Nested Biofabrication: Matryoshka-Inspired Intra-Embedded Bioprinting.

Engineering functional tissues and organs remains a fundamental pursuit in bio-fabrication. However, the accurate constitution of complex shapes and internal anatomical features of specific organs, including their intricate blood vessels and nerves, remains a significant challenge. Inspired by the Matryoshka doll, here a new method called "Intra-Embedded Bioprinting (IEB)" is introduced building upon existing embedded bioprinting methods. a xanthan gum-based material is used which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. IEB's capabilities in organ modeling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite is demonstrated. Further, a head phantom and a Matryoshka doll are 3D printed, exemplifying IEB's capability to manufacture intricate, nested structures. Toward the use case of IEB and employing an innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity is developed. Validation using a clinically-available chemotherapeutic drug illustrated its efficacy in reducing the tumor volume via perfusion over time. This method opens a new way of bioprinting enabling the creation of complex-shaped organs with internal anatomical features.

Nested biofabrication: Matryoshka-inspired Intra-embedded Bioprinting.

Engineering functional tissues and organs remains a fundamental pursuit in biofabrication. However, the accurate constitution of complex shapes and internal anatomical features of specific organs, including their intricate blood vessels and nerves, remains a significant challenge. Inspired by the Matryoshka doll, we here introduce a new method called 'Intra-Embedded Bioprinting (IEB),' building upon existing embedded bioprinting methods. We used a xanthan gum-based material, which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. We demonstrated IEB's capabilities in organ modelling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite. Further, a head phantom and a Matryoshka doll were 3D printed, exemplifying IEB's capability to manufacture intricate, nested structures. Towards the use case of IEB and employing innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, we developed a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity. Validation using a clinically-available chemotherapeutic drug illustrated its efficacy in reducing the tumor volume via perfusion over time. This method opens a new way of bioprinting enabling the creation of complex-shaped organs with internal anatomical features.

Galanin-like peptide and its correlation with androgen levels in patients with polycystic ovary syndrome.

INTRODUCTION: We aimed to investigate serum galanin-like peptide (GALP) levels and their correlation with hormonal and metabolic parameters in patients with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study included 48 women (age range, 18-44 years) with a diagnosis of PCOS, and a control group that included 40 healthy females (age range, 18-46 years). Waist circumference, body mass index (BMI), and Ferriman-Gallwey score were evaluated and plasma glucose, lipid profile, oestradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulphate (DHEA-S), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D (25(OH)D), fibrinogen, d-dimer, C-reactive protein (CRP), and GALP levels were measured in all study subjects. RESULTS: Waist circumference (p = 0.044) and Ferriman-Gallwey score (p = 0.002) were significantly higher in patients with PCOS compared to the control group. Among the metabolic and hormonal parameters studied, only total testosterone was significantly higher in patients with PCOS (p = 0.002). Also, the serum 25(OH)D level was significantly lower in the PCOS group (p = 0.001). CRP, fibrinogen, and D-dimer levels were all similar between the 2 groups. Serum GALP level was significantly higher in PCOS patients (p = 0.001). GALP was negatively correlated with 25(OH)D (r = -0.401, p = 0.002) and positively correlated with total testosterone values (r = 0.265, p = 0.024). Multiple regression analysis revealed that both total testosterone and 25(OH)D significantly contributed to GALP levels. CONCLUSIONS: Our study is the first in the literature to evaluate serum GALP levels in patients with PCOS. Increased GALP levels in PCOS and its association with total testosterone levels might show that GALP can act as an intermediary in increased GnRH-mediated LH release, which is one of the underlying pathogenetic mechanism of PCOS.

Serum neudesin levels in patients with polycystic ovary syndrome.

OBJECTIVES: We aimed to investigate serum neudesin levels that has neural, metabolic functions in patients with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study included 180 women (age range, 18-44 years) with a diagnosis of PCOS and a control group that included 100 healthy females (age range, 18-46 years). Body mass index (BMI), waist circumference, Ferriman-Gallwey score, was evaluated and plasma glucose, lipid profile, estradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulfate (DHEA-S), FSH, LH, free T3, free T4, thyroid stymulating hormone (TSH), anti-thyroperoxidase (anti-TPO) antibody and neudesin levels were evaluated in all participants. RESULTS: BMI and waist circumference were similar between two groups. Ferriman-Gallwey score was significantly higher in the patient group. Fasting blood glucose, HbA1C, lipid parameters except triglyceride levels, free T3, free T4, TSH, anti-TPO were similar between the two groups. Triglyceride, insulin and HOMA values were significantly higher in PCOS patients. While follicle-stimulating hormone (FSH), estradiol, progesterone, prolactin and DHEAS levels were similar, LH was significantly higher in patients with PCOS. Serum neudesin level was significantly lower in PCOS patients with respect to controls (p = 0.015). Neudesin was positively correlated with insulin (r = 0.224, p = 0.037), and progesterone (r = 0.716, p = 0.001). Multiple regression analysis revealed that neudesin correlated with only progesterone (beta = 0.308, p = 0.001). CONCLUSIONS: Due to the association of decreased levels of neudesin with PCOS and correlation of neudesin with progesterone, neudesin may be related with one of patophysiologic pathways of PCOS. Still, it is not certain that decreased neudesin is involved in the pathogenesis of PCOS or is the result of the disorder.

