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Background: Congenital heart disease is associated with an increased risk of smaller brain volumes and structural brain damage, and impaired growth of supratentorial brain structures in utero has been linked to poor neurodevelopmental outcomes. However, little is known on brainstem and cerebellar volumes in fetuses with congenital heart disease. Moreover, it is not clear whether impaired infratentorial growth, if present, is associated with only certain types of fetal cardiac defects or with supratentorial brain growth, and whether altered biometry is already present before the third trimester., Objective: This study aimed to investigate brainstem and cerebellar volumes in fetuses with congenital heart disease and to compare them to infratentorial brain volumes in fetuses with normal hearts. Secondarily, the study aimed to identify associations between infratentorial brain biometry and the type of cardiac defects, supratentorial brain volumes, and gestational age., Study Design: In this retrospective case-control study, 141 magnetic resonance imaging studies of 135 fetuses with congenital heart disease and 141 magnetic resonance imaging studies of 125 controls with normal hearts at 20 to 37 gestational weeks (median, 25 weeks) were evaluated. All cases and controls had normal birthweight and no evidence of structural brain disease or genetic syndrome. Six types of congenital heart disease were included: tetralogy of Fallot (n=32); double-outlet right ventricle (n=22); transposition of the great arteries (n=27); aortic obstruction (n=24); hypoplastic left heart syndrome (n=22); and hypoplastic right heart syndrome (n=14). First, brainstem and cerebellar volumes of each fetus were segmented and compared between cases and controls. In addition, transverse cerebellar diameters, vermian areas, and supratentorial brain and cerebrospinal fluid volumes were quantified and differences assessed between cases and controls. Volumetric differences were further analyzed according to types of cardiac defects and supratentorial brain volumes. Finally, volume ratios were created for each brain structure ([volume in fetus with congenital heart disease/respective volume in control fetus] × 100) and correlated to gestational age., Results: Brainstem (cases, 2.1 cm 3 vs controls, 2.4 cm 3 ; P<.001) and cerebellar (cases, 3.2 cm 3 vs controls, 3.4 cm 3 ; P<.001) volumes were smaller in fetuses with congenital heart disease than in controls, whereas transverse cerebellar diameters (P=.681) and vermian areas (P=.947) did not differ between groups. Brainstem and cerebellar volumes differed between types of cardiac defects. Overall, the volume ratio of cases to controls was 80.8% for the brainstem, 90.5% for the cerebellum, and 90.1% for the supratentorial brain. Fetuses with tetralogy of Fallot and transposition of the great arteries were most severely affected by total brain volume reduction. Gestational age had no effect on volume ratios., Conclusion: The volume of the infratentorial brain, which contains structures considered crucial to brain function, is significantly smaller in fetuses with congenital heart disease than in controls from midgestation onward. These findings suggest that impaired growth of both supra- and infratentorial brain structures in fetuses with congenital heart disease occurs in the second trimester. Further research is needed to elucidate associations between fetal brain volumes and neurodevelopmental outcomes in congenital heart disease., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Liposomes are phospholipid-based self-assembled nanoparticles. Various components can be solubilized in the lipid bilayer, encapsulated in the aqueous core or attached to the surface, making liposomes attractive platforms for multimodality functionalization. Here we describe theranostic liposomes delivering a magnetic resonance contrast agent (lipid derivative of gadopentetic acid) and a hydrophobic photosensitizer (zinc phthalocyanine, ZnPc) for photodynamic therapy of cancer. For the first time, this theranostic system was prepared by the microfluidic method. Analogous formulations were produced by thin lipid film hydration (TLH) with down-sizing performed by extrusion for comparison purposes. We demonstrated double the loading capacity of ZnPc into liposomes made by microfluidics compared to TLH/extrusion. Microfluidics resulted in the theranostic nanoliposomes characterized by sizes =2.5x smaller than vesicles prepared by TLH/extrusion. Increased relaxivity was observed for liposomes manufactured by microfluidics compared to TLH, despite a slightly lower Gd chelate recovery. We attributed the improved relaxation to the increased surface area/volume ratio of vesicles and decreased phosphatidylcholine/ZnPc molar ratio, which affected water molecules' diffusion through the liposomal membrane. Finally, we showed photodynamic efficacy of ZnPc loaded into theranostic liposomes in head and neck cancer model, resulting in IC 50 of 0.22 - 0.61 μM, depending on the formulation and cell line used. We demonstrate microfluidics' feasibility to be used for theranostic liposome manufacturing and co-entrapment of therapeutic and imaging components in a single-step process with a high yield., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The present study is focused on the development of liposomes bearing gadolinium chelate (GdLip) providing two functionalities for magnetic resonance imaging (MRI) and photodynamic therapy of cancer. A lipid derivative of gadolinium(III) diethylenetriamine pentaacetic acid salt (GdDTPA1) was inserted in the liposomal membrane and served as MRI contrast agent whereas a zinc phthalocyanine (ZnPc) was used as a model photosensitizer. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes. The characterization of different GdLip formulations involved evaluation of the liposomes size by nanoparticle tracking analysis, thermal phase behavior by differential scanning calorimetry and ZnPc-mediated singlet oxygen production. Furthermore, relaxivity measurements were performed as well as cytotoxicity and photodynamic activity against cancerous and normal cell lines was studied. Size and thermal behavior were only slightly influenced by GdLip composition, however it distinctly affected singlet oxygen production of ZnPc-loaded GdLip. The quantum yields of singlet oxygen generation by zinc phthalocyanine incorporated in GdLip containing cationic or/and pegylated lipids were smaller than those obtained for non-pegylated carriers with l-α-phosphatidylglycerol. In general, all formulations of GdLip, irrespectively of composition, were characterized by relaxivities higher than those of commercially used contrast agents (e.g. Magnevist®). NMR study has shown that the incorporation of ZnPc into the formulations of GdLip increases the relaxation parameters r 1 and r 2 , compared to the values for the non-loaded vesicles. GdDTPA1 did not influence the photodynamic activity of ZnPc against HeLa cells., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The chemical composition of nanoparticles (NPs) may be so designed as to provide measurability for numerous imaging techniques in order to achieve synergistic advantages. Innovative and unique structure of the core/shell ZnO@Gd 2 O 3 NPs possesses luminescent and magnetic properties, and is expected that they will become a new generation of contrast agents for Magnetic Resonance Imaging (MRI) and nanocarriers for theranostics. Thus, by surface biofunctionalization, it is possible to indicate particular nanoparticle compositions which provide efficient imaging, targeted drug delivery, and biocompatibility. Novel ZnO@Gd 2 O 3 NPs were synthesized and biofunctionalized by folic acid (FA) and doxorubicin (Doxo) to provide target and anticancer functions. Physicochemical analyses of the nanoparticles were performed. The biological study included a cytotoxicity in vitro, cellular distribution evaluation, as well as toxicity analyses, performed for the first time, on the in vivo zebrafish (Danio rerio) model. Nanoparticles were found to be effective double-function biomarkers (MRI T 2 contrast agents, fluorescent imaging). The biological study showed that ZnO@Gd 2 O 3 and ZnO@Gd 2 O 3 @OA-polySi@FA NPs are biocompatible in a particular concentration ranges. Conjugation with folic acid and/or doxorubicin resulted in effective drug delivery targeting. The in vivo results described the toxicology profile toward the zebrafish embryo/larvae, including new data concerning the survival, hatching ratio, and developmental malformations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Potassium ions are known to have an inhibitory effect on the sperm motility of salmonids. For this reason, the addition of K(+) to the extender is frequently applied. However, the effect of the addition of K(+) to the extender has not yet been tested. The aim of this study was to test the influence of potassium ion supplementation of the extender on the sperm motility parameters from five Salmonidae species (rainbow trout (Oncorhynchus mykiss), sex-reversed female rainbow trout, whitefish (Coregonus lavaretus), brown trout (Salmo trutta) and brook trout (Salvelinus fontinalis)). Semen samples were diluted in extender containing 0.18 M glucose in 9% methanol (GM) supplemented with 0, 20 or 40 mM potassium chloride. After thawing sperm were stored for 30, 60, 120 and 240 min at 4 °C. Our results demonstrated that the presence of potassium ions in the extender had a negative effect on percentage of motile sperm in four of the salmonid species. In contrast, potassium ions appeared to have a positive effect on percentage of post-thaw motile sperm in whitefish semen. However, this effect could be mimicked by changing the osmolality of the extender (which was achieved by increasing the glucose concentration to 0.22 M). The addition of potassium ions turned out to have no positive effect on post-thaw storage time. Our results suggest that osmolality, rather than potassium ions, seems to be essential for cryopreservation success of salmonids sperm. Further studies should focus on the effects of small changes in osmolality on the post-thaw quality of semen., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to test the influence of postthaw storage time on sperm motility parameters of brook trout (n = 9). Furthermore, we examined the effect of sperm-to-egg ratios of 300,000:1 and 600,000:1 on fertility of postthaw, cryopreserved, brook trout sperm. The application of a cryopreservation procedure produced very high postthaw sperm motility (56.8 ± 4.0%). The cryopreserved sperm of brook trout could be stored up to 60 minutes without loss of the percentage of sperm motility (52.0 ± 9.0%). The fertilization capacity of brook trout postthaw sperm was comparable with the fertilization rate of fresh semen at a sperm-to-egg ratio as low as 300,000:1 (42.4 ± 14.0% and 36.5 ± 11.0% for eyed and hatched stages, respectively). The possibility of postthaw semen storage for the prolonged time and the obtainment of high fertilization rate at low sperm-to-egg ratio can lead to the significant improvement of brook trout semen cryopreservation procedure., (Copyright © 2015 Elsevier Inc. All rights reserved.)