Fatty acid synthase as a potential new therapeutic target for cervical cancer.

Fatty acid synthase (FASN) is the rate-limiting enzyme for the de novo synthesis of fatty acids in the cytoplasm of tumour cells. Many tumour cells express high levels of FASN, and its expression is associated with a poorer prognosis. Cervical cancer is a major public health problem, representing the fourth most common cancer affecting women worldwide. To date, only a few in silico studies have correlated FASN expression with cervical cancer. This study aimed to investigate in vitro FASN expression in premalignant lesions and cervical cancer samples and the effects of a FASN inhibitor on cervical cancer cells. FASN expression was observed in all cervical cancer samples with increased expression at more advanced cervical cancer stages. The FASN inhibitor (orlistat) reduced the in vitro cell viability of cervical cancer cells (C-33A, ME-180, HeLa and SiHa) in a time-dependent manner and triggered apoptosis. FASN inhibitor also led to cell cycle arrest and autophagy. FASN may be a potential therapeutic target for cervical cancer, and medicinal chemists, pharmaceutical researchers and formulators should consider this finding in the development of new treatment approaches for this cancer type.

Non-conventional dysplasias of the tubular gut: a review and illustration of their histomorphological spectrum.

The increasing use of gastrointestinal endoscopic procedures has led to the recognition by histopathologists of non-conventional (or special-type) dysplasias of the gastrointestinal tract. These lesions can be recognised in association with prevalent underlying gastrointestinal conditions, such as Barrett oesophagus, chronic atrophic gastritis, and inflammatory bowel disease. The diagnosis of these special types can be challenging, and their biological behaviours are not fully characterised. The aim of this review is to provide a global view of non-conventional dysplastic lesions observed in the various segments of the tubular gastrointestinal tract and describe their salient features. Furthermore, as the clinical implications of these various subtypes have not been broadly tested in practice and are not represented in most management guidelines, we offer guidance on the best management practices for these lesions.

Comparative analysis of glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis. METHODS: We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted. RESULTS: For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.76-0.83), and areas under the ROC curve of .96 and .79, respectively. Glucose had a higher sensitivity (90%), with uncommon false-negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust. CONCLUSION: Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first-line test, particularly in small cysts with a limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis.

A comparative analysis of glucose and carcinoembryonic antigen in diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis.

BACKGROUND/AIMS: Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis. METHODS: We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (SROC) curve analysis were conducted. RESULTS: For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery and for glucose we included 5 studies with 460 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of 0.91 (95% CI, 0.86-0.94) and 0.67 (95% CI, 0.65-0.70), specificities of 0.75 (95% CI, 0.68-0.82) and 0.80 (95% CI, 0.76-0.83), and areas under the ROC curve (AUC) of 0.95 and 0.79, respectively. Glucose had a higher sensitivity (91%), with uncommon false negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust. CONCLUSION: Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first line test, particularly in small cysts with limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis.

Endoscopic ultrasound with fine needle aspiration is useful in pancreatic cysts smaller than 3 cm.

BACKGROUND: In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation). OBJECTIVE: To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. METHODS: Retrospective study of PCLs < 3 cm (2007-2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed. RESULTS: We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging-AUC = 0.80 versus AUC = 60. CONCLUSION: EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.

Pediatric Colorectal Cancer: A Heterogenous Entity.

INTRODUCTION: Colorectal cancer (CRC) is extremely rare in pediatric age. A poor outcome has been reported. AIMS: We aimed to characterize a group of pediatric CRC patients. MATERIALS AND METHODS: All patients with CRC below 18 years old registered in our Familial Cancer Risk Clinic (2002-2016) were included. Clinical and histologic features were evaluated. Germline mutations, microsatellite instability, and DNA mismatch repair proteins expression were analyzed. RESULTS: Five patients were included (3 males; mean age at diagnosis: 14.2 years (range, 9 to 17 y) and 4/5 had family history of cancer in second-degree relatives. With a maximum follow-up of 5.6 years, 2/5 patients died after 10 and 24 months, and 1 recurred after 15 months. All tumors were ≥pT3N2 and 3/5 presented signet ring cells/mucinous histology, corresponding to cases with stronger family history of cancer. Nevertheless, all CRCs analyzed (n=4) were microsatellite stable and/or expressed all mismatch repair proteins. Loss of heterozygosity for the 3 Bethesda dinucleotide markers was detected in 1/3 informative CRCs. A likely pathogenic germline MSH2 mutation was identified in only 1 patient. CONCLUSIONS: Pediatric CRC presented advanced disease and poor prognosis. These tumors had distinct histologic and molecular presentations, resembling features from different carcinogenic pathways, thus suggesting a heterogenous nature.

Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts.

BACKGROUND: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described. AIMS: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis. MATERIALS AND METHODS: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological. RESULTS: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis. CONCLUSION: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

The nonsense mutation MSH2 c.2152C>T shows a founder effect in Portuguese Lynch syndrome families.

The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.

Deep Friction Massage in the Management of Patellar Tendinopathy in Athletes: Short-Term Clinical Outcomes.

CONTEXT: Deep friction massage (DFM) is often used in the treatment of tendinopathies; however, the pressure applied may vary and interfere with the obtained results. OBJECTIVE: To assess whether the immediate effects of DFM on pain (pain intensity and time to onset of analgesia) and muscle strength are dependent on the pressure applied during the DFM application in athletes with patellar tendinopathy. DESIGN: Randomized, controlled, cross-over trial. SETTING: University research laboratory (institutional). PARTICIPANTS: Ten athletes with diagnosis of unilateral patellar tendinopathy (age 27.90 [5.24] y). INTERVENTIONS: All participants attended 4 sessions, 3 treatment sessions with DFM applied with different pressures (the mean pressure-previously determined for each participant-and the mean pressure ± 25%) and a control session, each of which was separated by 48 hours. MAIN OUTCOME MEASURES: Pain (intensity upon palpation and time to onset of analgesia), and muscle strength of knee extensors were assessed before and immediately after each session. RESULTS: Pain intensity changed significantly over time (F1,9 = 52.364; P < .001; ηp2=.853) and among sessions (F3,27 = 82.588; P < .001; ηp2=.902), with a significant interaction for group × time (F3,27 = 19.841; P < .001; ηp2=.688). The knee extensors strength did not change significantly over time (F1,9 = 2.240; P = .17; ηp2=.199), nor a significant interaction for session × time was observed (F3,27 = 3.276; P = .07; ηp2=.267). Regardless of the pressure applied, the time to onset of analgesia was not significantly different (F2,18 = 1.026; P > .05; ηp2=.102). CONCLUSION: It was shown that DFM induces an immediate reduction in pain intensity upon palpation, regardless of the pressure performed. Notwithstanding, the reader should take into account the small sample size and the caution needed in the results' interpretation.

SCC4 cell monolayers as an alternative sublingual barrier model: influence of nanoencapsulation on carvedilol transport.

OBJECTIVE: To evaluate, for the first time, the use of SCC4 cell monolayers as an alternative sublingual barrier model and study the influence of nanoencapsulation on carvedilol transport across SCC4 cell monolayers. SIGNIFICANCE: The sublingual cavity is an interesting route for administration of drugs with limited oral bioavailability due to hepatic first pass metabolism. By this route, the drug is directly absorbed into blood circulation. In this sense, mucoadhesive carvedilol-loaded nanocapsules (CAR-NC) were previously proposed for the administration of this drug by sublingual route. Carvedilol is used for cardiovascular diseases and suffers metabolism in liver when orally administrated. Nanoencapsulation of carvedilol controlled its permeation across porcine sublingual mucosa. METHODS: Carvedilol-loaded cationic nanocapsules were prepared by interfacial deposition of a preformed polymer. Drug permeation studies were carried out in Transwell® inserts. The integrity of cell monolayers after the drug transport was assessed by transepithelial electric resistance. Compatibility of the CAR-NC with the SCC4 cells was evaluated by the Sulforhodamine B assay. RESULTS: The drug permeated the cell monolayer by a controlled way when nanoencapsulated and this profile had a linear relation with those observed in porcine sublingual mucosa. The integrity of the cell monolayer was maintained after drug permeation and CAR-NC was no cytotoxic to SCC4 cells. CONCLUSION: Nanoencapsulated carvedilol permeated by a controlled and safe way by SCC4 cell monolayer. SCC4 cells monolayers may be used as in vitro model for sublingual drug transport studies in the development of novel formulations.

Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA.

BACKGROUND: Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS: To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS: We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS: There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS: In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.

Mucoadhesive Properties of Eudragit®RS100, Eudragit®S100, and Poly(ε-caprolactone) Nanocapsules: Influence of the Vehicle and the Mucosal Surface.

The use of polymers as mucoadhesive materials has been explored in several drug delivery systems. It is well known that the resulting mucoadhesiveness not only depends on the polymers by themselves, but also on the way they are delivered and on the application target. However, little attention has been given to the combined effect of such characteristics. Therefore, the objective of this study is to analyze the mucoadhesion resulting from combined effects of nanocapsules produced with polymers of different ionic properties, Eudragit®RS100, Eudragit®S100, or poly(ε-caprolactone), when they are incorporated into different vehicles (suspension, hydrogel, and powder) and applied on different mucosal surfaces (mucin, porcine vaginal, and buccal mucosa). Mucoadhesion was measured by a tensile stress tester. Our findings show that polymeric self-assembling as nanocapsules improved the mucoadhesion of the polymers. Eudragit®RS100 nanocapsules have the best performance, independently of the vehicle and surface used. Regarding the vehicle, hydrogels showed higher adhesion when compared to suspensions and powders. When considering different types of surfaces, mucin presented a similar pattern like the animal mucosa, but it overestimated the mucoadhesiveness of all formulations. In conclusion, this study demonstrated that the best strategy to achieve high mucoadhesive formulations is by incorporating Eudragit®RS100 nanocapsules in hydrogels. Moreover, mucin is a suitable substrate to compare and screen different formulations but not as a conclusive estimation of the mucoadhesion values that can be achieved. These results are summarized in a decision tree that can help to understand different strategies of combination of these factors and the expected outcomes.

Cationic Polymeric Nanocapsules as a Strategy to Target Dexamethasone to Viable Epidermis: Skin Penetration and Permeation Studies.

The present work aimed to evaluate the behavior of dexamethasone-loaded cationic polymericnanocapsules in hydrogels, regarding their in vitro drug release and skin drug retention and per- meation. Cationic polymeric nanocapsules prepared with Eudragit RS 100 as the polymeric wall had mean particle size of 139 +/- 3.6 nm, positive zeta potential (+11.38 +/- 1.7 mV), and high encapsulation efficiency (81 +/- 2%). After preparation, they were formulated as hydrogels, which showed non-Newtonian, plastic behavior, and acidic pH. Photon correlation spectroscopy analysis of these hydrogels demonstrated the presence of particles with mean particle size close to that of the original colloidal suspensions. The presence of dexamethasone-loaded nanocapsules in hydrogels promoted controlled drug release and an increase in the amount of drug delivered into viable epidermis, the main target tissue to topical glucocorticoid action. Moreover, the formulation did not increase the risk of drug penetration to dermis and permeation to the receptor compartment.

Differentiation reprogramming in gastric intestinal metaplasia and dysplasia: role of SOX2 and CDX2.

AIMS: Intestinal metaplasia (IM), which results from de-novo expression of CDX2, and dysplasia are precursor lesions of gastric cancer that are associated with an increased risk for cancer development. There is much evidence suggesting a role for the transcription factor SOX2 in gastric differentiation. The aim of this study was to attempt to establish the relationship of SOX2 with CDX2 and with the differentiation reprogramming that characterizes gastric carcinogenesis, to assess their involvement in IM and dysplasia. METHODS AND RESULTS: Characterization of gastric (SOX2, MUC5AC, and MUC6) and intestinal (CDX2 and MUC2) markers in normal gastric mucosa, in 55 foci of IM and in 26 foci of dysplasia, was performed by immunohistochemistry. SOX2 was expressed in the normal gastric mucosa, in the presumptive stem cell compartment, and was maintained in 7% of the complete (MUC5AC-negative) and 85% of the incomplete (MUC5AC-positive) IM subtypes. Twelve per cent of the dysplastic lesions expressed SOX2, and the association with MUC5AC was lost. CDX2 was present in all IMs and dysplastic lesions. CONCLUSIONS: SOX2 is associated with gastric differentiation in incomplete IM and is lost in the progression to dysplasia, whereas CDX2 is acquired de novo in IM and maintained in dysplasia. This suggests that the balance between gastric and intestinal differentiation programmes impacts on the gastric carcinogenesis cascade progression.

