Cross-linked hyaluronic acid sub-micron particles: in vitro and in vivo biodistribution study in cancer xenograft model.

This paper focused on the biodistribution of the cross-linked hyaluronic acid (HA-NPs) sub-micron particles in tumor-bearing mice. Solvent-non solvent method followed glutaraldehyde cross-linking utilized for the fabrication of HA-NPs. Size measurement and morphological analysis were performed by dynamic light scattering and electron microscopy, respectively and the size found to be in the range of 200-400 nm. In vitro viability in LNCaP cell line was assessed by water soluble tetrazolium assay after 24 h of exposure to sub-micron particles and no toxicity was found to higher concentration of 3 mg/mL. Internalization of particles in prostate cancer cell LNCaP were studied by confocal microscopy with FITC labeled submicron particles and involvement of hyaluronan receptor mediated uptake/endocytosis was confirmed by competitive assay. Biodistribution studies were performed in xenograft prostate cancer mice model with fluorophore labeled particles and monitored in tumoral parenchyma with strong fluorescence, meanwhile very less signal in liver, kidney and spleen while no fluorescence found in lung after 24 h of systemic administration; that shown ability of this HA based system to recognize cancer tissue. These result fetched that hyaluronic acid based system is selective for tumoral site and can be utilized to deliver bioactives in specific (targeting) and controlled (temporal) manner to cancerous tissue.

Quantifying Distances Between Non-Elliptical Clusters to Enhance the Identification of Meaningful Emotional Reactivity Subtypes.

Coordinated emotional responses across psychophysiological and subjective indices is a cornerstone of adaptive emotional functioning. Using clustering to identify cross-diagnostic subgroups with similar emotion response profiles may suggest novel underlying mechanisms and treatments.However, many psychophysiological measures are non-normal even in homogenous samples, and over-reliance on traditional elliptical clustering approaches may inhibit the identification of meaningful subgroups. Finite mixture models that allow for non-elliptical cluster distributions is an emerging methodological field that may overcome this hurdle. Furthermore, succinctly quantifying pairwise cluster separation could enhance the clinical utility of the clustering solutions. However, a comprehensive examination of distance measures in the context of elliptical and non-elliptical model-based clustering is needed to provide practical guidance on the computation, benefits, and disadvantages of existing measures. We summarize several measures that can quantify the multivariate distance between two clusters and suggest practical computational tools. Through a simulation study, we evaluate the measures across three scenarios that allow for clusters to differ in location, scale, skewness, and rotation. We then demonstrate our approaches using psychophysiological and subjective responses to emotional imagery captured through the Transdiagnostic Anxiety Study. Finally, we synthesize findings to provide guidance on how to use distance measures in clustering applications.

Immunogold labelling in environmental scanning electron microscopy: applicative features for complementary cytological interpretation.

We have combined environmental scanning electron microscopy (ESEM) and immunogold labelling (IGL) for the analysis of cell morphology and surface protein detection on human fine needle aspiration, which is processed in thin uniform monolayer (a single layer of cells) on a glass slide by Thin Prep technology. Among scanning electron microscopy techniques, we choose the environmental modality (ESEM) because it allows a slight manipulation of biological samples and an operational time comparable with cytological techniques. Moreover, the Thin Prep technology confirmed a reproducible cell monolayer on glass smear, minimizing problems for the determination of appropriate amount of material per slide. The first experimental data in ESEM-IGL on biological samples with fine needle aspiration Thin Prep, in human thyroid nodules, showed that cells retained their morphology and provided a clear IGL. The optimization of conditions (i.e. vacuum pressure, temperature and relative humidity) confirmed the possibility to observe an immunolabelled biological sample and morphological signal, joined with compositional informations, due to peculiar characteristics of gaseous secondary electron detector in ESEM. The ESEM-IGL and fine needle aspiration Thin Prep could be used in combination for the interpretation of cell morphology and cell surface immunolabelling. Our paper suggests this use as a powerful diagnostic tool in a pre-surgical evaluations, opening a new applicative window for electron microscopy.

Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial.

BACKGROUND: Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. METHODS: A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil® Plus® ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. KEY RESULTS: One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, P<.001) and group B (-35, 95% CI: -49 to -20, P<.001) when compared to group C. No significant difference was observed between Group A and Group B (mean difference: -9 minutes, 95% CI -23 to +5, P=.205). At day 28, 39 of 57 (68.4%) of infants in Group C responded to the treatment compared with 57 out of 60 patients (95%) of Group A and 51 out of 59 (86.4%) of Group B (P<.001). CONCLUSIONS: This study suggests that administration of M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02708238.

