Designed to Be Green, Economic, and Efficient: A Ketone-Ester-Alcohol-Alkane Blend for Future Spark-Ignition Engines.

Model-based fuel design can tailor fuels to advanced engine concepts while minimizing environmental impact and production costs. A rationally designed ketone-ester-alcohol-alkane (KEAA) blend for high efficiency spark-ignition engines was assessed in a multi-disciplinary manner, from production cost to ignition characteristics, engine performance, ecotoxicity, microbial storage stability, and carbon footprint. The comparison included RON 95 E10, ethanol, and two previously designed fuels. KEAA showed high indicated efficiencies in a single-cylinder research engine. Ignition delay time measurements confirmed KEAA's high auto-ignition resistance. KEAA exhibits a moderate toxicity and is not prone to microbial infestation. A well-to-wheel analysis showed the potential to lower the carbon footprint by 95 percent compared to RON 95 E10. The findings motivate further investigations on KEAA and demonstrate advancements in model-based fuel design.

German Diabetes Study - Baseline data of retinal layer thickness measured by SD-OCT in early diabetes mellitus.

PURPOSE: Recent studies highlighted that early diabetic neurodegeneration is present before microvascular changes are visible. Retinal neurodegeneration can decrease retinal layer thickness. We aimed to determine whether decreased retinal layer thickness is present already in the early time course of disease. METHODS: A cross-sectional analysis of patients and healthy adults from the German Diabetes Study (GDS, ClinicalTrials.gov Identifier number: CT01055093, https://clinicaltrials.gov/ct2/show/NCT01055093). Inclusion criteria were a diagnosis of diabetes mellitus (DM) within the last 12 months. Retinal layers thickness in the nasal pericentral segment was measured by spectral domain ocular coherence tomography (SD-OCT). For statistical analysis proc mixed (sas-version 9.4) was used. RESULTS: One hundred and seventy-eight eyes of 89 patients with type 1 DM (58 males, age 36 ± 11 years, BMI 25.5 ± 4.2 kg/m²) and 242 eyes of 121 patients with type 2 DM (84 males, age 53 ± 10 years, BMI 31.9 ± 6.3 kg/m²) with a disease duration of less than 1 year were compared to 76 eyes of 38 controls (27 males, age 41 ± 16 years, BMI 27.3 ± 6.4 kg/m²). Analysis of retinal layer thickness and visual function did not reveal a significant difference between patients and controls. CONCLUSION: In the early course of DM potential, neurodegeneration does not relate to measureable changes of retinal layer thickness.

Alterations of the outer retina in non-arteritic anterior ischaemic optic neuropathy detected using spectral-domain optical coherence tomography.

BACKGROUND: A characteristic disease pattern may be reflected by retinal layer thickness changes in non-arteritic anterior ischaemic optic neuropathy measured using spectraldomain optical coherence tomography. Retinal layer segmentation is enabled by advanced software. In this study, retinal layer thicknesses in acute and chronic non-arteritic anterior ischaemic optic neuropathy were compared. DESIGN: A single-centre cross-sectional analysis was used. PARTICIPANTS: A total of 27 patients (20 age-matched healthy eyes) were included: 14 with acute (<7 days) and 13 patients with chronic non-arteritic anterior ischaemic optic neuropathy. METHODS: Macular volume and 12° peripapillary ring optical coherence tomography scans were used. MAIN OUTCOME MEASURES: The peripapillary thicknesses of the following layers were determined by manual segmentation: retinal nerve fibres, ganglion cells + inner plexiform layer, inner nuclear layer + outer plexiform layer, outer nuclear layer + inner segments of the photoreceptors and outer segments of the photoreceptors to Bruch's membrane. Macular retinal layer thicknesses were automatically determined in volume cubes centred on the fovea. RESULTS: Peripapillary retinal swelling in acute nonarteritic anterior ischaemic optic neuropathy was attributable to retinal nerve fibre layer, ganglion cell layer/inner plexiform layer and outer nuclear layer/segments of the photoreceptors thickening. In chronic cases, peripapillary retinal nerve fibre layer, macular ganglion cell layer and inner plexiform layer thinning were observed. CONCLUSIONS: In acute non-arteritic anterior ischaemic optic neuropathy, the inner and outer peripapillary retinal layers are affected by thickness changes. In chronic cases, atrophy of the ganglion cells and their axons and dendrites is evident by inner retinal layer thinning.

