Endothelial keratoplasty combined with scleral fixation intraocular lens

describe, for the first time, the surgical management of two aphakic patients with corneal decompensation treated with concomitant ultrathin-Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and implantation of two different scleral-fixated (SF) intraocular lenses (IOLs), namely sutureless SF (SSF) Carlevale IOL (Soleko, Italy; Figure 1) or Morcher Type 90L IOL (Morcher GmbH, Germany; Figure 2). Both IOLs are hydrophilic acrylic. The Carlevale IOL is 13.2 mm long with a 6.5 mm optic plate, foldable and injectable through a 2.2 mm corneal tunnel. A T-shaped harpoon protrudes off the closed haptics and is designed to be externalized underneath a partial thickness scleral flap (Figure 1). The Morcher Type 90L IOL is 15 mm long with a 6.5 mm optic plate. The two C-loop haptics have an eyelet for the passage of the sutures for the scleral fixatio

Targeted search for the kinematic dipole of the gravitational-wave background

There is growing interest in using current and future gravitational-wave interferometers to search for anisotropies in the gravitational-wave background. One guaranteed anisotropic signal is the kinematic dipole induced by our peculiar motion with respect to the cosmic rest frame, as measured in other full-sky observables such as the cosmic microwave background. Our prior knowledge of the amplitude and direction of this dipole is not explicitly accounted for in existing searches by LIGO/Virgo/KAGRA, but could provide crucial information to help disentangle the sources which contribute to the gravitational-wave background. Here we develop a targeted search pipeline which uses this prior knowledge to enable unbiased and minimum-variance inference of the dipole magnitude. Our search generalises existing methods to allow for a time-dependent signal model, which captures the annual modulation of the dipole due to the Earth's orbit. We validate our pipeline on mock data, demonstrating that neglecting this time dependence can bias the inferred dipole by as much as $\sim10\%$. We then run our analysis on the full LIGO/Virgo O1+O2+O3 dataset, obtaining upper limits on the dipole amplitude that are consistent with existing anisotropic search results.Comment: 12 pages, 3 figure

Clinical outcomes of pre-loaded ultra-thin DSAEK and pre-loaded DMEK

Objective: To compare clinical outcomes and complications between pre-loaded ultra-thin Descemet stripping automated endothelialkeratoplasty (pl-UT-DSAEK) and pre-loaded Descemet membrane endothelial keratoplasty (pl-DMEK). Methods and analysis: Comparative study in patients with endothelial dysfunction associated with Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy who underwent pl-UT-DSAEK or pl-DMEK transplants. For both groups, the tissues were pre-loaded at the Fondazione Banca degli Occhi del Veneto (Venice, Italy) and shipped to The Royal Liverpool University Hospital (Liverpool, UK). Best corrected visual acuity (BCVA) and re-bubbling rates were the main outcome measures. Results: 56 eyes of 56 patients were included. 31 received pl-UT-DSAEK and 25 received pl-DMEK. At 12 months, BCVA (LogMAR) was significantly better for pl-DMEK (0.17±0.20 LogMAR) compared with pl-UT-DSAEK (0.37±0.37 LogMAR, p<0.01). The percentage of people that achieved ≥20/30 was significantly higher in the pl-DMEK group. The rate of re-bubbling, however, was significantly higher for pl-DMEK (44.0%) than for Pl-UT-DSAEK (12.9%), p<0.01. Conclusion: Pl-DMEK offers better BCVA than pl-UT-DSAEK. The higher re-bubbling rate associated with pre-loaded DMEK is of concern

Eye bank versus surgeon prepared DMEK tissues: influence on adhesion and re-bubbling rate

AIM: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues. METHODS: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study. RESULTS: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02). CONCLUSIONS: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease

BACKGROUND: Trimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer's disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease. METHODS: In this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample (n = 410) of individuals with Alzheimer's clinical syndrome (n = 40), individuals with mild cognitive impairment (MCI) (n = 35), and cognitively-unimpaired individuals (n = 335). Linear regression analyses were used to determine differences in CSF TMAO between groups (controlling for age, sex, and APOE ε4 genotype), as well as to determine relationships between CSF TMAO and CSF biomarkers of AD (phosphorylated tau and beta-amyloid) and neuronal degeneration (total tau, neurogranin, and neurofilament light chain protein). RESULTS: CSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ42) and neuronal degeneration (total tau and neurofilament light chain protein). CONCLUSIONS: These findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut-brain axis

An endoscopic modification of the simultaneous ‘above and below’ approach to large pituitary adenomas

Surgical resections of large-to-giant pituitary adenomas (PA) are technically challenging procedures. Tumors with a fibrous consistency or ‘hour-glass’ configurations are particularly difficult to remove completely and safely through the transsphenoidal route alone. Although the transcranial approach can facilitate the removal of a large suprasellar mass, it may be associated with significant bleeding within the intradural space. A simultaneous microscopic transcranial and transsphenoidal approach has been described as an alternative surgical strategy. We have further modified this ‘above and below’ approach by adopting endoscopic techniques for the transsphenoidal part of the procedure. This modified approach has the advantages of requiring only one operating microscope, and permitting freer maneuvers and easier orientation for both surgical teams. We present two patients successfully treated with this approach. Complete tumor removal was achieved and both patients achieved satisfactory functional recovery

Assessment of technological options and economical feasibility for cyanophycin biopolymer and high-value amino acid production

Major transitions can be expected within the next few decades aiming at the reduction of pollution and global warming and at energy saving measures. For these purposes, new sustainable biorefinery concepts will be needed that will replace the traditional mineral oil-based synthesis of specialty and bulk chemicals. An important group of these chemicals are those that comprise N-functionalities. Many plant components contained in biomass rest or waste stream fractions contain these N-functionalities in proteins and free amino acids that can be used as starting materials for the synthesis of biopolymers and chemicals. This paper describes the economic and technological feasibility for cyanophycin production by fermentation of the potato waste stream Protamylasse™ or directly in plants and its subsequent conversion to a number of N-containing bulk chemicals