Search

The essential COPI coat mediates retrieval of transmembrane proteins at the Golgi and endosomes following recruitment by the small GTPase, Arf1. ArfGAP proteins regulate COPI coats, but molecular details for COPI recognition by ArfGAPs remain elusive. Biochemical and biophysical data reveal how β′-COP propeller domains directly engage the yeast ArfGAP, Glo3, with a low micromolar binding affinity. Calorimetry data demonstrate that both β′-COP propeller domains are required to bind Glo3. An acidic patch on β′-COP (D437/D450) interacts with Glo3 lysine residues located within the BoCCS (binding of coatomer, cargo, and SNAREs) region. Targeted point mutations in either Glo3 BoCCS or β′-COP abrogate the interaction in vitro, and loss of the β′-COP/Glo3 interaction drives Ste2 missorting to the vacuole and aberrant Golgi morphology in budding yeast. These data suggest that cells require the β′-COP/Glo3 interaction for cargo recycling via endosomes and the TGN, where β′-COP serves as a molecular platform to coordinate binding to multiple proteins, including Glo3, Arf1, and the COPI F-subcomplex.

AIM: To investigate the efcacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) (ranibizumab) in treatment of retinopathy of prematurity (ROP). METHODS: A retrospective study of 24 infants (48 eyes) was conducted from April 2017 to July 2018. All infants were diagnosed with ROP and primarily treated with intravitreal anti-VEGF Ranibizumab (IVR). The treatment success was dened as complete regression of retinopathy and vascularization into zone 3. RESULTS: A total of 48 eyes were treated with ranibizumab. Mean birth weight was 1.47±0.32 kg. Gestational age at birth was 32.25±1.32wk, and post-menstrual age at treatment was 36.08±1.61wk. Aggressive posterior ROP was found in 41.7% of subjects. Mean follow-up period was 9.58±1.97 months. Treatment success was observed in 36/48 eyes (75%) with primary intervention only. Remaining six infants [12/48 eyes (25%)] required secondary laser to achieve treatment success. Retreatment occurred at a mean of 7.8 weeks after initial IVR treatment (range 6-10wk). CONCLUSION: Intravitreal anti-VEGF treatment of ROP with ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence.

The localization of proteins to the Golgi complex is a dynamic process requiring sorting signals in the cytosolic domains of resident Golgi proteins and retrograde vesicular trafficking. Disruptions in these signals or in the retrograde pathways often lead to mislocalization of Golgi proteins to the vacuole in budding yeast. The extent of vacuolar mislocalization can be quantified through colocalization of GFP-tagged Golgi proteins with fluorescent dyes that mark either the vacuole limiting membrane or the vacuole lumen. Manders' colocalization coefficient (MCC) is a useful tool for quantifying the degree of colocalization. However, the dilution of fluorescence signal intensity that occurs when GFP-tagged Golgi proteins mislocalize to the much larger vacuole is problematic for thresholding the images prior to calculating the MCC. In this chapter, we describe the use of Multi-Otsu thresholding in ImageJ to quantify the degree of GFP-tagged protein mislocalization to the vacuole. Furthermore, these methods can be applied to other colocalization events within the cell.

Integrating computational chemistry and toxicology can improve the read-across analog approach to fill data gaps in chemical safety assessment. In read-across, structure-related parameters are compared between a target chemical with insufficient test data and one or more materials with sufficient data. Recent advances have focused on enhancing the grouping or clustering of chemicals to facilitate toxicity prediction via read-across. Analog selection ascertains relevant features, such as physical-chemical properties, toxicokinetic-related properties (bioavailability, metabolism, and degradation pathways), and toxicodynamic properties of chemicals with an emphasis on mechanisms or modes of action. However, each human health end point (genotoxicity, skin sensitization, phototoxicity, repeated dose toxicity, reproductive toxicity, and local respiratory toxicity) provides a different critical context for analog selection. Here six end point-specific, rule-based schemes are described. Each scheme creates an end point-specific workflow for filling the target material data gap by read-across. These schemes are intended to create a transparent rationale that supports the selected read-across analog(s) for the specific end point under study. This framework can systematically drive the selection of read-across analogs for each end point, thereby accelerating the safety assessment process.

