Feasibility of a Novel Surface-Guided Setup Technique to Reproduce Neck Curvature Using two Regions of Interest.

PURPOSE: To improve the setup reproducibility of neck curvature using real-time optical surface imaging (OSI) guidance on 2 regions of interest (ROIs) to infer cervical spine (c-spine) curvature for surface-guided radiotherapy (SGRT) of head-and-neck (HN) and c-spine cancer. METHODS: A novel SGRT setup approach was designed to reproduce neck curvature with 2 ROIs: upper-chest ROI and open-face ROI. It was hypothesized that the neck curvature could be reproduced if both ROIs were aligned within ±3 mm/2˚ tolerance. This was tested prospectively in 7 volunteers using real-time 3D-OSI guidance and lateral 2D-photography verification after the 3D and 2D references were captured from the initial conventional setup. Real-time SGRT was performed to align chest-ROI and face-ROI, and the longitudinal distance between them was adjustable using a head-support slider. Verification of neck curvature anteriorly and posteriorly was achieved by overlaying edge-extracted lateral pictures. Retrospectively, the relationship between anterior surface and spinal canal alignment was checked in 11 patients using their simulation CT (simCT) and setup cone-beam CT (CBCT). After the anterior surface was rigidly aligned, the spinal canal alignment was checked and quantified using the mean-distance-to-agreement (MDA) and DICE similarity index, and surface-to-spine correlation was calculated. RESULTS: The reproducibility of neck curvatures using the 2xROI SGRT setup is verified and the mean neck-outline-matching difference is within ±2 mm in lateral photographic overlays. The chest-ROI alignment takes 110 ± 58 s and the face-ROI takes 60 ± 35 s. When the anterior body surface is aligned (MDA = 1.1 ± 0.6 mm, DICE = 0.96 ± 0.02,) the internal spinal canal is also aligned (MDA = 1.0 ± 0.3 mm, DICE = 0.84 ± 0.04) in 11 patients. The surface-to-spine correlation is c = 0.90 (MDA) and c = 0.85 (DICE). CONCLUSION: This study demonstrates the feasibility of the novel 2-ROI SGRT setup technique to achieve reproducible neck and c-spine curvature regardless of neck visibility and availability as ROI. Staff training is needed to adopt this unconventional SGRT technique to improve patient setup.

Synthesis of new phenothiazine derivatives: Molecular docking, assessment of cytotoxic activity and oxidant-antioxidant properties on PCS-201-012, HT-29, and SH-SY5Y cell lines.

Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC50) values of compound 3a were determined to be 218.72, 202.85, and 227.86 µM while the IC50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 µM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines.

Pharmacokinetic study of erlotinib in a pregnant woman with advanced non-small cell lung cancer and observation of the effects on the child growth.

AIMS: The aim of the study is to report the clinical and pharmacological observations from a pregnant patient treated with erlotinib in the second and third trimesters of pregnancy. METHODS: Maternal and neonatal blood levels and safety of erlotinib and its metabolites were evaluated. Child development was monitored for 6 years. RESULTS: A 31-year-old woman with stage IV lung adenocarcinoma with EGFR exon19 deletion began treatment with erlotinib 150 mg/day at 17 weeks of gestation. Although foetal growth retardation and oligohydramnios were observed at several times during the pregnancy, treatment was continued due to the severity of the maternal presentation, with ongoing foetal monitoring. The foetus seemed to tolerate and recover well without specific interventions. A healthy baby boy was delivered at 37 weeks gestation. The child grew and developed without any obvious issues. At last follow-up, at age 6 years, he was attending school at a grade appropriate for his age without health or developmental problems. Blood levels of erlotinib were 397-856 ng/mL at 18-37 weeks of gestation and 1190 ng/mL at 8 weeks postpartum. The blood concentration ratios of OSI-413-to-erlotinib ranged from 0.167 to 0.253 at 18-37 weeks of gestation, excluding 24 weeks, and 0.131 at 8 weeks postpartum. The maternal-to-foetal transfer rate of erlotinib, OSI-420 and OSI-413 were 24.5, 34.8 and 20.3%, respectively. CONCLUSION: Erlotinib use during the second and third trimester of pregnancy did not seem to cause any untoward effects on the developing foetus, or any long-lasting effects that could be detected during 6 years of follow-up of the child.

