Automatic assessment of scoliosis surgery outcome on trunk shape using left-right trunk asymmetry.

PURPOSE: To present a novel set of Left-Right Trunk Asymmetry (LRTA) indices and use them to assess the postoperative appearance of the trunk in Adolescent Idiopathic Scoliosis (AIS) patients. METHODS: We hypothesize that LRTA measurements provide complementary information to existing trunk asymmetry indices when documenting the outcome of scoliosis surgery. Forty-nine AIS patients with thoracic curves who underwent posterior spinal fusion were included. All had surface topography scans taken preoperatively and at least 6 months postoperatively. We documented spinal curvature using Radiographic Cobb angles, scoliometer readings and coronal balance. To evaluate Global Trunk Asymmetry (GTA), we used the standard measures of Back Surface Rotation (BSR) and Trunk Lateral Shift (TLS). To measure LRTA, we identified asymmetry areas as regions of significant deviation between the left and right sides of the 3D back surface. New parameters called Deformation Rate (DR) and Maximum Asymmetry (MA) were measured in different regions based on the asymmetry areas. We compared the GTA and LRTA changes with those in spinal curvature before and after surgery. RESULTS: The GTA indices, mainly TLS, showed improvement for more than 75% of patients. There was significant improvement of LRTA in the shoulder blades and waist regions (95% and 80% of patients respectively). CONCLUSION: We report positive outcomes for LRTA in the majority of patients, specifically in the shoulder blades and waist, even when no reduction of BSR is observed. The proposed indices can evaluate local trunk asymmetries and the degree to which they are improved or worsened after scoliosis surgery.

Exploring the journey of supporters in bereavement support groups: Experiences, sense-making, and social connections.

This study aimed to explore facilitators' experiences in bereavement support groups as they relate to their experiences of personal loss. Semi-structured interviews were conducted with nine facilitators who had experienced such grief, and data were analyzed qualitatively using a modified grounded theory approach (M-GTA). The analysis revealed two categories and nine subcategories: (i) 'Experiences in group activities,' encompassing positive and negative experiences during activities, and (ii) 'Structuring of Meaning,' the process of deciphering for oneself in relation to one's experience of loss and life. These two categories interacted with each other, and it was important for facilitators to find meaning in their activities, loss experiences, and lives for the stable continuation of bereavement support group activities. These findings underscore the importance of facilitators following and supporting the sense-making process.

Intelligent Complementary Multi-Modal Fusion for Anomaly Surveillance and Security System.

Recently, security monitoring facilities have mainly adopted artificial intelligence (AI) technology to provide both increased security and improved performance. However, there are technical challenges in the pursuit of elevating system performance, automation, and security efficiency. In this paper, we proposed intelligent anomaly detection and classification based on deep learning (DL) using multi-modal fusion. To verify the method, we combined two DL-based schemes, such as (i) the 3D Convolutional AutoEncoder (3D-AE) for anomaly detection and (ii) the SlowFast neural network for anomaly classification. The 3D-AE can detect occurrence points of abnormal events and generate regions of interest (ROI) by the points. The SlowFast model can classify abnormal events using the ROI. These multi-modal approaches can complement weaknesses and leverage strengths in the existing security system. To enhance anomaly learning effectiveness, we also attempted to create a new dataset using the virtual environment in Grand Theft Auto 5 (GTA5). The dataset consists of 400 abnormal-state data and 78 normal-state data with clip sizes in the 8-20 s range. Virtual data collection can also supplement the original dataset, as replicating abnormal states in the real world is challenging. Consequently, the proposed method can achieve a classification accuracy of 85%, which is higher compared to the 77.5% accuracy achieved when only employing the single classification model. Furthermore, we validated the trained model with the GTA dataset by using a real-world assault class dataset, consisting of 1300 instances that we reproduced. As a result, 1100 data as the assault were classified and achieved 83.5% accuracy. This also shows that the proposed method can provide high performance in real-world environments.

Nested Variational Chain and Its Application in Massive MIMO Detection for High-Order Constellations.

