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Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 ( p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores ( p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores ( p < 0.001), whereas Group 2 did not ( p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.

Purpose: To assess the rate of mental health diagnoses and selective serotonin reuptake inhibitor (SSRI) prescribing before and during the Coronavirus Disease 2019 pandemic., Methods: We conducted a cross-sectional study at an ambulatory pediatric clinic. A prepandemic (June 2018 to June 2019) and intrapandemic (June 2020 to June 2021) cohort were reviewed. The rate of mental health visits and new SSRI prescriptions were compared. Chi-squared analyses demonstrated a variance of statistical significance., Results: From 15,414 encounters (9,791 prepandemic and 5,623 intrapandemic), 397 mental health encounters were identified. 231 (4.1%) encounters occurred during the pandemic (vs. 1.7% prepandemic) and 63 (27.3%) SSRIs were prescribed (vs. 5.4% prepandemic). Mental health encounters (prevalence ratio 2.42, 95% confidence interval, 1.99-2.95, p < .001) and SSRI prescriptions (prevalence ratio 5.03, 95% confidence interval, 2.58-9.82, p < .001) were higher during the pandemic., Discussion: Our findings demonstrate increased rates of SSRI prescribing and mental health diagnoses during the Coronavirus Disease 2019 pandemic, suggesting an increased incidence of these conditions. Clinicians should be prepared to manage and screen for mental health conditions., (Published by Elsevier Inc.)

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer's test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 ( p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Background: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia., Methods: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months., Results: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome., Conclusions: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.)., (Copyright © 2022 Massachusetts Medical Society.)

Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups were compared. It is worth noting that the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs. 6.1 ± 1.3 IVTs; p = 0.0004). Therefore, TALF used as an adjuvant to RBZ reduces the need for RBZ-IVT retreatment with optimal visual and anatomic results.

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 10 6 CD34 + cells/kg) was 1 (range 1-4) and the median PLX administration time before apheresis was 11 h (range 1-18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1-5) and the mean number of CD34 + cells collected was 2.95 × 10 6 /kg (range 0-30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/μL was 11 days (range 3-31) and the median time to platelet recovery >20 × 10 3 /μL was 13 days (range 5-69). At 100 days after auto-HCT, the platelet count was 137 × 10 9 /L (range 7-340), the ANC was 2.3 × 10 9 /L (range 0.1-13.0), and the hemoglobin concentration was 123 g/L (range 79-165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34 + cell concentration on day +4 or low CD34 + cell yield on apheresis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards.

The Sitnikov problem is a classical problem broadly studied in physics which can represent an illustrative example of chaotic scattering. The relativistic version of this problem can be attacked by using the post-Newtonian formalism. Previous work focused on the role of the gravitational radius λ on the phase space portrait. Here we add two relevant issues on the influence of the gravitational radius in the context of chaotic scattering phenomena. First, we uncover a metamorphosis of the KAM islands for which the escape regions change insofar as λ increases. Second, there are two inflection points in the unpredictability of the final state of the system when λ≃0.02 and λ≃0.028. We analyze these inflection points in a quantitative manner by using the basin entropy. This work can be useful for a better understanding of the Sitnikov problem in the context of relativistic chaotic scattering. In addition, the described techniques can be applied to similar real systems, such as binary stellar systems, among others.

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined., Patients and Methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020., Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 10 9 /L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1)., Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19., Competing Interests: Competing interestsThe author(s) declare that they have no conflict of interests., (© The Author(s) 2020.)

Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetonide-loaded liposome formulation (TA-LF) as primary therapy in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods: Twelve eyes of 12 patients with ME secondary to BRVO were exposed to a topical instillation of 1 drop of TA-LF (TA 0.2%) 6 times a day for 12 weeks to evaluate safety and efficacy. Best corrected visual acuity (BCVA) intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit. In addition, the morphology of TA-LF was analyzed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Patients presented a significant improvement of BCVA and CFT without significant IOP modification ( P  = 0.94). Treated eyes showed BCVA improvement from 40 ± 12.05 to 64.83 ± 15.97 letters and CFT reduction from 682.91 ± 278.60 to 271.58 ± 57.66 μm after 12 weeks of TA-LF therapy ( P  < 0.001). No adverse events, including IOP rising, were registered. SEM analysis of liposomal formulations showed that liposome (LP) size depends on its concentration. As the concentration of TA increased, the average size of LPs and the number of larger particles increased as well. TEM study displayed that LP formulation efficiently solubilizes TA crystals in nanoparticles and encapsulates them. Conclusion: LPs can function as nanocarriers of TA and they could be used as topical ophthalmic primary therapy instead of intravitreal drugs in patients with ME secondary to BRVO.