Study on the effects of rapamycin and the mTORC1/2 dual inhibitor OSI-027 on the metabolism of colon cancer cells based on UPLC-MS/MS metabolomics.

mTORC1/2 dual inhibitors may be more effective than mTORC1 inhibitor rapamycin. However, their metabolic impacts on colon cancer cells remain unexplored. We conducted a comparative analysis of the anti-proliferative effects of rapamycin and the novel OSI-027 in colon cancer cells HCT-116, evaluating their metabolic influences through ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Our results demonstrate that OSI-027 more effectively inhibits colon cancer cell proliferation than rapamycin. Additionally, we identified nearly 600 metabolites from the spectra, revealing significant differences in metabolic patterns between cells treated with OSI-027 and rapamycin. Through VIP value screening, we pinpointed crucial metabolites contributing to these distinctions. For inhibiting glycolysis and reducing glucose consumption, OSI-027 was likely to be more potent than rapamycin. For amino acids metabolism, although OSI-027 has a broad effect as rapamycin, their effects in degrees were not exactly the same. These findings address the knowledge gap regarding mTORC1/2 dual inhibitors and lay a foundation for their further development and research.

Comparison of PaO2/FiO2 (PF ratio) to SpO2/FiO2 (SF ratio) and OI to OSI for Predicting Short Term Outcomes in Children with Acute Hypoxemic Respiratory Distress: A Prospective Observational Study.

OBJECTIVES: To compare PaO2/FiO2 (PF ratio) to SpO2/FiO2 (SF ratio) and oxygenation index (OI) to oxygenation saturation index (OSI) for predicting short term outcomes [mortality, progression to ventilation and ventilator free days (VFD)] and compare trends of S/F and OSI in predicting early mortality in children with acute hypoxemic respiratory distress. METHODS: This prospective observational study included 200 consecutive children with acute hypoxemic respiratory distress. Serial PF and SF ratios calculated at 0, 6, 24 and 48 h were compared and their trends were utilized for prediction of 28 d mortality. Same was done in ventilated patients using OI and OSI. RESULTS: SF ratio at admission had a 72% sensitivity and 60% specificity while PF had a sensitivity of 78% and a specificity of 75% for prediction of mortality. The area under the curve (AUC) for SF ratio was 0.82 (CI: 0.688-0.915). Serial SF ratios accurately predicted mortality. OI had sensitivity of 92% and specificity of 95% in predicting 24 and 48 h mortality. OSI had 95% sensitivity and 92% specificity in predicting mortality with AUC 1.000 (CI- 1.00-1.00) at 24 and 48 h post ventilation. Serially increasing OI and OSI trends had an inverse correlation with VFDs (p <0.01). CONCLUSIONS: SF is a reliable surrogate for PF and a useful predictor of progression to ventilation and survival at discharge while OSI is a useful marker of worsening hypoxia and mortality in ventilated patients.

Endovascular Treatment of Intracranial Aneurysm: The Importance of the Rheological Model in Blood Flow Simulations.

