The pre-Descemet's layer (Dua's layer, also known as the Dua-Fine layer and the pre-posterior limiting lamina layer): Discovery, characterisation, clinical and surgical applications, and the controversy

The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 μ m (range 6-16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals. The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK. The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations

An approach to reduce Descemet's membrane scrolling: Relevance to Descemet's membrane endothelial keratoplasty (DMEK)

Purpose: We aimed to determine whether Descemet’s membrane (DM) scrolling occurs primarily along the vertical or horizontal axis and establish whether oval trephination along the axis of least scrolling can reduce the grade of the scroll. Methods: The longest limbus-to-limbus axis on 28 sclerocorneal discs was taken as the horizontal axis. The horizontal (n = 7) or (right angles to it) vertical (n = 6) axis was marked on DM before peeling it off. The direction and grade of scrolling was observed. Narrow strips (3–4 mm wide) were then cut along the two axes (n = 4 each) and the scrolling pattern was observed. Ellipses (7 × 9 mm) of DM were punched along the two axes (n = 6 each) and the scrolls graded. Immunofluorescent staining for elastin on horizontal and vertical tissue sections from three DM samples was performed. The intensity and thickness of elastin staining were measured. Results: Twenty-four (85.72%) DM samples showed scrolling along the horizontal axis, none showed scrolling along the vertical axis, and four (14.28%) samples showed a spiral scroll, regardless of which axis was marked (grade 3.7 and 3.6). Vertically oval discs showed significantly reduced scrolling (grade 1.2) compared to horizontally oval discs (grade 3.5). Narrow strips of DM showed a similar scrolling pattern. Immunohistology showed no difference in any of the parameters examined along the two axes or from the center to the periphery. Conclusion: DM scrolls primarily along the horizontal axis. Vertically oval DM samples show minimal scrolling, which can be an advantage in DMEK. Differential scrolling is not determined by the distribution of elastin

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill & Melinda Gates Foundation

Unusual cross-ring SN2 reactions of [MH]− ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6