White Deposits Research Articles

Photoreceptor Degeneration in Homozygous Male Per2luc Mice During Aging.

The Per2luc mouse model developed by Takahashi laboratory is one of the most powerful models to study circadian rhythms in real time. In this study, we report that photoreceptors degenerate in male Per2luc mice during aging. Young (2.5- to 5-month-old) and aged (11- to 13.5-month-old) homozygous male Per2luc mice and C57BL/6J mice were used for this study. Retina structure and function were investigated via spectral domain optical coherence tomography (SD-OCT), fundus imaging, and electroretinography (ERG). Zonula occludens-1 (ZO-1) immunofluorescence was used to analyze the retinal pigment epithelium (RPE) morphology. Fundus examination revealed no difference between young Per2luc and wild-type (WT) mice. However, the fundus of aged Per2luc mice showed white deposits, suggestive of age-related drusen-like formation or microglia, which were absent in age-matched WT mice. No differences in retinal structure and function were observed between young Per2luc and WT mice. However, with age, Per2luc mice showed a significant reduction in total retinal thickness with respect to C57BL/6J mice. The reduction was mostly confined to the photoreceptor layer. Consistent with these results, we observed a significant decrease in the amplitude of a- and b-waves of the ERG in aged Per2luc mice. Analysis of the RPE morphology revealed that in aged Per2luc mice there was an increase in compactness and eccentricity with a decrease in solidity with respect to the values observed in WT, pointing toward signs of aging in the RPE of Per2luc mice. Our data demonstrate that homozygous Per2luc mice show photoreceptor degeneration during aging and a premature aging of the RPE.

EP24 Arthritis mutilans coexisting with three separate granulomatous diseases

Case report - IntroductionGranulomatous disorders are diverse in their aetiologies and presentations. We present an unusual case of severe psoriatic arthritis patient who subsequently developed multiple granulomatous diseases over time, granulomatous interstitial nephritis, granulomatous sarcoidosis with hilar lymphadenopathy and localised laryngeal granulomatous inflammation secondary to lambda type amyloidosis.Case report - Case description52-year-old gentleman with arthritis mutilans secondary to severe poorly controlled psoriatic arthritis was followed up in Rheumatology clinic. Earlier therapy with leflunomide and methotrexate provided inadequate control. Golimumab, despite giving a good response, was stopped in 2013 after 5 months of treatment due to acute kidney injury. Renal biopsy revealed granulomatous interstitial nephritis, thought to be Golimumab-induced based on the timing of usage and reversibility with discontinuation. He was then trialled on Ustekinumab and Secukinumab in 2016 and 2017 respectively with variable response.He also had a few-years history of voice change (high pitched) and sore throat which he attributed to recurrent colds. He denied dysphagia or breathlessness, and he did not have stridor. He has never smoked and only drank alcohol occasionally. ENT team noted white deposits on erythematous and thickened false vocal cords and posterior glottis with a thin web on microlaryngoscopy, which histologically proved to show granulomatous inflammation, potentially consisting of amyloid, although congo red stain was negative. On further investigation, including SAP scan, he was diagnosed with localised lambda type amyloid. Increasing throat pain and worsening dysphonia prompted change of management from conservative to a surgery at a specialist centre and an input from speech and language therapy team.During this time, consideration for Etanercept for his joint and skin disease was put on hold, pending further management of laryngeal amyloidosis. Furthermore, he presented to hospital with breathlessness in 2019, where his chest X-ray showed bulky right hilum and a follow-up CT chest revealed calcified right hilar and mediastinal lymphadenopathy, ground glass opacification and consolidation. Histology from hilar node was suggestive of sarcoidosis, with stain negative for amyloid.He underwent removal of false vocal cords for his symptomatic laryngeal amyloidosis. He continues to be followed up at the local Rheumatology, Dermatology and ENT team.Case report - DiscussionGranulomatous diseases have vast aetiologies, including infectious, immunological, neoplastic, and chemical-induced processes. The age at which they affect patients and tissue they involve also vary hugely. This is the first reported case of three seemingly unrelated granulomatous diseases occurring in a single patient with severe refractory psoriatic arthritis. Retrospective reassessment of the histology samples supported that these are three separate pathologies. It is very unusual for one patient to acquire multiple separate granulomatous diseases, which was why the diagnostic process of this patient was challenging. In this case, managing the original underlying psoriatic arthritis was particularly difficult due to interruptions of treatment for adverse drug effects and investigations and treatment of subsequent granulomatous diseases. The case also raises questions about possible currently unknown association between the pathologies.Case report - Key learning pointsKey points are the uniqueness of this case and that it highlighted the possibility of currently under-reported association between these three granulomatous conditions. As ever, a multidisciplinary approach to managing such a complex patient is important for the provision of good care.

