Surgical Options for the Refractive Correction of Keratoconus: Myth or Reality

Keratoconus provides a decrease of quality of life to the patients who suffer from it. The treatment used as well as the method to correct the refractive error of these patients may influence on the impact of the disease on their quality of life. The purpose of this review is to describe the evidence about the conservative surgical treatment for keratoconus aiming to therapeutic and refractive effect. The visual rehabilitation for keratoconic corneas requires addressing three concerns: halting the ectatic process, improving corneal shape, and minimizing the residual refractive error. Cross-linking can halt the disease progression, intrastromal corneal ring segments can improve the corneal shape and hence the visual quality and reduce the refractive error, PRK can correct mild-moderate refractive error, and intraocular lenses can correct from low to high refractive error associated with keratoconus. Any of these surgical options can be performed alone or combined with the other techniques depending on what the case requires. Although it could be considered that the surgical option for the refracto-therapeutic treatment of the keratoconus is a reality, controlled, randomized studies with larger cohorts and longer follow-up periods are needed to determine which refractive procedure and/or sequence are most suitable for each case

Comparison of visual and refractive results of Toric Implantable Collamer Lens with bioptics for myopic astigmatism

PURPOSE: To compare visual and refractive results of Toric Implantable Collamer Lens (TICL) and bioptics (ICL plus excimer corneal surgery) to treat myopic astigmatism. METHODS: Eighty-one eyes underwent TICL implantation and 83 eyes were treated with bioptics (corneal ablation was performed between 1.5 and 6 months after ICL implantation). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, adverse events, safety, and efficacy were evaluated 12 months postoperatively. RESULTS: At 12 months postoperatively, the mean spherical equivalent was -0.15 ± 0.36 diopters (D) in the TICL group and -0.08 ± 0.26 D in the bioptics group (p = 0.099). Sixty-six (81.5 %) and 78 (94.0 %) eyes were within ±0.50 D for TICL and bioptics groups, respectively. The mean Snellen UDVA was not statistically different between both procedures (p = 0.909); 53 (65.4 %) and 54 (65.1 %) eyes achieved at least 20/25 or better in TICL and bioptics groups, respectively. No eye had lost more than two lines of CDVA, and 32.1 % of eyes (26/81) in the TICL group and 57.8 % of eyes (48/83) in the bioptics group had better postoperative UDVA than preoperative CDVA (p < 0.001). Safety was not statistically different between groups (p = 0.464) while efficacy was significantly higher in the bioptics group (p = 0.000). Two eyes with a TICL were treated to correct TICL decentration. CONCLUSIONS: Bioptics showed slightly better outcomes in some clinical measures such as uncorrected visual acuity, efficacy, and refractive predictability. TICL implantation shows reliable results similar to bioptics. A single procedure with TICL implantation might be preferred, eliminating the inherent risks of laser treatments and the risks of a second surgical procedure.The authors have no proprietary interests in any of the materials mentioned in this article. This research was supported in part by a Universitat de Valencia Research Grant to Robert Montes-Mico (#SAF2009-13342 and #SAF2008-01114-E#) and Fundacao para a Ciencia e Tecnologia of Portugal through a Grant to Paulo Fernandes (#FCT-SFRH-BD-34303-2007#)

The Radiative Corrections to the Mass of the Kink Using an Alternative Renormalization Program

In this paper we compute the radiative correction to the mass of the kink in $\phi^4$ theory in 1+1 dimensions, using an alternative renormalization program. In this newly proposed renormalization program the breaking of the translational invariance and the topological nature of the problem, due to the presence of the kink, is automatically taken into account. This will naturally lead to uniquely defined position dependent counterterms. We use the mode number cutoff in conjunction with the above program to compute the mass of the kink up to and including the next to the leading order quantum correction. We discuss the differences between the results of this procedure and the previously reported ones.Comment: 8 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:0806.036

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility

Deubiquitinating enzymes are now emerging as potential therapeutic targets that control many cellular processes, but few have been demonstrated to control cell motility. Here, we show that ubiquitin-specific protease 17 (USP17) is rapidly and transiently induced in response to chemokines SDF-1/CXCL12 and IL-8/CXCL8 in both primary cells and cell lines, and that its depletion completely blocks chemokine-induced cell migration and cytoskeletal rearrangements. Using live cell imaging, we demonstrate that USP17 is required for both elongated and amoeboid motility, in addition to chemotaxis. USP17 has previously been reported to disrupt Ras localization and we now find that USP17 depletion blocks chemokine-induced subcellular relocalization of GTPases Cdc42, Rac and RhoA, which are GTPases essential for cell motility. Collectively, these results demonstrate that USP17 has a critical role in cell migration and may be a useful drug target for both inflammatory and metastatic disease

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance

Hyaluronan Binding Motifs of USP17 and SDS3 Exhibit Anti-Tumor Activity

BACKGROUND: We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells. Furthermore, USP17 and SDS3 mutually interact with each other to block cell proliferation in HeLa cells but the mechanism for this inhibition in cell proliferation is not known. We wished to investigate whether the HABMs of USP17 were responsible for tumor suppression activity. METHODOLOGY/PRINCIPAL FINDINGS: Similarly to USP17, we have identified that SDS3 also has three consecutive HABMs and shows direct binding with hyaluronan (HA) using cetylpyridinium chloride (CPC) assay. Additionally, HA oligosaccharides (6-18 sugar units) competitively block binding of endogenous HA polymer to HA binding proteins. Thus, administration of HA oligosaccharides antagonizes the interaction between HA and USP17 or SDS3. Interestingly, HABMs deleted USP17 showed lesser interaction with SDS3 but retain its deubiquitinating activity towards SDS3. The deletion of HABMs of USP17 could not alter its functional regulation on SDS3-associated HDAC activity. Furthermore, to explore whether HABMs in USP17 and SDS3 are responsible for the inhibition of cell proliferation, we investigated the effect of USP17 and SDS3-lacking HABMs on cell proliferation by soft agar, apoptosis, cell migration and cell proliferation assays. CONCLUSIONS: Our results have demonstrated that these HABMs in USP17 and its substrate SDS3 are mainly involved in the inhibition of anchorage-independent tumor growth

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease

ABSTRACT: Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxelbased morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies