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Chemical Science Jun 2024Lanthanide(iii) (Ln) complexes have desirable photophysical properties for optical bioimaging. However, despite their advantages over organic dyes, their use for...
Lanthanide(iii) (Ln) complexes have desirable photophysical properties for optical bioimaging. However, despite their advantages over organic dyes, their use for microscopy imaging is limited by the high-energy UV excitation they require and their poor ability to cross the cell membrane and reach the cytosol. Here we describe a novel family of lanthanide-based luminescent probes, termed dTAT[Ln·L], based on (i) a DOTA-like chelator with a picolinate moiety, (ii) a two-photon absorbing antenna to shift the excitation to the near infrared and (ii) a dimeric TAT cell-penetrating peptide for cytosolic delivery. Several Tb and Eu probes were prepared and characterized. Two-photon microscopy of live cells was attempted using a commercial microscope with the three probes showing the highest quantum yields (>0.15). A diffuse Ln emission was detected in most cells, which is characteristic of cytosolic delivery of the Ln complex. The cytotoxicity of these three probes was evaluated and the IC ranged from 7 μM to >50 μM. The addition of a single positive or negative charge to the antenna of the most cytotoxic compound was sufficient to lower significantly or suppress its toxicity under the conditions used for two-photon microscopy. Therefore, the design reported here provides excellent lanthanide-based probes for two-photon microscopy of living cells.
PubMed: 38939128
DOI: 10.1039/d4sc00896k -
Frontiers in Bioengineering and... 2024In an effort of gaining a better understanding of the lens mechanics, lenses samples are often used. Yet, tissue might undergo important postmortem changes depending...
INTRODUCTION
In an effort of gaining a better understanding of the lens mechanics, lenses samples are often used. Yet, tissue might undergo important postmortem changes depending on the unavoidable preservation method employed. The purpose of this study was to assess how various storage conditions and the removal of the lens capsule affect the mechanical properties of porcine lens samples.
METHODS
A total of 81 freshly enucleated porcine eyes were obtained and divided into six groups and preserved differently. In the first three groups, the lens within the intact eye was preserved for 24 h by: (i) freezing at -80°C (n = 12), (ii) freezing at -20°C (n = 12), and (iii) refrigeration at +8°C (n = 12). In the remaining groups, the lenses were immediately extracted and treated as follows: (iv) kept intact, no storage (n = 12), (v) decapsulated, no storage (n = 21), and (vi) immersed in Minimum Essential Medium (MEM) at +8°C (n = 12) for 24 h. Frozen lenses were thawed at room temperature. Each lens was compressed between two glass lamella and subjected, first to a period of relaxation during which the compression force was recorded and second to an oscillating micro-compression while the deformation was recorded with a total of 256 subsequent B-scans via optical coherence tomography. The corresponding axial strain was retrieved via phase-sensitive image processing and subsequently used as input for an inverse finite element analysis (iFEA) to retrieve the visco-hyperelastic material properties of the lenses.
RESULTS
After freezing at temperatures of -80°C and -20°C, the cortical strains increased by 14% ( = 0.01) and 34% ( < 0.001), and the nuclear strains decreased by 17% ( = 0.014) and 36% ( < 0.001), compared to the lenses tested immediately after postmortem, respectively. According to iFEA, this resulted from an increased ratio of the nuclear: cortical E-modulus (4.06 and 7.06) in -80°C and -20°C frozen lenses compared to fresh lenses (3.3). Decapsulation had the largest effect on the material constant C, showing an increase both in the nucleus and cortex. Preservation of the intact eye in the refrigerator induced the least mechanical alterations in the lens, compared to the intact fresh condition.
DISCUSSION
Combining iFEA with optical coherence elastography allowed us to identify important changes in the lens mechanics induced after different preserving methods.
PubMed: 38938986
DOI: 10.3389/fbioe.2024.1398659 -
Frontiers in Bioengineering and... 2024Conventional cephalomedullary nails (CMNs) are commonly employed for internal fixation in the treatment of reverse obliquity intertrochanteric (ROI) fractures. However,...
Comparative study of a novel proximal femoral bionic nail and three conventional cephalomedullary nails for reverse obliquity intertrochanteric fractures: a finite element analysis.