Intravitreal Dexamethasone Implant for the Treatment of Postoperative Macular Edema.

INTRODUCTION: Macular edema after cataract surgery (Irvine-Gass syndrome) or pars plana vitrectomy is a postoperative complication which can lead to permanent visual loss. Increased inflammatory substances, such as prostaglandins and cytokines, are discussed to be causative. Currently, there are no evidence-based guidelines for the treatment of postoperative macular edema. Intravitreal dexamethasone (DEX) could be effective by its anti-inflammatory effect. We examined the functional and morphological results of treatment with 0.7 mg intravitreal DEX implant (Ozurdex®). METHODS: In an observational study, we analyzed visual acuity (logMAR), intraocular pressure (IOP), clinical findings, and the central macular thickness (CMT, optical coherence tomography [OCT] Spectralis®, Heidelberg Engineering, 30° macular scan, 19 scans) of 12 eyes before and 1 month after the last DEX implantation (off-label use, Ozurdex®, Allergan, Inc., Irvine, CA, USA) for macular edema after cataract surgery or vitrectomy. Re-implantation was performed when OCT showed new intraretinal fluid along with a decrease in the patient's visual acuity. The mean follow-up was 14.4 ± 10.6 months. RESULTS: Twelve eyes of 12 patients (4 female, 8 male) with a mean age of 62.6 ± 11.9 years were treated with a mean of 2.5 ± 1.6 intravitreal DEX implant injections. Prior to injection, the visual acuity was 0.74 ± 0.34 logMAR and the CMT was 608 ± 129 µm. One month after the last injection (after a mean of 437 ± 322 days), the CMT normalized (300 ± 90 µm, p < 0.01) in all cases with a visual acuity of 0.49 ± 0.43 logMAR (p < 0.01). After 8.1 ± 5.3 months, recurring macular edema could be completely reduced by re-injection in 66% (8 patients). Four patients had no recurrence. Postinjection, the mean IOP was 17.4 ± 6.8 mm Hg. Postinjection, 7 patients required topical antiglaucomatous therapy. CONCLUSIONS: Treatment with an intravitreal DEX implant is an effective therapy for postoperative macular edema. Each injection leads to a complete resorption of the edema with a significant increase in visual acuity.

CXCR4 and CXCR7 Mediate TFF3-Induced Cell Migration Independently From the ERK1/2 Signaling Pathway.

PURPOSE: Trefoil factor family (TFF) peptides, and in particular TFF3, are characteristic secretory products of mucous epithelia that promote antiapoptosis, epithelial migration, restitution, and wound healing. For a long time, a receptor for TFF3 had not yet been identified. However, the chemokine receptor CXCR4 has been described as a low affinity receptor for TFF2. Additionally, CXCR7, which is able to heterodimerize with CXCR4, has also been discussed as a potential TFF2 receptor. Since there are distinct structural similarities between the three known TFF peptides, this study evaluated whether CXCR4 and CXCR7 may also act as putative TFF3 receptors. METHODS: We evaluated the expression of both CXCR4 and CXCR7 in samples of human ocular surface tissues and cell lines, using RT-PCR, immunohistochemistry, and Western blot analysis. Furthermore, we studied possible binding interactions between TFF3 and the receptor proteins in an x-ray structure-based modeling system. Functional studies of TFF3-CXCR4/CXCR7 interaction were accomplished by cell culture-based migration assays, flow cytometry, and evaluation of activation of the mitogen-activated protein (MAP) kinase signaling cascade. RESULTS: We detected both receptors at mRNA and protein level in all analyzed ocular surface tissues, and in lesser amount in ocular surface cell lines. X-ray structure-based modeling revealed CXCR4 and CXCR7 dimers as possible binding partners to TFF3. Cell culture-based assays revealed enhanced cell migration under TFF3 stimulation in a conjunctival epithelial cell line, which was completely suppressed by blocking CXCR4 and/or CXCR7. Flow cytometry showed increased proliferation rates after TFF3 treatment, while blocking both receptors had no effect on this increase. Trefoil factor family 3 also activated the MAP kinase signaling cascade independently from receptor activity. CONCLUSIONS: Dimers CXCR4 and CXCR7 are involved in TFF3-dependent activation of cell migration, but not cell proliferation. The ERK1/2 pathway is activated in the process, but not influenced by CXCR4 or CXCR7. These results implicate a dependence of TFF3 activity as to cell migration on the chemokine receptors CXCR4 and CXCR7 at the ocular surface.