The co-localization of carcinomas and adenomas favors a regional field defect in the colon: an observational study.

PURPOSE: Finding common genetic alterations in colorectal cancers (CRCs) and peri-tumoral mucosa first led to the notion of colonic field defects. The hypothesis of a genetically determined mosaicism would explain these defects and would make the co-localization of tumors likely. Our purpose was to indirectly test this hypothesis by searching for a possible correlation between the location of colorectal cancers and adenomas METHODS: This is a retrospective observational study. Patients operated for colorectal cancers at an oncological hospital, who had a full colonoscopy performed in the two peri-operative years, were surveyed. Sex, age, familial risk of cancer, tumor and adenoma locations, and the presence of adenomas larger than 1 cm, with villous component or high-grade dysplasia were recorded. STATISTICS: T test, chi-square, exact, logistic regression (SPSS18®). RESULTS: This study included 224 patients (57 % male, mean age 67.6 years), 45 % of which had synchronous adenomas. There was a significant correlation between cancer location and location of all adenomas (p = 0.01) and of adenomas larger than 1 cm (p = 0.01). Adenomas of the right colon were more frequent in patients with right colon cancer (p = 0.008), and the same was true on the left colon (p = 0.002). CONCLUSIONS: The strong correlation between the locations of CRC and synchronous adenomas, namely risk adenomas, may point to a common early defect. It does also suggest that hemicolectomy may always be the surgery of choice for colon cancer.

Long segments of columnar-lined lower esophagus are not always metaplastic.

The presence of columnar epithelium in the esophagus is associated with two conditions: Barrett's esophagus and heterotopic gastric mucosa. The former results from the metaplastic replacement of the normal distal squamous esophageal lining, is associated with gastroesophageal reflux and is a pre-neoplastic condition. The second is thought as a congenital condition, resulting from the incomplete squamous epithelialization of the esophagus during embryologic development. It is found mainly in the cervical esophagus. Histologically, Barrett's esophagus is composed of an admixture of cardiac mucosa, oxintocardiac mucosa and intestinal metaplasia. Most of heterotopic gastric mucosa consists of oxynticmucosa where the mucosal glands are straight and composed of parietal and chief cells.There are few reports of heterotopic gastric mucosa in the lower esophagus, generally presenting as small islands. In the present report, a series of four cases of large lower esophageal heterotopic gastric mucosa is described. All patients were initially misdiagnosed with Barrett's esophagus and referred for surveillance. The correct diagnosis was based in endoscopic and histological features. In all, a circular tiny strip of squamous mucosa was observed at endoscopy between the lower end of the columnarlined esophagus and the esophagogastric junction, defined as the proximal end of the gastric folds. Biopsy samples taken from the columnar-lined segments of the four patients showed pure oxyntic mucosa.When columnar-lined esophagus is observed in the distal esophagus not in continuity with gastric mucosa, the diagnosis of heterotopic gastric mucosa must be thought and confirmed histologically by the presence of pure oxyntic mucosa.

Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity.

