Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration.

OBJECTIVE: To analyse the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). RESULTS: The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. CONCLUSION: Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.

Ocular complications secondary to diode laser-assisted eyebrow epilation.

We describe two cases of ocular complications secondary to Diode laser assisted eyebrow epilation. Both included patients were women who underwent an eyebrow epilation procedure with Diode laser. A few hours after the procedure they started complaining with photophobia and blurred vision. They were diagnosed with anterior acute uveitis and treated with topical steroids and mydriatics. During the follow-up the presence of sequelae derived from the laser procedure (mydriasis and corectopia in both patients, cataract in the second one) was confirmed. Laser hair removal of the eyebrows can induce irreversible eye damage. Complete and reliable information regarding the potential side effects of this procedure and proper use of appropriate safety devices is mandatory. We point out the importance of the potential ocular side effects associated with these cosmetic devices.

Genistein does not inhibit TGF-beta1-induced conversion of human dermal fibroblasts to myofibroblasts.

Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

Ocular complications secondary to diode laser-assisted eyebrow epilation. / Complicaciones oculares secundarias a depilación de las cejas con láser diodo.

We describe two cases of ocular complications secondary to Diode laser assisted eyebrow epilation. Both included patients were women who underwent an eyebrow epilation procedure with Diode laser. A few hours after the procedure they started complaining with photophobia and blurred vision. They were diagnosed with anterior acute uveitis and treated with topical steroids and mydriatics. During the follow-up the presence of sequelae derived from the laser procedure (mydriasis and corectopia in both patients, cataract in the second one) was confirmed. Laser hair removal of the eyebrows can induce irreversible eye damage. Complete and reliable information regarding the potential side effects of this procedure and proper use of appropriate safety devices is mandatory. We point out the importance of the potential ocular side effects associated with these cosmetic devices.

Recommendations for eye care during the alarm state by the coronavirus disease pandemic COVID-19. / Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19.

OBJECTIVE: Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID-19). METHODS: COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of maximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. RESULTS: The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of personal protective equipment in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. CONCLUSIONS: During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up.

The expression of CD73 on pathological B-cells is associated with shorter overall survival of patients with CLL.

CD73 is a membrane-bound enzyme that catalyzes the extracellular conversion of adenosine monophosphate to adenosine. Adenosine is thought to play a role in promoting tumor growth and survival together with suppressing the host immune responses, which contribute to the multistep process of tumorigenesis. Here, we studied the expression of this antigen in chronic lymphocytic leukemia (CLL). The expression of CD73 was analyzed by multiparametric flow cytometry on normal and pathological B-cells from peripheral blood and bone marrow samples from 71 patients with CLL. Pathological B-cells expressed significantly lower levels of CD73 than normal B-cells (p<0.01). Patients with splenomegaly showed a higher expression of CD73 on pathological B-cells than patients without splenomegaly (p<0.05). The expression of CD73 also correlated with beta-2-microglobulin levels (p<0.05). Clinically, patients with higher levels of CD73 versus those with lower expression presented with shorter overall survival (median OS of 65 vs. 113 months, p<0.05). Our data indicate that CD73 may play a role in CLL pathophysiology, is correlated with poor clinical and biological prognostic factors and may be of potential value as a prognostic marker and therapeutic target.

Early Changes during Skin Repair Using Tissue-Engineered Dermal Template in a Full-Thickness Burn.

Rapid wound closure in extensively burned patients has remained one of the major unresolved issues of medicine. Integra® is the most widely established artificial skin, which is composed of a porous matrix of cross-linked bovine collagen and chondroitin 6-sulphate covered by a semi-permeable silicone layer. We present here a (immuno)histological study of a severely burned patient with a full-thickness burn treated with a tissue-engineered dermal template (Integra®) and split-thickness skin graft-based protocol. Immunohistochemical investigation of the artificial dermis revealed that immune cell infiltration reached its peak on day 10. Tissue immunophenotyping found an increase in CD3+ cells over the course of the study as well as CD4 and CD8 positivity on day 40, indicating remaining T-cell subpopulations. We observed weak/no infiltration of NK cells (CD56+). In conclusion, the use of bi-layer Integra® represents a feasible and safe procedure resulting in formation of non-irritating dermal substitutes.

Leber's idiopathic stellate neuroretinitis: diagnostic and therapeutic conflicts. / Neurorretinitis estrellada idiopática de Leber: conflictos diagnósticos y terapéuticos.

Three cases of patients with decreased visual acuity and papillitis at onset with subsequent macular star development after a few weeks are presented. Complementary tests were unremarkable in all included patients. Based on this clinical context, they were diagnosed with Leber's idiopathic stellate neuroretinitis, were treated with corticosteroids, as well as with antibiotics in 2cases. All patients showed favourable outcomes, although signs of papillary atrophy were observed in the affected eyes. Leber's idiopathic stellate neuroretinitis diagnosis can be challenging due to the wide spectrum of conditions that have to be ruled out. In addition, macular star may appear later on, which should not exclude its diagnosis. Use of antibiotics and/or corticosteroids is controversial considering its benign nature, but should be considered in selected severe cases. Moreover, the routine use of complementary tests should be carefully evaluated, mainly those that can be aggressive and/or expensive, which should be rationally used.

Organic waste as a sustainable feedstock for platform chemicals.

Biorefineries have been established since the 1980s for biofuel production, and there has been a switch lately from first to second generation feedstocks in order to avoid the food versus fuel dilemma. To a lesser extent, many opportunities have been investigated for producing chemicals from biomass using by-products of the present biorefineries, simple waste streams. Current facilities apply intensive pre-treatments to deal with single substrate types such as carbohydrates. However, most organic streams such as municipal solid waste or algal blooms present a high complexity and variable mixture of molecules, which makes specific compound production and separation difficult. Here we focus on flexible anaerobic fermentation and hydrothermal processes that can treat complex biomass as a whole to obtain a range of products within an integrated biorefinery concept.

Production of carboxylates from high rate activated sludge through fermentation.

The aim of this work was to study the key parameters affecting fermentation of high rate activated A-sludge to carboxylates, including pH, temperature, inoculum, sludge composition and iron content. The maximum volatile fatty acids production was 141mgCg(-1) VSSfed, at pH 7. Subsequently the potential for carboxylate and methane production for A-sludge from four different plants at pH 7 and 35°C were compared. Initial BOD of the sludge appeared to be key determining carboxylate yield from A-sludge. Whereas methanogenesis could be correlated linearly to the quantity of ferric used for coagulation, fermentation did not show a dependency on iron presence. This difference may enable a strategy whereby A-stage sludge is separated to achieve fermentation, and iron dosing for phosphate removal is only implemented at the B-stage.

Syphilitic placoid chorioretinitis. A case-report. / Coriorretinitis placoide sifilítica. Caso clínico.

CLINICAL CASE: We report the case of a 45-year-old woman, with unremarkable past medical history, who presented with acute visual loss in her left eye due to bilateral posterior uveitis. After the screening, she was diagnosed with acute syphilitic placoid chorioretinitis and was treated with intravenous penicillin. DISCUSSION: Clinical manifestations of ocular syphilis are extremely heterogeneous and may mimic several aetiologies. Anti-treponema treatment usually induces a quick and positive response in affected patients. Prompt and proper diagnosis of these patients is crucial, although anatomical and functional damage may persist.

Study of association of CTLA4 gene variants to non-anterior uveitis.

This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.

Integrated side-stream reactor for biological nutrient removal and minimization of sludge production.

