Induced pluripotent stem cells (iPSCs): Where are we and where are we heading?

Induced Pluripotent Stem Cells (iPSCs) offer a unique therapeutic tool. The extent of the ongoing clinical studies substantiates the role of these cells in a highly promising area of personalized medicine. The employment of this technology in translational research is on the horizon. However, still, many questions remain unanswered. In this review, we discussed certain challenges and difficulties currently faced during the safe and stable clinical application of iPSCs. Furthermore, we describe the potential therapeutic scenarios employing iPSCs for the betterment of human health and the improvement of the health care sector.

Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan.

OBJECTIVE: Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated. METHODS: DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma. RESULTS: Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; p = .011*) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; p = .0076*), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; p = .0081*), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; p = .008*), under recessive models, respectively, were significantly (p-values < .0125) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; p = .000147*), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; p = .003296*), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; p = .019063*), were significantly (p-values < .0125) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population. CONCLUSION: The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (p-values < .0125) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.Supplemental data for this article can be accessed.

Recent Developments in the Removal of Dyes from Water by Starch-Based Adsorbents.

Starch-based adsorbents have demonstrated excellent potential for the removal of various noxious dyes from wastewater. This review critically evaluates the recent progress in applications of starch-based adsorbents for the removal of dyes from water. The synthesis methods of starch-based composites and their effects on physicochemical characteristics of produced adsorbents are discussed. The removal of various dyes by starch-based adsorbents are described in detail, with emphasis on the effect of key parameters, adsorption mechanism and their reusability potential. The key challenges related to the synthesis and applications of starch-based adsorbents in water purification are highlighted. Based on the research gaps, recommendations for future research are made. The evaluation of starch-based adsorbents would contribute to the development of sustainable water treatment options in near future.

Identification of Causative agents associated with decay of Trees Twig and Orchards Die-back and their Impacts on Vessels of Citrus, Date Palm and Ficus.

The present work is concerned with the studies of the organism causing wood decay of twigs and branches of citrus orchards, date palm Phoenix dactylifera L, and ficus trees. A survey for the occurrence of this disease in the main growing areas was achieved by the researchers. The following species of citrus orchards [lime (C. aurantifolia), sweet orange (C. sinensis), and mandarin (C. reticulate)] were surveyed, and so date palm and ficus trees. However, the results showed that the incidence of this disease was about 100%. Laboratory examinations data revealed mainly two fungal species causing the disease: Physalospora rhodina (P.rhodina)  and Diaporthe citri (D. citri). In addition that, both fungi, which are P. rhodina and D. citri affected the vessels of tree tissues. According to the pathogenicity test, the fungus P. rhodina caused a breakdown of parenchyma cells, and the fungus D. citri caused the darkening of the xylem.

An Integrated Fuzzy Analytic Hierarchy Process (AHP) Model for Studying Significant Factors Associated with Frequent Lane Changing.

Frequent lane changes cause serious traffic safety concerns, which involve fatalities and serious injuries. This phenomenon is affected by several significant factors related to road safety. The detection and classification of significant factors affecting lane changing could help reduce frequent lane changing risk. The principal objective of this research is to estimate and prioritize the nominated crucial criteria and sub-criteria based on participants' answers on a designated questionnaire survey. In doing so, this paper constructs a hierarchical lane-change model based on the concept of the analytic hierarchy process (AHP) with two levels of the most concerning attributes. Accordingly, the fuzzy analytic hierarchy process (FAHP) procedure was applied utilizing fuzzy scale to evaluate precisely the most influential factors affecting lane changing, which will decrease uncertainty in the evaluation process. Based on the final measured weights for level 1, FAHP model estimation results revealed that the most influential variable affecting lane-changing is 'traffic characteristics'. In contrast, compared to other specified factors, 'light conditions' was found to be the least critical factor related to driver lane-change maneuvers. For level 2, the FAHP model results showed 'traffic volume' as the most critical factor influencing the lane changes operations, followed by 'speed'. The objectivity of the model was supported by sensitivity analyses that examined a range for weights' values and those corresponding to alternative values. Based on the evaluated results, stakeholders can determine strategic policy by considering and placing more emphasis on the highlighted risk factors associated with lane changing to improve road safety. In conclusion, the finding provides the usefulness of the fuzzy analytic hierarchy process to review lane-changing risks for road safety.

Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin.

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.

Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines.

In this study, we investigated the bioactive potential (antibacterial and antioxidant), anticancer activity and detailed phytochemical analysis of Selaginellarepanda (S. repanda) ethanolic crude extract for the very first time using different in vitro approaches. Furthermore, computer-aided prediction of pharmacokinetic properties and safety profile of the identified phytoconstituents were also employed in order to provide some useful insights for drug discovery. S. repanda, which is a rich source of potent natural bioactive compounds, showed promising antibacterial activity against the tested pathogenic bacteria (S. aureus, P. aeruginosa, E. coli and S. flexneri). The crude extract displayed favorable antioxidant activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 231.6 µg/mL) and H2O2 (IC50 = 288.3 µg/mL) molecules. S. repanda also showed favorable and effective anticancer activity against all three malignant cancer cells in a dose/time dependent manner. Higher activity was found against lung (A549) (IC50 = 341.1 µg/mL), followed by colon (HCT-116) (IC50 = 378.8 µg/mL) and breast (MCF-7) (IC50 = 428.3 µg/mL) cancer cells. High resolution-liquid chromatography-mass spectrometry (HR-LC-MS) data of S. repanda crude extract revealed the presence of diverse bioactive/chemical components, including fatty acids, alcohol, sugar, flavonoids, alkaloids, terpenoids, coumarins and phenolics, which can be the basis and major cause for its bioactive potential. Therefore, achieved results from this study confirmed the efficacy of S. repanda and a prospective source of naturally active biomolecules with antibacterial, antioxidant and anticancer potential. These phytocompounds alone with their favorable pharmacokinetics profile suggests good lead and efficiency of S. repanda with no toxicity risks. Finally, further in vivo experimental investigations can be promoted as probable candidates for various therapeutic functions, drug discovery and development.

Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against Schistosoma-Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach.

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

A novel nonsense mutation in the STS gene in a Pakistani family with X-linked recessive ichthyosis: including a very rare case of two homozygous female patients.

BACKGROUND: X-linked ichthyosis (XLI; OMIM# 308100) is a recessive keratinization disorder characterized by the presence of dark brown, polygonal, adherent scales on different parts of the body surface. It almost exclusively affects males and the estimated prevalence ranges from 1:2000-6000 in males worldwide. Extracutaneous manifestations are frequent including corneal opacities, cryptorchidism, neuropsychiatric symptoms or others. Up to 90% of XLI cases are caused by recurrent hemizygous microdeletion encompassing entire STS gene on chromosome Xp22.3, while only a minority of patients shows partial deletions or loss of function point mutations in STS. Larger deletions also involving contiguous genes are identified in syndromic patients. METHODS: Here, we report clinical and genetic findings of a large Pakistani family having 16 affected individuals including 2 females with XLI. Molecular karyotyping and direct DNA sequencing of coding region of the STS gene was performed. RESULTS: The clinical manifestations in affected individuals involved generalized dryness and scaling of the skin with polygonal, dark scales of the skin on scalp, trunk, limbs, and neck while sparing face, palms and soles. There were no associated extra-cutaneous features such as short stature, cryptorchidism, photophobia, corneal opacities, male baldness, and behavioral, cognitive, or neurological phenotypes including intellectual disability, autism or attention deficit hyperactivity disorder. Molecular karyotyping was normal and no copy number variation was found. Sanger sequencing identified a novel hemizygous nonsense mutation (c.287G > A; p.W96*), in exon 4 of STS gene in all affected male individuals. In addition, two XLI affected females in the family were found to be homozygous for the identified variant. CONCLUSIONS: This study is useful for understanding the genetic basis of XLI in the patients studied, for extending the known mutational spectrum of STS, diagnosis of female carriers and for further application of mutation screening in the genetic counseling of this family.

Short Term Traffic State Prediction via Hyperparameter Optimization Based Classifiers.

Short-term traffic state prediction has become an integral component of an advanced traveler information system (ATIS) in intelligent transportation systems (ITS). Accurate modeling and short-term traffic prediction are quite challenging due to its intricate characteristics, stochastic, and dynamic traffic processes. Existing works in this area follow different modeling approaches that are focused to fit speed, density, or the volume data. However, the accuracy of such modeling approaches has been frequently questioned, thereby traffic state prediction over the short-term from such methods inflicts an overfitting issue. We address this issue to accurately model short-term future traffic state prediction using state-of-the-art models via hyperparameter optimization. To do so, we focused on different machine learning classifiers such as local deep support vector machine (LD-SVM), decision jungles, multi-layers perceptron (MLP), and CN2 rule induction. Moreover, traffic states are evaluated using traffic attributes such as level of service (LOS) horizons and simple if-then rules at different time intervals. Our findings show that hyperparameter optimization via random sweep yielded superior results. The overall prediction performances obtained an average improvement by over 95%, such that the decision jungle and LD-SVM achieved an accuracy of 0.982 and 0.975, respectively. The experimental results show the robustness and superior performances of decision jungles (DJ) over other methods.

Thymic Stromal Lymphopoietin (TSLP) gene variant rs1837253 is significantly associated with Asthma prevalence in Pakistani Pashtun women.

Asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness and remodeling. Thymic stromal lymphopoietin (TSLP), a member of the interleukin-2 family of cytokines, is produced by activated lung and intestinal epithelial cells, mast, and other immune cells. Population-based studies identified associations between SNPs in the TSLP promoter region and asthma pathogenesis. In this study, we analyzed the genotypic association of TSLP rs1837253 with asthma predisposition in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Target DNA sequence of 250 asthmatics and an equal number of healthy individuals was PCR amplified, and allelic determination was performed by Sanger sequencing. Statistical analysis was conducted using chi-square tests and logistic regression analysis. Homozygous T/T genotype was frequent in the asthmatic subjects with a statistically significant level (P<0.05). Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive were tested while adjusting allele frequencies with covariates (gender and age). Combined C/T and T/T individuals had higher odds ratios of 3.00, 1.91, and 1.73 in co-dominant, dominant, and additive models with statistically significant P-values of 0.029*, 0.022*, and 0.02*, respectively. T allele of rs1837253 was associated with increased susceptibility to asthma among Pashtuns, particularly in females, and we corroborate rs1837253 as a SNP of interest with a potential functional role.

Efficient purification of CD4+ lymphocytes from peripheral blood progenitor cell products using affinity bead acoustophoresis.

Processing of peripheral blood progenitor cells (PBPC) for clinical transplantation or research applications aims to effectively isolate or deplete specific cell populations, utilizing primarily magnetic or fluorescence activated sorting methods. Here, we investigated the performance of microfluidic acoustophoresis for the separation of lymphocyte subsets from PBPC, and present a novel method for affinity-bead-mediated acoustic separation of cells which can otherwise not be acoustically discriminated. As the acoustic force on a particle depends on particle size, density and compressibility, targeting of cells by affinity specific beads will generate cell-bead complexes that exhibit distinct acoustic properties relative to nontargeted cells and are, thus, possible to isolate. To demonstrate this, PBPC samples (n = 22) were obtained from patients and healthy donors. Following density gradient centrifugation, cells were labeled with anti-CD4-coated magnetic beads (Dynal) and isolated by acoustophoresis and, for comparison, standard magnetic cell sorting technique in parallel. Targeted CD4+ lymphocytes were acoustically isolated with a mean (±SD) purity of 87 ± 12%, compared with 96 ± 3% for control magnetic sorting. Viability of sorted cells was 95 ± 4% (acoustic) and 97 ± 3% (magnetic), respectively. The mean acoustic separation efficiency of CD4+ lymphocytes to the target fraction was 65 ± 22%, compared with a mean CD4+ lymphocyte recovery of 56 ± 15% for magnetic sorting. Functional testing of targeted CD4+ lymphocytes demonstrated unimpaired mitogen-mediated proliferation capacity and cytokine production. Hematopoietic progenitor cell assays revealed a preserved colony forming ability of nontarget cells post sorting. We conclude that the acoustophoresis platform can be utilized to efficiently isolate bead-labeled CD4+ lymphocytes from PBPC samples in a continuous flow format, with preserved functional capacity of both target and nontarget cells. These results open up for simultaneous affinity-bead-mediated separation of multiple cell populations, something which is not possible with current standard magnetic cell separation technology. © 2014 International Society for Advancement of Cytometry.