Purpose: To culturally adapt into Spanish and validate the outcome "Pain: Adverse psychological response" (code 1306) in patients with chronic pain., Methods: A three-stage study was conducted: (a) translation and cultural adaptation, (b) content validation, and (c) clinical validation., Findings: The Spanish version of the outcome "Pain: Adverse psychological response" has high content validity ( 0.91). Fourteen indicators were organized into two factors. This version offers good reliability in both inter-observer agreement (kappa = 0.72) and internal consistency (alpha = 0.89)., Conclusions: The Spanish adaptation of "Pain: Adverse psychological response" is a reliable and valid instrument for the measurement of emotional aspects of chronic pain., Implications for Nursing Practice: The Spanish adaptation of this outcome offers nurses a set of structured indicators to measure the adverse emotional impact of chronic pain., (© 2019 NANDA International, Inc.)

Background and Purpose: The measurement of the effects of chronic pain on the patients is a challenge for nurses. The purpose was to translate into Spanish and to assess the psychometrics of the indicators of the nursing outcome "Pain: disruptive effects.", Methods: A three-stage study: (a) translation and cultural adaptation, (b) content validation, (c) clinical validation in 10 healthcare centers., Results: The Spanish version of the outcome "Pain: disruptive effects" has high content validity (CVI = .90) with 17 indicators organized into three factors. The Inter-observer agreement was good (kappa = .66) and the internal consistency high (alpha = .90)., Conclusions: The 17 indicators of the outcome "Pain: disruptive effects" has evidence of reliability and validity for assessing the harmful effects of chronic pain., (© Copyright 2019 Springer Publishing Company, LLC.)

Pain has a major impact on health and quality of life. Since the level of knowledge of painful conditions can influence how these are addressed and managed, assessing this knowledge in patients becomes crucial. As a result, it is necessary to have culturally adapted and validated instruments that specifically measure patients' knowledge of chronic pain management. The objective of this study was to carry out the Spanish cultural adaptation and the validation of the outcome Knowledge: Pain M anagement of the Nursing Outcomes Classification (NOC) in patients with chronic pain, defined as extent of understanding conveyed about causes, symptoms, and treatment of pain. A three-stage study was designed: 1) translation and cultural adaptation through an expert panel, 2) content validation, 3) clinical validation. This study provides nurses with a Spanish version of this scale adapted to their context, as well as a set of structured indicators to measure patients' knowledge about chronic pain. The results indicated that the culturally adapted Spanish version of the outcome Knowledge: Pain M anagement had a high level of content validity (CVI = 0.92), with 27 indicators being distributed between two factors. This version has been shown to be reliable in terms of inter-observer agreement (κ = 0.79) and internal consistency (α = 0.95). In conclusion, Knowledge: Pain M anagement has been shown to be reliable and valid to measure knowledge of chronic pain.

Purpose: To assess visual results, macular modifications, and the incidence of clinically significant macular edema (CSME) in patients using a topical triamcinolone acetonide-loaded liposomal formulation (TA-LF) after femtosecond laser-assisted cataract surgery (FLACS). Methods: Fifty-six eyes after FLACS were selected. Twenty-eight eyes in the combined therapy group (P + N) were treated with prednisolone 1% and nepafenac 0.1% for 21 days postoperatively, whereas 28 eyes in the TA-LF group received a liposomal formulation containing 2 mg/mL of TA (0.2%) for the same period of time. Follow-up visits at 1 day, 6 weeks, and 12 weeks after surgery consisted of visual acuity, contrast sensitivity (CS), central foveal thickness (CFT), total macular volume (TMV) measurements, and the detection of CSME. Results: CS improved in the TA-LF group (basal value: 1.087 ± 0.339 vs. 1.276 ± 0.147 at week 12, P  = 0.0346), whereas in the P + N group, CS was not different from the baseline (basal value: 1.130 ± 0.331 vs. 1.274 ± 0.133 at week 12, P  = 0.1276). There were similar increases in postoperative CFT and TMV in both groups. CFT and TMV significantly correlate with CS only in the TA-LF group. The r 2 for CFT and CS was 0.1963 ( P  = 0.0206), whereas the r 2 for TMV and CS was 0.3615 ( P  = 0.0007) at 12 weeks. No difference was observed in the incidence of CSME between the groups. Conclusion: TA-LF is associated with better CS outcomes compared to combined therapy after FLACS.