Multiple input multiple output (MIMO) technology necessitates detection methods with high performance and low complexity; however, the detection problem becomes severe when high-order constellations are employed. Variational approximation-based algorithms prove to deal with this problem efficiently, especially for high-order MIMO systems. Two typical algorithms named Gaussian tree approximation (GTA) and expectation consistency (EC) attempt to approximate the true likelihood function under discrete finite-set constraints with a new distribution by minimizing the Kullback-Leibler (KL) divergence. As the KL divergence is not a true distance measure, 'exclusive' and 'inclusive' KL divergences are utilized by GTA and EC, respctively, demonstrating different performances. In this paper, we further combine the two asymmetric KL divergences in a nested way by proposing a generic algorithm framework named nested variational chain. Acting as an initial application, a MIMO detection algorithm named Gaussian tree approximation expectation consistency (GTA-EC) can thus be presented along with its alternative version for better understanding. With less computational burden compared to its counterparts, GTA-EC is able to provide better detection performance and diversity gain, especially for large-scale high-order MIMO systems.

Disrupted white matter connectivity and organization of brain structural connectomes in tuberous sclerosis complex patients with neuropsychiatric disorders using diffusion tensor imaging.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network-based statistical (NBS) analysis. MATERIALS AND METHODS: Forty-two patients with a definitive diagnosis of TSC were recruited for this study. All patients underwent brain DTI examination using a 3 T magnetic resonance imaging system. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) values, and fractional anisotropy (FA) mapping in 52 tubers and white matter lesions were measured and compared with those of contralateral normal regions. GTA was performed on the inter-regional connectivity matrix, and NBS analysis was used to identify the significance of any connected subnetworks evident in the set of altered connections. For neurological severity subgrouping, a neurological severity score was assigned to TSC patients including those with ID, seizure, autism, and other neuropsychiatric disorders (NPDs). RESULTS: Significantly higher MD, AD, and RD, and lower FA values, were found in TSC lesions compared with those measured in contralateral normal regions for tubers (P < 0.05). GTA and NBS analysis provided better local segregation but worse global integration of the structural network (regular-like network) in TSC patients with ID, seizure, and higher Neurological Severity Score. Disrupted subnetworks in TSC patients with severe status included connections from the frontal lobe to the parietal lobe, temporal lobe to the caudate, and temporal lobe to the insula. DISCUSSION: DTI has the potential to provide valuable information about cytoarchitectural changes in TSC lesions beyond morphological MRI findings alone. Using GTA and NBS, current results provide the information of disrupted white matter connectivity and organization in TSC patients with different neuropsychological impairments.

Bartonella gene transfer agent: Evolution, function, and proposed role in host adaptation.

The processes underlying host adaptation by bacterial pathogens remain a fundamental question with relevant clinical, ecological, and evolutionary implications. Zoonotic pathogens of the genus Bartonella constitute an exceptional model to study these aspects. Bartonellae have undergone a spectacular diversification into multiple species resulting from adaptive radiation. Specific adaptations of a complex facultative intracellular lifestyle have enabled the colonisation of distinct mammalian reservoir hosts. This remarkable host adaptability has a multifactorial basis and is thought to be driven by horizontal gene transfer (HGT) and recombination among a limited genus-specific pan genome. Recent functional and evolutionary studies revealed that the conserved Bartonella gene transfer agent (BaGTA) mediates highly efficient HGT and could thus drive this evolution. Here, we review the recent progress made towards understanding BaGTA evolution, function, and its role in the evolution and pathogenesis of Bartonella spp. We notably discuss how BaGTA could have contributed to genome diversification through recombination of beneficial traits that underlie host adaptability. We further address how BaGTA may counter the accumulation of deleterious mutations in clonal populations (Muller's ratchet), which are expected to occur through the recurrent transmission bottlenecks during the complex infection cycle of these pathogens in their mammalian reservoir hosts and arthropod vectors.

3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation.

Glycosylation is the most ubiquitous post-translational modification in eukaryotes. N-glycan is attached to nascent glycoproteins and is processed and matured by various glycosidases and glycosyltransferases during protein transport. Genetic and biochemical studies have demonstrated that alternations of the N-glycan structure play crucial roles in various physiological and pathological events including progression of cancer, diabetes, and Alzheimer's disease. In particular, the formation of N-glycan branches regulates the functions of target glycoprotein, which are catalyzed by specific N-acetylglucosaminyltransferases (GnTs) such as GnT-III, GnT-IVs, GnT-V, and GnT-IX, and a fucosyltransferase, FUT8s. Although the 3D structures of all enzymes have not been solved to date, recent progress in structural analysis of these glycosyltransferases has provided insights into substrate recognition and catalytic reaction mechanisms. In this review, we discuss the biological significance and structure-function relationships of these enzymes.

