Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Clinicopathological profile, management and clinical outcomes in recurrent cases of ocular surface squamous neoplasia at a tertiary care centre.

PURPOSE: This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12 months and secondary outcome measure was complication associated with each treatment modality. RESULTS: The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12 months of follow-up in all 18 cases. CONCLUSION: The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.

Surgical outcomes of tarsofrontalis sling surgery using silicon rod versus supramaximal levator resection in unilateral congenital ptosis with poor levator function.

PURPOSE: To compare the surgical outcomes of tarsofrontalis sling surgery using silicon rod versus supramaximal levator resection in patients of unilateral congenital ptosis with poor levator function (≤ 4 mm). MATERIALS AND METHODS: This randomized control study was conducted over a period of 18 months. 44 patients were enrolled in the study group. The study population was randomly divided into two groups (22 in each group). In Group A, congenital ptosis was treated with tarsofrontalis sling surgery using silicon rod and supramaximal levator resection was done in the group B. Follow-up examination was done at postoperative day 1, one week, 1 month, 6 months and 12 months. Surgical outcome measures were change in marginal reflex distance-1 (MRD 1), vertical palpebral fissure height (VPFH) and inter-eyelid difference of margin reflex distance 1 and complications in two groups. RESULTS: The mean age of patients in group A was 7.25 ± 6.10 years ranging from 1-18 years and mean age of patients in group B was 5.64 ± 2.44 years ranging from 3 to 11 years. Good surgical outcome was obtained in 73-77% of both groups. MRD1and VPFH increased significantly after surgery from baseline in both the groups (p value < 0.001). Inter-eyelid MRD 1 difference also improved significantly in both groups following ptosis surgery. CONCLUSION: Both supramaximal levator resection and tarsofrontalis sling surgery are equally effective in cases of unilateral ptosis patients with poor levator function and should be part of the surgical armamentarium for treating congenital ptosis.

Efficacy and safety of injection Botulinum toxin in canalicular obstruction due to trauma.

Background: The treatment of epiphora has undergone tremendous change in the past, and minimally invasive techniques are being preferred over traditional surgical options. One of them is the use of Inj Botulinum toxin, but there are very few studies that have explored its role in treating post-traumatic epiphora. This study was undertaken to find out the safety and efficacy of injection Botulinum toxin in treating epiphora due to canalicular obstruction following trauma. Methods: A longitudinal interventional study was done, and a total of 50 patients were recruited. All patients were subjected to Inj Botulinum toxin in the lacrimal gland (10 units). The study was done for a period of 6 months, and patients were followed up for a period of another 6 months. Changes in Munk score, Schirmer test, and tear meniscus height were considered the main outcome measures. Results: In our study, there were 38 males and 12 females. The age of the patients varied from 24 yrs to 67 yrs. Inj Botulinum toxin was found to be effective in 80% (n = 40/50) of cases as they reported a reduction in watering from eyes after administration of this injection. The complication associated with this treatment was minimal in our study as four patients reported diplopia, whereas two patients developed Ptosis that resolved spontaneously within two months. Conclusion: Inj Botulinum toxin was found to be effective in epiphora caused by canalicular obstruction due to trauma. This treatment should be considered as an alternative treatment modality as it often leads to satisfactory reduction in epiphora in patients with less complications compared to surgical intervention.

Recurrent spontaneous subluxation of the eye globe managed with orbital decompression: A case report with literature review.

Spontaneous subluxation of the eyeball is a rare phenomenon as there are only few cases reported in the literature. It is a sight-threatening condition and very traumatising for the patient. The globe has to be reposited back within the socket immediately to save vision and to prevent exposure keratitis and optic neuropathy. In all published reports about subluxation of the eyeball, the underlying aetiology which was responsible for this condition was found. Herein, we report a case of recurrent spontaneous subluxation of the eyeball in which the cause could not be ascertained in a middle-aged male patient even after thorough clinical examination and investigation. The case was managed successfully with three-wall orbital decompression and tarsorrhaphy. The patient did not experience any episode of subluxation of the globe following surgery as orbital decompression increased the available space for the orbital contents, thereby averting its occurrence.

