Effect of Spherical Aberration on the Optical Quality after Implantation of Two Different Aspherical Intraocular Lenses

Purpose. To compare the effect of spherical aberration on optical quality in eyes with two different aspherical intraocular lenses. Methods. 120 eyes of 60 patients underwent phacoemulsification. In patients’ eyes, an aberration-free IOL (Aspira-aA; Human Optics) or an aberration-correcting aspherical IOL (Tecnis ZCB00; Abott Medical Optics) was randomly implanted. After surgery, contrast sensitivity and wavefront measurements as well as tilt and decentration measurements were performed. Results. Contrast sensitivity was significantly higher in eyes with Aspira lens under mesopic conditions with 12 cycles per degree (CPD) and under photopic conditions with 18 CPD (p=0.02). Wavefront measurements showed a higher total spherical aberration with a minimal pupil size of 4 mm in the Aspira group (0.05 ± 0.03) than in the Tecnis group (0.03 ± 0.02) (p=0.001). Strehl ratio was higher in eyes with Tecnis (0.28 ± 0.17) with a minimal pupil size larger than 5 mm than that with Aspira (0.16 ± 0.14) (p=0.04). In pupils with a minimum diameter of 4 mm spherical aberration had a significant effect on Strehl ratio, but not in pupils with a diameter less than 4 mm. Conclusions. Optical quality was better in eyes with the aberration-correcting Tecnis IOL when pupils were large. In contrast, this could not be shown in eyes with pupils under 4 mm or larger. This trial is registered with Clinicaltrials.gov NCT03224728

Assorted effects of TGFβ and chondroitinsulfate on p38 and ERK1/2 activation levels in human articular chondrocytes stimulated with LPS

SummaryObjectivesInadequate cellular response of chondrocytes to stress frequently terminates in osteoarthritis (OA). Adequate response is fundamentally modulated by concerted cytokine signaling events, directing degradation and synthesis of cartilage on articular surfaces where and whenever necessary. Transforming growth factor (TGF)β is a prominent mediator in cartilage anabolism, although particular catabolic activities are occasionally reported. Clearly, before the TGFβ signal gets through to the gene regulatory machinery, cross talk with modulators occurs.MethodWe tested the hypothesis whether chondroitinsulfate (CS) modulates cell signaling. TGFβ and/or soluble CS was added to human articular chondrocytes (HACs) and activation of p38 and extracellular signal related kinase (ERK)1/2 was determined by immunoblot analysis. Expression levels of mRNA of matrix metalloproteinase (MMP)-2, -3 and -13 were determined by real-time polymerase chain reaction (PCR).ResultsNo significant effects were observed unless cells were stimulated with lipopolysaccharide (LPS), invigorating catabolic metabolism in chondrocytes. LPS effects, however, were profoundly modulated by TGFβ, CS and both applied in combination. Most prominent, the silencing of p38 stress signal by CS was superimposable to that of TGFβ. Phospho-ERK1/2 levels were raised by TGFβ three-fold over LPS induced levels. In contrast, CS treatment, alone or combined with TGFβ, reduced phosphorylation significantly below LPS induced levels. Finally, suppression of LPS induced MMP-13 mRNA levels resulted with CS.ConclusionSoluble CS modulates signaling events in chondrocytes concurrent with MMP-13 down regulation. The effects observed suggest a feedback signaling mechanism cross talking with TGFβ-signal pathways and may serve an explanation, on the cellular level, for the beneficial effects found in clinical studies with pharmacologic application of CS

Giant crystals inside mitochondria of equine chondrocytes

The present study reports for the first time the presence of giant crystals in mitochondria of equine chondrocytes. These structures show dark contrast in TEM images as well as a granular substructure of regularly aligned 12 nm small units. Different zone axes of the crystalline structure were analysed by means of Fourier transformation of lattice-resolution TEM images proving the crystalline nature of the structure. Elemental analysis reveals a high content of nitrogen referring to protein. The outer shape of the crystals is geometrical with an up to hexagonal profile in cross sections. It is elongated, spanning a length of several micrometres through the whole cell. In some chondrocytes, several crystals were found, sometimes combined in a single mitochondrion. Crystals were preferentially aligned along the long axis of the cells, thus appearing in the same orientation as the chondrocytes in the tissue. Although no similar structures have been found in the cartilage of any other species investigated, they have been found in cartilage repair tissue formed within a mechanically stimulated equine chondrocyte construct. Crystals were mainly located in superficial regions of cartilage, especially in joint regions of well-developed superficial layers, more often in yearlings than in adult horses. These results indicate that intramitochondrial crystals are related to the high mechanical stress in the horse joint and potentially also to the increased metabolic activity of immature individuals.(VLID)353386

Long-term results 8 years after autologous osteochondral transplantation: 7 T gagCEST and sodium magnetic resonance imaging with morphological and clinical correlation

