Advances in Pancreatic Cancer Treatment by Nano-Based Drug Delivery Systems.

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review.

Solid-lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on.

Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overview.

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects.

Vulvar Hailey-Hailey disease treated with low-dose naltrexone: case report and literature review.

PURPOSE: To report a case of vulvar familial benign pemphigus, or Hailey-Hailey disease, treated successfully with low-dose naltrexone and to review the current literature. METHODS: We report a case of a 71-year-old white woman with vulvar Hailey-Hailey disease recalcitrant to topical corticosteroids. After treatment with low-dose naltrexone, 3 mg nightly was initiated, the lesions began to heal and 5 months later her skin showed no lesions. A literature review on the use of low-dose naltrexone for Hailey-Hailey disease was performed. We searched the PubMed/MEDLINE databases for previous case reports using the key words ''Pemphigus, Benign Familial'' and ''naltrexone". RESULTS: We found 35 more cases of Hailey-Hailey disease treated with naltrexone, showing promising results, reported until January 2020, with no major adverse effects. CONCLUSION: Low-dose naltrexone may represent a cost-effective and successful treatment modality in nongeneralized Hailey-Hailey disease without serious adverse effects. Future prospective studies are needed to investigate this interesting therapeutic option.

Modular coherent photonic-aided payload receiver for communications satellites.

Ubiquitous satellite communications are in a leading position for bridging the digital divide. Fulfilling such a mission will require satellite services on par with fibre services, both in bandwidth and cost. Achieving such a performance requires a new generation of communications payloads powered by large-scale processors, enabling a dynamic allocation of hundreds of beams with a total capacity beyond 1 Tbit s-1. The fact that the scale of the processor is proportional to the wavelength of its signals has made photonics a key technology for its implementation. However, one last challenge hinders the introduction of photonics: while large-scale processors demand a modular implementation, coherency among signals must be preserved using simple methods. Here, we demonstrate a coherent photonic-aided receiver meeting such demands. This work shows that a modular and coherent photonic-aided payload is feasible, making way to an extensive introduction of photonics in next generation communications satellites.

Association between Chagas disease and changes in the optic nerve and retinal nerve fiber layer.

PURPOSE: To test the hypothesis that Chagas disease predisposes to optic nerve and retinal nerve fiber layer alterations. METHODS: We conducted a cross-sectional study including 41 patients diagnosed with Chagas disease and 41 controls, paired by sex and age. The patients underwent ophthalmologic examinations, including intraocular pressure measurements, optic nerve and retinal nerve fiber layer screening with retinography, optical coherence tomography, and standard automated perimetry. RESULTS: All of the patients with Chagas disease had a recent cardiologic study; 15 (36.6%) had heart failure, 14 (34.1%) had cardiac form without left ventricular dysfunction, and 12 (29.3%) had indeterminate form. Optic nerve/retinal nerve fiber layer alterations were observed in 24 patients (58.5%) in the Chagas disease group and 7 controls (17.1%) (p£0.01). Among these, optic nerve pallor, optic nerve alterations suggestive of glaucoma, notch, peripapillary hemorrhage, and localized retinal nerve fiber layer defect were detected. Alterations were more prominent in patients with Chagas disease and heart failure (11 patients), although they also occurred in those with Chagas disease without left ventricular dysfunction (7 patients) and those with indeterminate form (6 patients). Optical coherence tomography showed that themean of the average retinal nerve fiber layer thickness measured 89 ± 9.7 mm, and the mean of retinal nerve fiber layer superior and inferior thickness measured 109 ± 17.5 and 113 ± 16.8 mm, respectively were lower in patients with Chagas disease. In controls, these values were 94 ± 10.6 (p=0.02); 117 ± 18.1 (p=0.04), and 122 ± 18.4 mm (p=0.03). CONCLUSION: Changes in optic nerve/ retinal nerve fiber layer were more prevalent in patients with Chagas disease.

