Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200400655

Controlled microwave heating in modern organic synthesis.

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Why most published research findings are false

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjogren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.

TFOS DEWS II pathophysiology report

The tarsal glands of Meibom (glandulae tarsales) are large sebaceous glands located in the eyelids and, unlike those of the skin, are unassociated with hairs. According to Duke-Elder and Wyler,1 they were first mentioned by Galenus in 200 AD and later, in 1666, they were described in more detail by the German physician and anatomist Heinrich Meibom, after whom they are named.

Lipids produced by the meibomian glands are the main component of the superficial lipid layer of the tear film that protects it against evaporation of the aqueous phase and is believed also to stabilize the tear film by lowering surface tension.2 Hence, meibomian lipids are essential for the maintenance of ocular surface health and integrity.

Although they share certain principal characteristics with ordinary sebaceous glands, they have several distinct differences in anatomy, location, secretory regulation, composition of their secretory product, and function.

Functional disorders of the meibomian glands, referred to today as meibomian gland dysfunction (MGD),3 are increasingly recognized as a discrete disease entity.4–8 In patients with dry eye disease, alterations in the lipid phase that point to MGD are reportedly more frequent than isolated alterations in the aqueous phase. In a study by Heiligenhaus et al.,9 a lipid deficiency occurred in 76.7% of dry eye patients compared with only 11.1% of those with isolated alterations of the aqueous phase. This result is in line with the observations by Shimazaki et al.10 of a prevalence of MGD in the absolute majority of eyes with ocular discomfort defined as dry eye symptoms. These observations noted that 64.6% of all such eyes and 74.5% of those excluding a deficiency of aqueous tear secretion were found to have obstructive MGD, or a loss of glandular tissue, or both.10 Horwath-Winter et al.11 reported MGD in 78% of dry eye patients or, if only non-Sjogren patients are considered, in 87% compared with 13% with isolated aqueous tear deficiency. It may thus be accepted that MGD is important, conceivably underestimated, and possibly the most frequent cause of dry eye disease due to increased evaporation of the aqueous tears.5,9–12

After some excellent reviews of MGD4,7,8,13,14 in the past, many new findings have been reported in recent years, and other questions remain to be identified and resolved. A sound understanding of meibomian gland structure and function and its role in the functional anatomy of the ocular surface15 is needed, to understand the contribution of the meibomian glands to dysfunction and disease. Herein, we seek to provide a comprehensive review of physiological and pathophysiological aspects of the meibomian glands.

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-1rohh1kg6i.pdf

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

TFOS DEWS II Management and Therapy Report

Iodide has been used empirically against different age-related eye diseases, including cataract. The purpose of the present study was to investigate the effect of iodide on selenite-induced cataract in rat lens. Young white rats received subcutaneously sodium selenite (20 and 30 nmol/g b.w.) on day 13 post partum (p.p.). Cataract development was measured by expert estimation and image data analysis. Potassium iodide (1.5 nmol/g b.w.) was given (1–5 times) i.p. at different times with respect to the selenite administration. Lens opacification was analyzed in selenite, selenite–iodide, iodide and control groups on day 7 after selenite administration. Iodide showed a significant protective effect against selenite cataract when injected 2 days (2 times) before selenite injection, i.e., on days 11 and 12 p.p. No significant effects on lens opacity were found: (1) after only one iodide injection (on day 12 p.p.), (2) after an initial iodide administration 1 h before selenite and (3) after injections of iodide once a day for 5 consecutive days. The protective effect of iodide was the same (about 50%) for both selenite doses used. There is a time-dependent protective influence of iodide against selenite cataract development. It is supposed that the anticataract effect of iodide could be based on direct or indirect antioxidant mechanisms.

https://iodineresearch.com/files/muranov_2004_iodide_cataracts_selenite.pdf

Protection by iodide of lens from selenite-induced cataract.

Purpose: To determine whether different contact lens care solutions for soft lenses cause damage to human conjunctival cells. Methods: Primary cultured human conj

Cytotoxicity evaluation of soft contact lens care solutions on human conjunctival fibroblasts.

Purpose: TNF-α has been suggested to participate in the pathogenesis of exfoliation glaucoma (XFG). The purpose of the present study was to investigate a hypothesized association between two common functional polymorphisms in the promoter region of the TNF-α gene (TNF-α –308 G>A, rs1800629, and TNF-α –238 G>A, rs361525) and the presence of XFG in a Caucasian population. Methods: The present case-control study comprised 408 participants (204 patients with XFG and 204 control subjects). Control subjects were matched for age and sex. Genotypes of the TNF-α –308 G>A and TNF-α –238 G>A polymorphisms were determined by polymerase chain reaction (restriction fragment length polymorphism). Results: No significant differences regarding genotype distribution or allelic frequencies were found between patients and control subjects (p>0.025). The presence of the TNF-α –308 G-allele was associated with an insignificant odds ratio of 0.98 (95% confidence interval [CI]: 0.66–1.46; p=0.99) while the presence of the TNF-α –238 G-allele was associated with an insignificant odds ratio of 0.64 (95% CI: 0.33–1.23; p=0.25). Conclusions: Our data suggest that both the TNF-α –308 G>A and the TNF-α –238 G>A polymorphisms are unlikely to be major risk factors for XFG in an European population of Caucasian descent.

/pdf/tnf-a-308-g-a-and-238-g-a-polymorphisms-are-not-major-risk-42gohm67uo.pdf

TNF-α -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma

Purpose Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between factor V Leiden, prothrombin 20210A, and retinal artery occlusion. Methods In the present retrospective case–control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of factor V Leiden and prothrombin 20210A alleles was determined by polymerase chain reaction. Results The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vstwo controls, P=0.65). Distribution of factor V Leiden genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls. Conclusion Our data suggest that factor V Leiden and prothrombin 20210A do not play a major role in patients with retinal artery occlusion.

/pdf/role-of-factor-v-leiden-and-prothrombin-20210a-in-patients-2bynp3402b.pdf

Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion

Background and Purpose— Proinflammatory cytokines including interleukin-6 (IL-6) are supposed to play a pivotal role in the development of atherosclerosis. A common polymorphism in the promoter of the IL-6 gene (IL-6 −174G>C) affects plasma IL-6 concentrations and has been suggested as a risk factor for cardiovascular disease. The aim of the present case-control study was to investigate the role of this polymorphism for retinal artery occlusion (RAO). Methods— One hundred eighty-two patients with RAO and 307 control subjects were genotyped for the IL-6 −174G>C polymorphism. Genotypes were determined by fluorogenic exonuclease (TaqMan) assay. Results— The prevalence of the CC genotype was significantly lower in patients with RAO than in control subjects (10.4% versus 19.9%; P=0.006). Homozygosity for the C allele was associated with an odds ratio of 0.50 (95% CI, 0.28 to 0.89) for RAO. Conclusions— The CC genotype of the IL-6 −174G>C polymorphism may be associated with a protective effect against RAO.

Otto Schmut

Papers

Protection by iodide of lens from selenite-induced cataract.

Cytotoxicity evaluation of soft contact lens care solutions on human conjunctival fibroblasts.

TNF-α -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma

Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion

Role of the Interleukin-6 −174 G>C Gene Polymorphism in Retinal Artery Occlusion