The wastewater from gold exploitation is well known for the toxic nature of recalcitrant cyanide metallic complexes. In this work the selectivity in the photocatalytic degradation of gold mining wastewater (Fe(CN)63-) using suspended TiO2 with alcoholic and organic acid scavengers in a mini-CPC photoreactor with a 30 W UV-A LED as an artificial source of light was evaluated. The study was done in four stages: 1. load catalyst determination, 2. combination of scavengers in a typical photocatalytic degradation, 3. evaluation of scavenger concentration and 4. kinetic study. The decomposition into CN- and Fe removal of the cyanocomplex were tracked. It was observed that formic acid (FA) and t-butanol (t-ButOH) were the best scavengers for the photocatalytic degradation under anoxic conditions. The best concentrations of acceptors used in the study were 10 mM FA and 10 mM t-ButOH at 20 W m-2 of UV-A power, reaching 80% degradation of Fe(CN)63-, 40% Fe removal and 18 ppm of free cyanide CN release to the liquid phase. The electrical efficiency of oxidation per order (EEo) was increased by about 50% with the addition of scavengers instead of traditional anoxic photocatalytic treatment. It was proved that the photocatalytic decomposition of the Fe cyanocomplex was done through the photoreduction path of the metal complex.

Purpose: To report tolerability, safety, and efficacy of a topical triamcinolone acetonide-loaded liposomes formulation (TA-LF) in targeting the macular area in patients with refractory pseudophakic cystoid macular edema (PCME)., Methods: For tolerability, safety and efficacy evaluation, 12 eyes of 12 patients with refractory PCME were exposed to one drop of TA-LF (TA at 0.2%) every 2 h for 90 days or until best-corrected visual acuity (BCVA) was achieved. Intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit., Results: Patients with refractory PCME under TA-LF therapy showed a significant improvement in BVCA and CFT without significant IOP modification (P = 0.94). On average CFT decreased to 206.75 ± 135.72 μm and BCVA improved to 20.08 ± 10.35 letters (P < 0.0005). BCVA was achieved at 10.58 ± 6.70 weeks (range 2-18). TA-LF was well tolerated in all cases. Neither ocular surface abnormalities nor adverse events were recorded., Conclusion: TA-LF was well tolerated and improved BCVA and CFT on patients with refractory PCME.

Purpose: The purpose of this study was to evaluate the feasibility and safety of office-based vitreoretinal procedures., Methods: Patients undergoing primary elective pars plana vitrectomy were elected for surgery in an office-based setting (performed in a minor procedure room under topical anesthesia [TA] and oral anxiolysis). Rates of surgical objective achievement, surgical timing, and comfort were recorded to evaluate feasibility. Intraoperative and postoperative adverse events were assessed to evaluate safety., Results: Office-based vitrectomy surgery was performed in 34 eyes of 30 patients. The mean surgical time was 12.351 ± 8.21 min. Surgical objectives were achieved in 100% of cases. The mean best-corrected visual acuity improvement was 9.08 letters (P < 0.0001). During most parts of the procedure, no patient reported pain or discomfort. Neither intraoperative nor postoperative adverse events were reported until the final follow-up visit., Conclusion: Office-based vitreoretinal procedures under TA could be as feasible and as safe as vitreoretinal procedures under conventional anesthesia., Competing Interests: There are no conflicts of interest

Purpose: To achieve a safer alternative to intravitreal injection of corticosteroids, we developed and characterized triamcinolone acetonide-loaded liposomes formulations (TA-LFs) to be used topically for vitreoretinal drug delivery., Methods: Four different 0.2% TA-LFs (TA-LF1 to TA-LF4) were generated and submitted to physicochemical characterization. Posteriorly, an ex vivo diffusion assay was performed using rabbit corneas as membranes. Finally, concentrations of triamcinolone acetonide (TA) were determined by high-performance liquid chromatography in ocular tissues from New Zealand white rabbits after multiple topical doses of TA-LF2 (6 times per day, 14 days). In addition, toxicity and tolerability of TA-LF2 was evaluated by cell viability assay and eye examination of study animals, respectively., Results: TA-LF2 was the most stable formulation maintaining a stable hidrogenion potential (pH) at 30 and 40°C and even improving encapsulation with higher temperature. TA-LF2 and TA-LF3 presented the best diffusion performance in vitro reaching the highest TA concentrations after 8 h of follow-up. In vivo diffusion and pharmacokinetics analysis showed that concentrations of TA in retina and vitreous reached the highest peak at 12 h after topical administration of TA-LF2 (252.10 ± 90.00 ng/g and 32.6 ± 10.27 ng/g, respectively) and subsequently decline to 24.0 ± 11.72 ng/g and 19.5 ± 13.14 ng/g, respectively, at 14 days of follow-up. Finally, cell viability was unaffected by TA-LF2, and no increase in intraocular pressure nor ocular alterations were observed after topical administration of this formulation in rabbits., Conclusion: TA-loaded liposomes, administered topically, can deliver TA in the vitreous cavity and reach the retina efficiently.

