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1.
Laryngoscope Investig Otolaryngol ; 9(5): e70010, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39346784

ABSTRACT

Objective: To analyze medical device reports (MDR) submitted to the Food and Drug Administration's (FDA) Manufacturer and User Device Facility Experience (MAUDE) database to identify adverse events (AEs) in patients implanted with novel active bone conduction hearing implants (BCIs). Methods: We conducted a search of the FDA MAUDE database on the newest generation of BCIs. Data were collected concerning device malfunctions, patient injuries, factors triggering these incidents, and the subsequent actions taken. Results: In total, 93 (16.7%) device malfunctions and 465 (83.3%) patient injuries with 358 subsequent interventions were identified, resulting in 558 AEs. Although the absolute AE number per device cannot be identified, the following trends were detected: Among the 494 AEs associated with OSI200, 55 (11.1%) reported device malfunctions and 454 (88.9%) cited patient injuries. Out of the 64 AEs linked to BCI602, 28 (59.4%) were associated with malfunctions, whereas 26 (40.6%) involved patient injuries. The most frequently reported particular AEs for the OSI200 were infection (n = 171, 34.6%), extrusion of the device (n = 107, 21.7%), and pain (n = 51, 10.3%). Conversely, no device output (n = 20, 31.3%) and loss of osseointegration (n = 7, 10.9%) were the most reported AEs for the BCI602. Various AEs led to 214 explanations and 77 revision surgeries. Sixty-seven AEs reported conservative treatment. Conclusion: The current study provides an overview of the most commonly reported complications with new active BCIs. Although providing an overview, given the limitations of the FDA MAUDE database, our results have to be interpreted with caution. Level of Evidence: 4.

2.
Comput Biol Med ; 181: 109037, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39168015

ABSTRACT

Accurate imaging reports of the aortic valve indicate that the diameter of the aortic annulus changes regularly during a cardiac cycle. Most of these studies aim to demonstrate the proper method for estimating the aortic annulus diameter before performing TAVR surgery, revealing that the aortic annulus is dynamic and not constant throughout the cardiac cycle. This raises the question of how fixing the aortic annulus might affect valve function, which is a question that still needs to be addressed. Therefore, the present study seeks to address this question and elucidate the dynamic impact of the aortic annulus on aortic valve hemodynamics. Two computational models based on this hypothesis were created and solved, and then their results were compared. Both models are identical, except for the intrinsic dynamic nature of the aortic annulus. One model consists of the dynamic behavior, and the other simulates a fixed annulus, resembling the effect of a TAVR operation, SAVR, or any phenomenon that eliminates the dynamic nature of the annulus. Our research findings indicate that the dynamic nature of the annulus enhances blood flow (+2.7 %), increases mean velocity (+11.9) and kinetic energy density (+34 %), prolongs momentum retention during systole, stabilizes the flow jet at the end of systole, reduces the required pressure to keep the leaflets open (-40.9 % at 0.3s), and sustains ventricular pressure superiority (+9.4 %) over the aorta for a longer duration (+17.7 % of systole), a crucial factor in preventing backflow during aortic valve closure. Based on these results, more attention should be paid to the dynamic nature of the annulus.


Subject(s)
Aortic Valve , Hemodynamics , Models, Cardiovascular , Humans , Aortic Valve/physiology , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Hemodynamics/physiology , Computer Simulation
3.
Technol Cancer Res Treat ; 23: 15330338241271946, 2024.
Article in English | MEDLINE | ID: mdl-39109645

ABSTRACT

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.