A Refinement of the Robertson-Schrödinger Uncertainty Principle and a Hirschman-Shannon Inequality for Wigner Distributions.

We propose a refinement of the Robertson-Schrödinger uncertainty principle (RSUP) using Wigner distributions. This new principle is stronger than the RSUP. In particular, and unlike the RSUP, which can be saturated by many phase space functions, the refined RSUP can be saturated by pure Gaussian Wigner functions only. Moreover, the new principle is technically as simple as the standard RSUP. In addition, it makes a direct connection with modern harmonic analysis, since it involves the Wigner transform and its symplectic Fourier transform, which is the radar ambiguity function. As a by-product of the refined RSUP, we derive inequalities involving the entropy and the covariance matrix of Wigner distributions. These inequalities refine the Shanon and the Hirschman inequalities for the Wigner distribution of a mixed quantum state ρ . We prove sharp estimates which critically depend on the purity of ρ and which are saturated in the Gaussian case.

Reconfigurable monitoring and control system for tunable optical delay lines.

In this Letter, we propose a monitoring and control system (MCS) for operating tunable optical delay lines (TODLs), regardless of their operation principle and implementation technology. The monitoring system resorts to two out-of-band pilot tones added to the input optical signal. The amplitude and phase difference between tones are retrieved to the control system, which calculates and applies the TODL control signals. The MCS was validated using a Mach-Zehnder delay interferometer-based TODL, implemented in three different silicon photonic integrated circuits (PICs). The three PICs resort to different kinds of phase shifters based on thermo-optic, carrier-injection, and carrier-depletion effects. The proposed MCS enabled tuning the delay within the entire range of the TODL in all tested PICs. The scalability of the MCS for large-scale photonic beamformers is discussed.

ECCO essential requirements for quality cancer care: Melanoma.

BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are explanations and descriptions of challenges, organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. MELANOMA: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for melanoma. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams and specialised treatments is guaranteed to all patients with melanoma.

An unexpected near term pregnancy in a rudimentary uterine horn.

Unicornuate uterus occurs due to a complete or partial nondevelopment of one Mullerian duct; sometimes it is associated with a rudimentary horn, which can communicate or not with uterine cavity or contain functional endometrium. Pregnancy in a rudimentary horn is rare and the outcome almost always unfavorable, usually ending in rupture during the first or second trimester with significant morbidity and mortality. Despite the availability and advances on imagiologic procedures, recognition of this ectopic pregnancy is frequently made at laparotomy after abdominal pain and collapse. The authors describe a case of a primigravida with 34 weeks of gestation admitted with a preeclampsia with severity criteria. A cesarean for fetal malpresentation was done and, unexpectedly, a rudimentary horn pregnancy was found with a live newborn. In the literature, few reports of a horn pregnancy reaching the viability with a live newborn are described, enhancing the clinical importance of this case. A review of literature concerning the epidemics, clinical presentation, and appropriate management of uterine horn pregnancies is made.

[Logistic regression analysis in the combination of diagnostic methods in glaucoma]. / Análise de regressão logística na combinação de métodos propedêuticos no diagnóstico do glaucoma.