SummaryObjectiveTo correlate long-term clinical outcome and the results of morphological as well as advanced biochemical magnetic resonance imaging (MRI) techniques [T2-mapping, glycosaminoglycan chemical exchange saturation transfer (gagCEST), sodium-23-imaging] in patients after autologous osteochondral transplantation (AOT) in knee joints.MethodNine AOT patients (two female and seven male; median age, 49) had clinical [International Knee Documentation Committee (IKDC), modified Lysholm, visual analog scale (VAS)] and radiological long-term follow-up examinations at a median of 7.9 years (inter-quartile range, 7.7–8.2). Standard morphological MRI and T2-mapping of cartilage were performed on a 3 T MR unit. Biochemical imaging further included sodium-23-imaging and chemical exchange saturation transfer (CEST) imaging at 7 T. The Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) score was used for quantitative assessment of morphological MRI.ResultsClinical outcome was good with a median modified Lysholm score of 90. Median VAS revealed 1.0 and median MOCART score 75 points. The difference between native and repair cartilage was statistically significant for all three biochemical imaging techniques. The strongest correlation was found between the results of the advanced biochemical imaging methods sodium-23 and CEST [ρ = 0.952, 95% confidence interval (CI): (0.753; 0.992)]. Comparing the results from morphological and biochemical imaging, a correlation was found between MOCART score and CEST ratio [ρ = −0.749, 95% CI: (−0.944; −0.169)]. Comparing the results from clinical scores with MRI, a correlation between modified Lysholm and T2-mapping [ρ = −0.667, 95% CI: (−0.992; −0.005)] was observed.ConclusionLong-term clinical outcome in patients 7.9 years after AOT was good, but did not correlate with morphological and biochemical imaging results except for T2-mapping

Topology and Organization of the Salmonella typhimurium Type III Secretion Needle Complex Components

The correct organization of single subunits of multi-protein machines in a three dimensional context is critical for their functionality. Type III secretion systems (T3SS) are molecular machines with the capacity to deliver bacterial effector proteins into host cells and are fundamental for the biology of many pathogenic or symbiotic bacteria. A central component of T3SSs is the needle complex, a multiprotein structure that mediates the passage of effector proteins through the bacterial envelope. We have used cryo electron microscopy combined with bacterial genetics, site-specific labeling, mutational analysis, chemical derivatization and high-resolution mass spectrometry to generate an experimentally validated topographic map of a Salmonella typhimurium T3SS needle complex. This study provides insights into the organization of this evolutionary highly conserved nanomachinery and is the basis for further functional analysis

The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas

Objective Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical treatment options for cartilage defects, as well as magnetic resonance imaging (MRI) of such defects. Thus, the aim of this study was to introduce the MOCART 2.0 knee score — an incremental update on the original MOCART score — that incorporates this progression. Materials and Methods The volume of cartilage defect filling is now assessed in 25% increments, with hypertrophic filling of up to 150% receiving the same scoring as complete repair. Integration now assesses only the integration to neighboring native cartilage, and the severity of surface irregularities is assessed in reference to cartilage repair length rather than depth. The signal intensity of the repair tissue differentiates normal signal, minor abnormal, or severely abnormal signal alterations. The assessment of the variables "subchondral lamina," "adhesions," and "synovitis" was removed and the points were reallocated to the new variable "bony defect or bony overgrowth." The variable "subchondral bone" was renamed to "subchondral changes" and assesses minor and severe edema-like marrow signal, as well as subchondral cysts or osteonecrosis-like signal. Overall, a MOCART 2.0 knee score ranging from 0 to 100 points may be reached. Four independent readers (two expert readers and two radiology residents with limited experience) assessed the 3 T MRI examinations of 24 patients, who had undergone cartilage repair of a femoral cartilage defect using the new MOCART 2.0 knee score. One of the expert readers and both inexperienced readers performed two readings, separated by a four-week interval. For the inexperienced readers, the first reading was based on the evaluation sheet only. For the second reading, a newly introduced atlas was used as an additional reference. Intrarater and interrater reliability was assessed using intraclass correlation coefficients (ICCs) and weighted kappa statistics. ICCs were interpreted according to Koo and Li; weighted kappa statistics were interpreted according to the criteria of Landis and Koch. Results The overall intrarater (ICC = 0.88, P < 0.001) as well as the interrater (ICC = 0.84, P < 0.001) reliability of the expert readers was almost perfect. Based on the evaluation sheet of the MOCART 2.0 knee score, the overall interrater reliability of the inexperienced readers was poor (ICC = 0.34, P < 0.019) and improved to moderate (ICC = 0.59, P = 0.001) with the use of the atlas. Conclusions The MOCART 2.0 knee score was updated to account for changes in the past decade and demonstrates almost perfect interrater and intrarater reliability in expert readers. In inexperienced readers, use of the atlas may improve interrater reliability and, thus, increase the comparability of results across studies

MR imaging of osteochondral grafts and autologous chondrocyte implantation

Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years

Purpose: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. Methods: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. Conclusions: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions