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 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.

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.

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.

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.

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.

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.

Smart Home IoT Network Risk Assessment Using Bayesian Networks.

A risk assessment model for a smart home Internet of Things (IoT) network is implemented using a Bayesian network. The directed acyclic graph of the Bayesian network is constructed from an attack graph that details the paths through which different attacks can occur in the IoT network. The parameters of the Bayesian network are estimated with the maximum likelihood method applied to a data set obtained from the simulation of attacks, in five simulation scenarios. For the risk assessment, inferences in the Bayesian network and the impact of the attacks are considered, focusing on DoS attacks, MitM attacks and both at the same time to the devices that allow the automation of the smart home and that are generally the ones that individually have lower levels of security.

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.

Infants' Biological Sensitivity to the Effects of Maternal Social Support: Evidence Among Mexican American Families.

The identification of infants who are most susceptible to both negative and positive social environments is critical for understanding early behavioral development. This study longitudinally assessed the interactive effects of infant vagal tone (respiratory sinus arrhythmia; RSA) and maternal social support on behavioral problems and competence among 322 low-income Mexican American mother-infant dyads (infants: 54.1% female) and explored sex differences. Infant RSA was calculated from resting HR data at 6 weeks of age. Mothers reported on general social support, partner support, and family support at 6 months, and infant behavioral problems and competence at 1 year. Two-way interactions (RSA × support source) were evaluated to predict behavioral problems and competence, adjusting for covariates. Results indicated higher competence among infants with lower RSA whose mothers reported higher general support or higher partner support. Interactive effects on behavior problems of RSA with maternal partner or family support were only found for female infants: Girls with higher RSA showed more behavior problems when mothers reported low support, but fewer problem levels in the context of high support. Our results suggest that infant RSA is an important moderator of the effects of the early social environment on early development.

Cryogenic Fabrication of Dry Powders to Enhance the Solubility of a Promising Anticancer Drug, SHetA2, for Oral Administration.

SHetA2 is a novel anticancer drug with poor aqueous solubility. In formal toxicological studies, Kolliphor HS 15 was used as a solubilizing agent to increase the oral bioavailability of SHetA2. The purpose of this study was to formulate SHetA2 and Kolliphor HS 15 as solid powders to facilitate their filling in hard gelatin capsules for clinical trials. Two manufacturing processes, ultra-rapid freeze-drying (URFD) and spray freeze drying (SFD), were employed to fabricate solid powders of SHetA2-Kolliphor HS 15 and trehalose. The morphology, size, flowability, and compressibility of URFD-SHetA2 and SFD-SHetA2 powders were characterized. The crystallinity and apparent maximum solubility of SHetA2 in both powders were also determined. SFD-SHetA2 powders were spherical in shape, small, and with a wide size distribution while the URFD-SHetA2 powders were irregularly shaped and big but with a narrower distribution. DSC and XRD analyses indicated that SHetA2 was mostly amorphous in both powders. The flow of both powders was categorized as "good" (angle of repose < 35°). The uniformity of drug content in URFD-SHetA2 powders was more variable than that in SFD-SHetA2 powders. The solubility profile of SHetA2 in both powders SGF exhibited a transient supersaturation "spring effect" due to the drug's amorphousness followed by extended supersaturation "parachute effect" at approximately 6 µg/ml for both powders compared to 0.02 ± 0.01 µg/ml for unprocessed drug. In conclusion, both URFD and SFD formed solid SHetA2 Kolliphor powders that are possible formulation candidates to be filled in hard gelatin capsules for clinical trials.

3D Printing of Metformin HCl PVA Tablets by Fused Deposition Modeling: Drug Loading, Tablet Design, and Dissolution Studies.

The main aim of this work was to 3D print metformin HCl-loaded PVA (ML-PVA) tablets by fused deposition modeling. A modified solvent diffusion approach was used to improve drug loading. PVA filaments were placed in metformin HCl solution in ethanol containing low water content (10%(v/v)) to enhance the drug's solubility. The physicochemical properties of ML-PVA filaments were characterized before and after printing. Lastly, ML-PVA filaments were printed into channeled tablet designs to increase their surface area available for dissolution. The loading of metformin HCl onto PVA filament has significantly increased from 0.08 ± 0.02% in metformin HCl solution in absolute ethanol to 1.40 ± 0.02% in ethanol-water (9:1). The IR spectra of PVA filament soaked in ethanol-water depicted higher peak intensity at 1138 cm-1, indicating higher degree of crystallinity. Thermal analysis of the soaked PVA filaments showed higher melting enthalpies yet lower melting temperature (Tm) compared to unprocessed PVA. ML-PVA filaments were successfully printed into round-channeled tablets (10% infill) with higher surface area and area/volume ratios compared with the solid ones. The inclusion of channels in the tablet design modified their printing pattern causing an unexpected increase in their mass. The dissolution profiles of ML-PVA tablets were mainly dependent on their area/mass ratios. Our results show a simple approach to increase metformin HCl loading onto PVA and reveal the significance of tablet design, infill percentage, and printing pattern as they dictate the area, volume, and the mass of the tablet which impact its dissolution rate.