Crystalline Deposits in New Display Cases at the Rijksmuseum: Characterisation and Origin

ABSTRACT An unusual phenomenon occurred in new display cases at the Rijksmuseum four months after their installation in April 2013. White deposits were visible on glass windows, silicone door gaskets, black structural adhesive seals, and on works of art. The works of art most affected by these deposits were bronze sculptures, wooden and waxed objects, tempera, and oil paintings. In this study the deposits were chemically characterised using (pyrolysis-)gas chromatography-mass spectrometry ((Py-)GC-MS), µ-Raman spectroscopy (µ-Raman), ion chromatography (IC), and scanning electron microscopy combined with energy dispersive X-ray spectroscopy (SEM-EDX). Five chemically different crystalline deposits were found. They were identified as organic salts of the base 2,2,6,6-tetramethyl-4-piperidinol (TMP-ol), a secondary amine, and five different carboxylic acids. It was found that TMP-ol, which is part of the UV-light stabiliser Tinuvin-770, emitted from the structural adhesive Terostat-9220. Terostat-9220 was used in large quantities in the display cases to adhere glass windows to metal parts. The carboxylic acids derived from both construction materials used to build the cases and from conservation materials present on the exhibited works of art. The carboxylic acids involved were 2,4-dichlorobenzoic acid, formic acid, methacrylic acid, palmitic acid, and an unknown carboxylic acid, respectively emitted from peroxide-cured silicone gaskets, panels of medium-density fibreboard (MDF), UV-adhesive, beeswax containing products, and from an unknown acidic conservation product or binding medium. The identification of the crystalline deposits was supported by their syntheses in the laboratory. Since 2013, similar deposits have been observed in a number of museum collections worldwide. A treatment for preventing further growth of the deposits was developed and applied in the Rijksmuseum showcases.

Role for Retinoic Acid-Related Orphan Receptor Alpha (RORα) Expressing Macrophages in Diet-Induced Obesity.

The transcription factor RORα plays an important role in regulating circadian rhythm, inflammation, metabolism, and cellular development. Herein we show a role for RORα-expressing macrophages in the adipose tissue in altering the metabolic state of mice on a high-fat diet. The expression of Rora and RORA is elevated in white adipose tissue from obese mice and humans when compared to lean counterparts. When fed a high-fat diet Rora reporter mice revealed increased expression of Rora-YFP in macrophages in white adipose tissue deposits. To further define the potential role for Rora-expressing macrophages in the generation of an aberrant metabolic state Rorafl/flLysMCre/+ mice, which do not express Rora in myeloid cells, were maintained on a high-fat diet, and metabolic parameters assessed. These mice had significantly impaired weight gain and improved metabolic parameters in comparison to Rorafl/fl control mice. Further analysis of the immune cell populations within white adipose tissue deposits demonstrates a decrease in inflammatory adipose tissue macrophages (ATM). In obese reporter mouse there was increased in Rora-YFP expressing ATM in adipose tissue. Analysis of peritoneal macrophage populations demonstrates that within the peritoneal cavity Rora-expression is limited to myeloid-derived macrophages, suggesting a novel role for RORα in macrophage development and activation, which can impact on metabolism, and inflammation.