Hemodynamics in intracranial aneurysm strongly depends on the non-Newtonian blood behavior due to the large number of suspended cells and the ability of red blood cells to deform and aggregate. However, most numerical investigations on intracranial hemodynamics adopt the Newtonian hypothesis to model blood flow and predict aneurysm occlusion. The aim of this study was to analyze the effect of the blood rheological model on the hemodynamics of intracranial aneurysms in the presence or absence of endovascular treatment. A numerical investigation was performed under pulsatile flow conditions in a patient-specific aneurysm with and without the insertion of an appropriately reconstructed flow diverter stent (FDS). The numerical simulations were performed using Newtonian and non-Newtonian assumptions for blood rheology. In all cases, FDS placement reduced the intra-aneurysmal velocity and increased the relative residence time (RRT) on the aneurysmal wall, indicating progressive thrombus formation and aneurysm occlusion. However, the Newtonian model largely overestimated RRT values and consequent aneurysm healing with respect to the non-Newtonian models. Due to the non-Newtonian blood properties and the large discrepancy between Newtonian and non-Newtonian simulations, the Newtonian hypothesis should not be used in the study of the hemodynamics of intracranial aneurysm, especially in the presence of endovascular treatment.

The impact of dry eye disease on retinal image quality in children.

BACKGROUND AND OBJECTIVES: Dry eye disease (DED) is increasingly prevalent, resultinginhigher morbidityamong children. This study evaluates the impact of DED severity on visual quality using double-pass technology, focusing on dynamic observation of the ocular light scatter in pediatric DED cases. METHOD: In this non-interventional, cross-sectional study, a mild DED group (37 cases, 37 eyes), a moderate DED group (40 cases, 40 eyes), and a control group of healthy children (35 cases, 35 eyes) were examined. Measurements included the Schirmer I test, tear film break-up time (BUT), and vision-related quality of life assessments using the Modified Ocular Surface Disease Index (OSDI) questionnaires. Participants underwent visual quality analysis using double-pass technology, which measured the modulation transfer function cut-off frequency value, Strehl ratio, objective scatter index (OSI), and OQAS-II value (OQAS-II value 100%, OQAS-II value 20%, and OQAS-II value 9%) under natural conditions. Additionally, dynamic changes in OSI post-blinking, Tear film mean-OSI , and the corresponding standard deviation OSI were recorded. RESULTS: Statistically significant differences were observed among the groups in modulation transfer function cutoff, Strehl ratio, OSI, OQAS-II value 100 %, OQAs-II value 20 %, OQAs-II value 9 %, tear film mean OSI, and standard deviation OSI (P < 0.05). As DED severity increased, tear film mean OSI significantly rose, while modulation transfer function cutoff, strehl ratio, OQAS-II value 100 %, OQAS-II value 20 %, OQAS-II value 9 % notably declined. All optical quality parameters were correlated with BUT, with no association observed with age, sex, or Schirmer I test. CONCLUSION: Dual-channel technology objectively assesses visual quality in pediatric DED, demonstrating that tear film scattering significantly affects retinal imaging and visual quality in children with DED.

Validation of the Onychomycosis Severity Index in a Brazilian population.

Onychomycosis is the most frequent nail disorder, but unfortunately, curative treatment is still a challenge, and commonly the infection recurs. A widely disseminated system to accurately assess and classify the severity of this disease, such as the MASI score for melasma or PASI for psoriasis, is lacking in the literature. In 2011, Carney et al. established and successfully validated the Onychomycosis Severity Index (OSI), proving it to be a simple and reproducible tool. To validate the Onychomycosis Severity Index in a Brazilian population. Four experienced dermatologists were taught how to use the OSI system, and then evaluated photographs of 24 nails. There was no consultation between the dermatologists, and the results were evaluated by an impartial third party. A statistically significant (p<0.001) high degree of agreement was observed between the evaluators and overall OSI score (mild, moderate or severe) as well as its subcategories (area of involvement, proximity to the nail matrix and presence of dermatophytoma or hyperkeratosis). OSI is a very useful tool to improve the clinical assessment of onychomycosis and support clinical trial inclusion criteria (p<0.001). It also provides important prognostic data and allows for a better follow-up of treatment efficacy.

Kinetic study of thermal degradation of flaxseed oil and moringa oil blends with physico-chemical, oxidative stability index (OSI) and shelf-life prediction.