The control of chronic pain is a major challenge for patients and health care professionals. To culturally adapt the Nursing Outcomes Classification outcome "Pain control" (PC) to the Spanish health care setting and to analyze its psychometric properties and sensitivity to change. A study of three stages was designed: (1) Translation and cultural adaptation by translation-back-translation method, (2) content validation by a group of experts, and (3) observational-longitudinal study in patients with chronic pain. Patient sampling was nonprobabilistic, and participants completed forms and questionnaires and responded to a question on pain. Statistical analysis included descriptive analysis, content validity index (for global PC and each indicator), principal component analysis, Spearman's test, Cronbach's α, Cohen's κ coefficient, and Wilcoxon range test. The new Spanish version of "Pain control" was semantically equivalent to the original, with a mean content validity index of 0.96. The clinical study included 88 patients with long-term pain, and the mean (standard deviation) interval between assessments (baseline and final) was 29.33 (8.05) days. Thirteen indicators were organized into two components. There was divergent but not convergent validity with the Change Pain Scale and Brief Pain Inventory. Between-observer agreement was κ = 0.48 and internal consistency was α = 0.85. No differences were found between mean baseline and final scores. The Spanish version of "Pain control," culturally adapted and structured in two components (13 indicators), is useful to assess and monitor pain control in patients with chronic pain., (Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to evaluate the psychometric properties and sensitivity to change of the Spanish version of the Pain Level Outcome Scale., Methods: This article applied observational longitudinal validation study with patients suffering from acute pain at three hospitals., Findings: The study included 73 patients. Inter-rater agreement was kappa = .88 and internal consistency α = .93. Principal components analysis yielded four components that explained 81.86% of the variance; the correlation with the Numerical Pain Intensity Scale was r = -.81., Conclusions: The version with 17 indicators shows good psychometric properties and adequate sensitivity to change. A Spanish version of the Pain Level Outcome Scale with 17 indicators is proposed as a structured multidimensional instrument to help nurses choose the most appropriate indicators for assessing patients' pain., (© 2015 NANDA International, Inc.)

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.

Aims: To translate and culturally adapt the Pain Level outcome to the Spanish context to validate the contents of the Spanish version of the «Pain level» outcome., Method: The original English version of the «Pain level» outcome was translated into Spanish (twice); then back-translated into English, and all the discrepancies were resolved after consulting with NOC authors. A panel consisting of 21 experts in pain care assessed this culturally adapted Spanish version, in order to score the content validity. In the first step, the experts scored the adequacy of each indicator to the concept «Pain level». In the second round, three new indicators were scored. The Statistical analysis included content validity index (CVI), probability of agreement by chance, and modified kappa statistic., Results: A Spanish version was developed including label, definition, two groups of indicators, and two measurement scales. This version is fully adapted to the Spanish context and language. A set of 21 indicators (19 translated and two new) was selected, and 4 were deleted (three translated and one new). The CVI-average score was 0.83 and the CVI-universal agreement was 0.05., Conclusion: The Spanish-version of the outcome «Pain level» is semantically and culturally to adapted to a Spanish context and preserves equivalency with the original. Content validation has identified indicators useful for practice. The clinimetric properties (validity and reliability) of the adapted version could be tested in a clinical study with people suffering from acute pain., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

As wireless sensor networks are usually deployed in unattended areas, security policies cannot be updated in a timely fashion upon identification of new attacks. This gives enough time for attackers to cause significant damage. Thus, it is of great importance to provide protection from unknown attacks. However, existing solutions are mostly concentrated on known attacks. On the other hand, mobility can make the sensor network more resilient to failures, reactive to events, and able to support disparate missions with a common set of sensors, yet the problem of security becomes more complicated. In order to address the issue of security in networks with mobile nodes, we propose a machine learning solution for anomaly detection along with the feature extraction process that tries to detect temporal and spatial inconsistencies in the sequences of sensed values and the routing paths used to forward these values to the base station. We also propose a special way to treat mobile nodes, which is the main novelty of this work. The data produced in the presence of an attacker are treated as outliers, and detected using clustering techniques. These techniques are further coupled with a reputation system, in this way isolating compromised nodes in timely fashion. The proposal exhibits good performances at detecting and confining previously unseen attacks, including the cases when mobile nodes are compromised.