Objective: The literature predicting difficulties during Laparoscopic Cholecystectomy (LC) for Acute Gallstone Pancreatitis (AGP) is mainly focused on the timing of operation. In our experience, LC for AGP is rarely difficult irrespective of the timing of operation. The aim of this study was to assess intra- operative difficulties in mild AGP patients to verify this observation. Material and Methods: A retrospective analysis of all consecutive patients who underwent LC for mild AGP between 2014 and 2018 in a single centre was performed. Patients with known alcohol abuse, post-endoscopic retrograde cholangiopancreaticography (ERCP) induced pancreatitis, and those with chronic pancreatitis were excluded. Univariate weighted analysis was performed with 11 factors, with a linear threshold boundary defined as the mean distance between the four degrees of difficulty (DoD 1-4). Results: Ninety-six patients (Male= 33, median age= 56; Female= 63, median age= 52) were analysed. Majority of the patients were an ASA of two (n= 50; 52%) with a median BMI of 28 (range 18-50). Five procedures were technically difficult (DoD≥ 3) and only one procedure was converted to open operation. Univariate analysis showed that duration of pancreatitis >6 days (p= 0.002) and evidence of acute cholecystitis (p< 0.05) are associated with a difficult LC (DoD≥ 3). The rest of the factors did not influence DoD. Conclusion: Based on this result, we suggest that LC for mild AGP is rarely difficult, and this finding can be used in practice for selecting these patients for training lists.

Deciphering mechanisms controlling SNARE localization within the Golgi complex is crucial to understanding protein trafficking patterns within the secretory pathway. SNAREs are also thought to prime coatomer protein I (COPI) assembly to ensure incorporation of these essential cargoes into vesicles, but the regulation of these events is poorly understood. Here, we report roles for ubiquitin recognition by COPI in SNARE trafficking and in stabilizing interactions between Arf, COPI, and Golgi SNAREs in Saccharomyces cerevisiae. The ability of COPI to bind ubiquitin, but not the dilysine motif, through its N-terminal WD repeat domain of β′-COP or through an unrelated ubiquitin-binding domain is essential for the proper localization of Golgi SNAREs Bet1 and Gos1. We find that COPI, the ArfGAP Glo3, and multiple Golgi SNAREs are ubiquitinated. Notably, the binding of Arf and COPI to Gos1 is markedly enhanced by ubiquitination of these components. Glo3 is proposed to prime COPI–SNARE interactions; however, Glo3 is not enriched in the ubiquitin-stabilized SNARE–Arf–COPI complex but is instead enriched with COPI complexes that lack SNAREs. These results support a new model for how posttranslational modifications drive COPI priming events crucial for Golgi SNARE localization.

The evolutionary rates of functionally related genes often covary. We present a gene coevolution network inferred from examining nearly 3 million orthologous gene pairs from 332 budding yeast species spanning ~400 million years of evolution. Network modules provide insight into cellular and genomic structure and function. Examination of the phenotypic impact of network perturbation using deletion mutant data from the baker’s yeast Saccharomyces cerevisiae , which were obtained from previously published studies, suggests that fitness in diverse environments is affected by orthologous gene neighborhood and connectivity. Mapping the network onto the chromosomes of S. cerevisiae and Candida albicans revealed that coevolving orthologous genes are not physically clustered in either species; rather, they are often located on different chromosomes or far apart on the same chromosome. The coevolution network captures the hierarchy of cellular structure and function, provides a roadmap for genotype-to-phenotype discovery, and portrays the genome as a linked ensemble of genes.