The thermal degradation kinetics of flaxseed oil (FSO) and moringa oil (MO) blends with soyabean oil (SOY; 80%), rice bran oil (RBO; 80%), cotton seed oil (CSO; 80%) and sunflower oil (SFO; 80%) with Rancimat equipment. There was no significant (p ≤ 0.05) difference observed in the specific gravity (SG), density (D), and refractive index (RI) values of the MO and FSO blends, while the rancidity parameters showed the opposite variations. The FTIR spectra showed absorption bands at 966 cm-1, 1097 cm-1, 1160 cm-1, 1217 cm-1, 1377 cm-1, 1464 cm-1, 1743 cm-1, 2945 cm-1, 2852 cm-1 and 3008 cm-1. Oil blends' kinetic degradation (Ea, ΔH, ΔS, A) is represented by the semilogarithmic relationship between the oxidative stability index (OSI) and temperature. The activation energy (Ea) ranged from 77.1 ± 0.21 to 106.9 ± 0.03 kJ/mol and 73.2 ± 0.01 to 104.4 ± 0.02 kJ/mol for flaxseed oil (FSO) and moringa oil (MO) blends, respectively. The enthalpy (ΔH) and entropy (ΔS) ranged from 67.3 to 121.6 kJ/mol, and - 60.2 to - 8.4 J/mol, and 63.55 to 95.59 kJ/mol and - 20.66 to - 4.11 J/mol for FSO blends and MO blends, respectively.

Disclosing Potential Therapeutic Targets Associated With Osimertinib Resistance in the Non-small Cell Lung Cancer Cell Line H1975.

BACKGROUND/AIM: Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is a highly effective and valuable treatment option for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations, such as T790M. However, acquired resistance ultimately limits its clinical application. In this study, we aimed to identify potential targets for overcoming osimertinib resistance. MATERIALS AND METHODS: The H1975/OSI cell line was induced in vitro through intermittent induction. Cell activity was measured using a cell counting kit-8 assay. Uni-omics and multi-omics analyses were conducted on the transcriptomic and proteomic (4D label-free) expression profiles, which involved differential expression analysis, GO functional annotation and KEGG pathway enrichment analysis, as well as correlation analysis of transcription factors and PPI network. RESULTS: H1975/OSI cells showed resistance towards osimertinib with IC50 values approximately 5.25-fold higher than H1975 cells. A total of 2519 genes were found to be differentially expressed genes (DEGs) and 1533 proteins were found to be differentially abundant proteins (DAPs). Furthermore, 147 genes that were differentially expressed at both the transcription and protein levels (TPGs) were identified as being differentially expressed in both the transcriptome and proteome. It was revealed that many pathways related to the structure and function of ribosomes, as well as metabolites, were altered. The highest connectivity genes of 147 TPGs included NOP56, DDX21, PDCD11, CCNB1, and TOP2A. The hub genes of the transcriptional regulatory network included DDX21, KPNA2, DDX5, BRCA1, LMNB1, and HIF1A. CONCLUSION: Collectively, our high-throughput analysis uncovered functional properties that interacted with gene signatures of H1975/OSI cells, and highlighted certain pathways and eleven hub genes that may be the potential targets for improving clinical osimertinib resistance.

Simultaneous quantification of atorvastatin, erlotinib and OSI-420 in rat serum and liver microsomes using a novel liquid chromatography-mass spectrometry method.

Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor used in the treatment of cancer. Atorvastatin is a statin commonly applied to treat hypercholesterolemia. In humans, both compounds are metabolized by CYP3A4 and are transported by OATP2B1, ABCB1 and ABCG2. We aimed to generate and validate a bioanalytical method for simultaneous determination of atorvastatin, erlotinib and its major metabolite OSI-420 applicable to biological samples. Quantification of erlotinib, OSI-420, and atorvastatin was achieved with an Agilent high-performance liquid chromatography system 1100/1200 coupled to a triple quadrupole G6410B. The method involved separation over the column Kinetex C8 (100 × 3 mm, 2.6 µm) using 2 mM ammonium acetate (pH 4.0) and acetonitrile as eluent. The method was assessed for selectivity, accuracy, recovery, matrix effect, and stability over a range from 1 to 4,000 ng/mL according to the respective guidelines. We applied the bioanalytical method to quantify the formation of OSI-420 in liver microsomes isolated from male and female Wistar rats. The optimized experiment revealed slower formation in microsomes of female compared to male rats, in which we observed lower amounts of CYP3A1 by Western blot analysis. Moreover, the presence of atorvastatin inhibited the CYP3A-mediated metabolism of erlotinib. Serum obtained from a drug-drug interaction study performed in male rats was also analyzed using the validated method. Non-compartmental pharmacokinetic analysis revealed a lower clearance of erlotinib when atorvastatin was co-administered. However, for atorvastatin we observed a lower systemic exposure in presence of erlotinib. In summary, we report a method to detect OSI-420, erlotinib and atorvastatin applicable to samples from ex vivo and in vivo studies.

Comparison of setup accuracy of optical surface image versus orthogonal x-ray images for VMAT of the left breast using deep-inspiration breath-hold.

To compare the setup accuracy of optical surface image (OSI) versus orthogonal x-ray images (2DkV) using cone beam computed tomography (CBCT) as ground truth for radiotherapy of left breast cancer in deep-inspiration breath-hold (DIBH). Ten left breast DIBH patients treated with volumetric modulated arc therapy (VMAT) were studied retrospectively. OSI, 2DkV, and CBCT were acquired weekly at treatment setup. OSI, 2DkV, and CBCT were registered to planning CT or planning DRR based on a breast surface region of interest (ROI), bony anatomy (chestwall and sternum), and both bony anatomy and breast surface, respectively. These registrations provided couch shifts for each imaging system. The setup errors, or the difference in couch shifts between OSI and CBCT were compared to those between 2DkV and CBCT. A second OSI was acquired during last beam delivery to evaluate intrafraction motion. The median absolute setup errors were (0.21, 0.27, 0.23 cm, 0.6°, 1.3°, 1.0°) for OSI, and (0.26, 0.24, 0.18 cm, 0.9°, 1.0°, 0.6°) for 2DkV in vertical, longitudinal and lateral translations, and in rotation, roll and pitch, respectively. None of the setup errors was significantly different between OSI and 2DkV. For both systems, the systematic and random setup errors were ≤0.6 cm and ≤1.5° in all directions. Nevertheless, larger setup errors were observed in some sessions in both systems. There was no correlation between OSI and CBCT whereas there was modest correlation between 2DkV and CBCT. The intrafraction motion in DIBH detected by OSI was small with median absolute translations <0.2 cm, and rotations ≤0.4°. Though OSI showed comparable and small setup errors as 2DkV, it showed no correlation with CBCT. We concluded that to achieve accurate setup for both bony anatomy and breast surface, daily 2DkV can't be omitted following OSI for left breast patients treated with DIBH VMAT.

Pathophysiology of intracranial aneurysms in monozygotic twins: A rare case study from hemodynamic perspectives.

Hemodynamic mechanisms of the formation and growth of intracranial aneurysms (IA) in monozygotic twins (MTs) are still under-reported. To partially fill such knowledge gap, this study employed an experimentally validated numerical model to compare hemodynamics in 3 anatomical and 5 ablation study neurovascular models from a rare pair of MTs in terms of 7 critical hemodynamic parameters. Numerical results showed significant differences in hemodynamics between the MTs, although they share the same genes, indicating that genetic mutation and environmental factors might affect neurovascular morphologies and cause hemodynamic changes. After virtual removals of IAs in the ablation study, the locations where the aneurysmal sac/bleb generated in bifurcated anterior cerebral arteries (ACAs) register a locally high instantaneous wall shear stress (IWSS) of 52.9 and 70.1 Pa at the systolic peak in twin A and twin B, respectively. Same scenario can be observed in the distribution of instantaneous wall shear stress gradient (IWSSG), with 571.1 Pa/mm for twin A and 301.3 Pa/mm for twin B due to aggressive blood impingements, leading to IA generation. The fenestrated complex approaching ACA bifurcations in twin A may assist IA growth and rupture, via. Causing abnormal IWSS of 116.3 Pa, IWSSG of 832.5 Pa/mm, and oscillatory shear index (OSI) of 0.49. The bleb in twin B has high risks of progression and possible rupture as the IA suffers relatively low IWSS and high OSI. Additionally, IA generation can change blood flow rates in each connected artery, then affecting blood supplies to associated tissues and organs.

