A Versatile Photocrosslinkable Silicone Composite for 3D Printing Applications.

Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. Its properties can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped constructs were achieved with integrated electronics, which greatly extends its potential applications towards soft robotics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for tissue engineering. Altogether, this material offers a myriad of potential applications (i.e., soft robotics, microfluidics, bioprinting) by providing a facile approach to develop complicated 3D structures and interconnected channels.

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.

A Versatile Photocrosslinkable Silicone Composite for 3D Printing Applications.

Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, 3D printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. The proposed silicone composite can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped micro- and macro-constructs were achieved with integrated electronics, which greatly extends its potential applications towards developing complex flexible parts for soft robotics and prosthetics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for medical and tissue engineering use. Altogether, this material offers a myriad of potential applications in material and medical fields by providing a facile approach to develop complicated 3D structures and interconnected channels that can further advance microfluidics and soft-robotics research.

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 influence of different maternal pushing positions on birth outcomes at the second stage of labor in nulliparous women.

OBJECTIVES: To assess the effects on neonatal and maternal outcomes of different pushing positions during the second stage of labor in nulliparous women. METHODS: This prospective study included 102 healthy, pregnant, nulliparous women who were randomly allocated to either of two positions: a squatting using bars (n = 51), or a supine position modified to 45 degree of semi-fowler (n = 51) during the second stage of labor. Duration of the second stage of labor, maternal pain, postpartum blood loss, abnormal fetal heart rate patterns that required intervention, and newborn outcomes were compared between the two groups. RESULTS: The trial showed that women who adopted the squatting position using bars experienced a significant reduction in the duration of the second stage of labor; they were less likely to be induced, and their Visual Analog Scale score was lower than those who were allocated the supine position modified to 45 degree of semi-fowler during second stage of labor (p < 0.05). There were no significant differences with regard to postpartum blood loss, neonatal birth weight, Apgar score at one and five minutes, or admission to the Neonatal Intensive Care Unit. CONCLUSIONS: In healthy nulliparous women, adopting a squatting position using bars was associated with a shorter second stage of labor, lower Visual Analog Scale score, more satisfaction, and a reduction in oxytocin requirements compared with adopting the supine position. For Turkish women, the squatting position is easy to adopt as it is more appropriate in terms of Turkish social habits and traditions.

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.

Elucidation of multiple-point interactions of pyranine fluoroprobe during the gelation.

We have studied the multiple-point interactions of the pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt; 3sPyOH) fluoroprobe with polymer chains during the free-radical polymerization of acrylamide (AAm) by using the steady state fluorescence measurements. We observed a considerable blue shift from 515nm to 406nm in the emission spectra due to a C-O ether bond formation between the hydroxylic oxygen of 3sPyOH and a terminal C-atom of the growing AAm chain. Furthermore ionic (electrostatic) interactions occur between the three ionized sulfonic acid groups (SO(3)(-)) of 3sPyOH and protonated amide groups on the AAm chains. These electrostatic interactions also cause a gradual red shift in the maximum of the short-wavelength-peak, from 406nm to 430nm. The results showed that the pyranine can be used as a probe for real time monitoring of the polymerization process of AAm system since it monitors both the progression of the polymerization via chemical binding over OH group and the change in the local density of the polymerizing sample by means of the gradual red shift in the short-wavelength-peak via ionic interactions over SO(3)(-) groups.

Testing percolation theory in the laboratory: measuring the critical exponents and fractal dimension during gelation.

Real-time fluorescence measurements have been developed for measuring the fractal dimension d_{f} and critical exponents gamma and beta simultaneously during the sol-gel transition of acrylamide bisacrylamide cross-linking copolymerization. We observed that d_{f} passes through a minimum value of approximately 2.5 at a critical time t_{c} and crossover to 3 above it. The exponents gamma and beta , measured at t_{c} , were found to be around 1.8 and 0.45, respectively. All parameters d_{f} , beta , and gamma measured at the critical point t_{c} agree with three-dimensional percolation results.

Transition between collapsed state phases and the critical swelling of a hydrogen bonding gel: poly(methacrylic acid-co-dimethyl acrylamide).

Transition between collapsed state phases and discontinuous volume phase transition for a hydrogen bonding gel, poly(methacrylic acid-co-dimethyl acrylamide), were observed by using both the volume measurements and fluorescence intensity of the pyranine fluoroprobe (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt) bonded to the gel by means of electrostatic interactions. In the collapsed state, while there is no appreciable change in the volume of the gel, a considerable variation in the fluorescence intensity occurred around 30 degrees C signaling a second order phase transition between collapsed state phases, from relatively frozen to a fluctuating phase. Our analysis of the data around 30 degrees C indicates that the critical point of gel volume transition belongs to the so-called mean-field universality class, as predicted in Onuki [Phys. Rev. A 38, 2192 (1988)] and by Golubovic and Lubensky [Phys. Rev. Lett. 63, 1082 (1989)]. The relaxation time for the equilibrium swelling critically depends on the temperature and diverges near 60 degrees C, where both fluorescence intensity and the volume of the gel change drastically and indicate the discontinuous volume phase transition. The swelling kinetics of the critical gel during the discontinuous volume phase transition can be modeled best with the first term in the expansion of the Li-Tanaka equation for a long initial period of the swelling time.

