GMMA and Glycoconjugate Approaches Compared in Mice for the Development of a Vaccine against <i>Shigella flexneri</i> Serotype 6

Shigella infections are one of the top causes of diarrhea throughout the world, with Shigella flexneri being predominant in developing countries. Currently, no vaccines are widely available and increasing levels of multidrug-resistance make Shigella a high priority for vaccine development. The serotype-specific O-antigen moiety of Shigella lipopolysaccharide has been recognized as a key target for protective immunity, and many O-antigen based candidate vaccines are in development. Recently, the Generalized Modules for Membrane Antigens (GMMA) technology has been proposed as an alternative approach to traditional glycoconjugate vaccines for O-antigen delivery. Here, these two technologies are compared for a vaccine against S. flexneri serotype 6. Genetic strategies for GMMA production, conjugation approaches for linkage of the O-antigen to CRM197 carrier protein, and a large panel of analytical methods for full vaccine characterization have been put in place. In a head-to-head immunogenicity study in mice, GMMA induced higher anti-O-antigen IgG than glycoconjugate administered without Alhydrogel. When formulated on Alhydrogel, GMMA and glycoconjugate elicited similar levels of persistent anti-O-antigen IgG with bactericidal activity. Glycoconjugates are a well-established bacterial vaccine approach, but can be costly, particularly when multicomponent preparations are required. With similar immunogenicity and a simpler manufacturing process, GMMA are a promising strategy for the development of a vaccine against Shigella

safety and efficacy of galactogogues substances that induce maintain and increase breast milk production

Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding

Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series

ABSTRACT:INTRODUCTION: We describe three different fetal or neonatal outcomes in the offspring of a mother who had persistent circulating thyrotropin receptor antibodies despite having undergone a total thyroidectomy several years before. CASE PRESENTATION: The three different outcomes were an intrauterine death, a mild and transient fetal and neonatal hyperthyroidism and a severe fetal and neonatal hyperthyroidism that required specific therapy. CONCLUSIONS: The three cases are interesting because of the different outcomes, the absence of a direct correlation between thyrotropin receptor antibody levels and clinical signs, and the persistence of thyrotropin receptor antibodies several years after a total thyroidectomy

Does Presentation Format Influence Visual Size Discrimination in Tufted Capuchin Monkeys (Sapajus spp.)?

Most experimental paradigms to study visual cognition in humans and non-human species are based on discrimination tasks involving the choice between two or more visual stimuli. To this end, different types of stimuli and procedures for stimuli presentation are used, which highlights the necessity to compare data obtained with different methods. The present study assessed whether, and to what extent, capuchin monkeys\u27 ability to solve a size discrimination problem is influenced by the type of procedure used to present the problem. Capuchins\u27 ability to generalise knowledge across different tasks was also evaluated. We trained eight adult tufted capuchin monkeys to select the larger of two stimuli of the same shape and different sizes by using pairs of food items (Experiment 1), computer images (Experiment 1) and objects (Experiment 2). Our results indicated that monkeys achieved the learning criterion faster with food stimuli compared to both images and objects. They also required consistently fewer trials with objects than with images. Moreover, female capuchins had higher levels of acquisition accuracy with food stimuli than with images. Finally, capuchins did not immediately transfer the solution of the problem acquired in one task condition to the other conditions. Overall, these findings suggest that - even in relatively simple visual discrimination problems where a single perceptual dimension (i.e., size) has to be judged - learning speed strongly depends on the mode of presentation

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased fromone in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

Attention to social stimuli is modulated by sex and exposure time in tufted capuchin monkeys

The dot-probe task is an experimental procedure commonly used to study how animals (including humans) pay attention to different stimuli. In this study, we evaluated how different durations of image exposure modulate the response to this task and how male and female tufted capuchin monkeys (Sapajus spp.) respond to different social stimuli. Subjects were shown pairs of images of unfamiliar conspecifics: a male vs. a female or two individuals grooming vs. two individuals not engaged in grooming. With shorter image exposures (250 ms) both sexes responded faster to (i.e., biased their attention towards) images of unfamiliar males compared to females, and were unaffected by images of grooming compared to nongrooming. With longer image exposures (1000 ms) females biased their attention towards images of unfamiliar females, while males did not show any difference; in contrast, males biased their attention towards images of grooming compared to nongrooming, while females did not show any difference. We interpret these results as showing that responses to the dot-probe task with different image exposures reflect different attentional phenomena, and that the two sexes differ in how social stimuli affect their attention

Touch improves visual discrimination of object features in capuchin monkeys (Sapajus spp.)

Primates perceive many object features through vision and touch. To date, little is known on how the synergy of these two sensory modalities contributes to enhance object recognition. Here, we investigated in capuchin monkeys (N=12) whether manipulating objects and retaining tactile information enhanced visual recognition of geometrical object properties on different scales. Capuchins were trained to visually select the rewarded one of two objects differing in size, shape (larger-scale) or surface structure (smaller-scale). Objects were explored in two experimental conditions: the Sight condition prevented capuchins from touching the chosen object; the Sight and Touch condition allowed them to touch the selected object. Our results indicated that tactile information increased the capuchins’ learning speed for visual discrimination of object features. Moreover, the capuchins’ learning speed was higher in both size and shape discrimination compared to surface discrimination regardless of the availability of tactile input. Overall, our data demonstrated that the acquisition of tactile information about object features was advantageous for the capuchins and allowed them to achieve high levels of visual accuracy faster. This suggests that information from touch potentiated object recognition in the visual modality

Nafion®-containing solid lipid nanoparticles as a tool for anticancer pt delivery: preliminary studies

Preliminary studies of nanoparticles based on the perfluorosulfonic acid resin Nafion® have been carried out with the aim of establishing an ionic connection with the protonable phosphine 1,3,5-triaza-7-phosphaadamantane (PTA), suitable for the coordination of platinum. Nafion®-containing nanoparticles (NAF) were produced by homogenization followed by ultrasonication method. After production, NAF were characterized in term of size, morphology and in vitro cytotoxicity. The PCS studies showed that the Z-Average mean diameter was around 250 nm. Moreover, the polydispersity index showed a monodimensional distribution of nanoparticles. Cryo-TEM analysis showed a uniform and homogenous population of particles, characterized by the presence of both ovoidal and needle-like structures. To evaluate the in vitro cytotoxicity, NAF were tested on human cancer cell lines K562 and A2780. No cytotoxic effect was found on both cell lines. By 13P-NMR measures, it is here proved that the strongly acidic sulfonic groups of Nafion®-containing nanoparticles (NAF) can act as protonating agents for PTA. The protonation occurs selectively at nitrogen, hence protonated PTA maintains its ability to coordinate platinum via its phosphorus atom

Proton MR spectroscopy in Pelizaeus-Merzbacher disease without point mutation in PLP gene

Descrizione di due pazienti con Sindrome di Pelizaeus-Merzbacher ad esordio neonatale