Evaluation of Magnesium-Phosphate Particle Incorporation into Co-Electrospun Chitosan-Elastin Membranes for Skin Wound Healing.

Major challenges facing clinicians treating burn wounds are the lack of integration of treatment to wound, inadequate mechanical properties of treatments, and high infection rates which ultimately lead to poor wound resolution. Electrospun chitosan membranes (ESCM) are gaining popularity for use in tissue engineering applications due to their drug loading ability, biocompatibility, biomimetic fibrous structure, and antimicrobial characteristics. This work aims to modify ESCMs for improved performance in burn wound applications by incorporating elastin and magnesium-phosphate particles (MgP) to improve mechanical and bioactive properties. The following ESCMs were made to evaluate the individual components' effects; (C: chitosan, CE: chitosan-elastin, CMg: chitosan-MgP, and CEMg: chitosan-elastin-MgP). Membrane properties analyzed were fiber size and structure, hydrophilic properties, elastin incorporation, MgP incorporation and in vitro release, mechanical properties, degradation profiles, and in vitro cytocompatibility with NIH3T3 fibroblasts. The addition of both elastin and MgP increased the average fiber diameter of CE (~400 nm), CMg (~360 nm), and CEMg (565 nm) compared to C (255 nm). Water contact angle analysis showed elastin incorporated membranes (CE and CEMg) had increased hydrophilicity (~50°) compared to the other groups (C and CMg, ~110°). The results from the degradation study showed mass retention of ~50% for C and CMg groups, compared to ~ 30% seen in CE and CEMg after 4 weeks in a lysozyme/PBS solution. CMg and CEMg exhibited burst-release behavior of ~6 µg/ml or 0.25 mM magnesium within 72 h. In vitro analysis with NIH3T3 fibroblasts showed CE and CEMg groups had superior cytocompatibility compared to C and CMg. This work has demonstrated the successful incorporation of elastin and MgP into ESCMs and allows for future studies on burn wound applications.

Half-fluence photodynamic therapy in peripapillary circumscribed choroidal haemangiomas.

PURPOSE: To evaluate the safety and efficacy of half-fluence photodynamic therapy (PDT) as treatment for symptomatic peripapillary circumscribed choroidal haemangiomas (CCHs). METHODS: In this prospective, interventional case series; 11 patients with symptomatic peripapillary CCHs presenting to a single centre were treated with half-fluence PDT using verteporfin 6 mg/m2 with fluence of 25 mJ/cm2 (standard is 50 mJ/cm2) and other standard settings. Patients were evaluated at baseline, four weeks, twelve weeks and twenty-four weeks post-PDT treatment with best corrected visual acuity (BCVA), ultrasonography, spectral domain optical coherence tomography (SD-OCT), visual evoked potential and angiographic studies. RESULTS: Eleven patients with peripapillary CCHs received half-fluence PDT. The BCVA significantly improved to 0.558 ± 0.118 at four weeks post-treatment (P = 0.014), to 0.494 ± 0.114 at twelve weeks (P = 0.006) and 0.441 ± 0.125 at twenty-four weeks (P = 0.007) from baseline levels of 1.017 ± 0.075 on log MAR scales. Similar improvement was observed in central macular thickness (CMT) of 78.50 ± 13.73 µm (P = 0.001) at four weeks; 114.70 ± 27.73 µm (P = 0.003) at twelve weeks and 174.60 ± 23.13 µm (P = 0.001) at twenty-four weeks post-treatment. A single session of re-treatment was required in 18% (n = 2) of patients which also showed complete resolution at last follow-up. No complications were observed without any significant change in retinal nerve fibre layer (RNFL) thickness at six months follow-up. CONCLUSIONS: Half-fluence PDT can be an effective and safe treatment option for peripapillary CCHs which results in both anatomical and functional improvements with no observable complications.