Validación del inventario de socialización organizacional en México

Objetivo: Generar una versión válida y confiable en población mexicana del inventario de socialización organizacional de taormina (OSI), validada por Bravo-Sánz (2001). Método: A partir de los puntajes obtenidos en el OSI se realizó en AMOS 23,0 un análisis factorial confirmatorio con máxima verosimilitud con los 20 ítems y factores originales (entrenamiento, apoyo de los compañeros, comprensión y perspectivas de futuro). La muestra se compuso por 489 trabajadores con una media de edad de 36 años. Resultados: Los resultados del AFC mostraron que, aunque el modelo se ajustaba de forma adecuada con los ítems originales, la validez y confiabilidad de constructo solo se obtuvieron al disminuir la cantidad de factores desechando el de comprensión. Se obtuvo un ajuste de modelo CMIN/DF= 2,02, CFI=0,97, AGFI= 0,94, RMSEA 0,046, SRMR 0,038. Conclusiones: Se logró un modelo válido (AVE >0,50) en todos sus factores y confiable (CR>0,74) en todos sus elementos con un total de 11 ítems con sus baremos para población. Esta versión del inventario de socialización puede ser empleada en población mexicana, lo cual incidirá en investigaciones organizacionales, administrativas, psicológicas con diversas temáticas para determinar la adaptación a la cultura organizacional.

Objective: The objective of this research was to generate a valid and reliable version of the taormina organizational socialization inventory (OSI) for the Mexican population, validated by Bravo-Sánz (2001). Method: Based on the scores obtained in the OSI, a confirmatory factor analysis was carried out in AMOS 23,0 with maximum likelihood with the 20 original items and factors (training, peer support, understanding and future perspectives). The sample was made up of 489 workers with a mean age of 36 years. Results: The results of the CFA showed that, although the model adjusted adequately with the original items, the validity and reliability of the construct were only obtained by reducing the number of factors, discarding the comprehension factor. A model fit CMIN/DF= 2,02, CFI=0,97, AGFI= 0,94, RMSEA 0,046, SRMR .038 was obtained. Conclusions: A valid model (AVE >0,50) was achieved in all its factors and a reliable one (CR>0,74) in all its elements with a total of 11 items with their scales for the population. This version of the socialization inventory can be used in the Mexican population, which will affect organizational, administrative, psychological research with various themes to determine adaptation to organizational culture.

Assisted reproductive technology and interactions between serum basal FSH/LH and ovarian sensitivity index.

Objectives: This study aimed to investigate whether the FSH (follicle-stimulating hormone)/LH (Luteinizing hormone) ratio correlates with ovarian response in a cross-sectional retrospective study of a population with normal levels of anti-Müllerian hormone (AMH). Methods: This was a retrospective cross-sectional study with data obtained from medical records from March 2019 to December 2019 at the reproductive center in the Affiliated Hospital of Southwest Medical University. The Spearmans correlation test evaluated correlations between Ovarian sensitivity index (OSI) and other parameters. The relationship between basal FSH/LH and ovarian response was analyzed using smoothed curve fitting to find the threshold or saturation point for the population with mean AMH level (1.1

Risk Factors to Predict Post-Operative Organ/Space Infection After Appendectomy in the Pediatric Population: A Retrospective Case Control Analysis.