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results.

The improvement of odometry systems in collaborative robotics remains an important challenge for several applications. Social odometry is a social technique which confers the robots the possibility to learn from the others. This paper analyzes social odometry and proposes and follows a methodology to improve its behavior based on cooperative reputation systems. We also provide a reference implementation that allows us to compare the performance of the proposed solution in highly dynamic environments with the performance of standard social odometry techniques. Simulation results quantitatively show the benefits of this collaborative approach that allows us to achieve better performances than social odometry.

The reliable operation of modern infrastructures depends on computerized systems and Supervisory Control and Data Acquisition (SCADA) systems, which are also based on the data obtained from sensor networks. The inherent limitations of the sensor devices make them extremely vulnerable to cyberwarfare/cyberterrorism attacks. In this paper, we propose a reputation system enhanced with distributed agents, based on unsupervised learning algorithms (self-organizing maps), in order to achieve fault tolerance and enhanced resistance to previously unknown attacks. This approach has been extensively simulated and compared with previous proposals.

Security in wireless sensor networks is difficult to achieve because of the resource limitations of the sensor nodes. We propose a trust-based decision framework for wireless sensor networks coupled with a non-deterministic routing protocol. Both provide a mechanism to effectively detect and confine common attacks, and, unlike previous approaches, allow bad reputation feedback to the network. This approach has been extensively simulated, obtaining good results, even for unrealistically complex attack scenarios.

By using finite Lyapunov exponent distributions, we get insight into both the local and global properties of a dynamical flow, including its nonhyperbolic behavior. Several distributions of finite Lyapunov exponents have been computed in two prototypical four-dimensional phase-space Hamiltonian systems. They have been computed calculating the growth rates of a set of orthogonal axes arbitrarily pointed at given intervals. We analyze how such distributions serve or not for tracing the orbit nature and local flow properties such as the unstable dimension variability, as the axes are allowed or not to tend to the largest stretching direction. The relationship between the largest and closest to zero exponent distribution is analyzed. It shows a linear dependency at short intervals, related to the number of degrees of freedom of the system. Finally, the hyperbolicity indexes, associated to the shadowing times, are calculated. They provide interesting information at very local scales, even when there are no Gaussian distributions and the values cannot be regarded as random variables.

The Hénon-Heiles Hamiltonian is investigated in the context of chaotic scattering, in the range of energies where escaping from the scattering region is possible. Special attention is paid to the analysis of the different nature of the orbits, and the the invariant sets, such as the stable and unstable manifolds and the chaotic saddle. Furthermore, a discussion on the average decay time associated to the typical chaotic transients, which are present in this problem, is presented. The main goal of this paper is to show, by using various computational methods, that the corresponding exit basins of this open Hamiltonian are not only fractal, but they also verify the more restrictive property of Wada. We argue that this property is verified by typical open Hamiltonian systems with three or more escapes.

Background: To determine variability, if exists, in interleukin-6 (IL-6) response by different cell cultures stimulated by Borrelia burgdorferi., Methods: Five human embryonic diploid fibroblast cell lines (three of them of lung origin) and four human synovial cell cultures were used. Induction of IL-6 was made with B. burgdorferi B31 culture and E. coli lipopolysaccharide (LPS). IL-6 was determined by a commercial EIA (Coaliza IL-6)., Results: All cell cultures produced IL-6 under basal conditions and responded after adding E. coli LPS. The IL-6 production after B. burgdorferi stimulation was higher than that induced by LPS with three out the four synovial cell cultures and lowest with lung fibroblasts., Conclusions: The ability of B. burgdorferi to stimulate IL-6 production depends on the nature and origin of cell cultures. This variability and the fact that the most reactive cell cultures were those of synovial precedence may correlated with some clinical aspects of the Lyme disease.

Patellar tendon avulsion is a rare complication of total knee arthroplasty. An easy surgical technique that involves suturing the tendon into a groove carved in the tibial tubercle and tension band wiring is described. Two cases are presented, with an average follow-up period of 21 months. Good clinical results were obtained in each case. No postoperative complications occurred.