Integrated processes to reduce in situ the sludge production in wastewater treatment plants are gaining attention in order to facilitate excess sludge management. In contrast to post-treatments, such as anaerobic digestion which is placed between the activated sludge system and dewatering processes, integrated technologies are placed in the sludge return line. This study evaluates the application of an anoxic side-stream reactor (SSR) which creates a physiological shock and uncouples the biomass metabolism and diverts the activity from assimilation for biosynthesis to non-growth activities. The effect of this system in biological nutrient removal for both nitrogen and phosphorus was evaluated for the anaerobic, anoxic and aerobic reactors. The RedOx potential within the SSR was maintained at -150 mV while the sludge loading rate was modified by increasing the percentage of recycled activated sludge feed to the SSR (0 and 40% at laboratory scale and 0, 10, 50 and 100% at pilot scale). The use of the SSR presented a slight reduction of phosphorus removal but maintained the effluent quality to the required discharge values. Nitrogen removal efficiency increased from 75 to 86% while reducing the sludge production rate by 18.3%.

[Bilateral herpetic keratouveitis in an immunocompetent patient]. / Queratouveítis herpética bilateral en paciente inmunocompetente.

CASE REPORT: We report the case of an immunocompetent male who presented with a limbal-adjacent scleritis and interstitial keratitis in the left eye. A few days later a new dendritiform ulcer in his right eye and bilateral progressive worsening with granulomatous uveitis in both eyes were observed. A thorough review of systems revealed positive serum IgM titles for herpes simplex virus. DISCUSSION: In the context of a bilateral keratouveitis refractory to conventional treatment it is mandatory to rule out the herpetic origin based on the different forms of clinical presentation of this virus.

[Treatment of presumed tuberculous uveitis affecting the posterior segment: diagnostic confirmation and long term outcomes]. / Tratamiento de las uveítis tuberculosas presuntas del segmento posterior: confirmación diagnóstica y resultados a largo plazo.

OBJECTIVE: To determine the level of agreement with the presumed diagnosis and long term clinical outcomes after antituberculous therapy (ATT) in a group of patients with presumed tuberculous uveitis (PTU) affecting the posterior segment. METHODS: Retrospective case series. RESULTS: A total of 17 patients with chronic refractory or newly diagnosed uveitis affecting the posterior segment were included. All included patients were diagnosed with PTU and received ATT. Median follow-up after ATT was 34 months (range 2-60). Complete control of inflammation was observed in 14/17 patients (82.3%) during the treatment period, and only 4/17 patients (23.5%) had a uveitis relapse over the entire follow-up period after ATT. All patients who had uveitis relapses (4/4), but none from the remaining group (0/13), required immunosuppressive therapy of some kind after ATT. The response to ATT was able to confirm diagnosis of PTU in 14/17 (82.3%) included patients. CONCLUSION: When a clinical suspicion of PTU affecting the posterior segment exists, ATT may be highly effective for both confirming the diagnosis and resolving the inflammatory process. Thus, ATT may offer additional advantages, such as preventing latent-tuberculosis reactivations due to immunosuppressive therapy, and decreasing the number and/or severity of uveitis relapses in some patients. Prospective, randomized studies including a larger number of patients are required to support these and other potential advantages of ATT in such patients.

Biocatalysed sulphate removal in a BES cathode.

Sulphate reduction in a biological cathode and physically separated from biological organic matter oxidation has been studied in this paper. The bioelectrochemical system was operated as microbial fuel cell (for bioelectricity production) to microbial electrolysis cell (with applied voltage). Sulphate reduction was not observed without applied voltage and only resulted when the cathodic potential was poised at -0.26V vs. SHE, with a minimum energy requirement of 0.7V, while maximum removal occurred at 1.4V applied. The reduction of sulphate led to sulphide production, which was entrapped in the ionic form thanks to the high biocathode pH (i.e. pH of 10) obtained during the process.

Minimization of sludge production by a side-stream reactor under anoxic conditions in a pilot plant.

This study evaluates the application of an anoxic side-stream reactor in the sludge return line of a conventional activated sludge system for the reduction of biomass production. The oxidation-reduction potential was maintained at -150 mV while the applied sludge loading rate was modified by changing the percentage of return sludge treated in this reactor. The observed yield from the conventional system (0.513 kg VSS kg(-1) COD) was continuously reduced when the portion of return sludge treated was increased. A maximum reduction of 18.3% of the observed yield was obtained treating the whole sludge return line. The sludge age maintained through the experiment. The organic matter removal was not deteriorated, even improved, by the proposed plant modification. Thus, simply applying an anoxic side-stream reactor would decrease the final volume of waste sludge while maintaining the sludge retention time and would, in fact, decrease the economic costs in terms of sludge handling.