PURPOSE
Conventional cephalomedullary nails (CMNs) are commonly employed for internal fixation in the treatment of reverse obliquity intertrochanteric (ROI) fractures. However, the limited effectiveness of conventional CMNs in addressing ROI fractures results in significant implant-related complications. To address challenges associated with internal fixation, a novel Proximal Femoral Bionic Nail (PFBN) has been developed.
METHODS
In this study, a finite element model was constructed using a normal femoral specimen, and biomechanical verification was conducted using the GOM non-contact optical strain measurement system. Four intramedullary fixation approaches-PFBN, Proximal Femoral Nail Antirotation InterTan nail (ITN), and Gamma nail (Gamma nail)-were employed to address three variations of ROI fractures (AO/OTA 31-A3). The biomechanical stability of the implant models was evaluated through the calculation of the von Mises stress contact pressure and displacement.
RESULTS
Compared to conventional CMNs, the PFBN group demonstrated a 9.36%-59.32% reduction in the maximum VMS at the implant. The A3.3 ROI fracture (75% bone density) was the most unstable type of fracture. In comparison to conventional CMNs, PFBN demonstrated more stable data, including VMS values (implant: 506.33 MPa, proximal fracture fragment: 34.41 MPa), contact pressure (13.28 MPa), and displacement (17.59 mm).
CONCLUSION
Compared to the PFNA, ITN, and GN, the PFBN exhibits improvements in stress concentration, stress conduction, and overall model stability in ROI fractures. The double triangle structure aligns better with the tissue structure and biomechanical properties of the proximal femur. Consequently, the PFBN has significant potential as a new fixation strategy for the clinical treatment of ROI fractures.
PubMed: 38938983
DOI: 10.3389/fbioe.2024.1393154 -
Frontiers in Bioengineering and... 2024Combination therapy with oral administration of several active ingredients is a popular clinical treatment for cancer. However, the traditional method has poor...
Combination therapy with oral administration of several active ingredients is a popular clinical treatment for cancer. However, the traditional method has poor convenience, less safety, and low efficiency for patients. The combination of traditional pharmaceutical techniques and advanced material conversion methods can provide new solutions to this issue. In this research, a new kind of hybrid film was created via coaxial electrospraying, followed by a casting process. The films were composed of Reglan and 5-fluorouracil (5-FU)-loaded cellulose acetate (CA) core-shell particles in a polyvinylpyrrolidone (PVP) film matrix. Microscopic observations of these films demonstrated a solid cross section loaded with core-shell particles. X-ray diffraction and Fourier-transform infrared tests verified that the Reglan and 5-FU loaded in the films showed amorphous states and fine compatibilities with the polymeric matrices, i.e., PVP and CA, respectively. dissolution tests indicated that the films were able to provide the desired asynchronous dual-drug delivery, fast release of Reglan, and sustained release of 5-FU. The controlled release mechanisms were shown to be an erosion mechanism for Reglan and a typical Fickian diffusion mechanism for 5-FU. The protocols reported herein pioneer a new approach for fabricating biomaterials loaded with multiple drugs, each with its own controlled release behavior, for synergistic cancer treatment.
PubMed: 38938981
DOI: 10.3389/fbioe.2024.1398730 -
JACC. Advances Jun 2024The long-term impact of Kawasaki disease on coronary arteries in vivo is unclear.
BACKGROUND
The long-term impact of Kawasaki disease on coronary arteries in vivo is unclear.
OBJECTIVES
The purpose of this study was to investigate coronary arteries in the late convalescent phase, we followed patients with Kawasaki disease who developed coronary artery aneurysms (CAAs).
METHODS
We followed 24 patients and used optical coherence tomography at a median of 16.6 years after the onset of Kawasaki disease.
RESULTS
Of 72 coronary arteries, optical coherence tomography was performed on 61 arteries: 17 with a persistent CAA, 29 with a regressed CAA, and 15 without a CAA. Between-group comparison was performed by chi-square or Fisher's exact test, and intimal thickening (17 vs 29 vs 15, all 100%, = NA) and medial disruption (17 [100%] vs 29 [100%] vs 14 [93%], = 0.25) were commonly observed in the investigated arteries. Advanced features of atherosclerosis were more frequently seen in arteries with persistent CAAs than in those with regressed CAAs and in those without CAAs: calcification (12 [71%] vs 5 [17%] vs 1 [7%], < 0.001), microvessels (12 [71%] vs 10 [35%] vs 4 [27%], = 0.020), cholesterol crystals (6 [35%] vs 2 [7%] vs 0 [0%], = 0.009), macrophage accumulation (11 [65%] vs 4 [14%] vs 4 [27%], = 0.002), and layered plaque (8 [47%] vs 11 [38%] vs 0 [0%], = 0.004).