Induction of Rhodobacter capsulatus Gene Transfer Agent Gene Expression Is a Bistable Stochastic Process Repressed by an Extracellular Calcium-Binding RTX Protein Homologue.

Bacteriophage-like gene transfer agents (GTAs) have been discovered in both of the prokaryotic branches of the three-domain phylogenetic tree of life. The production of a GTA (RcGTA) by the phototrophic alphaproteobacterium Rhodobacter capsulatus is regulated by quorum sensing and a phosphorelay homologous to systems in other species that control essential functions such as the initiation of chromosome replication and cell division. In wild-type strains, RcGTA is produced in <3% of cells in laboratory cultures. Mutants of R. capsulatus that exhibit greatly elevated production of RcGTA were created decades ago by chemical mutagenesis, but the nature and molecular consequences of the mutation were unknown. We show that the number of cells in a population that go on to express RcGTA genes is controlled by a stochastic process, in contrast to a genetic process. We used transposon mutagenesis along with a fluorescent protein reporter system and genome sequence data to identify a gene, rcc00280, that encodes an RTX family calcium-binding protein homologue. The Rc280 protein acts as an extracellular repressor of RcGTA gene expression by decreasing the percentage of cells that induce the production of RcGTA.IMPORTANCE GTAs catalyze horizontal gene transfer (HGT), which is important for genomic evolution because the majority of genes found in bacterial genomes have undergone HGT at some point in their evolution. Therefore, it is important to determine how the production of GTAs is regulated to understand the factors that modulate the frequency of gene transfer and thereby specify the tempo of evolution. This work describes a new type of genetic regulation in which an extracellular calcium-binding protein homologue represses the induction of the Rhodobacter capsulatus GTA, RcGTA.

Structural basis for the glycosyltransferase activity of the Salmonella effector SseK3.

The Salmonella-secreted effector SseK3 translocates into host cells, targeting innate immune responses, including NF-κB activation. SseK3 is a glycosyltransferase that transfers an N-acetylglucosamine (GlcNAc) moiety onto the guanidino group of a target arginine, modulating host cell function. However, a lack of structural information has precluded elucidation of the molecular mechanisms in arginine and GlcNAc selection. We report here the crystal structure of SseK3 in its apo form and in complex with hydrolyzed UDP-GlcNAc. SseK3 possesses the typical glycosyltransferase type-A (GT-A)-family fold and the metal-coordinating DXD motif essential for ligand binding and enzymatic activity. Several conserved residues were essential for arginine GlcNAcylation and SseK3-mediated inhibition of NF-κB activation. Isothermal titration calorimetry revealed SseK3's preference for manganese coordination. The pattern of interactions in the substrate-bound SseK3 structure explained the selection of the primary ligand. Structural rearrangement of the C-terminal residues upon ligand binding was crucial for SseK3's catalytic activity, and NMR analysis indicated that SseK3 has limited UDP-GlcNAc hydrolysis activity. The release of free N-acetyl α-d-glucosamine, and the presence of the same molecule in the SseK3 active site, classified it as a retaining glycosyltransferase. A glutamate residue in the active site suggested a double-inversion mechanism for the arginine N-glycosylation reaction. Homology models of SseK1, SseK2, and the Escherichia coli orthologue NleB1 reveal differences in the surface electrostatic charge distribution, possibly accounting for their diverse activities. This first structure of a retaining GT-A arginine N-glycosyltransferase provides an important step toward a better understanding of this enzyme class and their roles as bacterial effectors.

Altered brain functional networks in Internet gaming disorder: independent component and graph theoretical analysis under a probability discounting task.

