Epithelial ingrowth following laser in situ keratomileusis (LASIK): prevalence, risk factors, management and visual outcomes

The number of laser in situ keratomileusis (LASIK) procedures is continuing to rise. Since its first application for correcting simple refractive errors over 25 years ago, the role of LASIK has extended to treat other conditions, including postkeratoplasty astigmatism/ametropia, postcataract surgery refractive error and presbyopia, among others. The long-term effectiveness, predictability and safety have been well established by many large studies. However, due to the creation of a potential interface between the flap and the underlying stroma, interface complications such as infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth may occur. Post-LASIK epithelial ingrowth (PLEI) is an uncommon complication that usually arises during the early postoperative period. The reported incidence of PLEI ranged from 0%–3.9% in primary treatment to 10%–20% in retreatment cases. It can cause a wide spectrum of clinical presentations, ranging from asymptomatic interface changes to severe visual impairment and flap melt requiring keratoplasty. PLEI can usually be treated with mechanical debridement of the affected interface; however, additional interventions, such as alcohol, mitomycin C, fibrin glue, ocular hydrogel sealant, neodymium:yttriumaluminum garnet laser and amniotic membrane graft, may be required for recurrent or refractory cases. The aims of this review are to determine the prevalence and risk factors of PLEI; to describe its pathogenesis and clinical features and to summarise the therapeutic armamentarium and the visual outcome of PLEI

A rare case of occupational lung disease – Talcosis

Talcosis/ Talcpneumoconiosis is one of the rarer forms of magnesium silicate induced lung disease, It usually occurs in the fourth decade and affects people working in talc related industries like roof, shingle, pharmaceutical companies, talcum powder industries, electric ceramics, rubber industry etc. We report a case of talc pneumoconiosis/talcosis in a 51yr old male who presented with breathlessness and dry cough for the past 5 yrs and progressively worsening for the past 5 days. Who was working in a talcum powder manufacturing company for >28yrs in the packaging section. The diagnosis was possible by history, clinical examination, Chest X-ray, PFT/DLCO, HRCT chest, Bronchoscopy & Trans bronchial lung biopsy showing interstitial fibrosis

A critical role for lymphatic endothelial heparan sulfate in lymph node metastasis

Abstract Background Lymph node metastasis constitutes a key event in tumor progression. The molecular control of this process is poorly understood. Heparan sulfate is a linear polysaccharide consisting of unique sulfate-modified disaccharide repeats that allow the glycan to bind a variety of proteins, including chemokines. While some chemokines may drive lymphatic trafficking of tumor cells, the functional and genetic importance of heparan sulfate as a possible mediator of chemokine actions in lymphatic metastasis has not been reported. Results We applied a loss-of-function genetic approach employing lymphatic endothelial conditional mutations in heparan sulfate biosynthesis to study the effects on tumor-lymphatic trafficking and lymph node metastasis. Lymphatic endothelial deficiency in N-deacetylase/N-sulfotransferase-1 (Ndst1), a key enzyme involved in sulfating nascent heparan sulfate chains, resulted in altered lymph node metastasis in tumor-bearing gene targeted mice. This occurred in mice harboring either a pan-endothelial Ndst1 mutation or an inducible lymphatic-endothelial specific mutation in Ndst1. In addition to a marked reduction in tumor metastases to the regional lymph nodes in mutant mice, specific immuno-localization of CCL21, a heparin-binding chemokine known to regulate leukocyte and possibly tumor-cell traffic, showed a marked reduction in its ability to associate with tumor cells in mutant lymph nodes. In vitro modified chemotaxis studies targeting heparan sulfate biosynthesis in lymphatic endothelial cells revealed that heparan sulfate secreted by lymphatic endothelium is required for CCL21-dependent directional migration of murine as well as human lung carcinoma cells toward the targeted lymphatic endothelium. Lymphatic heparan sulfate was also required for binding of CCL21 to its receptor CCR7 on tumor cells as well as the activation of migration signaling pathways in tumor cells exposed to lymphatic conditioned medium. Finally, lymphatic cell-surface heparan sulfate facilitated receptor-dependent binding and concentration of CCL21 on the lymphatic endothelium, thereby serving as a mechanism to generate lymphatic chemokine gradients. Conclusions This work demonstrates the genetic importance of host lymphatic heparan sulfate in mediating chemokine dependent tumor-cell traffic in the lymphatic microenvironment. The impact on chemokine dependent lymphatic metastasis may guide novel therapeutic strategies