CONCLUSIONS
Long after onset of Kawasaki disease, all arteries showed pathological changes. Arteries with persistent CAAs had more advanced features of atherosclerosis than those with regressed CAAs and those without CAAs.
PubMed: 38938853
DOI: 10.1016/j.jacadv.2024.100937 -
Frontiers in Physiology 2024Although compartmentalization of the eye seems to promote its experimental manipulation, drug penetration to its posterior part is severely limited by hard barriers thus... (Review)
Review
Although compartmentalization of the eye seems to promote its experimental manipulation, drug penetration to its posterior part is severely limited by hard barriers thus hindering drug development for eye diseases. In particular, angiogenesis-related retinal diseases share common mechanisms and are responsible for the majority of cases of blindness. Their prevalence is globally increasing mostly because of the increased incidence of systemic pathologies in the adult. Despite the number of preclinical findings demonstrating the efficacy of novel treatments, therapy of retinal neovascular diseases still remains confined to intravitreal anti-vascular endothelial growth factor treatments with some extension to anti-inflammatory therapy. In the of preclinical findings aimed to develop novel avenues for future therapies, most compounds, despite their efficacy in experimental models, do not seem to meet the criteria for their therapeutic application. In particular, the groove between preclinical findings and their clinical application increases instead of decreasing and the attempt to bridging the gap between them creates intense frustration and a sense of defeat. In this complex scenario, we will discuss here the role that overactivation of the sympathetic system plays in retinal vessel proliferation in response to hypoxia using the oxygen-induced retinopathy (OIR) model. The potential application of the beta-adrenoceptor (β-AR) blockade with propranolol to the treatment of retinopathy of prematurity will be also discussed in light of preclinical findings in the OIR model and clinical trials using propranolol in preterm infants either or as eye drops.
PubMed: 38938747
DOI: 10.3389/fphys.2024.1408605 -
Case Reports in Ophthalmological... 2024To the best of our knowledge, we present the first case of type II acute macular neuroretinopathy (AMN) exhibiting in a patient suffering from malarial retinopathy...
To the best of our knowledge, we present the first case of type II acute macular neuroretinopathy (AMN) exhibiting in a patient suffering from malarial retinopathy concomitant with cerebral malaria acquired after travelling to West Africa without taking the necessary antimalarial prophylaxis. The patient complained of bilateral blurring of vision after being removed off sedation whilst at the intensive care unit. Subsequent examination revealed bilateral retinal haemorrhages, cotton-wool spots, and foveal pigmentary changes in keeping malarial retinopathy. Macular optical coherence tomography (OCT) revealed patchy hyperreflective changes at the level of the outer plexiform and outer nuclear layers (ONL) in keeping with the areas of deep capillary plexus flow void noted on OCT-angiography (OCT-A). This case report sheds more light on the extent of neurosensory retinal ischaemia in malarial retinopathy and showcases a new imaging biomarker which may be utilized in assessing and quantifying the functional deficit created by this disease.
PubMed: 38938742
DOI: 10.1155/2024/1577127 -
Journal of Surgical Case Reports Jun 2024Orbital metastasis originating from breast carcinoma, particularly ductal carcinoma, represents a rare clinical entity, with lobular carcinoma usually being more common....
Orbital metastasis originating from breast carcinoma, particularly ductal carcinoma, represents a rare clinical entity, with lobular carcinoma usually being more common. Long-term surveillance in breast cancer patients is crucial for early detection of metastasis. Herein, we present a case of a 70-year-old woman with a history of left ductal breast carcinoma, diagnosed and treated 12 years ago. She then developed left eye vision loss, diplopia, enophthalmos, and chemosis in October 2024. Imaging revealed orbital metastasis involving the left superior and lateral rectus extraocular muscles. Biopsy confirmed the diagnosis of orbital metastases arising from ductal breast carcinoma. This case underscores the significance of long-term surveillance in breast cancer patients, as metastasis can manifest years after the initial diagnosis. Despite its rarity, orbital metastasis warrants consideration in the differential diagnosis of ocular symptoms in patients with a history of breast carcinoma. Treatment primarily aims at palliation and preserving visual function, with prognosis typically poor.