Subject(s)
Cone-Beam Computed Tomography , Head and Neck Neoplasms , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Image-Guided , Humans , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Male , Radiotherapy, Image-Guided/methods , Female , Cone-Beam Computed Tomography/methods , Radiotherapy Planning, Computer-Assisted/methods , Middle Aged , Feasibility Studies , Aged , Neck , Adult , Reproducibility of Results , Imaging, Three-Dimensional/methods , Cervical Vertebrae/diagnostic imaging
4.
Curr Issues Mol Biol ; 46(8): 8903-8913, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39194743

ABSTRACT

This study was designed to investigate the effects of vitamin D and mannitol in an experimental rat ovarian torsion model. Thirty-two female Wistar albino rats were randomly classified as group 1: (sham), group 2: (detorsion), group 3: (detorsion + mannitol), group 4: (detorsion + vitamin D) and group 5: (detorsion + mannitol + vitamin D) (for each group n = 8). All groups were subjected to bilateral adnexal torsion for 2 h except for group 1. Bilateral adnexal detorsion was performed in all groups except for group 1. Groups 3 and 5 intraperitoneally received the injection of mannitol at a dose of 0.3 mg/kg 30 min before detorsion. Also, the group's 4 and 5 orally received vitamin D in a dose of 500 IU/kg/day for two weeks before torsion. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and proliferating cell nuclear antigen (PCNA) levels were analyzed. According to the histopathological analyses, ovarian tissue damage and follicle counting were evaluated. TOS, OSI and histopathologic score values of ovarian tissue were significantly lower in group 5 than groups 2, 3 and 4 (p < 0.05). The PCNA level was significantly higher in group 5 than in groups 2, 3 and 4 (p < 0.05). A strong negative correlation was found between OSI and PCNA in groups 2, 3, 4 and 5 (r = -0.92, p = 0.01; r = -0.98, p < 0.0001; r = -0.98, p < 0.0001 and r = -0.96, p = 0.0002, respectively). The numbers of primordial follicles in group 5 (p < 0.001) and primary follicles in group 4 (p < 0.001) were significantly higher when compared to group 2. Based on the results of this study, it could be suggested that combination treatment of mannitol with vitamin D is more effective in reversing tissue damage induced by ischemia-reperfusion (I/R) injury in the ovarian torsion model than administration of only an agent.

5.
J Cancer Educ ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180626

ABSTRACT

Oncology is a field of medicine projected to face provider shortages as cancer prevalence rises. Moreover, the diversity of oncologists remains subpar compared to that of the general population despite initiatives to increase the number of students from underrepresented backgrounds (UIM). Thus, first-year UIM medical students interested in oncology were invited to participate in a 4-week oncology summer internship (OSI) to gain clinical exposure and mentorship experiences. The OSI connected students with oncologists for mentorship, provided tours of oncologic facilities, and coordinated shadowing opportunities. The impact of the OSI was assessed via a mixed-methods approach. Pre- and post-survey data were collected from eight of the nine OSI students. Quantitative data demonstrated improvement of students' understanding of oncology as a discipline, for example its training pathways (p = .02), and awareness of patient experiences in oncology, for example socioeconomic challenges (p = .008). Students reported an increased ability to identify with those in oncology and identify mentors in the field (p = .03 and p = .05, respectively). Qualitative data demonstrated continued interest in oncology with increased commentary on the patient experience and social determinants of health. Post-survey, students provided more commentary on the need for diversity in the field and possible increased professional connections in medicine. The OSI improved students' understanding of oncology and oncology patient experiences with potentially increased identification of and connection with others in the field. Further work will focus on assessing the impact of future OSIs on professional identity formation.

6.
Arch Pharm (Weinheim) ; : e2400281, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39058899

ABSTRACT

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.

7.
Br J Clin Pharmacol ; 90(10): 2554-2561, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38889797

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Erlotinib Hydrochloride , Lung Neoplasms , Pregnancy Complications, Neoplastic , Quinazolines , Humans , Erlotinib Hydrochloride/pharmacokinetics , Erlotinib Hydrochloride/administration & dosage , Erlotinib Hydrochloride/adverse effects , Erlotinib Hydrochloride/therapeutic use , Pregnancy , Female , Adult , Lung Neoplasms/drug therapy , Pregnancy Complications, Neoplastic/drug therapy , Male , Carcinoma, Non-Small-Cell Lung/drug therapy , Child , Quinazolines/pharmacokinetics , Quinazolines/administration & dosage , Quinazolines/therapeutic use , Quinazolines/blood , Pregnancy Trimester, Third , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Infant, Newborn , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Pregnancy Trimester, Second , Child Development/drug effects , ErbB Receptors/genetics , Adenocarcinoma/drug therapy
8.
Indian J Pediatr ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847998

ABSTRACT

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.