Adalimumab specifically induces CD3(+) CD4(+) CD25(high) Foxp3(+) CD127(-) T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study.

AIM: To explore immunoregulatory and anti-inflammatory pathways specifically targeted by a subcutaneous anti-TNFαdrug-adalimumab-which might be relevant for controlling refractory uveitis. DESIGN: Non-randomized pilot intervention study on the effects of adalimumab on Treg populations and plasma VEGF levels in refractory uveitis patients. Inflammatory and immunological parameters were measured in 12 patients before therapy, and 1 and 6 months after therapy, and analyzed in the context of ophthalmological outcomes. The results were compared with those obtained in 10 systemic prednisone-treated uveitis patients. RESULTS: After 1 month of treatment, all patients responded, with 67% of adalimumab group and 80% of the corticosteroid group achieving inactivity (P=0.5). Unlike steroid-treated patients, a significant increase in T-regulatory CD4(+) CD25(high) Foxp3(+) CD127(-) cells was observed in adalimumab patients after 1 month of treatment, and maintained after 6 months (P=0.003). A significant adalimumab-specific drop in plasma VEGF was observed after 1 and 6 months of treatment (P=0.019). In every single patient, Tregs but not VEGF correlated with disease activity. CONCLUSIONS: In refractory uveitis patients treated with adalimumab, clinical efficacy may be mediated through upregulation of Tregs in addition to modulation of VEGF-mediated inflammatory pathways. These biological properties, which were not observed in patients treated with corticosteroids, may reflect the specificity of TNF-αtargeting.

Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review.

To assess the effectiveness of ketorolac vs control for prevention of acute pseudophakic cystoid macular edema (CME). The following databases were searched: Medline (1950-June 11, 2011), The Cochrane Library (Issue 2, 2011), and the TRIP Database (up to 11 June 2011), using no language or other limits. Randomized controlled clinical trials (RCTs) were included that consisted of patients with acute pseudophakic cystoid macular edema, those comparing ketorolac with control, and those having at least a minimum follow-up of 28 days. In the four RCTs evaluating ketorolac vs control, treatment with ketorolac significantly reduced the risk of CME development at the end of treatment (≈ 4 weeks) compared to control (P=0.008; 95% confidence interval (0.03-0.58)). When analyzed individually, each individual study was statistically nonsignificant in its findings with the exception of one study. When the pooled relative risk was calculated, the large sample size of this systematic review led to overall statistical significance, which is attributable to the review's large sample size and not to the individual studies themselves. In this systematic review of four RCTs, two of which compared ketorolac with no treatment and two of which evaluated ketorolac vs placebo drops, treatment with ketorolac significantly reduced the risk of developing CME at the end of ≈ 4 weeks of treatment compared with controls. These results, however, should be interpreted with caution considering the paucity of large randomized clinical trials in the literature.

Enhancing aerobic granulation for biological nutrient removal from domestic wastewater.

This study focuses on the enhancement of aerobic granulation and biological nutrient removal maintenance treating domestic wastewater. Two sequencing batch reactors (SBRs) were inoculated with either only floccular sludge (100%-floc SBR) or supplemented with 10% crushed granules (90%-floc SBR). Granules developed in both reactors. The 100%-floc SBR achieved 75% of nitrogen and 93% of phosphorus removal at the end of the performance, but some floccular sludge remained in the system. The 90%-floc SBR became fully granulated and finished with 84% and 99% of nitrogen and phosphorus removal, respectively. Regarding biological phosphorus removal, nitrite was identified as an inhibitor of the process. Nitrite levels lower than 5 mg N-NO2-L(-1) were used for anoxic phosphate uptake while higher concentrations inhibited the process.