PURPOSES: In this research was studied the diagnostic ability of the Heidelberg Retinal Tomograph (HRT II), GDx nerve fiber analyzer (GDx), Short-wavelenght Automated Perimetry (SWAP) and Frequency-doubling technology (FDT), all of them together and also separately in the diagnosis of glaucoma. METHODS: Sixty glaucomatous patients and 60 normal ones were submitted to examination with the technology of HRT II, GDx, FDT and SWAP. In the interpretation of HRT, based on the Moorfields regression analysis, were considered abnormal when at least one area of the neuroretinal ring was outside the bounds of normality. GDx was defined as altered, when it was observed that at least one index was considered by equipment program as outside of normal limits, excluding the index symmetry, or when "the deviation from normal graph" appeared a quadrant with significance below 5%. The FDT was considered abnormal when at least one region tested presented with severe defects, or two contiguous moderate defects in at least two reliable tests. For SWAP was adopted the abnormality criteria proposed by Anderson. Logistic regression analysis was performed. RESULTS: When the technologies were studied separately, the Logistic regression analysis showed better odds ratio rates to test positive for glaucoma with HRT (22.49), followed by EAP (21.71), FDT (3.97) and GDx (2.73). When positive tests were associated with different technologies, the odds ratios increased. In cases with HRT, FDT and PAA tests, outside normal bounds, the odds ratio was 252.6. Concerning the HRT, GDx and PAA the result have changed to 173.1. When we associate positive tests from different technologies, the odds ratio of glaucomatous patients have increased considerably, reaching 689.7 with all the tests outside normal bounds, which have happened with 26 patients of this study. CONCLUSIONS: The Logistic Regression analysis confirmed that the abnormal tests of HRT and PAA have shown to be the highest reasons for glaucoma occurrence. The association of abnormal tests increased the odds ratio, especially when the HRT and PAA were out of normal bounds.

Silicone Ahmed glaucoma valve with and without intravitreal triamcinolone acetonide for neovascular glaucoma: randomized clinical trial.

PURPOSE: To compare the effect on intraocular pressure (IOP) of the silicone Ahmed glaucoma valve with and without an intravitreal injection of triamcinolone acetonide. PATIENTS AND METHODS: Forty-nine patients with clinically uncontrolled neovascular glaucoma were included in the study; 22 were randomly assigned to the study group (silicone Ahmed glaucoma valve implant with intravitreal triamcinolone acetonide) and 27 to the control group (silicone Ahmed glaucoma valve). IOP was the primary outcome measure in this study. The secondary outcome measure was success, defined by IOP lower than 22 mm Hg and higher than 5 mm Hg, and no serious complications. Success rates in both the groups were compared using Kaplan-Meier survival curves and the log-rank test. IOP levels were compared using mixed linear model analysis to correct for repeated measures correlation. RESULTS: Forty-three patients, 18 in the study group and 25 in the control group, completed the study (follow-up of 12 mo). The mean IOP was significantly lower after 1 year in both the groups (P<0.001). The mean IOP in the first month of follow-up was lower in the study group (control; 20.4±9.7, study; 13.6±6.5, P<0.01). The success rate at 1 year was 78% for the study group and 76% for the control group (P=0.82). Complication rates were not different between the groups. CONCLUSIONS: Intravitreal injection of triamcinolone acetonide in neovascular glaucoma did not affect the intermediate-term success of the silicone Ahmed valve nor reduce the incidence of complications. The mean IOP spike in the first month was lower in the triamcinolone group.

[Discriminant analysis of patients with primary open-angle glaucoma by color Doppler exam and visual field]. / Análise discriminante dos pacientes portadores de glaucoma primário de ângulo aberto através do exame de Doppler colorido e do campo visual.

PURPOSE: To determine if variables from color Doppler and visual field exam could discriminate normal from glaucomatous eyes. METHODS: Prospectively, 36 patients with primary open-angle glaucoma (glaucoma group) and 20 normal volunteers (control group) were studied. Gender, age, central corneal thickness, intraocular pressure, Octopus automated perimetry global indices (mean defect and loss variance) and several parameters of the color Doppler (peak systolic velocity and resistivity index) were compared between groups. RESULTS: There was no statistically significant difference in age, central corneal thickness and intraocular pressure. Discriminant analysis showed that the variables: resistivity index (RI) in the short posterior ciliary artery (SPCA), mean defect (MD) and loss variance (LV) had presented significant influence for the positive diagnosis of glaucoma. The gotten discriminant function was: -3.637 + 0.109 x MD + 0.028 x LV + 4.325 x RI SPCA. Considering score -1.61, the probability of positive diagnosis of glaucoma was 90%. CONCLUSION: Through discriminant analysis it was possible to identify which of the color Doppler variables that associated to the visual field variables allowed differentiate normal from glaucomatous patients. These variables were: resistivity index in the short posterior ciliary artery, and the visual field variables, mean defect and loss variance.