9.
Bioengineering (Basel) ; 11(6)2024 May 21.
Article in English | MEDLINE | ID: mdl-38927758

ABSTRACT

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.

10.
Invest New Drugs ; 42(4): 418-427, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38916794

ABSTRACT

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.


Subject(s)
Colonic Neoplasms , Imidazoles , Mechanistic Target of Rapamycin Complex 1 , Mechanistic Target of Rapamycin Complex 2 , Metabolomics , Sirolimus , Triazines , Humans , Cell Proliferation/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , HCT116 Cells , Imidazoles/pharmacology , Imidazoles/therapeutic use , Liquid Chromatography-Mass Spectrometry , Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 2/antagonists & inhibitors , Mechanistic Target of Rapamycin Complex 2/metabolism , Metabolomics/methods , Sirolimus/pharmacology , Sirolimus/therapeutic use , Tandem Mass Spectrometry , Triazines/pharmacology , Triazines/therapeutic use
11.
Cont Lens Anterior Eye ; 47(3): 102168, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38641524

ABSTRACT

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.


Subject(s)
Dry Eye Syndromes , Quality of Life , Humans , Dry Eye Syndromes/physiopathology , Dry Eye Syndromes/diagnosis , Female , Cross-Sectional Studies , Male , Child , Retina/diagnostic imaging , Tears/physiology , Tears/chemistry , Tears/metabolism , Adolescent , Surveys and Questionnaires , Visual Acuity/physiology
12.
Eur J Dermatol ; 34(1): 51-54, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38557458

ABSTRACT

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.


Subject(s)
Nail Diseases , Onychomycosis , Humans , Antifungal Agents/therapeutic use , Brazil , Nail Diseases/drug therapy , Nails , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Treatment Outcome , Clinical Trials as Topic
13.
J Food Sci Technol ; 61(4): 675-687, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38410269

ABSTRACT

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.

14.
Anticancer Res ; 43(12): 5459-5474, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38030186

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , ErbB Receptors/genetics , Proteomics , Drug Resistance, Neoplasm/genetics , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Cell Line, Tumor , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/pharmacology , Nuclear Proteins/genetics , Minor Histocompatibility Antigens
15.
J Pharm Biomed Anal ; 236: 115716, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37722165

ABSTRACT

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.


Subject(s)
Microsomes, Liver , Tandem Mass Spectrometry , Humans , Male , Female , Rats , Animals , Erlotinib Hydrochloride/pharmacology , Atorvastatin , Rats, Wistar , Chromatography, Liquid/methods , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods
16.
J Appl Clin Med Phys ; 24(12): e14117, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37535396

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Female , Retrospective Studies , X-Rays , Cone-Beam Computed Tomography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Breath Holding
17.
Comput Biol Med ; 163: 107198, 2023 09.
Article in English | MEDLINE | ID: mdl-37354818

ABSTRACT

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.


Subject(s)
Intracranial Aneurysm , Humans , Arteries , Hemodynamics , Hydrodynamics , Intracranial Aneurysm/diagnostic imaging , Stress, Mechanical , Twins, Monozygotic
18.
rev. psicogente ; 26(49)jun. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1536977

ABSTRACT

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.

19.
Front Endocrinol (Lausanne) ; 14: 1086924, 2023.
Article in English | MEDLINE | ID: mdl-37206442

ABSTRACT

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

Subject(s)
Follicle Stimulating Hormone , Ovarian Follicle , Female , Animals , Retrospective Studies , Cross-Sectional Studies , Reproductive Techniques, Assisted , Follicle Stimulating Hormone, Human
20.
Surg Infect (Larchmt) ; 24(5): 462-467, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37103971

ABSTRACT

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.


Subject(s)
Appendicitis , Laparoscopy , Humans , Child , Appendectomy/adverse effects , Appendectomy/methods , Appendicitis/surgery , Appendicitis/complications , Retrospective Studies , Case-Control Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Factors
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