PubMed: 38938683
DOI: 10.1093/jscr/rjae428 -
Frontiers in Psychiatry 2024Aberrant fixation and scan paths in visual searches have been repeatedly reported in schizophrenia. The frontal eye fields (FEF) and thalamus may be responsible for...
INTRODUCTION
Aberrant fixation and scan paths in visual searches have been repeatedly reported in schizophrenia. The frontal eye fields (FEF) and thalamus may be responsible for fixation and scan paths. These two regions are connected by superior thalamic radiation (STR) in humans. Studies have reported reduced fixation numbers and shortened scan path lengths in individuals with attenuated psychosis syndrome (APS) and schizophrenia. In this study, we hypothesized that STRs in the white matter fiber bundles of impairments underlie abnormalities in fixation and scan path length in individuals with APS.
METHODS
Twenty-one individuals with APS and 30 healthy controls participated in this study. All participants underwent diffusion tensor imaging, and fractional anisotropy (FA) values of the left and right STR were analyzed using the novel method TractSeg. The number of eye fixations (NEF), total eye scanning length (TESL), and mean eye scanning length (MESL), derived using the exploratory eye movement (EEM) test, were adopted to evaluate the fixation and scan path length. We compared the FA values of the bilateral STR and EEM parameters between the APS and healthy control groups. We investigated the correlation between bilateral STR and EEM parameters in the APS and healthy control groups.
RESULTS
NEF, TESL, MESL, and the FA values of the left STR were significantly reduced in individuals with APS compared to healthy controls. The left STR FA value in the APS group was significantly positively correlated with the MESL ( = 0.567, = 0.007). In addition, the right STR FA value of the APS group was significantly correlated with the TESL ( = 0.587, = 0.005) and MESL ( = 0.756, = 0.7×10).
DISCUSSION
These results demonstrate that biological changes in the STR, which connects the thalamus and FEF, underlie abnormalities in fixation and scanning. Recently, aberrations in the thalamus-frontal connection have been shown to underlie the emergence of psychotic symptoms. STR impairment may be a part of the biological basis of APS in individuals with subthreshold psychotic symptoms.
PubMed: 38938465
DOI: 10.3389/fpsyt.2024.1323786 -
Frontiers in Medicine 2024To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GAT) and SUOER SW-500 Rebound Tonometer.
INTRODUCTION
To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GAT) and SUOER SW-500 Rebound Tonometer.
METHODS
This was a retrospective observational study where 205 eyes of 106 glaucoma patients had their IOPs measured by 2 fellowship trained ophthalmologists. Data were analyzed using the Bland-Altman method of differences. Correlation was measured using the Pearson coefficient.
RESULTS
Most of our patients were Chinese (88.7%) and female (51.9%). The average age was 66.9 years. The range of IOPs as measured by GAT was 2 to 58 mm Hg. Using the Bland-Altman method to compare GAT and SUOER SW-500 Rebound Tonometer. The tonometer overestimated the IOP by 0.5 mm Hg in the right eye and underestimated it by 0.1 mm Hg in the left eye. Overall, the tonometer overestimated the IOP by 0.2 mmHg. The Tonometer IOP correlated well with GAT, with a Pearson coefficient of correlation() of 0.89 ( < 0.001) for the right eye and 0.86 ( < 0.001) for the left eye, respectively. In patients with GAT IOP ≥ 21 mm Hg ( = 25), the Tonometer underestimated the IOP by 2.96 mm Hg.
DISCUSSION
The IOP measurements from the SUOER SW-500 Rebound Tonometer correlates well with the conventional GAT in measuring the IOP within normal ranges of IOP. SUOER SW-500 Rebound Tonometer may be of use, especially if the risk of transmission of infection is high considering that the probes are disposable. It is easy to use and its small size and portability makes it useful in situations where the patient is unable to be examined at the slit lamp.
PubMed: 38938385
DOI: 10.3389/fmed.2024.1269332