A pseudo-differential calculus on non-standard symplectic space; Spectral and regularity results in modulation spaces.

The usual Weyl calculus is intimately associated with the choice of the standard symplectic structure on [Formula: see text]. In this paper we will show that the replacement of this structure by an arbitrary symplectic structure leads to a pseudo-differential calculus of operators acting on functions or distributions defined, not on [Formula: see text] but rather on [Formula: see text]. These operators are intertwined with the standard Weyl pseudo-differential operators using an infinite family of partial isometries of [Formula: see text] indexed by [Formula: see text]. This allows us to obtain spectral and regularity results for our operators using Shubin's symbol classes and Feichtinger's modulation spaces.

Lack of circadian change of concentration of C-type natriuretic peptide in rabbit aqueous humor.

PURPOSE: To determine whether there is a circadian change of the concentration of C-type natriuretic peptide (CNP) in rabbit aqueous humor. METHODS: Forty-one male white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All groups consisted of four animals but two had more animals to increase the power of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested by Pearson's correlation. The mean of two eyes was considered for analysis. Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test and COSINOR analysis. RESULTS: There were no significant differences between the 6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and dark), the C-type natriuretic peptide concentration of the light group was lower, 2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but did not reach a significant difference (t test; p = 0.23). COSINOR analysis was not statistically significant (R% = 7.72 p = 0.209). CONCLUSION: These data demonstrate that the concentration of CNP in aqueous humor did not show a statistically significant circadian change in rabbits entrained to a 12 h light: 12 h dark lighting schedule.

No changes in anatomical and functional glaucoma evaluation after trabeculectomy.

PURPOSE: To assess the influence of glaucoma filtration surgery on anatomical and functional tests for glaucoma evaluation. METHODS: Twenty-five eyes (25 patients) with primary open-angle glaucoma were evaluated, prospectively. Data were collected on vision acuity, intraocular pressure, standard automated perimetry, frequency doubling technology perimetry, scanning laser polarimetry (GDx) and confocal scanning laser ophthalmoscopy (HRT II) before and 3-6 months after surgery. RESULTS: Mean (+/-SD) pre- and postoperative visual acuities (logMAR) were 0.28 (+/-0.18) and 0.30 (+/-0.17), respectively (P=0.346). In a mean time of 4.5 (+/-1.1) months after surgery, the mean preoperative intraocular pressure of 20.7 (+/-5.4) mmHg decreased to 11.04 (+/-2.52) mmHg (P<0.001). The results of the standard automated perimetry, frequency doubling technology perimetry, scanning laser polarimetry and confocal scanning laser ophthalmoscopy diagnostic methods revealed no significant difference (P>0.162) between pre and postoperative values and no significant correlation (P>0.296) between intraocular pressure reduction and value changes. CONCLUSION: No significant change on any test variable was detected after glaucoma filtration surgery. Trabeculectomy does not appear to influence standard automated perimetry, frequency doubling technology perimetry, scanning laser polarimetry and confocal scanning laser ophthalmoscopy (HRT II) results after a 4.5-month period of surgery in early to moderate glaucoma.

Influence of pupillary diameter, ciliary muscle tone, and ambient light on nerve fiber layer measurements with scanning laser polarimetry.

PURPOSE: To evaluate the influence of the pupillary diameter, ciliary muscle tone, and room light on nerve fiber layer measurements with the scanning laser polarimeter (GDx). METHODS: One randomly selected eye of ten normal volunteers was examined with the GDx in a two-day protocol under eight testing conditions (pilocarpine 1%, phenylephrine 10%, tropicamide 1%, or no drops with room lights on or off). The twelve parameters, obtained by the GDx, were compared under the eight testing conditions, using two way ANOVA for repeated measurements and Tukey HSD post hoc test. RESULTS: Ten of the twelve parameters were statistically significantly different (P < 0.05) when measured under the three medication or no medication conditions, controlling for the ambient light status. There were no significant differences when measured with the light on or off, controlling for use of drops. CONCLUSIONS: Nerve fiber layer measurements with the GDx were influenced by drugs affecting pupillary diameter, but not by the status of room light or ciliary muscle tone.