Raman spectroscopy is a fast and sensitive technique able to identify molecular changes in biological specimens. Herein, we report on three cases where Raman microspectroscopy was used to distinguish normal vs. oesophageal adenocarcinoma (OAC) (case 1) and Barrett’s oesophagus vs. OAC (cases 2 and 3) in a non-destructive and highly accurate fashion. Normal and OAC tissues were discriminated using principal component analysis plus linear discriminant analysis (PCA-LDA) with 97% accuracy (94% sensitivity and 100% specificity) (case 1); Barrett’s oesophagus vs. OAC tissues were discriminated with accuracies ranging from 98 to 100% (97–100% sensitivity and 100% specificity). Spectral markers responsible for class differentiation were obtained through the difference-between-mean spectrum for each group and the PCA loadings, where C–O–C skeletal mode in β-glucose (900 cm−1), lipids (967 cm−1), phosphodioxy (1296 cm−1), deoxyribose (1456 cm−1) and collagen (1445, 1665 cm−1) were associated with normal and OAC tissue differences. Phenylalanine (1003 cm−1), proline/collagen (1066, 1445 cm−1), phospholipids (1130 cm−1), CH2 angular deformation (1295 cm−1), disaccharides (1462 cm−1) and proteins (amide I, 1672/5 cm−1) were associated with Barrett’s oesophagus and OAC tissue differences. These findings show the potential of using Raman microspectroscopy imaging for fast and accurate diagnoses of oesophageal pathologies and establishing subtle molecular changes predisposing to adenocarcinoma in a clinical setting. Graphical abstract Graphical abstract demonstrating how oesophageal tissue is processed through Raman mapping analysis in order to detect spectral differences between stages of oesophageal transformation to adenocarcinoma Electronic supplementary material The online version of this article (10.1007/s00216-020-02637-1) contains supplementary material, which is available to authorized users.

Introduction:COVID-19 pandemic has multiple ocular manifestations. We report 2 cases of central serous chorioretinopathy, following COVID19 infection. Case Presentation: We diagnosed two middle aged patients with central serous chorioretinopathy one week post COVID-19 infection. Both patients were admitted in COVID-19 ward. Case 1 was a male diabetic and required ventilator assisted respiration. Case 2 was a female patient with no systemic diseases. Both patients were given intravenous (IV) methylprednisolone for 2 weeks followed by oral prednisolone. Case 1developed CSCR in right eye while the other patient developed CSCR in both eyes. Conclusion: The possibility of developing CSCR should be kept in mind by the treating physician in Covid 19 patients treated with steroids. Early involvement of ophthalmologist can lead to timely and effective management of same

Orthologous gene coevolution—which refers to gene pairs whose evolutionary rates covary across speciation events—is often observed among functionally related genes. We present a comprehensive gene coevolution network inferred from the examination of nearly three million orthologous gene pairs from 332 budding yeast species spanning ∼400 million years of eukaryotic evolution. Modules within the network provide insight into cellular and genomic structure and function, such as genes functioning in distinct cellular compartments and DNA replication. Examination of the phenotypic impact of network perturbation across 14 environmental conditions using deletion mutant data from the baker’s yeast Saccharomyces cerevisiae suggests that fitness in diverse environments is impacted by orthologous gene neighborhood and connectivity. By mapping the network onto the chromosomes of S. cerevisiae and the opportunistic human pathogen Candida albicans, which diverged ∼235 million years ago, we discovered that coevolving orthologous genes are not clustered in either species; rather, they are most often located on different chromosomes or far apart on the same chromosome. The budding yeast coevolution network captures the hierarchy of eukaryotic cellular structure and function, provides a roadmap for genotype-to-phenotype discovery, and portrays the genome as an extensively linked ensemble of genes.

The second wave of COVID-19 in India was associated with higher incidence of Mucormycosis. We report a rare case of 40-year-old Asian male, with Type 2 diabetes mellitus who presented with bilateral sudden loss of vision, ptosis, proptosis, total ophthalmoplegia and central retinal artery occlusion. Computed tomography followed by magnetic resonance imaging was suggestive of bilateral sinusitis, orbital cellulitis, optic neuritis and gross intracranial involvement. Considering his general condition and guarded prognosis for survival, exenteration was deferred. After detailed literature research, we found very few reports of bilateral orbital involvement in cases of COVID-19 associated ROCM. Even after early diagnosis and prompt treatment of ROCM, patient succumbed to the illness. Covid 19 associated bilateral rhino-orbital-cerebral mucormycosis may be a marker of mortality in the affected population.