Abstract 537: Combination of Mitochondrial and Cytosolic Antioxidant Upregulated MSC Therapy Improves Non-Alcoholic Fatty Liver Disease (NAFLD)

Introduction: Diabetes and obesity are known to cause adipose inflammation, elevated oxidative stress by reactive oxygen species (ROS) accumulation. In this report we studied the effect of human adipose derived mesenchymal stroma cells (MSCs) overexpressing antioxidants both mitochondrial (Sod2) and cytosolic (Catalase) to reduce oxidative stress and systemic inflammation in DIO mouse model. Methods: C57BL/6J male mice (4–6 weeks old) were obtained from the Jackson Lab. Obesity, glucose intolerance, and insulin resistance were induced by feeding the mice a 60% fat high-fat diet (HFD) for 12 weeks. Mouse adipose-derived MSCs and adenovirus constructs containing GFP (Null, SOD2 and Catalase), were obtained. Liver and fat tissues gene expression, liver and fat depots H& E staining and liver triglycerides (L-TG) were quantified. Results: Triglyceride assay confirmed reduced liver fat accumulation in animals that received combination -MSCs. The gene expression analysis by qPCR for liver and omental fat shows upregulation of Ucp1, Pgc1a and Prdm16 genes with concomitant increase in all antioxidant (Sod2, Sod3 and Catalase) mRNA expression. Further the systemic TNF-α levels were decreased in the mice received MSC-Sod2+catalase. Glucose tolerance showed a improvement trend with low area under curve (AUC) values for mice that received MSCs with both Sod2 and catalase upregulated compared to control null group. Discussion: The combination effect of both mitochondrial and cytosolic anti-oxidants reduced systemic inflammation and liver triglyceride levels in diet induced obesity mouse model compared to SOD2, Catalase and Null MSCs. An increase mRNA expression of genes associated with browning of white adipose tissue deposits might have contributed to improvement in NAFLD along with systemic reduction in TNF-α. Genetically modified MSC therapy can be a promising option for treating obesity and diabetes.

Chemical–physical–mechanical stability of MKG mortars under sulfate attacks

Geopolymer-based materials have attracted increasing interest in construction and infrastructure engineering due to their high mechanical properties but low carbon dioxide emissions. However, it remains unclear whether this type of material can work in a stable way in harsh environments. This study investigated the chemical–physical–mechanical stability of metakaolin-based geopolymer (MKG) mortars under the immersing actions of sodium sulfate and magnesium sulfate solutions up to 180 days by testing their visual appearance, mass, dimensions, strength, microstructure and chemical components. Results show that the immersion actions do not cause obvious changes in mass, dimensions or compressive and flexural strengths of the MKG mortars. A white deposit, consisting of magnesium hydroxide, magnesium sulfate, magnesium carbonate and magnesium silicate aluminate hydrate, appeared on the surfaces of the high-alkali MKG specimens immersed in magnesium sulfate solution for 30 days, and disappeared at later ages due to the continual consumption of magnesium hydroxide. Mg–Na exchanges occurred for the MKG mortars immersed in magnesium sulfate solution. Overall, the chemical–physical–mechanical stability of geopolymer-based materials depends on the material components and interactions with the environment. Caution should be used before any engineering applications, and relevant issues deserve further rigorous investigation in the future.

SAT-652 Increased Fibroblast Growth Factor 21 Protein Expression via in Vivo Delivery of a Liver-Specific Expression Plasmid

Fibroblast growth factor 21 (FGF21) is an important liver-secreted hormone that activates thermogenesis in white and brown fat deposits. In various models of obesity, FGF21 administration consistently facilitates weight loss and improved metabolic function. Several FGF21 variants, which have been engineered to improve protein stability and solubility in solutions containing preservatives, are currently in human clinical trials. In addition, in vivo FGF21 gene therapy using viral vector is being explored as an alternative therapeutic approach. In this study, we present a simpler method of in vivo FGF21 gene therapy, in which liver-specific delivery of an unpackaged plasmid construct expressing an HA-tagged FGF21 protein increases de novo hepatic FGF21 production and secretion in mice. Our data show that FGF21 protein expression can be successfully restored into the livers of FGF21 conditional knockout mice for at least two weeks after a single tail vein injection with the expression plasmid, and that the HA-tagged protein is secreted and readily detectable in serum. In wild-type C57BL6/J mice, in vivo plasmid delivery significantly increased hepatic FGF21 protein 2.3-fold after two weeks, and was associated with reduced body mass and a 14% reduction in fasting serum glucose. In addition, elevated hepatic FGF21 levels correlated with a 27% decrease in the ratio of fat to body mass, visibly smaller subcutaneous and visceral white fat adipocytes, and a 3.3-fold increase in uncoupling protein 1-dependent mitochondrial respiration in the white fat. Together, these data suggest that in vivo plasmid delivery may potentially be an effective strategy for promoting hepatic FGF21 expression in models of obesity. We are currently testing this hypothesis with experiments in high-fat diet-challenged mice.