Biochar synthesis from mineral and ash-rich waste biomass, part 2: characterization of biochar and co-pyrolysis mechanism for carbon sequestration

The increase in mineral and ash-rich waste biomass (MWB) generation in emerging economies poses critical environmental problems and bottlenecks the solid waste and wastewater treatment systems. Transforming these MWB such as sewage sludge from wastewater treatment (SSW) to biochar can be a sustainable method for their disposal and resource recovery. However, such biochar has limited applicability due to the relatively low organic content and possibly contaminated nature of SSW. This may be offset through combined pyrolysis with other MWB, which can also support municipal solid waste management. Studies on this MWB co-pyrolysis are lacking and have not yet seen successful long-term implementation. This work is the second part of authors’ research encompassing an analytical and lab-scale investigation of biochar production from MWB through pyrolysis for the case of Chennai city, India. Here, the physicochemical properties of biochar derived from lab-scale co-pyrolysis of SSW with other MWB such as anaerobic digestate from waste to energy plants of food, kitchen or market waste fermentation, and banana peduncles (BP) collected from vegetable markets and their thermolysis mechanism are comprehensively investigated for purpose of carbon sequestration. Also, a novel preliminary investigation of the effect of sample weight (scaling effect) on the analytical pyrolysis of biomass (BP as model substrate) is undertaken to elucidate its impact on the heat of pyrolysis and carbon distribution in resultant biochar. The maximum carbon sequestration potential of the derived biochar types is 0.22 kg CO2 kg−1 biomass. The co-pyrolysis of MWB is exothermic and governed by the synergetic effects of the components in blends with emission profiles following the order CO2 > CH4 > CO > NH3. Co-pyrolysis reduced the heavy metal enrichment in SSW biochar. The derived biochars can be an immediate source of N, P and S in nutrient-deficient acidic soils. The biochar has only up to 4-ring polyaromatic compounds and a residence time longer than 1 h at 500 °C is necessary to improve carbonization. The heat released during analytical pyrolysis of the model biomass and distribution of carbon in the resultant biochar are significantly influenced by scaling effects, drawing attention to the need for a more detailed scaling investigation of biomass pyrolysis

YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the first time that VEGF-C signaling is necessary for valve morphogenesis. We have also discovered that the transcriptional co-activators YAP and TAZ are required to maintain PROX1 expression in LVs and LVVs in response to VEGF-C signaling. Deletion o

Young onset diabetes in Asian Indians is associated with lower measured and genetically determined beta-cell function:an INSPIRED study

Aims/hypothesis: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored. Methods: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan’s Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank. Results: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively. Conclusions/interpretation: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function

Activation of Crtc2/Creb1 in skeletal muscle enhances weight loss during intermittent fasting

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating during the feeding period. ADF downregulated most of the mitochondrial electron transport genes, and other regulators of mitochondrial function, that were substantially reversed by Crtc2-driven transcription. Glucocorticoids acted with AMPK to drive atrophy and mitophagy, which was reversed by Crtc2/Creb1 signaling. Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb1 regulates metabolism and weight loss

Intelligent Chiral Sensing Based on Supramolecular and Interfacial Concepts

Of the known intelligently-operating systems, the majority can undoubtedly be classed as being of biological origin. One of the notable differences between biological and artificial systems is the important fact that biological materials consist mostly of chiral molecules. While most biochemical processes routinely discriminate chiral molecules, differentiation between chiral molecules in artificial systems is currently one of the challenging subjects in the field of molecular recognition. Therefore, one of the important challenges for intelligent man-made sensors is to prepare a sensing system that can discriminate chiral molecules. Because intermolecular interactions and detection at surfaces are respectively parts of supramolecular chemistry and interfacial science, chiral sensing based on supramolecular and interfacial concepts is a significant topic. In this review, we briefly summarize recent advances in these fields, including supramolecular hosts for color detection on chiral sensing, indicator-displacement assays, kinetic resolution in supramolecular reactions with analyses by mass spectrometry, use of chiral shape-defined polymers, such as dynamic helical polymers, molecular imprinting, thin films on surfaces of devices such as QCM, functional electrodes, FET, and SPR, the combined technique of magnetic resonance imaging and immunoassay, and chiral detection using scanning tunneling microscopy and cantilever technology. In addition, we will discuss novel concepts in recent research including the use of achiral reagents for chiral sensing with NMR, and mechanical control of chiral sensing. The importance of integration of chiral sensing systems with rapidly developing nanotechnology and nanomaterials is also emphasized