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH. OBJECTIVE: It was aimed to investigate the association between the mental status of patients with HoFH and healthy lifestyle behaviors. METHODS: This subgroup analysis of the A-HIT1 population included the data of patients aged ≥18 years with a clinical diagnosis of HoFH undergoing therapeutic LDL apheresis. Besides the demographic and clinical characteristics of patients, healthy lifestyle behaviors were assessed, and psychiatric symptoms were screened by Symptom Check List (SCL-90-R). RESULTS: The highest percentage for pathology was observed in dimensions of obsessive-compulsive, somatization, interpersonal sensitivity, and depression in SCL-90-R. Patients with any cardiovascular condition have more psychiatric symptoms in different fields of SCL-90-R. The outcomes of the correlative analysis indicated that lower the age of the first coronary event better the psychiatric status, probably denoting a better adaptation to disease and its treatment. Among 68 patients, 36 patients were not exercising regularly. Patients with regular physical activity had significantly lower scores in most dimensions of SCL-90-R and there was no association between regular physical activity and other investigated variables. The strongest predictor of regular exercising was global severity index of SCL-90-R. CONCLUSION: In the HoFH population, there was a high prevalence of mental disturbances. Better psychiatric status was associated with regular exercising. Therefore, assessing the mental status of patients with HoFH and referring patients in need, to a psychiatrist, may improve the outcome of patients.

Does the ACR TI-RADS scoring allow us to safely avoid unnecessary thyroid biopsy? single center analysis in a large cohort.

INTRODUCTION: The American College of Radiology (ACR) has recently proposed a guideline that recommends clinicians to perform thyroid fine-needle aspiration biopsy (FNAB) on the basis of ultrasound features. In this study, we focused on nodules for which no biopsy is recommended by the ACR Thyroid Imaging, Reporting and Data System (TI-RADS) guideline. SUBJECTS AND METHODS: Two-thousand eight-hundred and forty-seven consecutive patients with thyroid nodules who underwent FNAB according to the 2009 American Thyroid Association (ATA) guideline were included. The nodules were re-classified according to the ACR TI-RADS guideline as benign (TR1), not suspicious (TR2), mildly suspicious (TR3), moderately suspicious (TR4) and highly suspicious (TR5). The TR3 category was stratified into two subcategories as regard to the nodule size (TR3; <25 mm and TR3; ≥25 mm). RESULTS: Two-hundred and thirty-three (8.2%) patients with non-diagnostic FNABs were excluded. When the TR2 and TR3; <25 mm categories were merged, FNAB was suggestive of thyroid cancer in 17 of 1382 patients (1.2%). FNAB revealed Bethesda IV-VI in 5 of 273 patients with the TR3; ≥25 mm category (1.8%), in 61 of 896 patients with the TR4 category (6.8%), and in 18 of 63 of patients with the TR5 category (28.6%). The ACR TI-RADS scoring was 98.8% (95% CI: 98 to 99.3) specific for identification of a benign nodule. CONCLUSION: Our data suggest that ACR TI-RADS scoring is an applicable and potentially cost-effective approach to determine thyroid nodules to be biopsied, although a small proportion of thyroid cancers would be missed.

The maximum standardized uptake value of metastatic site in 18 F-FDG PET/CT predicts molecular subtypes and survival in metastatic breast cancer: An Izmir Oncology Group study.

PURPOSE: The purpose of this study was to analyse the association between the 18F-2-deoxy-2-fluorodeoxyglucose maximum standardized uptake value (SUVmax) of metastatic sites and molecular subtypes and survival in metastatic breast cancer (MBC) patients. METHODS: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed in 176 MBC patients before any therapeutic intervention. The FDG uptakes of metastatic sites were evaluated using the SUVmax. Histopathological prognostic parameters, such as the tumor size, grade, lymph node involvement, lymphovascular invasion, estrogen (ER), progesterone receptors (PR), HER2 status and Ki67 were determined from the primary breast tumor tissue. The SUVmax of the metastatic sites was assessed in relation to the molecular subtypes and survival in univariate and multivariate analyses. Cox regression analysis was used to evaluate the associations between SUVmax measurements and overall survival (OS). RESULTS: The mean SUVmax of 176 tumors was 8.0. Among the subtypes 49 (28.8%) were luminal A, 51 (28.9%) luminal B, 35 (19.8%) HER2-overexpressing, and 41 (23.2%) triple- negative, and the corresponding means of SUVmax were 5.6, 7.4, 11.4, 11.0, respectively. A cut-off value of ≤8.4 yielded 80% sensitivity and 57.1% specificity with an area under the receiver operating characteristics curve (AUC) of 0.731 for predicting that a tumor was of the luminal A subtype. A cut-off value of SUVmax ≥10.05 yielded 62.9% sensitivity and 67.4% specificity with an AUC of 0.648 for predicting a HER2 overexpressing subtype. A cut-off value of SUVmax ≥9.25 yielded 61% sensitivity and 64.4% specificity with an AUC of 0.660 for predicting a triple-negative subtype. The SUVmax could not effectively differentiate patients with luminal B subtype. Cox regression analysis showed that in patients with MBC, a SUVmax ≤7.55 acted as an independent negative prognostic factor for OS (hazard ratio/HR = 1.552). CONCLUSION: The SUVmax of metastatic sites on pretreatment 18F-FDG PET/CT may be an independent prognostic factor for the diagnosis of molecular phenotypes and survival in MBC patients.