Oxide Film Structure on Aluminum Alloy 6000 Series Cylindrical Ingot Surface

Electron microscopy and energy dispersion analysis are used to reveal structural features of an oxide film in the region of white deposit areas that are visually detected on the surface of cylindrical ingots of 6000 series aluminum alloy after homogenizing annealing. It is shown that a loose film of aluminum and magnesium oxides with an anomalously high Mg content (up to 45 at.%) and micropores are typical for these areas. Diffusion flow of magnesium towards the surface during homogenizing annealing gives rise to its chemical potential gradient occurring as a result of oxidation processes occurring during annealing. Reasons are determined for the occurrence of white deposit areas connected with formation at an ingot surface of mineral salt oxides and organic compounds from dried liquid used for cooling during ingot semi-continuous casting.

A novel homozygous frameshift variant in the cellular retinaldehyde-binding protein 1 (RLBP1) gene causes retinitis punctata albescens.

Retinitis punctata albescens is a form of retinitis pigmentosa characterized by white fleck-like deposits in the fundus, in most cases caused by pathogenic variants in RLBP1 gene. The purpose of this work is to report the phenotypic and genotypic data of a patient with retinitis punctata albescens carrying a deletion in the RLBP1 gene. An 8-year-old Caucasian female has been complaining of nyctalopia for the last 2 years. No other ocular symptoms were present. No relevant past medical or familiar history was described. At clinical examination, the patient's best-corrected visual acuity was 20/20 in both eyes. Anterior segment evaluation and intraocular pressure were normal in both eyes. At fundoscopy, multiple punctate whitish-yellow fleck-like lesions were observed in the proximity of temporal superior and inferior vascular arcades. Scotopic electroretinogram demonstrated severely reduced rod response, without improvement or recovery of rod system function after prolonged dark adaptation. Blood DNA samples of this patient and from her parents were screened for causal variants in RLBP1, RDH5, and PRPH2. A probable pathogenic frameshift variant was identified in homozygosity in the RLBP1 gene with an autosomal recessive transmission as another cause of retinitis punctata albescens. This DNA variant will aid ongoing functional studies and add to our understanding of the molecular pathology about RLBP1-associated retinopathies.

Heart Dysfunction Following Long-Term Murine Cytomegalovirus Infection: Fibrosis, Hypertrophy, and Tachycardia.

Human cytomegalovirus (HCMV) is associated with increased risk of chronic diseases of the heart and vasculature, including myocarditis, atherosclerosis, and transplant vasculopathy. To investigate CMV infection of the heart, murine cytomegalovirus (MCMV) was used to evaluate both acute and latent infection and the subsequent phenotypic and functional consequences of infection. Female BALB/c mice were intraperitoneally (i.p.) inoculated with 1 × 106 pfu of MCMV and evaluated at 14 and 50 days postinfection (dpi). At each time point, echocardiography was used to evaluate cardiac function and histology was conducted for phenotypic evaluation. MCMV replication in the heart was detected as early as 3 dpi and was no longer detectable at 14 dpi. Infected animals had significant cardiac pathology at 14 and 50 dpi when compared to uninfected controls. Histology revealed fibrosis of the heart as early as 14 dpi and the presence of white fibrous deposits on the surface of the heart. Functional evaluation showed significantly increased heart rate and muscle thickening in the latently infected animals when compared to the control animals. At 50 dpi, latent virus was measured by explant reactivation assay, demonstrating that MCMV establishes latency and is capable of reactivation from the heart, similar to other tissues such as spleen and salivary glands. Collectively, these studies illustrate that MCMV infection results in phenotypic alterations within the heart as early as 14 dpi, which progress to functional abnormalities during latency. These findings are similar to sinus tachycardia and hypertrophy of the heart muscle observed in cases of HCMV-induced acute myocarditis.