Effect of Mirabegron in Men With Overactive Bladder and Erectile Dysfunction: A Prospective Observational Study.

BACKGROUND: As it has been observed that the erect penis has been the epitome of virility for the male community for decades, it became necessary to search for alternative treatments for the cause. So, the study was performed to evaluate the potential impact of mirabegron in men with mild to moderate erectile dysfunction (ED) and overactive bladder (OAB). METHODS: It was a prospective, observational study that was carried out at the Department of Urology at Rajendra Institute of Medical Sciences, Ranchi, for a duration of two years and included a total of two hundred fifty patients. The individuals included had a diagnosis of mild to moderate erectile dysfunction (ED) along with symptoms of OAB. The overactive bladder questionnaire (OAB-q) score and the International Index of Erectile Dysfunction-5 (IIEF-5) score were used, respectively, to measure the impact of mirabegron on ED and OAB. Then, the changes in ED and OAB were evaluated at two, four, eight, and 12 weeks. RESULTS: Among the total 250 patients recruited, around 32.5% of them had mild ED, 17.5% were diagnosed with mild to moderate ED, and 50% suffered from moderate ED. The IIEF-5 scores improved by four points or more in 86.25%, 91.25%, and 71.25% of patients after four, eight, and 12 weeks, respectively. OAB-q scores were likewise shown to decline in the fourth (13.1 ± 4.3) and eighth (12.8 ± 4.2) weeks when compared to the baseline (17.4 ± 5.5). Also, adverse events reported did not hamper the progress of the study. CONCLUSION: The study concluded that mirabegron has a beneficial impact on controlling OAB symptoms among men diagnosed with mild to moderate ED. The effects last for only eight weeks, and then they decline. Furthermore, mirabegron was well-tolerated among patients and had no safety concerns with its use.

Identification of TBK1 inhibitors against breast cancer using a computational approach supported by machine learning.

Introduction: The cytosolic Ser/Thr kinase TBK1 is of utmost importance in facilitating signals that facilitate tumor migration and growth. TBK1-related signaling plays important role in tumor progression, and there is need to work on new methods and workflows to identify new molecules for potential treatments for TBK1-affecting oncologies such as breast cancer. Methods: Here, we propose the machine learning assisted computational drug discovery approach to identify TBK1 inhibitors. Through our computational ML-integrated approach, we identified four novel inhibitors that could be used as new hit molecules for TBK1 inhibition. Results and Discussion: All these four molecules displayed solvent based free energy values of -48.78, -47.56, -46.78 and -45.47 Kcal/mol and glide docking score of -10.4, -9.84, -10.03, -10.06 Kcal/mol respectively. The molecules displayed highly stable RMSD plots, hydrogen bond patterns and MMPBSA score close to or higher than BX795 molecule. In future, all these compounds can be further refined or validated by in vitro as well as in vivo activity. Also, we have found two novel groups that have the potential to be utilized in a fragment-based design strategy for the discovery and development of novel inhibitors targeting TBK1. Our method for identifying small molecule inhibitors can be used to make fundamental advances in drug design methods for the TBK1 protein which will further help to reduce breast cancer incidence.