Background: Post-operative organ/space infection (OSI) is associated with prolonged hospital stay or re-admission. Here, we explore the predictors for OSI in pediatric patients after appendectomy. Patients and Methods: Among post-appendectomy pateints, the OSI was reviewed. A multicenter case control study was conducted to explore the risk factors for OSI among pediatric patients with appendicitis after appendectomy between January 2009 and December 2019. The potential risk factors associated with OSI were explored using multivariable logistic regression methods. Results: In the current cohort, 723 patients fulfilled the OSI criteria. According to multivariable logistic regression analysis, the occurrence of OSI was associated with complicated appendicitis (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.03-3.686; p = 0.016), the lower the level of pre-operative lymphocyte-C-reactive protein (LCR; OR, 14.42; 95% CI, 1.57-73.26; p < 0.001), pan-peritonitis (OR, 4.36; 95% CI, 1.34-21.66; p = 0.006), systemic inflammatory response syndrome (SIRS; OR, 8.22; 95% CI, 1.84-49.63; p < 0.001), and abscess presentation (OR, 11.32; 95% CI, 2.03-61.86; p < 0.001). The receiver operating characteristic (ROC) curve evaluation further confirmed the relatively high accuracy of the above factors to predict OSI. Conclusions: The identified potential risk factors in the current research can be used for OSI identification in patients after appendectomy. Recognition of the risk factors may allow the choice of the treatment process more reasonably.

Organic anion-transporting polypeptide 2B1 knockout and humanized mice; insights into the handling of bilirubin and drugs.

Organic anion transporting polypeptide 2B1 (OATP2B1/SLCO2B1) facilitates uptake transport of structurally diverse endogenous and exogenous compounds. To investigate the roles of OATP2B1 in physiology and pharmacology, we established and characterized Oatp2b1 knockout (single Slco2b1-/- and combination Slco1a/1b/2b1-/-) and humanized hepatic and intestinal OATP2B1 transgenic mouse models. While viable and fertile, these strains exhibited a modestly increased body weight. In males, unconjugated bilirubin levels were markedly reduced in Slco2b1-/- compared to wild-type mice, whereas bilirubin monoglucuronide levels were modestly increased in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice. Single Slco2b1-/- mice showed no significant changes in oral pharmacokinetics of several tested drugs. However, markedly higher or lower plasma exposure of pravastatin and the erlotinib metabolite OSI-420, respectively, were found in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice, while oral rosuvastatin and fluvastatin behaved similarly between the strains. In males, humanized OATP2B1 strains showed lower conjugated and unconjugated bilirubin levels than control Slco1a/1b/2b1-deficient mice. Moreover, hepatic expression of human OATP2B1 partially or completely rescued the impaired hepatic uptake of OSI-420, rosuvastatin, pravastatin, and fluvastatin in Slco1a/1b/2b1-/- mice, establishing an important role in hepatic uptake. Expression of human OATP2B1 in the intestine was basolateral and markedly reduced the oral availability of rosuvastatin and pravastatin, but not of OSI-420 and fluvastatin. Neither lack of Oatp2b1, nor overexpression of human OATP2B1 had any effect on fexofenadine oral pharmacokinetics. While these mouse models still have limitations for human translation, with additional work we expect they will provide powerful tools to further understand the physiological and pharmacological roles of OATP2B1.

Association between HOMA-IR and ovarian sensitivity index in women with PCOS undergoing ART: A retrospective cohort study.