A Comparative Study of Green Inhibitors for Galvanized Steel in Aqueous Solutions

This study investigates the morphology, composition and corrosion resistance of hot dip galvanized (HDG) steel bolts in fresh water, 1% NaCl saltwater in the presence of protective compounds L-Tryptophan and three conventional corrosion inhibitors: Inhibitor 1-VCI (amine-carboxylates-based), Inhibitor 2 (based on carboxylate acid), and Inhibitor 3 (water-based, carboxylate acid). Quantitative tests performed include gravimetric analysis and electrochemical techniques, such as linear polarization, Tafel extrapolation, and Electrochemical Impedance Spectroscopy (EIS). Electrochemical measurements determined the polarization resistance Rp, corrosion rate vcorr, and corrosion potential Ecorr. Furthermore, Scanning Electron Microscopy (SEM) and ATR-FTIR spectrometry were used to evaluate and characterize the formed layers on the surface of hot-dip galvanized steel samples. The results reveal that upon corrosion new compounds are formed onto the exposed areas of the treated bolts such as zinc-carbonates, zinc-hydroxides, etc. The presence of these compounds on the surface of the HDG steel bolts hinders the corrosion process by reducing the rate of the anodic and cathodic reactions. The gravimetric test showed that L-tryptophan in distilled water has mass increase, resulting from the formation of white deposits on the sample surface. In fresh water and distilled water, the best corrosion resistance was achieved with Inhibitor 1-VCI, while L-tryptophan showed best results in 1% NaCl solution.

Simulation study for the formation of alkaline efflorescence on bauxite residue disposal areas following the phosphogypsum addition

Bauxite residue is a solid, highly alkaline byproduct generated in the alumina refining process. The process that forms the fine white salt deposits on the surface of bauxite residue disposal areas (BRDAs) following prolonged dry periods, and which also forms on products made from reused residues (sintered bricks, etc.), is known as efflorescence. It not only seriously affects the utilization of bauxite residue in building materials, but also creates potential dust pollution around the BRDAs, which means it would require sustained and intensive resources to manage and transform its alkalinity. Through a laboratory simulation experiment using soil leaching columns, we show that the extent of bauxite residue efflorescence is affected by many factors, including porosity, initial water content, bauxite residue particle size. The main soluble mineral precipitates of efflorescence are Na2CO3 and NaHCO3. Addition of phosphogypsum, a common amendment to reduce dispersion and promote removal of Na+ through leaching, shifted the composition of effloresced salts to favor Na2SO4·10H2O. SEM and Na K-edge X-ray absorption near-edge structure (XANES)spectroscopy demonstrated that free alkali migrates to the residue surface to precipitate as a uniform agglomerate in the efflorescence process, which also changes the chemical form of Na-containing minerals in the bauxite residue and the mesoscale spatial distribution of Na (soft X-ray scanning transmission microscopy imaging). Free alkali migration with water is the main driver of efflorescence, and this work also demonstrated that phosphogypsum can reduce the generation of alkaline efflorescence for ameliorating alkaline dust pollution from bauxite residue.

Efficacy of Topical Insulin Therapy for Chronic Trophic Ulcers in Patients with Leprosy: A Randomized Interventional Pilot Study.

Chronic trophic ulcers (CTUs), especially those located over the plantar region, are a leading cause of deformity and disability in patients with leprosy. Despite the various treatment modalities available, CTUs can be chronic and refractory to treatment. The successful use of topical insulin in various types of wounds led researchers to evaluate its safety and efficacy in the treatment of plantar CTUs. Forty-two patients who had completed a multidrug treatment for leprosy were recruited and randomized into two groups. In the test group, 23 patients received 10 units (0.1 mL) of topical insulin (Actrapid) in 1 mL of normal saline twice daily over treated areas. The placebo group (n = 19) received topical normal saline only. The primary end point was the proportion of patients with complete wound closure by 12 weeks. Secondary end points included time to healing, wound area reduction, Physician Global Assessment of Efficacy scores, and Dermatology Life Quality Index scores at the end of 12 weeks. The majority of CTUs (80%) were situated over the forefoot; the metatarsal head of the hallux was the most common site (86%). Wound healing was faster (0.61 ± 0.31 vs 0.14 ± 0.42 cm per week, P < .0001), and the number of days to complete healing was significantly shorter in the test group compared with the placebo group (31.5 ± 17.6 vs 44.3 ± 16.2 days, P = .02). The only observed adverse effect in the test group was white granular deposits over the CTU (n = 10). Topical insulin therapy may be a safe, efficacious, cheap, and easily available treatment option in CTUs among patients with leprosy.