Analyzing injury severity of three-wheeler motorized rickshaws: A correlated random parameters approach with heterogeneity in means.

Traffic crashes involving three-wheeler motorized rickshaw (3-WMR) are alarming public health and socioeconomic concerns in developing countries. While most of the earlier studies have dealt with safety analysis of four- and two-wheelers, there is a noticeable gap in understanding the safety dynamics, especially the risk factors affecting the crashes involving 3-WMR. The present study aims to address this gap by exploring potential risk factors influencing 3-WMR crashes, utilizing a correlated random parameters multinomial logit model with heterogeneity in means (CRPMNLMHM). This modeling framework advances the classic random parameters model by capturing associations among random parameters, providing a more comprehensive understanding of crash risks associated with 3-WMR. The empirical analysis draws on three years of traffic crash records (2017-2019) maintained by RESCUE 1122 in Rawalpindi city, Pakistan. A comparative assessment between the modeling frameworks demonstrated that CRPMNLMHM outperformed its counterparts. Model assessment for heterogeneity in the means identifies two significant variables, i.e., young age and nighttime, which yield statistically significant random parameters. In addition, the model's results suggest that fatal and severe injury outcomes in 3-WMR crashes are affected by several attributes related to temporal characteristics (weekend, nighttime, and off-peak indicators), driver profiles (young, older aged, and speeding), posted speed limits (>70 kmph), weather conditions (raining), and crash characteristics (collision with pedestrians, trucks, or 3-WMR overturning). The present study's findings offer invaluable insights, emphasizing the significance of considering for unobserved heterogeneity in variables contributing to the injury severity of 3-WMR crashes. Moreover, in light of the findings, a set of policy implications are suggested, which will guide safety practitioners to develop more effective countermeasures to address safety issues associated with 3-WMRs.

ANN-based swarm intelligence for predicting expansive soil swell pressure and compression strength.

This research suggests a robust integration of artificial neural networks (ANN) for predicting swell pressure and the unconfined compression strength of expansive soils (PsUCS-ES). Four novel ANN-based models, namely ANN-PSO (i.e., particle swarm optimization), ANN-GWO (i.e., grey wolf optimization), ANN-SMA (i.e., slime mould algorithm) alongside ANN-MPA (i.e., marine predators' algorithm) were deployed to assess the PsUCS-ES. The models were trained using the nine most influential parameters affecting PsUCS-ES, collected from a broader range of 145 published papers. The observed results were compared with the predictions made by the ANN-based metaheuristics models. The efficacy of all these formulated models was evaluated by utilizing mean absolute error (MAE), Nash-Sutcliffe (NS) efficiency, performance index ρ, regression coefficient (R2), root mean square error (RMSE), ratio of RMSE to standard deviation of actual observations (RSR), variance account for (VAF), Willmott's index of agreement (WI), and weighted mean absolute percentage error (WMAPE). All the developed models for Ps-ES had an R significantly > 0.8 for the overall dataset. However, ANN-MPA excelled in yielding high R values for training dataset (TrD), testing dataset (TsD), and validation dataset (VdD). This model also exhibited the lowest MAE of 5.63%, 5.68%, and 5.48% for TrD, TsD, and VdD, respectively. The results of the UCS model's performance revealed that R exceeded 0.9 in the TrD. However, R decreased for TsD and VdD. Also, the ANN-MPA model yielded higher R values (0.89, 0.93, and 0.94) and comparatively low MAE values (5.11%, 5.67, and 3.61%) in the case of PSO, GWO, and SMA, respectively. The UCS models witnessed an overfitting problem because the aforementioned R values of the metaheuristics were 0.62, 0.56, and 0.58 (TsD), respectively. On the contrary, no significant observation was recorded in the VdD of UCS models. All the ANN-base models were also tested using the a-20 index. For all the formulated models, maximum points were recorded to lie within ± 20% error. The results of sensitivity as well as monotonicity analyses depicted trending results that corroborate the existing literature. Therefore, it can be inferred that the recently built swarm-based ANN models, particularly ANN-MPA, can solve the complexities of tuning the hyperparameters of the ANN-predicted PsUCS-ES that can be replicated in practical scenarios of geoenvironmental engineering.