Comparação do volume da gota e custo do tratamento dos genéricos de maleato de timolol 0, 5 por cento / Drop volume and cost of treatment with generic 0.5 percent timolol maleate preparations

OBJETIVO: Comparar o volume da gota das medicações genéricas de maleato de timolol a fim de determinar o custo real do tratamento em relação à medicação de referência. MÉTODOS: Foi determinado o volume da gota do Timoptol® 0,5 por cento (Merck Sharp & Dome) e dos genéricos maleato de timolol 0,5 por cento dos laboratórios Allergan-Lok, Cristália e Falcon. Cinco frascos de 5 ml de cada medicação foram adquiridos no mercado. Dez gotas de cada frasco foram pesadas em balança de precisão individualmente, bem como, um mililitro de cada frasco para a determinação do volume da gota. Com base no volume da gota foi calculada a duração média em dias e o custo anual, considerando-se o gasto diário de 4 gotas e o preço máximo ao consumidor publicado em maio de 2003 com alíquota de 18 por cento. RESULTADOS: Observaram-se diferenças estatisticamente significantes do volume da gota entre as medicações (p<0,0001 por cento). A maior gota foi a do maleato de timolol 0,5 por cento Allergan-Lok (35,1 æl) e a menor do maleato de timolol Falcon (27,3 æl). A medicação de referência (Timoptol®) proporcionou gota média de 27,9 æl. O custo anual do tratamento foi de R$ 68,87 para o Timoptol, de R$ 72,76 para o maleato de timolol Allergan-Lok, de R$ 50,00 para o maleato de timolol Cristália e de R$ 43,11 para o maleato de timolol Falcon (p<0,0001). O maleato de timolol Allergan-Lok foi estatisticamente mais caro que os demais sendo 68,8 por cento mais oneroso que o mais barato. CONCLUSAO: Existem diferenças no volume da gota das medicações genéricas acarretando diferenças no custo anual do tratamento. O volume da gota deve ser considerado na análise de qualidade dos medicamentos antiglaucomatosos genéricos.

Comparison between results of trabeculectomy in primary congenital glaucoma with and without the use of mitomycin C.

PURPOSE: To evaluate the results of trabeculectomy with and without the use of mitomycin C in children with primary congenital glaucoma. METHODS: The authors retrospectively studied the data of 91 patients who underwent the first trabeculectomy for primary congenital glaucoma, with 19 years of follow-up. Success criteria were set with two distinct values of intraocular pressure: lower or equal to 15 mm Hg or lower than 21 mm Hg and separately analyzed. RESULTS: Among the studied patients, 61 had undergone trabeculectomy without mitomycin C and 30 with mitomycin C. The comparison between the groups of patients showed age homogeneity (P = 0.152) and did not demonstrate any difference in preoperative (P = 0.234) and postoperative (P = 0.907) intraocular pressure. Success rates through time, for both pressure limits was not different between the groups. Both age and the presence of previous trabeculotomy did not influence the success of trabeculectomy through time, for the two pressure limits considered. The complication rate was higher among the patients who received mitomycin C (P = 0.010). CONCLUSIONS: The success of trabeculectomy for primary congenital glaucoma with mitomycin C was not different than that of trabeculectomy with mitomycin C in the studied patients. Mitomycin C was associated with a higher incidence of complications.

O atendimento oftalmologico de criancas carentes com estrabismo / Ophthalmological evaluation of needy children with strabismus

Avaliar o tempo decorrido entre o aparecimento do estrabismo e a primeira consulta oftalmologica em pacientes carentes, com inicio de quadro antes...