Introduction: Insulin resistance (IR) may play a central role in the pathophysiology of polycystic ovary syndrome (PCOS). Controlled ovarian stimulation (COS) in PCOS women in the setting of assisted reproductive technology (ART) is always a challenge for clinicians. However, it remains unclear whether IR in women with PCOS correlates with reduced ovarian sensitivity to exogenous gonadotropin (Gn). This study aimed to explore the association between homeostasis model assessment of insulin resistance (HOMA-IR) and ovarian sensitivity index (OSI). Methods: In this retrospective cohort study, we explored the association between Ln HOMA-IR and Ln OSI based on smoothing splines generated by generalized additive model (GAM). Then the correlation between HOMA-IR and OSI was further tested with a multivariable linear regression model and subgroup analysis. Results: 1508 women with PCOS aged 20-39 years undergoing their first oocyte retrieval cycle were included consecutively between 2018 until 2022. We observed a negative association between Ln HOMA-IR and Ln OSI by using smoothing splines. In multivariable linear regression analysis, the inverse association between Ln HOMA-IR and Ln OSI was still found in PCOS women after adjustment for potential confounders (ß = -0.18, 95% CI -0.25, -0.11). Compared with patients with the lowest tertile of HOMA-IR, those who had the highest tertile of HOMA-IR had lower OSI values (ß = -0.25, 95% CI -0.36, -0.15). Discussion: Our study provided evidence for the inverse correlation between IR and the ovarian sensitivity during COS in PCOS women. Herein, we proposed new insights for individualized manipulation in PCOS patients with IR undergoing ART.

Comparison of Oxidative Stress Levels in Healthy Children and Children with Allergic Rhinitis.

Background/aim: Allergic rhinitis (AR) is characterized by chronic inflammation of the nasal mucosa. Under the influence of exogenous factors - allergens, reactive oxygen species (ROS) are released during cellular metabolism. They induce a series of pathological changes in the mucosa. Oxidative stress is а result of an imbalance between the production of ROS and the ability to neutralize them. The aim of this study is to compare the levels of oxidative stress between healthy children and children with allergic rhinitis. Material and methods: A total number of 60 children were included (30 healthy children and 30 children with AR). The oxidative stress index was determined by using the FRAS 5 (Free Radical Analytical System) Bravo system. Demographic characteristics, medical history, children's living conditions and eating habits were obtained from the questionnaire. Anthropometric measurements and the absolute number of eosinophils in the peripheral smear were performed on each child. Results: This study showed high oxidative stress index and a significantly higher value of the absolute number of eosinophils in the peripheral smear in children with AR in comparison to healthy children (p<0.05). The group of children with AR had more atopic characteristics and was more exposed to passive smoking than healthy children. Conclusion: Compared to healthy children, children with AR have a high index of oxidative stress, despite of the very high mean value of the concentration of water-soluble antioxidants in serum (PAT test) in the group of children with AR.

How does hemodynamics affect rupture tissue mechanics in abdominal aortic aneurysm: Focus on wall shear stress derived parameters, time-averaged wall shear stress, oscillatory shear index, endothelial cell activation potential, and relative residence time.

An abdominal aortic aneurysm (AAA) is a critical health condition with a risk of rupture, where the diameter of the aorta enlarges more than 50% of its normal diameter. The incidence rate of AAA has increased worldwide. Currently, about three out of every 100,000 people have aortic diseases. The diameter and geometry of AAAs influence the hemodynamic forces exerted on the arterial wall. Therefore, a reliable assessment of hemodynamics is crucial for predicting the rupture risk. Wall shear stress (WSS) is an important metric to define the level of the frictional force on the AAA wall. Excessive levels of WSS deteriorate the remodeling mechanism of the arteries and lead to abnormal conditions. At this point, WSS-related hemodynamic parameters, such as time-averaged WSS (TAWSS), oscillatory shear index (OSI), endothelial cell activation potential (ECAP), and relative residence time (RRT) provide important information to evaluate the shear environment on the AAA wall in detail. Calculation of these parameters is not straightforward and requires a physical understanding of what they represent. In addition, computational fluid dynamics (CFD) solvers do not readily calculate these parameters when hemodynamics is simulated. This review aims to explain the WSS-derived parameters focusing on how these represent different characteristics of disturbed hemodynamics. A representative case is presented for spatial and temporal formulation that would be useful for interested researchers for practical calculations. Finally, recent hemodynamics investigations relating WSS-related parameters with AAA rupture risk assessment are presented. This review will be useful to understand the physical representation of WSS-related parameters in cardiovascular flows and how they can be calculated practically for AAA investigations.