Efficacité de la réhabilitation visuelle de patients atteints de dégénérescence marginale pellucide adaptés en lentilles sclérales SPOT

To assess visual improvementin patients with pellucidmarginaldegeneration (PMD) after fitting with SPOT® scleral contact lenses (Scleral Protection & Ocular Treatment, Laboratoires d'Appareillage Oculaire, Amphion-Les-Bains, France). We report a case series of 5 patients with PMD and unsatisfactory refractive correction managed at Clermont-Ferrand university hospital from January to December 2018 fitted with customized SPOT scleral lenses. We assessed the best-corrected visual acuity (BVCA) before and after fitting with SPOT, keratometric data and tolerability of the scleral lenses. Nine eyes of 5 patients aged 51.8±8.47 years were fitted. The BVCA was significantly improved from 0.51 logMAR (±0.39) to 0.04 logMAR (±0.07) (P<0.001). Sixty-six percent of the patients recovered optimal BVCA. No serious adverse event was reported. The presence of whitish deposits and an inordinate amount of manipulation required were the main disadvantages of the lenses. Nevertheless, all the patients considered them to be comfortable. Fitting PMD patients who have failed conventional optical devices with SPOT scleral lenses significantly improves BCVA, without serious adverse events, allowing surgery to be deferred even when it appears to be unavoidable.

Carcinoid Heart Disease: How to Diagnose and Treat in 2020?

Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.

Colmatation of reservair rocks in the operation of oil fields as a result of cation exchange

By analyzing the changes in seawater pumped to maintain reservoir pressure (FPD), the anhydrous granitoid reservoir of the White Tiger deposit, in which the cracks are partially filled with calcium minerals (calcite and lomontite), shows that these minerals interact with the injected seawater. Hydrogeochemical modeling of this process showed that cations of seawater are first sodium and then magnesium displace calcium from the lomonite exchange complex, which leads to precipitation of anhydrite and a small amount of calcite. The incoming water dissolves the anhydrite and precipitates it downstream, forming a gradually expanding annular region with a constant increase in the amount of precipitated anhydrite. As a result, there is a decrease in the permeability of the fracture medium due to the filling of the cracks with anhydrite. A large amount of calcium in the associated waters when they rise to the surface causes the precipitation of calcite in the production wells and surface equipment. The transition of drilling to ever greater depths, where the rocks contain lomontite almost everywhere, requires taking into account the phenomena of cation exchange between the injected water and the rock in the predictions of scaling.

Efficacy of visual rehabilitation of patients with pellucid marginal degeneration fitted with SPOT® scleral contact lenses

To assess visual improvement in patients with pellucid marginal degeneration (PMD) after fitting with SPOT® scleral contact lenses (Scleral Protection & Ocular Treatment, Laboratoires d'Appareillage Oculaire, Amphion-Les-Bains, France). We report a case series of 5 patients with PMD and unsatisfactory refractive correction managed at Clermont-Ferrand university hospital from January to December 2018 fitted with customized SPOT scleral lenses. We assessed the best-corrected visual acuity (BCVA) before and after fitting with SPOT, keratometric data and tolerability of the scleral lenses. Nine eyes of 5 patients aged 51.8±8.47 years were fitted. The BCVA was significantly improved from 0.51 logMAR (±0.39) to 0.04 logMAR (±0.07) (P<0.001). Sixty-six percent of the patients recovered optimal BCVA. No serious adverse event was reported. The presence of whitish deposits and an inordinate amount of manipulation required were the main disadvantages of the lenses. Nevertheless, all the patients considered them to be comfortable. Fitting PMD patients who have failed conventional optical devices with SPOT scleral lenses significantly improves BCVA, without serious adverse events, allowing surgery to be deferred even when it appears to be unavoidable.