In situ monitoring of the synthesis of a pyranine-substituted phthalonitrile derivative via the steady-state fluorescence technique.

A new approach based on fluorescence quenching of a chromophore, pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt, POH), was established for monitoring the synthesis of the pyranine-substituted phthalonitrile derivative POPht. 4-Nitrophthalonitrile binds to the POH through nitro elimination, by means of a nucleophilic aromatic substitution reaction in a basic medium, and forms phthalonitrile (Pht) bearing deprotonated POH units, Pht + POH --> POPht. This binding process results in a considerable blue shift (from 515 to 430 nm) in the fluorescence emission spectra of POH. Besides, the fluorescence intensities of unreacted pyranines and POPht molecules in the reacting mixture decrease as they are quenched by nitrite appearing as one of the byproducts. POH, therefore, acts as both an aromatic substituent for Pht and a fluorescence probe for monitoring the substitution reaction. Thus, the change in the fluorescence spectra introduces a novel method for in situ monitoring of the synthesis of the phthalonitrile derivative POPht. This new material may have a potential to synthesize the phthalocyanine having an enhanced fluorescence property and solubility in an aqua medium that would result in a desired candidate molecule in many applications of phthalocyanines.

Can the glass transition in bulk polymers be modeled by percolation picture?

Recent observations (Eur. Phys. J. E 9, 135 (2002)) showed that the vitrification process, which sets in during the linear bulk methyl methacrylate (MMA) polymerization carried out below glass transition temperatures, can be modelled by static percolation picture. To generalize this observation for different kind of bulk linear or crosslinked polymers not enough data are present in the literature. To cover partly this deficit we studied the glass transition of MMA and styrene (Sty) crosslinking copolymerization in varying ratios of MMA and Sty. Both the fluorescence intensity I and the lifetime tau of pyrene (Py) used as a nanosecond in situ fluoroprobe were monitored during the gelation time. Both I and tau increase dramatically as a result of the reduced mobility of the probes trapped in the "glassy" regions, appearing near the glass transition point. The average size of the glassy regions just below, and the strength of the infinite network formed upon the connection of the glassy regions above the glass transition point tg obey power law relations. The data around tg were interpreted on the basis of the percolation theory and we observed that the corresponding exponents gamma and beta give static percolation values independent of the polymer composition.

Direct test of the critical exponents at the sol-gel transition.

The steady state fluorescence technique was used to study the sol-gel transition for the solution-free radical cross-linking polymerization of acrylamide (AAm), with N,N'-methylenebis (acrylamide) as cross linker in the presence of ammonium persulfate as an initiator. Pyranine (8-hydroxypyrene-1, 3,6-trisulfonic acid, trisodium salt) is used as a fluoroprobe for monitoring the polymerization. Pyranine molecules start to bind to acrylamide polymer chains upon the initiation of the polymerization, thus the spectra of the bonded pyranines shift to the shorter wavelengths. Fluorescence spectra from the bonded pyranines allows one to monitor the sol-gel transition, without disturbing the system mechanically, and to test the universality of the sol-gel transition as a function of some kinetic parameters such as polymer concentration, cross-linker concentration, and temperature. Observations around the critical point show that there are three regimes for AAm concentration in which the exponents differ drastically. The gel fraction exponent beta and the weight average degree of polymerization exponent gamma agree best with the static percolation results for higher acrylamide concentrations above 1M, but they cross over from percolation to mean-field (Flory-Stockmayer) values when the AAm concentration is lower than 2M. For very low polymer concentrations, below which the system can not form the gel, the exponents differ considerably from both the percolation and the mean-field values.

Fluorescence study on the phase transition of hydrogen-bonding gels.

A technique based on steady-state fluorescence measurements is introduced to study the discontinuous volume phase transition of hydrogen-bonding gel. The fluorescence light intensity of pyranine (1-Hydroxypyrene-3, 6, 8-trisulfonic acid) bonded to the gel by means of methacryl amino-propyl-trimethyl ammonium chloride was monitored during the swelling of poly(methacrylic acid-co-dimethyl acrylamide) copolymer in water as a function of temperature. A discontinuous volume phase transition around 60 degrees C and an additional phase around 30 degrees C, which may be interpreted as the freely fluctuating phase in a collapsed state, were observed when the fluorescence intensity changes.