OBJECTIVES: Internet gaming disorder (IGD) is becoming a matter of concern around the world. However, the neural mechanism underlying IGD remains unclear. The purpose of this paper is to explore the differences between the neuronal network of IGD participants and that of recreational Internet game users (RGU). METHODS: Imaging and behavioral data were collected from 18 IGD participants and 20 RGU under a probability discounting task. The independent component analysis (ICA) and graph theoretical analysis (GTA) were used to analyze the data. RESULTS: Behavioral results showed the IGD participants, compared to RGU, prefer risky options to the fixed ones and spent less time in making risky decisions. In imaging results, the ICA analysis revealed that the IGD participants showed stronger functional connectivity (FC) in reward circuits and executive control network, as well as lower FC in anterior salience network (ASN) than RGU; for the GTA results, the IGD participants showed impaired FC in reward circuits and ASN when compared with RGU. CONCLUSIONS: These results suggest that IGD participants were more sensitive to rewards, and they were more impulsive in decision-making as they could not control their impulsivity effectively. This might explain why IGD participants cannot stop their gaming behaviors even when facing severe negative consequences.

The Protease ClpXP and the PAS Domain Protein DivL Regulate CtrA and Gene Transfer Agent Production in Rhodobacter capsulatus.

Several members of the Rhodobacterales (Alphaproteobacteria) produce a conserved horizontal gene transfer vector, called the gene transfer agent (GTA), that appears to have evolved from a bacteriophage. The model system used to study GTA biology is the Rhodobacter capsulatus GTA (RcGTA), a small, tailed bacteriophage-like particle produced by a subset of the cells in a culture. The response regulator CtrA is conserved in the Alphaproteobacteria and is an essential regulator of RcGTA production: it controls the production and maturation of the RcGTA particle and RcGTA release from cells. CtrA also controls the natural transformation-like system required for cells to receive RcGTA-donated DNA. Here, we report that dysregulation of the CckA-ChpT-CtrA phosphorelay either by the loss of the PAS domain protein DivL or by substitution of the autophosphorylation residue of the hybrid histidine kinase CckA decreased CtrA phosphorylation and greatly increased RcGTA protein production in R. capsulatus We show that the loss of the ClpXP protease or the three C-terminal residues of CtrA results in increased CtrA levels in R. capsulatus and identify ClpX(P) to be essential for the maturation of RcGTA particles. Furthermore, we show that CtrA phosphorylation is important for head spike production. Our results provide novel insight into the regulation of CtrA and GTAs in the RhodobacteralesIMPORTANCE Members of the Rhodobacterales are abundant in ocean and freshwater environments. The conserved GTA produced by many Rhodobacterales may have an important role in horizontal gene transfer (HGT) in aquatic environments and provide a significant contribution to their adaptation. GTA production is controlled by bacterial regulatory systems, including the conserved CckA-ChpT-CtrA phosphorelay; however, several questions about GTA regulation remain. Our identification that a short DivL homologue and ClpXP regulate CtrA in R. capsulatus extends the model of CtrA regulation from Caulobacter crescentus to a member of the Rhodobacterales We found that the magnitude of RcGTA production greatly depends on DivL and CckA kinase activity, adding yet another layer of regulatory complexity to RcGTA. RcGTA is known to undergo CckA-dependent maturation, and we extend the understanding of this process by showing that the ClpX chaperone is required for formation of tailed, DNA-containing particles.

Transfer of antibiotic-resistance genes via phage-related mobile elements.

Antibiotic resistance is a major concern for society because it threatens the effective prevention of infectious diseases. While some bacterial strains display intrinsic resistance, others achieve antibiotic resistance by mutation, by the recombination of foreign DNA into the chromosome or by horizontal gene acquisition. In many cases, these three mechanisms operate together. Several mobile genetic elements (MGEs) have been reported to mobilize different types of resistance genes and despite sharing common features, they are often considered and studied separately. Bacteriophages and phage-related particles have recently been highlighted as MGEs that transfer antibiotic resistance. This review focuses on phages, phage-related elements and on composite MGEs (phages-MGEs) involved in antibiotic resistance mobility. We review common features of these elements, rather than differences, and provide a broad overview of the antibiotic resistance transfer mechanisms observed in nature, which is a necessary first step to controlling them.

Biochemical characterization of the retaining glycosyltransferase glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis.