Proteomic and cell biological profiling of the renal phenotype of the mdx-4cv mouse model of Duchenne muscular dystrophy

The X-linked inherited muscle wasting disease Duchenne muscular dystrophy, which is caused by primary abnormalities in the membrane cytoskeletal protein dystrophin, is a multi-system disorder. Highly progressive forms of dystrophinopathy are associated with a complex secondary pathophysiology, including renal dysfunction. It was therefore of interest to carry out a systematic survey of potential proteome-wide changes in the kidney of the established mdx-4cv mouse model of dystrophinopathy. Of 5878 mass spectrometrically identified kidney proteins, 82 versus 142 proteins were shown to be decreased or increased, respectively, in association with muscular dystrophy. The most decreased versus increased protein species are the ACSM3 isoform of mitochondrial acyl-coenzyme A synthetase and the FABP1 isoform of fatty acid binding protein, respectively. Both proteomic findings were verified by immunofluorescence microscopy and immunoblot analysis. Interestingly, haematoxylin/eosin staining indicated diffuse whitish deposits in the mdx-4cv kidney, and an increased intensity of Sudan Black labelling of kidney cells revealed ectopic fat deposition. Although the proteomic results and cell biological findings do not demonstrate a direct functional link between increased FABP1 and fat accumulation, the results suggest that the up-regulation of FABP1 may be related to abnormal fat metabolism. This makes FABP1 potentially a novel pathobiochemical indicator for studying kidney abnormalities in the mdx-4cv model of dystrophinopathy.

Sustainability Analysis of Marble Sector in Buner

Marble is an ornamental stone, extremely popular for use as architectural and sculptural purposes. Nonrenewable marble resources in Khyber Pakhtunkhwa (KP), Pakistan are mostly mined by conventional mining methods(producing irregular shaped blocks) instead of using mechanized mining producing regular shaped blocks.Conventional mining methods are more economical but are less environment friendly due to more quantity of wasteproduced. While, mechanized marble mining has a better recovery, reduces mining cost (processing and transportation)and is less environmentally hazardous. In this study a situation and sustainability analysis of marble mining operationsat Buner, the most productive marble mining cluster in KP, Pakistan, is carried out. Buner has about 1.4 billion tons ofmarble resources and contributes around 51 percent of total country’s marble production. Analytical Hierarchy Process(AHP) is used on the basis of key sustainability factors (economic, technical, social, environmental and safety) forselection of most sustainable mining methods. The analysis revealed that conventional mining is least sustainable andproduces maximum waste, cracks, irregular shaped blocks, high working faces, back break, rock falls and accidents. Itwas concluded and recommended that these conventional mining methods should be replaced with the more sustainablemining methods i.e. semi-mechanized (controlled blasting / expansion material) at sunny grey and get black marbledeposits and mechanized mining (rope cutting) at Bampokha No.1 and Chagharzai white marble deposits.

Sustainability Analysis of Marble Sector in Buner

Marble is an ornamental stone, extremely popular for use as architectural and sculptural purposes. Nonrenewable marble resources in Khyber Pakhtunkhwa (KP), Pakistan are mostly mined by conventional mining methods(producing irregular shaped blocks) instead of using mechanized mining producing regular shaped blocks.Conventional mining methods are more economical but are less environment friendly due to more quantity of wasteproduced. While, mechanized marble mining has a better recovery, reduces mining cost (processing and transportation)and is less environmentally hazardous. In this study a situation and sustainability analysis of marble mining operationsat Buner, the most productive marble mining cluster in KP, Pakistan, is carried out. Buner has about 1.4 billion tons ofmarble resources and contributes around 51 percent of total country’s marble production. Analytical Hierarchy Process(AHP) is used on the basis of key sustainability factors (economic, technical, social, environmental and safety) forselection of most sustainable mining methods. The analysis revealed that conventional mining is least sustainable andproduces maximum waste, cracks, irregular shaped blocks, high working faces, back break, rock falls and accidents. Itwas concluded and recommended that these conventional mining methods should be replaced with the more sustainablemining methods i.e. semi-mechanized (controlled blasting / expansion material) at sunny grey and get black marbledeposits and mechanized mining (rope cutting) at Bampokha No.1 and Chagharzai white marble deposits.