Copper (Cu) nanocomposite catalysts with gallium (Ga) and aluminum (Al) were prepared using the simultaneous co-precipitation digestion method. The catalysts were characterized by N2 adsorption, N2...

Background: Elective surgery is the treatment of choice for symptomatic giant hiatus hernia (GHH), and quality of life (QoL) has become an important outcome measure following surgery. The aim of this study is to review the literature assessing QoL following repair of GHH. Methodology: A systematic literature search was performed by two reviewers independently to identify original studies evaluating QoL outcomes after GHH surgery. MeSH terms such as paraoesophageal; hiatus hernia; giant hiatus hernia and quality of life were used in the initial search. Original studies in English language using validated questionnaires on humans were included. Review articles, conference abstracts and case reports and studies with duplicate data were excluded. Results: Two hundred and eight articles were identified on initial search, of which 38 studies (4404 patients) were included. Studies showed a significant heterogeneity in QoL assessment tools, surgical techniques and follow-up methods. All studies assessing both pre-operative and post-operative QoL (n = 31) reported improved QoL on follow-up after surgical repair of GHH. Improvement in QoL following GHH repair was not affected by patient age, surgical technique or the use of mesh. Recurrence of GHH after surgery may, however, adversely impact QoL. Conclusion: Surgical repair of GHH improved QoL scores in all the 38 studies. The impact of recurrence on QoL needs further assessment. The authors also recommend uniform reporting of surgical outcomes in future studies.

Background: Patients with a giant hiatus hernia may present with acute symptoms caused by obstruction, strangulation, perforation and uncontrolled bleeding. Emergency surgical repair has been associated with significant mortality and even greater morbidity. The aim of this study is to investigate the short-term outcomes following emergency repair of giant hiatus hernias.Methods: Data were retrospectively collected for all patients who underwent emergency surgical repair of giant hiatus hernia in a university teaching hospital between 2009 and 2019. Outcomes were short-term morbidity and mortality. We also assessed the association of clinical predictor covariates, including age, ASA class and time to surgery, with risk for major morbidity.Results: Thirty-seven patients with a median age of 68 years were identified. Following surgery, 9 patients (24.3%) developed organ dysfunction that required admission to the intensive care unit. Two patients (5.4%) underwent revision surgery and 3 (8.1%) developed pneumothorax that necessitated chest drain insertion. The commonest complication was pneumonia, which occurred in 13 patients (35.1%). Two deaths (5.4%) occurred within 30 days from surgery.Conclusions: Emergency repair of giant hiatus hernia is associated with high rates of major morbidity, which includes poor functional status, further interventions, repeat surgery, and admission to the intensive care unit. Larger studies are warranted for long-term follow-up to assess post-operative quality of life is needed for asymptomatic patients and for those undergoing emergency surgery.

Barrett’s oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett’s oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett’s oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett’s oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett’s oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett’s oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials.

Direct one-pot hydrogenation of furfural (FFR) to cyclopentanone (CPO) was investigated over different silica-supported Pd catalysts. Among these, 4% Pd on fumed silica (4%Pd/f-SiO2) showed remarkable results, achieving almost 98% furfural (FFR) conversion with ∼89% selectivity and 87% yield to cyclopentanone at 165 °C and 500 psig H2 pressure. More interestingly, the fumed-silica-supported catalyst tuned the selectivity toward the rearrangement product, i.e., cyclopentanone, whereas all of the other supports were found to give ring hydrogenation as well as side chain hydrogenation products due to their parent Brönsted acidity and specific support properties. X-ray diffraction data revealed the presence of different phases of the face-centered cubic lattice of metallic Pd along with lowest crystallite size of 15.6 nm in the case of the silica-supported Pd catalyst. However, Pd particle size was found to be in the range of 5–13 nm with even dispersion over the silica support, confirmed by high-resolution transmission electron microscopy analysis. While studying the effect of reaction parameters, it was observed that lower temperature gave low furfural conversion of 58% with only 51% CPO selectivity. Similarly, higher H2 pressure lowered CPO selectivity with subsequent increase in 2-methyl furan and ring hydrogenation product 2-methyl furan and 2-methyl tetrahydrofuran. Thus, as per the requirement, the product selectivity can be tuned by varying the type of support and/or the reaction parameters suitably. With the help of several control experiments and the characterization data, a plausible reaction pathway was proposed for the selective formation of cyclopentanone.