Evaluating helmet-wearing of single-vehicle overspeeding motorcycle crashes: Insights from temporal instability in parsimonious pooled framework.

OBJECTIVE: A lower helmet-wearing rate and overspeeding in Pakistan are critical risk behaviors of motorcyclists, causing severe injuries. To explore the differences in the determinants affecting the injury severities among helmeted and non-helmeted motorcyclists in motorcycle crashes caused by overspeeding behavior, single-vehicle motorcycle crash data in Rawalpindi city for 2017-2019 is collected. Considering three possible crash injury severity outcomes of motorcyclists: fatal injury, severe injury and minor injury, the rider, roadway, environmental, and temporal characteristics are estimated. METHODS: To provide a mathematically simpler framework, the current study introduces parsimonious pooled random parameters logit models. Then, the standard pooled random parameters logit models without considering temporal effects are also simulated for comparison. By comparing the goodness of fit measure and estimation results, the parsimonious pooled random parameters logit model is suitable for capturing the temporal instability. Then, the non-transferability among helmeted and non-helmeted overspeeding motorcycle crashes is illustrated by likelihood ratio tests and out-of-sample prediction, and two types of models provide robust results. The marginal effects are also calculated. RESULTS: Several variables, such as age, cloudy and weekday indicators illustrate temporal instability. Moreover, several variables are observed to only show significance in non-helmeted models, showing non-transferability across helmeted and non-helmeted models. CONCLUSIONS: More educational campaigns, regulation and enforcement, and management countermeasures should be organized for non-helmeted motorcyclists and overspeeding behavior. Such findings also provide research reference for the risk-compensating behavior and self-selected group issues under overspeeding riding considering the usage of helmets.

Bioactive profiling of Rumex vesicarius L. from the Hail region of Saudi Arabia: a study on its phytochemical and elemental analysis, antibiofilm, antibacterial, antioxidant properties, and molecular docking analysis.

Background: Rumex vesicarius is a wild leafy plant belonging to the family Polygonaceae, renowned for its therapeutic benefits. The genus Rumex comprises approximately 150 species distributed globally. Objective: The study aimed to investigate the biological activities of R. vesicarius using in vitro and in silico methods. Methods: Rumex vesicarius was collected from the mountains in Hail and extracted with methanol. The phytochemical composition was qualitatively determined using colorimetric detection methods. Additional analyses included elemental analysis, in silico docking, antioxidant, antibacterial, and anti-biofilm properties. Results: The extract contained various classes of phytochemicals, including flavonoids, phenolics, tannins, terpenes, and saponins. Sixteen constituents were identified through molecular docking, revealing inhibition against the filamentous temperature-sensitive protein Z (FtsZ), a crucial factor in bacterial cell division. Six compounds exhibited low binding scores ranging from -8.3 to -5.0 kcal/mol, indicating efficient interaction at the active site. Elemental analysis identified 15 elements, with potassium being the most abundant, followed by calcium, aluminum, silicon, iron, phosphorus, sulfur, magnesium, titanium, strontium, zinc, manganese, bromine, and chromium. Antioxidant analysis revealed significant properties at lower concentrations compared to ascorbic acid, butylated hydroxytoluene, and ß-carotene. Antibacterial analysis demonstrated inhibitory effects on Bacillus subtilis MTCC121 and Pseudomonas aeruginosa MTCC 741, with inhibition zones of 13.67 ± 1.0 mm and 11.50 ± 1.0 mm, respectively. The MIC and MBC values ranged from 250 to 500 µg/mL. R. vesicarius also exhibited anti-biofilm activity. Conclusion: Wild-grown R. vesicarius from the mountains of Hail is rich in bioactive phytochemicals and essential minerals, exhibiting notable antioxidant and antibacterial properties.

