Myositis: A Rare First Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems with a variety of clinical manifestations and serological abnormalities. Overt myositis is a rare and not well-studied manifestation of SLE, which is associated with a more severe disease course and may be overlooked by clinicians. This case report describes a rare first presentation of SLE with myositis. An 18-year-old female patient presented with a three-month history of generalized muscle weakness, polyarthralgia, and rashes. Physical examination revealed malar rash, a dry scaly pigmented rash affecting the flanks, and a non-blanching purpuric rash with mottled discoloration and a well-defined ulceration, affecting both hands, suggestive of vasculitis. A pigmented atrophic patch on the right upper chest was also suggestive of discoid lupus. Further examination findings included bilateral upper and lower limb weakness affecting proximal muscles (Medical Research Council (MRC) grade 3/5) more than the distal muscles (MRC grade 4/5). The patient's investigation panel revealed leukopenia, anemia, elevated liver enzymes, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as significant elevation in creatinine kinase. Further antibody testing revealed positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith, and anti-U1-ribonucleoprotein (U1RNP), along with electrodiagnostic study supporting the diagnosis of SLE complicated by myositis and vasculitis. Treatment was initiated with prednisolone, hydroxychloroquine, methotrexate, folic acid, and omeprazole with sunscreen. Over the next several months, the patient demonstrated significant clinical and laboratory improvement, regaining full muscle power, with her vasculitis rash also improving and steroid tapering initiated to avoid side effects. This case highlights the importance of recognizing myositis as a rare potential first presentation of SLE and the need for heightened clinical awareness as early diagnosis and treatment is vital for improving long-term outcomes. This case adds to the existing literature and provides a reference for future clinical encounters with such complex cases.

The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats.

Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson's trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

Outcomes of Zone II Flexor Tendon Repair Under General Versus Wide Awake Local Anesthesia: A Randomized Controlled Trial.

PURPOSE: Wide awake local anesthesia no tourniquet (WALANT) is gaining popularity with flexor tendon repair. We hypothesized that results of zone II flexor tendon repair performed under WALANT would be superior to those performed under general anesthesia (GA). METHODS: A randomized controlled trial was conducted to compare results of repair of zone II flexor tendon lacerations under WALANT versus GA. Following sample size estimation, 86 digits were included and randomized into two groups. All surgeries were performed by a single surgeon using a six-stranded core stitch and running epitenon suture. All patients followed the same early active rehabilitation protocol. The primary outcome was recovery calculated using the Strickland and Glogovac criteria. Secondary outcomes included rupture rate, complication rate, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. All outcomes were reported at the 6-month visit for all patients. RESULTS: Of the 86 digits, three were lost to follow-up. Analysis was performed on 43 digits in the WALANT group and 40 in the GA group. Demographic characteristics including age and sex were comparable in both groups. Rupture of the repair occurred in two digits in each of the WALANT and GA groups. An excellent or good outcome was achieved in 49% and 56% of the digits in the WALANT and GA groups, respectively. This difference was not statistically significant. DASH scores averaged 12.9 and 8.4 for the WALANT and GA groups, respectively. CONCLUSIONS: WALANT may not be superior to GA in regards function, rates of rupture, and patient-reported outcomes in repair of zone II flexor tendon lacerations. Surgeons can be confident in choosing either technique if rigorous patient selection, sound surgical technique, and proper hand therapy are employed. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing. METHODS: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}. RESULTS: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes-identified across 10 genome sequencing studies-in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC. CONCLUSION: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients.

Security Analysis for Smart Healthcare Systems.

The healthcare industry went through reformation by integrating the Internet of Medical Things (IoMT) to enable data harnessing by transmission mediums from different devices, about patients to healthcare staff devices, for further analysis through cloud-based servers for proper diagnosis of patients, yielding efficient and accurate results. However, IoMT technology is accompanied by a set of drawbacks in terms of security risks and vulnerabilities, such as violating and exposing patients' sensitive and confidential data. Further, the network traffic data is prone to interception attacks caused by a wireless type of communication and alteration of data, which could cause unwanted outcomes. The advocated scheme provides insight into a robust Intrusion Detection System (IDS) for IoMT networks. It leverages a honeypot to divert attackers away from critical systems, reducing the attack surface. Additionally, the IDS employs an ensemble method combining Logistic Regression and K-Nearest Neighbor algorithms. This approach harnesses the strengths of both algorithms to improve attack detection accuracy and robustness. This work analyzes the impact, performance, accuracy, and precision outcomes of the used model on two IoMT-related datasets which contain multiple attack types such as Man-In-The-Middle (MITM), Data Injection, and Distributed Denial of Services (DDOS). The yielded results showed that the proposed ensemble method was effective in detecting intrusion attempts and classifying them as attacks or normal network traffic, with a high accuracy of 92.5% for the first dataset and 99.54% for the second dataset and a precision of 96.74% for the first dataset and 99.228% for the second dataset.

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.

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.

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 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.