Cerebral Aspergillosis Complicating COVID Recovery.

How to cite this article: Sampley S, Bhasin D, Singh H, Mishra S. Cerebral Aspergillosis Complicating COVID Recovery. Indian J Crit Care Med 2022;26(4):535-536.

Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Outcome of pediatric retinal detachment using high-density silicone oil.

BACKGROUND: The high-density silicone oil (Densiron), a mixture of F6H8 with silicone oil, has been used in the management of retinal detachment (RD) complicated by the presence of proliferative vitreoretinopathy (PVR) with varying rate of anatomical success and visual outcomes. METHODS: We conducted a prospective interventional case series of 22 eyes in 22 children less than 18 years diagnosed with complicated retinal detachment complicated by the presence of PVR in inferior quadrant. RESULTS: The mean age of the patients was 8.45 ± 3.36 years. There were 14 male and 8 female children. Five patients presented with total RD, 5 had subtotal RD and remaining 10 with inferior retinal detachment. There were 8 children with PVR C1, 13 with PVR C2, 3 with PVR C3. All patient's had macula off RD at presentation. The anatomical success in the form of attached retina was achieved in 21 (95.45%) eyes. Standard three-port pars plana vitrectomy without scleral buckling under general anesthesia was surgical technique employed in all cases. CONCLUSION: Densiron can be an important tamponade agent in pediatric retinal detachment complicated by PVR with increased success rate of retinal re-attachment.

Enhancing the magnetic and inductive heating properties of Fe3O4 nanoparticles via morphology control.

Fe3O4 nanoparticles (NPs) with different shapes have been prepared by a 'solventless' synthesis approach to probe shape anisotropy effects on the magnetic and inductive heating properties. Various shapes including spheres, octahedrons, cubes, rods, wires, and multipods are obtained through alterations in reaction conditions such as the ratio of precursor to surfactant content and heating rate. Magnetic and Mössbauer measurements reveal better stoichiometry in anisotropic-shaped Fe3O4 NPs than that in the spherical and multipod NPs. As a result, the magnetization value of the anisotropic-shaped NPs approaches the value for bulk material (∼86 emu g-1). More surprisingly, the Verwey transition, which is a characteristic phase transition of bulk magnetite structure, is observed near 120 K in the anisotropic-shaped NPs, which further corroborates the fact that these NPs possess better stoichiometry compared to the spherical and multipod-shaped NPs. Other than the improved magnetic properties, these anisotropic-shaped NPs are more effective for hyperthermia applications. For example, compared to the conventional spherical NPs, the nanowires show much higher SAR value up to 846 W g-1, making them a potential candidate for practical hyperthermia treatment. In particular, the octahedral NPs shows an SAR value higher than the same size spherical NPs, which demonstrates the importance of occurrence of the Verwey transition in Fe3O4 NPs for better stoichiometric and higher heating.

Arjunarishta alleviates experimental colitis via suppressing proinflammatory cytokine expression, modulating gut microbiota and enhancing antioxidant effect.