SHetA2 Dry Powder Aerosols for Tuberculosis: Formulation, Design, and Optimization Using Quality by Design.

Tuberculosis (TB) is a life threatening pulmonary infection caused by Mycobacterium tuberculosis (MTB). Current treatments are complex, lengthy, and associated with severe side effects that decrease patient compliance and increase the probability of the emergence of drug resistant strains. Thus, more effective drugs with little to no side effects are needed to diversify the armamentarium against the global TB epidemic. SHetA2, an anticancer compound with null toxicity at doses much higher than the effective dose, was recently discovered to be active against MTB. In the present study, a dry powder formulation of SHetA2 for pulmonary delivery was developed to overcome its poor aqueous solubility and to maximize its concentration in the lungs, the main site of TB infection. Using quality by design (QbD) methodology, three different formulations of SHetA2 microparticles (MPs) were designed, manufactured, and optimized, SHetA2 alone, SHetA2 PLGA, and SHetA2 mannitol MPs, to maximize the drug dose, target alveolar macrophages, and increase drug solubility, respectively. The resulting three SHetA2 MP formulations had spherical shape with particle size ranging from 1 to 3 µm and a narrow size distribution, suitable for uniform delivery to the alveolar region of the lungs. Upon dispersion with the Aerolizer dry powder inhaler (DPI), all three SHetA2 MP formulations had aerodynamic diameters smaller than 3.3 µm and fine particle fractions (FPF4.46) greater than 77%. SHetA2 remained chemically stable after MP manufacture by spray drying, but the drug transformed from the crystalline to the amorphous form, which significantly enhanced the solubility of SHetA2. Using a custom-made dissolution apparatus, the FPF4.46 of SHetA2 MP dissolved much faster and to a greater extent (21.19 ± 4.40%) than the unprocessed drug (3.51 ± 0.9%). Thus, the physicochemical characteristics, in vitro aerosol performance, and dissolution rate of the optimized SHetA2 MPs appear to be suitable to achieve therapeutic concentrations in the lungs.

Isolation and partial characterization of 3 nontoxic d-galactose-specific isolectins from seeds of Momordica balsamina.

Three isolectins denoted hereforth MBaL-30, MBaL-60, and MBaL-80 were isolated from seeds extract of Momordica balsamina by 30%, 60%, and 80% ammonium sulfate saturations, respectively. The native molecular weights of these lectins, as judged by gel filtration, were 108, 56, and 160 kDa, respectively. On SDS-PAGE, under reduced condition, 27 kDa band was obtained for all isolectins. The lectins hemagglutinating activities were variably inhibited by d-galactose (minimum inhibitory concentrations = 12.5mM, 50mM, and 0.391mM, respectively). MBaL-30 and -60 could agglutinate all human blood types with slight preference for the A and O blood groups, whereas MBaL-80 did not agglutinate B and AB blood types. The 3 isolectins were purified from crude seeds extract, collectively, in a single step on the affinity matrix Lactamyl-Seralose 4B; this purified lectin fraction, which contains all isolectins, is termed MBaL. The N-terminal of MBaL till the 25th amino acid was NLSLSELDFSADTYKSFIKNLRKQL, which shares 88% sequence identity with Momordica charantia lectin type-2 ribosomal inactivating protein from Momordica charantia and 50% with momordin II from Momordica balsamina. MBaL retained 100% activity at up to 50°C for 30 minutes. MBaL-30 and MBaL-60 exhibited maximum activities in the pH range between 4 and 8, while MBaL-80 was showing maximum activity in the pH range between 3 and 5. Treatment of MBaL-30 and MBaL-60 with EDTA completely abolished their hemagglutinating activities. Addition of Zn and Fe ions to the ethylenediaminetetraacetic acid-treated MBaL-30 and MBaL-60 lectins did not only regained the loss of activity but also resulted in 200% to 300% increase in activity, respectively. MBaL-30 and -60 agglutinated gram positive Listeria monocytogenes and Staphylococcus aureus, whereas MBaL-30 could merely agglutinate Escherichia coli. None of these lectins could arrest bacterial growth. Addition of MBaL to cancer cell lines (Gastric cancer cell line (AGS) and Gastric cencer cell line (MKN45), Glioblastoma (ECV-304), and Human urinary bladder cancer cell line (U87-MG)) at varying concentrations did not cause statistically significant changes on cell growth and viability.

Family Support and Family Negativity as Mediators of the Relation between Acculturation and Postpartum Weight in Low-Income Mexican-Origin Women.

