-Arid Condition.

Nowadays, the production of new mango cultivars is increased in many countries worldwide. The soil application of hydrogel represents a novel approach in the fruit trees industry. This investigation aims to study the effect of adding hydrogel (as soil conditioner) on the growth and yield of Shelly cv. mango trees. The experimental groups were assigned to a control group and three other treated groups, including 250, 500, or 750 g hydrogel∙tree-1. The results demonstrated that all applications of hydrogel composite had higher vegetative growth parameters, yield, and fruit quality characteristics of Shelly cv. mango trees compared to the control. The treatment of 750 g hydrogel∙tree-1 had higher values of vegetative growth parameters such as the leaf area, shoot length and tree canopy volume, compared to the control group and the other treatments. Similarly, higher values for yield and fruit quality were observed in the treatment of 750 g hydrogel∙tree-1. In conclusion, different amounts of hydrogel agent can improve the production and fruit quality of Shelly cv. mango trees in arid and semi-arid conditions in a dose-dependent manner.

Integrative Application of Foliar Yeast Extract and Gibberellic Acid Improves Morpho-Physiological Responses and Nutrient Uptake of Solidago virgaurea Plant in Alkaline Soil.

Alkaline soils have fertility issues due to poor physical qualities, which have a negative impact on crop growth and output. Solidago is used in flower arrangements, bouquet filler, and traditional medicine. The possible biological fertilizers' eco-friendly and cost-effective nature favours farmers because of the vital role in soil productivity and environmental sustainability. A field experiment was performed during two successive seasons to explore the effect of applying yeast extract (YE) at (0, 0.5, 1.0, and 1.5 g/L) and/or gibberellic acid (GA3) at (control, 100, 200, and 300 ppm) on the morpho-physiological parameters, macronutrients, and biochemical constituents of Solidago virgaurea. The results emphasize that YE (1.5 g/L) and/or GA3 (300 ppm) treatments show the highest significant increase in plant growth (i.e., plant height, no. of branches, fresh and dry weight of shoots); photosynthetic efficiency (i.e., chlorophyll (a), chlorophyll (b) and total carotenoids); macronutrient content (i.e., N, P, and K); and biochemical constituents (i.e., total soluble sugars, total phenolic, total flavonoids, and total glycosides). The study results recommend using YE and GA3 in combination at concentrations of 1.5 g/L and 300 ppm, respectively, to improve Solidago production sustainability under alkaline soil conditions.

Mean platelet volume to lymphocyte ratio and platelet distribution width to lymphocyte ratio in Iraqi patients diagnosed with systemic lupus erythematosus.

Introduction: The mean platelet volume to lymphocyte ratio (MPVLR) and platelet distribution width to lymphocyte ratio (PDWLR) have the potential to serve as markers of inflammation which may indicate disease activity. The mean platelet volume to lymphocyte ratio and PDWLR were assessed in patients with systemic lupus erythematosus (SLE) in this study. Material and methods: Sixty-two patients with systemic lupus erythematosus and 79 controls who were age and gender matched were included. Their sociodemographic information, as well as disease activity scores based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), disease duration, current medications, lymphocytes, platelets, platelet distribution width (PDW), and mean platelet volume (MPV), anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), and complement components (C3, C4) were recorded. The correlations of MPVLR and PDWLR with disease activity and some laboratory parameters were analyzed. Results: Lupus patients had significantly higher median (interquartile range) values for MPVLR and PDWLR than controls (5.69 [1.16-23.67] vs. 4.40 [2.78-11.93], p = 0.009) and 10.51 (2.87-79.37) vs. 5.21 (2.88-14.66), p < 0.001] respectively. According to the ROC curve, > 7.53 was the best PDWLR cut-off value for predicting SLE with a sensitivity of 71%, a specificity of 87% and an accuracy of 82.6%, whereas the optimum MPVLR cut-off value was > 6.46 with a sensitivity of 45.2%, a specificity of 88.9% and an accuracy of 76.8%. In addition, MPVLR had a significant positive correlation with SLEDAI (r = 0.34, p = 0.008). However, there was no significant correlation between PDWLR and SLEDAI (r = 0.23, p = 0.067). Furthermore, PDWLR had a significant positive correlation with PDW (r = 0.482, p < 0.001), while MPVLR had a significant negative correlation with C3 level (r = -0.260, p = 0.042). Both PDWLR and MPVLR were positively correlated with nephritis (r = 0.388, p = 0.002; r = 0.246, p = 0.038, respectively). Conclusions: The platelet distribution width to lymphocyte ratio can be considered as an assisting biomarker in the diagnosis of SLE with the other clinical and serological parameters. The mean platelet volume to lymphocyte ratio may be used in the evaluation of disease activity in SLE patients.

Integrated Clinical Environment Security Analysis Using Reinforcement Learning.

Many communication standards have been proposed recently and more are being developed as a vision for dynamically composable and interoperable medical equipment. However, few have security systems that are sufficiently extensive or flexible to meet current and future safety requirements. This paper aims to analyze the cybersecurity of the Integrated Clinical Environment (ICE) through the investigation of its attack graph and the application of artificial intelligence techniques that can efficiently demonstrate the subsystems' vulnerabilities. Attack graphs are widely used for assessing network security. On the other hand, they are typically too huge and sophisticated for security administrators to comprehend and evaluate. Therefore, this paper presents a Q-learning-based attack graph analysis approach in which an attack graph that is generated for the Integrated Clinical Environment system resembles the environment, and the agent is assumed to be the attacker. Q-learning can aid in determining the best route that the attacker can take in order to damage the system as much as possible with the least number of actions. Numeric values will be assigned to the attack graph to better determine the most vulnerable part of the system and suggest this analysis to be further utilized for bigger graphs.