Traditional ayurvedic medicine, Arjunarishta (AA) is used to treat several inflammatory conditions including dysentery associated with blood. The formulation is a decoction of Terminalia arjuna (Roxb.) Wight and Arn. (TA), Madhuca indica J.F.Gmel., Vitis vinifera L., Woodfordia fruticosa (L.) Kurz., and Saccharum officinarum L. Terminalia arjuna, a major constituent of this formulation has been recognized for anti-inflammatory effects. This study aimed at evaluating beneficial effects of AA and probable mechanism of action in Trinitrobenzenesulphonicacid (TNBS) induced colitis model. Response to AA treatment was explored through determination of disease activity index (DAI), histological assessment and damage scores, colonic pro-inflammatory cytokine/chemokine expression and estimation of oxidative stress biomarkers. Improvement in gut microbiome and plasma zinc level was also assessed. Study findings directed therapeutic effects of AA treatment in colitis model by attenuating the colitis symptoms such as weight loss, diarrhoea, blood in stool; histological damage; and downregulated expression of pro-inflammatory cytokines/chemokine (TNF-α, IL-1ß, IL-6) and MCP-1). Similarly reduced oxidative stress by decreased level of Nitric Oxide (NO), Myeloperoxidase (MPO), Malondialdehyde (MDA) and enhanced level of Catalase (CAT), Superoxide dismutase (SOD) and Reduced Glutathione (GSH) was also witnessed. In addition, an improved beneficial fecal microbiome profile and restored plasma zinc status was revealed compared to the TNBS control group. The present study directs that downregulated pro-inflammatory cytokines/chemokine expression, enhancement of antioxidant effect, increased plasma zinc status and promising role in modulating fecal microbiome might be potential mechanisms for the therapeutic effect of AA treatment against colitis.

Molecular and Cellular Factors Associated with Racial Disparity in Breast Cancer.

Recent studies have demonstrated that racial differences can influence breast cancer incidence and survival rate. African American (AA) women are at two to three fold higher risk for breast cancer than other ethnic groups. AA women with aggressive breast cancers show worse prognoses and higher mortality rates relative to Caucasian (CA) women. Over the last few years, effective treatment strategies have reduced mortality from breast cancer. Unfortunately, the breast cancer mortality rate among AA women remains higher compared to their CA counterparts. The focus of this review is to underscore the racial differences and differential regulation/expression of genetic signatures in CA and AA women with breast cancer. Moreover, immune cell infiltration significantly affects the clinical outcome of breast cancer. Here, we have reviewed recent findings on immune cell recruitment in the tumor microenvironment (TME) and documented its association with breast cancer racial disparity. In addition, we have extensively discussed the role of cytokines, chemokines, and other cell signaling molecules among AA and CA breast cancer patients. Furthermore, we have also reviewed the distinct genetic and epigenetic changes in AA and CA patients. Overall, this review article encompasses various molecular and cellular factors associated with breast cancer disparity that affects mortality and clinical outcome.

Silencing of the Hsp70-specific nucleotide-exchange factor BAG3 corrects the F508del-CFTR variant by restoring autophagy.

The protein chaperones heat shock protein 70 (Hsp70) and Hsp90 are required for de novo folding of proteins and protect against misfolding-related cellular stresses by directing misfolded or slowly folding proteins to the ubiquitin/proteasome system (UPS) or autophagy/lysosomal degradation pathways. Here, we examined the role of the Bcl2-associated athanogene (BAG) family of Hsp70-specific nucleotide-exchange factors in the biogenesis and functional correction of genetic variants of the cystic fibrosis transmembrane conductance regulator (CFTR) whose mutations cause cystic fibrosis (CF). We show that siRNA-mediated silencing of BAG1 and -3, two BAG members linked to the clearance of misfolded proteins via the UPS and autophagy pathways, respectively, leads to functional correction of F508del-CFTR and other disease-associated CFTR variants. BAG3 silencing was the most effective, leading to improved F508del-CFTR stability, trafficking, and restoration of cell-surface function, both alone and in combination with the FDA-approved CFTR corrector, VX-809. We also found that the BAG3 silencing-mediated correction of F508del-CFTR restores the autophagy pathway, which is defective in F508del-CFTR-expressing cells, likely because of the maladaptive stress response in CF pathophysiology. These results highlight the potential therapeutic benefits of targeting the cellular chaperone system to improve the functional folding of CFTR variants contributing to CF and possibly other protein-misfolding-associated diseases.

Loss of αB-crystallin function in zebrafish reveals critical roles in the development of the lens and stress resistance of the heart.