BACKGROUND: Obesity presents a significant health concern among low-income, ethnic minority women of childbearing age. PURPOSE: The study investigated the influence of maternal acculturation, family negativity, and family support on postpartum weight loss among low-income Mexican-origin women. METHODS: Low-income Mexican-origin women (N=322; 14% born in the U.S.) were recruited from a prenatal clinic in an urban area of the Southwest U.S. Acculturation was assessed during a prenatal home visit (26-38 weeks gestation), and post-birth family support and general family negativity were assessed at 6 weeks postpartum. Objective maternal weight measures were obtained at five time points across the first postpartum year. RESULTS: Higher acculturation predicted higher family support and family negativity. Higher family support predicted decreasing weight across the first postpartum year, and higher family negativity predicted higher weight at 6 weeks postpartum and increasing weight across the first postpartum year. In combination, family negativity and support mediated the impact of acculturation on postpartum weight gain. CONCLUSIONS: Cultural and family-related factors play a significant role in postpartum weight gain and loss for low-income Mexican-origin women.

Pharmacokinetics of Inhaled Rifampicin Porous Particles for Tuberculosis Treatment: Insight into Rifampicin Absorption from the Lungs of Guinea Pigs.

Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration. RIF microparticles were prepared by spray drying a solution of RIF and L-leucine (9:1), and the resulting particles were characterized for their physicochemical properties. Animals received RIF either as intravenous solution (iv), as oral suspension of micronized RIF (ORS) and RIF-PPs (ORPP), or by insufflation of the PPs (IRPP). Plasma samples were collected at preselected time points, and bronchoalveolar lavage (BAL) was performed at the end of the study. RIF concentrations in biological samples were analyzed by HPLC. Plasma concentration versus time data was analyzed by compartmental and noncompartmental methods. RIF PPs were thin walled porous particles with mass median aerodynamic diameter (MMAD) of 4.8±0.1 µm, GSD=1.29±0.03, and fine particle fraction below 5.8 µm of 52.9±2.0%. RIF content in the resulting particles was 91.8±0.1%. Plasma concentration vs time profiles revealed that the terminal slope of the iv group was different from that of the oral or pulmonary groups, indicating the possibility of flip-flop kinetics. RIF from IRPP appeared to be absorbed faster than that of ORPP or ORS as evidenced by higher RIF plasma concentrations up until 2 h. Notably, similar AUC (when corrected by dose), similar CL, λ, and half-life were obtained after oral administration of RIF at 40 mg/kg and pulmonary administration of RIF at 20 mg/kg. However, RIF in the IRPP group had a shorter Tmax and higher bioavailability than orally dosed groups. In addition, RIF concentrations in the BAL of animals in the IRPP group were 3-4-fold larger than those in the orally dosed groups. The disposition in ORS and ORPP were best described by a model with two sequential compartments, whereas the disposition of IRPP was best described by a two parallel compartment model. The advantages of delivering RIF by the pulmonary route are demonstrated in the present study. These include achieving higher RIF concentrations in the lungs and similar systemic levels after pulmonary delivery of one-half of the oral nominal dose. This is expected to result in a more effective treatment of pulmonary TB, as shown previously in published efficacy studies.

Assessment of blood donation intention among medical students in Pakistan--An application of theory of planned behavior.

OBJECTIVE: Theory of Planned Behavior proposes a model which can measure how human actions are guided. It has been successfully utilized in the context of blood donation. We employed a decision-making framework to determine the intention of blood donation among medical students who have never donated blood before the study. METHODS: Survey responses were collected from 391 medical students from four various universities on a defined questionnaire. The tool composed of 20 questions that were formulated to explain donation intention based on theory of planned behavior. The construct included questions related to attitude, subjective norm and perceived behavior control, descriptive norm, moral norm, anticipated regret, donation anxiety and religious norm. Pearson's correlational relationships were measured between independent and dependent variables of intention to donate blood. ANOVA was applied to observe the model fit; a value of 0.000 was considered statistically significant. A multiple regression analysis was conducted to explore the relative importance of the main independent variables in the prediction of intention. Multi-collinearity was also evaluated to determine that various independent variables determine the intention. The reliability of measures composed of two items was assessed using inter-item correlations. RESULTS: Three hundred and ninety-one medical students (M:F; 1:2.2) with mean age of 21.96 years ± 1.95 participated in this study. Mean item score was 3.8 ± 0.83. Multiple regression analysis suggested that perceived behavioral control, anticipated regret and attitude were the most influential factors in determining intention of blood donation. Donation anxiety was least correlated and in fact bore a negative correlation with intention. ANOVA computed an F value of 199.082 with a p-value of 0.000 indicating fitness of model. The value of R square and adjusted R square was 0.811 and 0.807 respectively indicating strong correlation between various independent and dependent variables. CONCLUSIONS: Medical students as novice blood donors showed a positive attitude toward blood donation. Theory of planned behavior can be successfully utilized in determining the antecedents toward blood donation behavior.

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 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.