Circular Penile Skin Fasciocutaneous Ventral Onlay Flap Urethroplasty as an Alternative to Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Complex Long-Segment Urethral Stricture: A Retrospective Study.

Background A urethral stricture is the narrowing of the urethra that results in symptoms of obstruction. It can appear anywhere along the male urethra's length and has a variety of causes. The circular penile fasciocutaneous flap is employed in the successful single-stage reconstruction of long-segment complex anterior urethral strictures especially when the buccal mucosa is unavailable due to various reasons. The study has tried to identify a surgical technique that is more beneficial for the treatment of urethral strictures. Objective The objective of this research was to evaluate the outcomes of circular penile skin fasciocutaneous ventral onlay flap urethroplasty (group A) and the outcomes of dorsal onlay buccal mucosal graft urethroplasty (group B) in the management of complex long-segment penile urethral stricture. Methods In this retrospective study between December 2012 and December 2022, 60 patients with long-segment complex penile urethral stricture who underwent urethroplasty at our center were evaluated. Patients were divided into two groups according to the flap used (dorsal onlay buccal mucosal graft urethroplasty was used in 30 patients (group B), and circular penile fasciocutaneous flap (single stage) was used in 30 patients (group A)). The success rate and the mean peak flow rate were also calculated post-operation to identify the effectiveness of the surgical procedure used for urethral strictures. Results The study consisted of 60 patients in total. Group A's mean age was determined to be 51.2±16.2 years, whereas group B's mean age was determined to be 40.7±16.8 years. Preoperatively, the median urethral stricture length was 69 mm in group A (range: 20-100 mm) and 56 mm in group B (range: 30-110 mm). The intraoperative median length of the urethral stricture was 82 mm in group A (range: 20-120 mm) and 65 mm in group B (range: 40-140 mm). The mean peak flow rate was 30.9±6.8 mL/s in group A compared to 18.1±4.9 mL/s in group B. The success rate for group A was 89.7%, while the success rate for group B was 75.9%. Conclusion For complex long-segment urethral strictures, circular penile skin fasciocutaneous ventral onlay flap urethroplasty has a higher rate of success and fewer complications than dorsal onlay buccal mucosal graft urethroplasty. Along with success rate, it has a better mean peak flow rate and lower complications.

A Study of Normal Renal Dimensions at Ultrasonography and Their Influencing Factors in an Indian Population.

Background: Kidney dimensions play one of the most vital roles in the diagnosis and identification of any renal disease. Renal dimensions are generally used in clinical practices to determine the size of the kidney as well as correlate with renal function to have a better understanding of acute and chronic renal diseases. This study aimed to find out the normal renal dimensions with the help of ultrasonography and their impact on the Indian population. Methods: Renal dimensions, which include parenchymatous thickness and length as well as the width of about 60 healthy adult Indian populations, were estimated with the help of sonography, and a detailed study has been performed on the difference observed based on age, sex, height, weight, body mass index, and body surface area. Results: There was no particular difference found on the basis of width and length between the left and right kidneys; however, the parenchymal thickness between the left and right has been shown to have a significant difference. The mean width, length, and parenchymal thickness were 4.6 ± 0.43, 9.64 ± 0.62, and 2.03 ± 0.1 cm, respectively. While doing estimation based on gender, it has been observed that there is a noticeable difference in width but no difference in height or parenchymal thickness. A significant diversity has been observed in patients in age groups above 49 compared to other age groups. A positive correlation with body weight, body height, and body mass index has also been observed in some cases. Conclusion: The given study has attempted to define the standard reference for renal dimension in the Indian census. The observations made in the given study demonstrated the possibility of renal dimensions being smaller in the Indian population in contrast to those of the Western population, which are much larger.