Genetic mutations in the human small heat shock protein αB-crystallin have been implicated in autosomal cataracts and skeletal myopathies, including heart muscle diseases (cardiomyopathy). Although these mutations lead to modulation of their chaperone activity in vitro, the in vivo functions of αB-crystallin in the maintenance of both lens transparency and muscle integrity remain unclear. This lack of information has hindered a mechanistic understanding of these diseases. To better define the functional roles of αB-crystallin, we generated loss-of-function zebrafish mutant lines by utilizing the CRISPR/Cas9 system to specifically disrupt the two αB-crystallin genes, αBa and αBb We observed lens abnormalities in the mutant lines of both genes, and the penetrance of the lens phenotype was higher in αBa than αBb mutants. This finding is in contrast with the lack of a phenotype previously reported in αB-crystallin knock-out mice and suggests that the elevated chaperone activity of the two zebrafish orthologs is critical for lens development. Besides its key role in the lens, we uncovered another critical role for αB-crystallin in providing stress tolerance to the heart. The αB-crystallin mutants exhibited hypersusceptibility to develop pericardial edema when challenged by crowding stress or exposed to elevated cortisol stress, both of which activate glucocorticoid receptor signaling. Our work illuminates the involvement of αB-crystallin in stress tolerance of the heart presumably through the proteostasis network and reinforces the critical role of the chaperone activity of αB-crystallin in the maintenance of lens transparency.

Cannabinoid Signaling in Cancer.

The family of chemical structures that interact with a cannabinoid receptor are broadly termed cannabinoids. Traditionally known for their psychotropic effects and their use as palliative medicine in cancer, cannabinoids are very versatile and are known to interact with several orphan receptors besides cannabinoid receptors (CBR) in the body. Recent studies have shown that several key pathways involved in cell growth, differentiation and, even metabolism and apoptosis crosstalk with cannabinoid signaling. Several of these pathways including AKT, EGFR, and mTOR are known to contribute to tumor development and metastasis, and cannabinoids may reverse their effects, thereby by inducing apoptosis, autophagy and modulating the immune system. In this book chapter, we explore how cannabinoids regulate diverse signaling mechanisms in cancer and immune cells within the tumor microenvironment and whether they impart a therapeutic effect. We also provide some important insight into the role of cannabinoids in cellular and whole body metabolism in the context of tumor inhibition. Finally, we highlight recent and ongoing clinical trials that include cannabinoids as a therapeutic strategy and several combinational approaches towards novel therapeutic opportunities in several invasive cancer conditions.

Size-dependent magnetic and inductive heating properties of Fe3O4 nanoparticles: scaling laws across the superparamagnetic size.

An efficient heat activating mediator with an enhanced specific absorption rate (SAR) value is attained via control of the iron oxide (Fe3O4) nanoparticle size from 3 to 32 nm. Monodispersed Fe3O4 nanoparticles are synthesized via a seed-less thermolysis technique using oleylamine and oleic acid as the multifunctionalizing agents (surfactant, solvent and reducing agent). The inductive heating properties as a function of particle size reveal a strong increase in the SAR values with increasing particle size up to 28 nm. In particular, the SAR values of ferromagnetic nanoparticles (>16 nm) are strongly enhanced with the increase of ac magnetic field amplitude than that for the superparamagnetic (3-16 nm) nanoparticles. The enhanced SAR values in the ferromagnetic regime are attributed to the synergistic contribution from the hysteresis and susceptibility loss. Specifically, the 28 nm Fe3O4 nanoparticles exhibit an enhanced SAR value of 801 W g-1 which is nearly an order higher than that of the commercially available nanoparticles.

Study on Impact of Iron and Folic Acid on the Plasma Trace Minerals in Pregnant Anemic Women.