Glucosyl-3-phosphoglycerate synthase (GpgS) catalyzes the first step in the biosynthesis of glucosyl glycerate, the putative precursor used in building methylated polysaccharides in mycobacteria. Enzymes from Mycobacterium tuberculosis (MtGpgS) and related species have been structurally characterized and subjected to basic kinetic analyses, but more in-depth kinetic analysis is currently lacking. Dead-end inhibition studies with MtGpgS suggest an ordered kinetic mechanism with 3-phosphoglycerate (3-PGA) binding first, followed by UDP-glucose, in contrast to previous reports. At higher concentrations, 3-PGA exhibits competitive substrate inhibition vs. UDP-glucose, suggesting 3-PGA can bind to either binding site on the enzyme. Parabolic noncompetitive inhibition plots by a 3-PGA analog also support this conclusion. The effect of varying pH on the catalytic parameters indicates single ionizable residue involved catalysis (pKa=6.3) that must be deprotonated for full activity. A solvent kinetic isotope effect of 2.0±0.3 on kcat is consistent with a proton in flight during the rate-determining step. Site-directed mutagenesis studies identify several residues critical for interactions with substrates. Although the residues are conserved among other glycosyltransferase families catalyzing similar reactions, the effect of substitutions varies between families suggesting that conserved areas play different catalytic roles in each family.

Weapon Violence Dataset 2.0: A synthetic dataset for violence detection.

In the current era, satisfying the appetite of data hungry models is becoming an increasingly challenging task. This challenge is particularly magnified in research areas characterised by sensitivity, where the quest for genuine data proves to be elusive. The study of violence serves as a poignant example, entailing ethical considerations and compounded by the scarcity of authentic, real-world data that is predominantly accessible only to law enforcement agencies. Existing datasets in this field often resort to using content from movies or open-source video platforms like YouTube, further emphasising the scarcity of authentic data. To address this, our dataset aims to pioneer a new approach by creating the first synthetic virtual dataset for violence detection, named the Weapon Violence Dataset (WVD). The dataset is generated by creating virtual violence scenarios inside the photo-realistic video game namely: Grand Theft Auto-V (GTA-V). This dataset includes carefully selected video clips of person-to-person fights captured from a frontal view, featuring various weapons-both hot and cold across different times of the day. Specifically, WVD contains three categories: Hot violence and Cold violence (representing the violence category) as well as No violence (constituting the control class). The dataset is designed and created in a way that will enable the research community to train deep models on such synthetic data with the ability to increase the data corpus if the needs arise. The dataset is publicly available on Kaggle and comprises normal RGB and optic flow videos.

Gene transfer agents: structural and functional properties of domesticated viruses.

Horizontal exchange of DNA between bacteria and archaea is prevalent and has major potential implications for genome evolution, plasticity, and population fitness. Several transfer mechanisms have been identified, including gene transfer agents (GTAs). GTAs are intricately regulated domesticated viruses that package host DNA into virus-like capsids and transfer this DNA throughout the bacterial community. Several important advances have recently been made in our understanding of these unusual particles. In this review, we highlight some of these findings, primarily for the model GTA produced by Rhodobacter capsulatus but also for newly identified GTA producers. We provide key insights into these important genetic elements, including the differences between GTAs from their ancestral bacteriophages, their regulation and control, and their elusive evolutionary function.

Development and Characterization of Modified Gelatin-Based Cling Films with Antimicrobial and Antioxidant Activities and Their Application in the Preservation of Cherry Tomatoes.

The utilization of functional cling films presents a promising approach to alleviate post-harvest spoilage caused by microbial activity, oxidative metabolism, and moisture loss in agricultural products. To overcome the environmental problems of conventional packaging materials, in this study, we developed functional fruit and vegetable cling films based on glycidyltrimethylammonium chloride and rosemarinic acid cross-linked gelatin (RQ-GEL). The results indicate that the prepared RQ-GEL film possesses excellent UV light barrier properties and mechanical performance. RQ-GEL inhibited S. aureus and E. coli by 93.79% and 92.04%, respectively. DPPH and ABTS free radical scavenging activities were as high as 87.69% and 84.6%. In the cherry tomato preservation experiment, when compared to uncovered samples, the RQ-GEL group had a 29.77% reduction in weight loss and a significant 26.92% reduction in hardness. Meanwhile, the RQ-GEL group delays the decline of fruit total soluble solids and titratable acidity content, and prolongs the preservation period of cherry tomatoes. Hence, RQ-GEL cling film is poised to emerge as a promising packaging material for the post-harvest preservation of agricultural products.

Viriforms-A New Category of Classifiable Virus-Derived Genetic Elements.