Isolation and Investigation of Presumptive Murine Lacrimal Gland Stem Cells.

PURPOSE: Aqueous tear deficiency due to lacrimal gland insufficiency is one of the major causes of dry eye disease. In severe cases, such as Sjogren's syndrome, Stevens-Johnson syndrome, or ocular cicatricial pemphigoid, therapy with artificial tears is often insufficient to relieve severe discomfort, prevent progressive ocular surface disease, or enable visual rehabilitation by corneal transplantation. Cell or organ generation from stem cells, resulting in tear-like secretion, presents an option as a suitable alternative treatment. To obtain deeper insights into lacrimal gland stem cells we analyzed murine lacrimal glands for markers of pluripotency, self-renewal, and differentiation. METHODS: A special, patented technique with mechanical and enzymatic digestion was used to generate high numbers of cells in vitro from murine lacrimal glands. These presumptive "murine lacrimal gland stem cells" ("mLGSCs") can be propagated as monolayer cultures over multiple passages. By means of RT-PCR, Western blot, and immunohistochemistry, markers of pluripotency and differentiation were demonstrated. Hanging drop culture was used to build organoid bodies from mLGSCs to investigate their spontaneous differentiation in three-dimensional culture with histology, immunohistochemistry, and transmission electron microscopy methods. RESULTS: Isolated mLGSCs were cultured over more than 65 passages. Murine lacrimal gland stem cells expressed markers of pluripotency such as Nanog, Sox2, Kruppel-like factor 4 (Klf4), as well as early-lineage markers of all three germ layers. Three-dimensional culture of these cells revealed their ability to differentiate into various cell types. CONCLUSIONS: Our results suggest that mLGSCs were isolated and cultured successfully. These cells have the ability to differentiate into all three germ layers. The results provide further insights into lacrimal gland stem cell physiology for engineering of a lacrimal gland construct to treat severe cases of tear deficiency in the future.

Evaluation of Meibomian Gland Dysfunction and Local Distribution of Meibomian Gland Atrophy by Non-contact Infrared Meibography.

AIMS: The main purpose of this study was to investigate the relationship between Meibomian gland atrophy (meiboscore) and Meibomian gland expressibility. In addition, the local distribution of Meibomian gland loss was analyzed. METHODS: A retrospective analysis of 128 patients (92 women and 36 men, 57 ± 17 years) from our dry eye clinic was performed. Infrared meibography was performed using the Keratograph 5 M (Oculus, Wetzlar, Germany) and evaluated with a scoring system introduced by Arita et al. RESULTS: A significant inverse correlation between Meibomian gland atrophy measured by meibography and expressible Meibomian glands (r = -0.197, p = 0.003) as well as between meiboscore and TBUT (r = -0.1615, p = 0.012) was found. There also was a significant correlation between the total meiboscore and the age (r = 0.33, p < 0.0001). We could find a strong and highly significant correlation between the total meiboscore and the individual meiboscore of the upper eyelid (r = 0.905, p < 0.0001) and the lower eyelid (r = 0.892, p < 0.0001). There was no significant difference of Meibomian gland atrophy between the individual thirds of the upper eyelid, but for the lower eyelid, we could find a higher degree of Meibomian gland atrophy in the nasal third compared with the middle and the temporal third (Dunn's post hoc test, p < 0.0001). CONCLUSIONS: Meibomian gland atrophy seems to be not constant over the tarsal plate but the examination of the lower tarsus might be sufficient in most of the cases. The correlation of the meiboscore with functional dry eye parameters suggest that in patients with detectable Meibomian gland atrophy there is also an impaired Meibomian gland function. However, meibography seems not to be sufficient as a single test for the diagnosis of MGD. For the future larger, prospective studies are needed to confirm these results and further evaluate the potential of meibography in the diagnosis of MGD.