Iron deficiency anemia is one of the causes that lead to significant mortality and morbidity among pregnant women and fetus. The present study was undertaken to explore oral iron supplementation can modify the metal contents in pregnant anemic women. Iron and folic acid supplementations was given to 500 anemic women (mild = 200, moderate = 200, and severe = 100) and 100 age matched non-anemic controls daily for 100 days. Blood index values and plasma trace minerals were estimated as per standard protocols. Haemoglobin and ferritin levels were found significantly increased (p < 0.001) in anemic and control subjects after treatment. Moreover, the serum transferring receptor levels and total iron binding capacity were found significantly decreased in all treated groups. Iron (Fe), zinc (Zn) and copper (Cu) levels were found increased (p < 0.01) after oral iron supplementation groups. Moreover, selenium (Se) manganese (Mn) and were found to be decreased in all treated groups. Data provides the conclusion that iron and folic acid supplementation recovered the essential trace minerals, except manganese, which may lead to various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.

Comparison of balloon dacryocystorhinostomy with conventional endonasal endoscopic dacryocystorhinostomy for relief of acquired distal nasolacrimal drainage obstruction and its impact on quality of life: A prospective, randomized, controlled study.

BACKGROUND: We compared balloon dacryocystorhinostomy with conventional endoscopic dacryocystorhinostomy for the management of acquired distal nasolacrimal obstruction and the quality of life post procedure. METHODS: 98 patients, aged 10-73 years, were recruited and randomized into 2 groups of 49 each who underwent conventional endoscopic dacryocystorhinostomy (group 1) and 9 mm balloon assisted endoscopic dacryocystorhinostomy (group 2). Follow-up sessions were conducted at 3, 6 and 12 months post-op. RESULTS: Group 2 showed significantly shorter mean operative time (25.10 min versus 29.82; p < 0.001), lesser pain in the post-op evening (mean 2.12 versus 2.9 on NRS-11 pain scale; p < 0.001) as well as on first post-op day (mean 1.08 versus 1.73; p < 0.001). Success was achieved in 89.79% in group 1 and 93.87% in group 2 at 3 months (p = 0.46) which declined due to recurrences to 85.71% and 87.75% respectively at 12 months (p = 0.76). Complications occurred in 14 cases in group 1 and in 10 cases in group 2 (p = 0.34). All were minor. Mean GBI scores (for quality of life assessment) at 12 months follow-up were 27.20 and 28.38 respectively (p = 0.08). CONCLUSION: The efficacy, safety and quality of life of balloon dacryocystorhinostomy and conventional endoscopic dacryocystorhinostomy were comparable. In addition, balloon dacryocystorhinostomy had significantly shorter operative time and lesser post-op pain.

Expression of Cataract-linked γ-Crystallin Variants in Zebrafish Reveals a Proteostasis Network That Senses Protein Stability.

The refractivity and transparency of the ocular lens is dependent on the stability and solubility of the crystallins in the fiber cells. A number of mutations of lens crystallins have been associated with dominant cataracts in humans and mice. Of particular interest were γB- and γD-crystallin mutants linked to dominant cataracts in mouse models. Although thermodynamically destabilized and aggregation-prone, these mutants were found to have weak affinity to the resident chaperone α-crystallin in vitro To better understand the mechanism of the cataract phenotype, we transgenically expressed different γD-crystallin mutants in the zebrafish lens and observed a range of lens defects that arise primarily from the aggregation of the mutant proteins. Unlike mouse models, a strong correlation was observed between the severity and penetrance of the phenotype and the level of destabilization of the mutant. We interpret this result to reflect the presence of a proteostasis network that can "sense" protein stability. In the more destabilized mutants, the capacity of this network is overwhelmed, leading to the observed increase in phenotypic penetrance. Overexpression of αA-crystallin had no significant effects on the penetrance of lens defects, suggesting that its chaperone capacity is not limiting. Although consistent with the prevailing hypothesis that a chaperone network is required for lens transparency, our results suggest that αA-crystallin may not be efficient to inhibit aggregation of lens γ-crystallin. Furthermore, our work implicates additional inputs/factors in this underlying proteostasis network and demonstrates the utility of zebrafish as a platform to delineate mechanisms of cataract.