[Seroepidemiology of Chagas disease in the Province of Jujuy]. / Seroepidemiología de la enfermedad de Chagas en la Provincia de Jujuy.

Chagas disease is the principal zoonosis of the Province of Jujuy where it represents a major public health problem. In this paper the results of a serological screening of T. cruzi infection carried out in the Province of Jujuy are analyzed to determine the general prevalence, age and geographic distribution, sex ratio, prevalence in foreign population and their relation with migratory process. In every individual (N = 16482) indirect hemagglutination (IHA) and immunofluorescence (TIF) tests have been carried out. In 5879 of them the birth place in the territory of the Province and the number of foreign individuals (313, all Bolivians) were confirmed. Based on these data the individuals were grouped according to: a) the four geographical regions of the Province located at different altitude levels, Puna, Quebrada, Valle and Ramal; b) towns placed on or away from the main routes of communication of the Province. For the statistical analysis the X2 and Z tests were employed. The results show that: 1) the general prevalence was of 11.50%; 2) no differences existed between the sexes: 3) the region with the highest prevalence was the Valley (12.84%) followed by Ramal (10.43%), Quebrada (8.53%) and Puna (2.98%); 4) differences of the serum prevalence can be observed between the residents on and away from the main routes of communication denoting the existence of a migratory effect in the distribution of chagasic infection; 5) prevalence differences exist between naturalized foreigns (39.30%) and Argentines (10.25%), data which strengthen the previous remark. Except for the general prevalence, there are no similar serological surveys which might allow us to establish relationships with our results of which the outstanding one is the influence of the migratory aspect upon the prevalence and distribution of T. cruzi in the Province of Jujuy.

[Chagas diseases seroepidemiology in schoolchildren of Jujuy]. / Seroepidemiología de la enfermedad de Chagas en escolares de Jujuy.

Chagas disease constitutes the main zoonosis in the province of Jujuy, Argentina, where it is one of the most important issues in public health. The purpose of this paper is to analyze the results of a serologic evaluation carried out for a seven-year period among schoolchildren in the Jujenean capital city. The population under study consisted of all seventh grade students of all schools in San Salvador de Jujuy. They were classified into three socioeconomic levels: High, Medium and Low levels. Indirect hemagglutination and immunofluorescence tests were performed. Percentages of seroprevalence were determined by sex, age group, and socioeconomic level. To analyze and check results, the following tests were applied: ANOVA, Tukey's and chi-square test. General prevalence was 1.95% with inter-annual statistically non-significant variations. Statistically significant variations were found among: 1) sex, where the feminine sex exhibited higher seroprevalence; 2) age groups, in which 12-year-olds showed higher seroprevalence; 3) socioeconomic levels, where seroprevalence increased as socioeconomic level decreased. Chagasic seroprevalence in children populations is an indicator that allows assessing both transmission risks in the community and the efficiency of preventive measures to control the vector. Data resulting from this study would indicate: 1) an adequate control both of non-vectorial transmission as well as of the vector, since no temporal variation was recorded in seroprevalence in the age-group analyzed; 2) higher seroprevalence in children belonging to a lower socioeconomic level, probably due to migrations of already-infected mothers coming from neighboring endemic, less epidemiologically controlled areas.

The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice.

BACKGROUND AND PURPOSE: Osteoporosis is a condition characterized by a decrease in bone density, which decreases its strength and results in fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved in the regulation of skeletal remodelling. The aim of this study was to investigate the possible modulation of bone mass mediated by the transient receptor potential vanilloid type 1 channel (TRPV1) in vivo and in vitro. EXPERIMENTAL APPROACH: A multidisciplinary approach, including biomolecular, biochemical and morphological analysis, was used to investigate the involvement of TRPV1 in changes in bone density in vivo and osteoclast activity in vitro, in wild-type and Trpv1(-/-) mice, that had undergone ovariectomy or had a sham operation. KEY RESULTS: Genetic deletion of Trpv1 as well as pharmacological inhibition/desensitization of TRPV1 signalling dramatically reduced the osteoclast activity in vitro and prevented the ovariectomy-induced bone loss in vivo, whereas the expression of cannabinoid type 2 (CB2 ) receptors was increased. CONCLUSIONS AND IMPLICATIONS: These findings highlight the pivotal role TRPV1 channels play in bone resorption and suggest a possible cross-talk between TRPV1 and CB2 receptors. Based on these results, hybrid compounds acting on both TRPV1 and CB2 receptors in an opposite manner could provide a future pharmacological tool for the treatment of diseases associated with disturbances in the bone remodelling process.