The acid functionality of montmorillonite clay K 10 (MMT-K 10) was found to play a key role to give 1,2-pentanediol (1,2-PeDO) in Pd catalysed furfural hydrogenation. Among various Pd loadings on MMT-K 10, 3% Pd/MMT-K 10 catalyst exhibited excellent performance giving almost complete conversion of FFR and the highest selectivity of 66% to 1,2-PeDO. Py-IR of the catalyst evidenced the presence of Bronsted acidity which was responsible in C5-O cleavage of furan ring after the formation of furfuryl alcohol which is the first step intermediate in FFR hydrogenation. At a lower temperature of 140 °C, highest selectivity of 56% was achieved for FAL while increase in temperature to 220 °C, enhanced the selectivity to 1,2-PeDO. Keeping the temperature constant at 220 °C, increase in H 2 pressure from 500 to 750 psig, resulted in decrease in 1,2-PeDO selectivity from 66 to 34% with proportionate increase in THFAL selectivity. Thus as per the requirement, the product selectivities can be tailored by varying the reaction parameters suitably. Several control experiments were also performed the results of which combined with the characterization data allowed to propose a plausible reaction pathway for the formation of 1,2-PeDO.

Both alkyl esters and γ-valerolactone (GVL) derived from levulinic acid (LA) have applications as renewable transportation fuel/fuel additives. Non-noble metal cobalt supported on La2O3 catalyst was developed for efficient cascade LA hydrogenation to GVL via esterification. LA hydrogenation in methanol alone yielded methyl levulinate (MeLA) as a major product along with 43% of GVL. Interestingly, hydrogenation in water gave almost complete selectivity to GVL; nevertheless, it was associated with significant metal leaching. Suppression of metal leaching and enhancement in selectivity to GVL could be achieved by a methanol/water (95:5) solvent system. XRD analysis of La2O3-supported catalysts evidenced the characteristic peaks of a mixture of La2O3 and La(OH)3 phases. Basicity, as well as acidity, of the catalyst as determined by CO2 and NH3 TPD was due to these La2O3, Co–La, and La(OH)3 phases which played an important role in directing the product selectivity in levulinic acid hydrogenation. At the low te...

Various iridium supported carbon catalysts were prepared and screened for the direct hydrogenation of furfural (FFR) to 2-methyl furan (2-MF). Amongst these, 5% Ir/C showed excellent results with complete FFR conversion and highest selectivity of 95% to 2-MF at a very low H2 pressure of 100 psig. Metallic (Ir°) and oxide (IrO2) phases of Ir catalyzed the first step hydrogenation involving FFR to FAL and subsequent hydrogenation to 2-MF, respectively. This was confirmed by XPS analysis and some control experiments. At a low temperature of 140 °C, almost equal selectivities of FAL (42%) and 2-MF (43%) were observed, while the higher temperature (220 °C) favored selective hydrodeoxygenation. At optimized temperature, 2-MF was formed selectively while higher pressure and higher catalyst loading favored ring hydrogenation of furfural rather than side chain hydrogenation. With the combination of several control experimental results and detailed catalyst characterization, a plausible reaction pathway has been proposed for the selective formation of 2-MF. The selectivity to various other products in FFR hydrogenation can be manipulated by tailoring the reaction conditions over the same catalyst.

Single step conversion of furfural to ring hydrogenation and decarbonylation products, 2-methyltetrahydrofuran (2-MeTHF) and tetrahydrofuran (THF) in high selectivity was achieved by controlling the particle size of Pd/C catalyst. The particle size variation of Pd/C catalysts in the range of 3.8 to 22 nm could be achieved by employing different reducing agents. Of particular interest was the NaBH4 reduced catalyst (Pd−B/C), which gave the lowest crystallite size of 4.8 nm due to incorporation of B into the inner lattices of Pd−Pd. This phase was evidenced by a characteristic XRD peak of Pd−B at 2θ=38.85 O as well as a shift of (111) peak (40.07 O) of Pd towards the lower value (39.8 O). As compared to formaldehyde reduced catalyst (Pd−F/C), Pd−B/C catalyst completely suppressed the formation of furfuryl alcohol to give > 65 % selectivity to 2-MeTHF and THF. At 180 OC, almost equal distribution of side chain hydrogenation and ring opening products, 2-MF (45 %) and PeDO (37 %), respectively, was observed while, higher temperature clearly favoured ring hydrogenation and decarbonylation reactions to give 2-MeTHF and THF.

The aim of this study was to determine whether Raman spectroscopy combined with chemometric analysis can be applied to interrogate biofluids (plasma, serum, saliva and urine) towards detecting oesophageal stages through to oesophageal adenocarcinoma (normal/squamous epithelium, inflammatory, Barrett's, low-grade dysplasia [LGD], high-grade dysplasia [HGD], and oesophageal adenocarcinoma [OAC]). The chemometric analysis of the spectral data was performed using principal component analysis (PCA), successive projections algorithm (SPA) or genetic algorithm (GA) followed by quadratic discriminant analysis (QDA). The GA-QDA model using a few selected wavenumbers for saliva and urine samples achieved 100% classification for all classes. For plasma and serum, the GA-QDA model achieved excellent accuracy in all oesophageal stages (>90%). The main GA-QDA features responsible for sample discrimination were: 1012 cm (C-O stretching of ribose), 1336 cm (Amide III and CH wagging vibrations from glycine backbone), 1450 cm (methylene deformation), and 1660 cm (Amide I). The results of this study are promising and support the concept that Raman on biofluids may become a useful and objective diagnostic tool to identify oesophageal disease stages from squamous epithelium to OAC. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Diagnostic tools for the detection of early-stage oesophageal adenocarcinoma (OAC) are urgently needed. Our aim was to develop an accurate and inexpensive method using biofluids (plasma, serum, saliva or urine) for detecting oesophageal stages through to OAC (squamous; inflammatory; Barrett's; low-grade dysplasia; high-grade dysplasia; OAC) using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. ATR-FTIR spectroscopy coupled with variable selection methods, with successive projections or genetic algorithms (GA) combined with quadratic discriminant analysis (QDA) were employed to identify spectral biomarkers in biofluids for accurate diagnosis in a hospital setting of different stages through to OAC. Quality metrics (Accuracy, Sensitivity, Specificity and F-score) and biomarkers of disease were computed for each model. For plasma, GA-QDA models using 15 wavenumbers achieved 100% classification for four classes. For saliva, PCA-QDA models achieved 100% for the inflammatory stage and high-quality metrics for other classes. For serum, GA-QDA models achieved 100% performance for the OAC stage using 13 wavenumbers. For urine, PCA-QDA models achieved 100% performance for all classes. Selected wavenumbers using a Student's t-test (95% confidence interval) identified a differentiation of the stages on each biofluid: plasma (929 cm−1 to 1431 cm−1, associated with DNA/RNA and proteins); saliva (1000 cm−1 to 1150 cm−1, associated with DNA/RNA region); serum (1435 cm−1 to 1573 cm−1, associated with methyl groups of proteins and Amide II absorption); and, urine (1681 cm−1 to 1777 cm−1, associated with a high frequency vibration of an antiparallel β-sheet of Amide I and stretching vibration of lipids). Our methods have demonstrated excellent efficacy for a rapid, cost-effective method of diagnosis for specific stages to OAC. These findings suggest a potential diagnostic tool for oesophageal cancer and could be translated into clinical practice.

Partial hemifacial hyperplasia is a rare congenital malformation characterized by prominent unilateral overdevelopment of some of the hard and soft tissues of the face. This uncommon diagnosis should be considered while examining facial asymmetry. We report a case of slowly enlarging right facial swelling which turned out to be enlarged zygomtic arch. Complete evaluation led us to believe continued condylar hyperactivity as the underlying reason for worsening deformity. We offer an explanation for the same. Minimal surgical intervention led to significant aesthetic improvement which was patients main concern.