The International Committee on Taxonomy of Viruses (ICTV) recently accepted viriforms as a new polyphyletic category of classifiable virus-derived genetic elements, juxtaposed to the polyphyletic virus, viroid, and satellite nucleic acid categories. Viriforms are endogenized former viruses that have been exapted by their cellular hosts to fulfill functions important for the host's life cycle. While morphologically resembling virions, particles made by viriforms do not package the viriform genomes but instead transport host genetic material. Known viriforms are highly diverse: members of family Polydnaviriformidae (former Polydnaviridae) have thus far been found exclusively in the genomes of braconid and ichneumonid parasitoid wasps, whereas the completely unrelated gene transfer agents (GTAs) are widely distributed among prokaryotes. In addition, recent discoveries likely extend viriforms to mammalian genomes. Here, we briefly outline the properties of these viriform groups and the first accepted and proposed ICTV frameworks for viriform classification.

Mechanistic insights into Schizosaccharomyces pombe GT-A family protein Pvg3 in the biosynthesis of pyruvylated ß1,3-galactose of N-linked oligosaccharides.

N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated ß1,3-linked Gal (PvGalß) at the non-reducing end. The PvGalß unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for ß-galactosylation in fission yeast is poorly understood. To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalß biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2+ or pvg5+, suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a ß1,3-galactosyltransferase, and not for its localization to the Golgi. Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type ß1,3-galactosyltransferase. Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for ß-(1→3) bond formation. Yeast two-hybrid assay showed that Pvg5 physically interacts with Pvg3 and the pyruvyltransferase Pvg1. Collectively, these results provide insight into ß-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalß biosynthesis.

Utility of Gynecological Teaching Associates.

Introduction Gynecological teaching associates (GTAs) are trained to teach the pelvic exam using themselves as models, and it has been hypothesized that their use can improve learners' confidence and interpersonal skills. This study aims to gain greater insight into whether the use of GTAs is associated with increased medical students' confidence when performing the pelvic exam during clinical rotations. Methods An email survey was distributed to medical students in two different classes at a single United States Medical Licensing Examination (USMLE)-accredited medical school: one that learned the pelvic exam using GTAs and one that did not. A Fisher's exact test was performed to determine associations between the use of GTAs and confidence in performing the pelvic exam, with a p-value of <0.01. Results Out of the 85 survey participants, 68 had performed a pelvic exam in the clinical setting and thus rated their confidence level. Of the 38 students who learned using a GTA, 66% (p<0.0024) reported a confidence level of four or five (out of five) compared to 50% of the 30 students who were not able to practice using a GTA. There was a statistically significant difference in the confidence levels of students who practiced on GTAs compared to those who did not. Discussion Our findings demonstrated that students who were able to learn the pelvic exam using GTAs reported higher confidence levels when subsequently performing a pelvic exam in a clinical setting. Conclusion Our findings support investment in GTA programming for teaching the pelvic exam in medical school curricula.

P-glycoprotein mechanical functional analysis using in silico molecular modeling: Pharmacokinetic variability according to ABCB1 c.2677G > T/A genetic polymorphisms.

P-glycoprotein (P-gp) is a widely membrane-expressed multi-drug transporter. It is unclear whether the pharmacokinetic diversity of P-gp substrates is highly dependent on ABCB1 polymorphisms encoding P-gp. The purpose of this study is to analyze the mechanistic function of P-gp through in silico molecular modeling and to approach the resolution of controversy over pharmacokinetic differences according to ABCB1 polymorphisms. P-gp conformations of apo, ligand-docked, and outward-facing states can be modeled based on structural information of human P-gp. And polymorphic P-gp structures were constructed through homology modeling. ABCB1 c.2677G > T/A (Ala893Ser/Thr), did not correspond to P-gp's nucleotide-binding-domain (NBD) or drug-binding-pocket (DBP) or involve mechanical conformational changes. Although amino acid substitution by ABCB1 c.2677G > T/A caused a 30 % increased strain in an α-helix hinge between the NBD and DBP in P-gp's internal tunnel, there were no overall structural changes compared to wild-type. ABCB1 c.2677G > T/A may increase torsional energy, impacting conformational change rate, but this does not significantly affect P-gp's general functioning. Fexofenadine docking into P-gp's DBP explained the substrate interaction, but no effect by ABCB1 c.2677G > T/A was confirmed. Our findings provide additional insights useful in resolving the debate about the influence of ABCB1 polymorphisms on the interindividual pharmacokinetic variability of P-gp substrates.