OBJECTIVE: To develop non-toxic aqueous ocular drug delivery systems containing prednisolone by means of its nanoencapsulation. MATERIALS AND METHODS: Nanocapsules were prepared by interfacial deposition of preformed polymer [poly(ε-caprolactone) or Eudragit® RS100]. Particle size distribution was determined by laser diffractometry, photon correlation spectroscopy and nanoparticle tracking analysis. Ocular irritation and cytotoxicity were evaluated in vitro on the chorioallantoic membrane (CAM) and rabbit corneal epithelial cell line, respectively. RESULTS AND DISCUSSION: Nanocapsules showed mean particle sizes between 100 and 300 nm and prednisolone encapsulation efficiency of around 50%. Controlled release of prednisolone occurred for 5 h for both formulations according to the biexponential model. Both formulations were found to be non-irritant in the CAM test and non-cytotoxic toward rabbit corneal epithelial cells. CONCLUSIONS: Encapsulation of prednisolone in nanocapsules was reported for the first time, being suitable for producing eye drops for the treatment of ocular inflammatory and no eye toxicity was indicated.

Castor oil and mineral oil nanoemulsion: development and compatibility with a soft contact lens.

CONTEXT: The non-invasive ophthalmic therapy has a drawback: low residence time in the eye socket. Nanoparticles and contact lenses have been studied as promising ocular drug delivery systems. OBJECTIVE: To develop a nanoemulsion and evaluate its compatibility with a soft contact lens as a potential strategy for ocular delivery. MATERIALS AND METHODS: The formulations were developed by spontaneous emulsification and fully characterized. Two drops of nanoemulsion were instilled on the surface of a commercial contact lens and its transparency was measured using a UV-Vis spectrophotometer. Before and after the instillation of the drops, the morphology (scanning electron microscopy - SEM) and ion permeability of the lenses were analyzed. RESULTS: The formulations had a mean particle size of 234 nm, polydispersity below 0.16, zeta potential of -8.56 ± 3.49 mV, slightly acid pH, viscosity ≈1.2 mPa s(-1) and spherical-shaped particles. Nanoemulsion was non-irritant (hen's egg test-chorioallantoic membrane), which was confirmed by the cytotoxicity studies in the SIRC cell cultures. After instillation, SEM analysis showed nanodroplets inside and on the surface of the lenses, although their transparency remained near 100%. No significant differences were found between lens ion permeability coefficients before and after instillation. CONCLUSIONS: Formulations presented appropriate physicochemical characteristics and suitability for ocular application. The contact lens remained transparent and ion-permeable after association with the formulation.

Breathing, postural stability, and psychological health: a study to explore triangular links.

Objective: This study aims to test the hypothesis that breathing can be directly linked to postural stability and psychological health. A protocol enabling the simultaneous analysis of breathing, posture, and emotional levels in university students is presented. This aims to verify the possibility of defining a triangular link and to test the adequacy of various measurement techniques. Participants and Procedure: Twenty-three subjects (9 females and 14 males), aged between 18 and 23 years, were recruited. The experiment consisted of four conditions, each lasting 3 minutes: Standard quiet standing with open eyes 1), with closed eyes 2), and relaxed quiet standing while attempting deep abdominal breathing with open eyes 3) and with closed eyes 4). These latter two acquisitions were performed after subjects were instructed to maintain a relaxed state. Main Outcome Measures: All subjects underwent postural and stability analysis in a motion capture laboratory. The presented protocol enabled the extraction of 4 sets of variables: Stabilometric data, based on the displacement of the center of pressure and acceleration, derived respectively from force plate and wearable sensors. Postural variables: angles of each joint of the body were measured using a stereophotogrammetric system, implementing the Helen Hayes protocol. Breathing compartment: optoelectronic plethysmography allowed the measurement of the percentage of use of each chest compartment. Emotional state was evaluated using both psychometric data and physiological signals. A multivariate analysis was proposed. Results: A holistic protocol was presented and tested. Emotional levels were found to be related to posture and the varied use of breathing compartments. Abdominal breathing proved to be a challenging task for most subjects, especially females, who were unable to control their breathing patterns. In males, the abdominal breathing pattern was associated with increased stability and reduced anxiety. Conclusion: In conclusion, difficulties in performing deep abdominal breathing were associated with elevated anxiety scores and decreased stability. This depicts a circular self-sustaining relationship that may reduce the quality of life, undermine learning, and contribute to muscular co-contraction and the development of musculoskeletal disorders. The presented protocol can be utilized to quantitatively and holistically assess the healthy and/or pathological condition of subjects.