Mycobacterium ulcerans mycolactone interferes with adhesion, migration and proliferation of primary human keratinocytes and HaCaT cell line.

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactone has been linked to its apoptogenic activity. We explored if low mycolactone concentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocyte populations, keratinocyte stem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyte line, HaCaT.

N-N bond formation in Ugi processes: from nitric acid to libraries of nitramines.

The Ugi reaction has drawn considerable attention over the years leading to numerous libraries of heterocycles and various extensions changing the nature of the components of the coupling. We report here the use of nitric acid as carboxylic acids surrogates, displaying the first aminative Ugi-type reaction leading to nitramines.

The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development.

Background: Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin-bilirubin (ALBI) grade is a validated index of liver function in patients with HCC.

Aim: To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment.

Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases.

Osteopontin (OPN) regulates the immune response at multiple levels. Physiologically, it regulates the host response to infections by driving T helper (Th) polarization and acting on both innate and adaptive immunity; pathologically, it contributes to the development of immune-mediated and inflammatory diseases. In some cases, the mechanisms of these effects have been described, but many aspects of the OPN function remain elusive.

Mode of action of Cr(VI) in immunocytes of earthworms: Implications for animal health.

Chromium (Cr) is one of the major and most detrimental pollutant, widely present in the environment as a result of several anthropogenic activities. In mammalian cells, Cr(VI) is known to enhance reactive oxygen species (ROS) production and to cause toxic and genotoxic effects. Less commonly investigated are the effects and mode of action of this contaminant in invertebrates, particularly in soil organisms.

When cervical pain is actually migraine: An observational study in 207 patients.

Introduction A large proportion of migraine patients remain undiagnosed or misdiagnosed in Italy. In our experience, many migraineurs self-diagnose their condition as "cervical pain attack" or "cervical pain syndrome" (CP), assuming cervical spine pathology as the cause. We aimed to phenotype and classify the headache of patients with self-diagnosed CP, and to describe this sample of patients.

Transorbital Sonography and Visual Outcome for the Diagnosis and Monitoring of Optic Neuritis.

Background And Purpose: Transorbital sonography (TOS) is a promising tool to support the clinical diagnosis of optic neuritis (ON) by showing thickening of optic nerve. In this study, we aimed to define its specific role in follow-up of ON patients.

Methods: We measured ultrasonography parameters and visual acuity (VA) at presentation and after 1 year in 45 patients with newly diagnosed ON.

Definition of the Labile Capping Bond Effect in Lanthanide Complexes.

Two macrocyclic ligands containing a cyclen unit, a methyl group, a picolinate arm, and two acetate pendant arms attached to two nitrogen atoms of the macrocycle either in trans (1,7-H Medo2 ampa = 2,2'-(7-((6-carboxypyridin-2-yl)methyl)-10-methyl-1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid) or in cis (1,4-H Medo2 ampa) positions are reported. These ligands provide eight-coordination to the Ln ions, leaving a coordination position available for a water molecule that occupies a capping position in the twisted square antiprismatic polyhedron (1,4-H Medo2 ampa) or one of the positions of the square antiprism (1,7-H Medo2 ampa). The charge neutral [Gd(1,7-Medo2 ampa)] complex presents an unprecedentedly low water-exchange rate (k =8.

Dopamine exacerbates mutant Huntingtin toxicity via oxidative-mediated inhibition of autophagy in SH-SY5Y neuroblastoma cells: Beneficial effects of anti-oxidant therapeutics.

Neuronal cell death in Huntington's Disease (HD) is associated with the abnormal expansions of a polyglutamine (polyQ) tract in the huntingtin protein (Htt) at the N-terminus that causes the misfolding and aggregation of the mutated protein (mHtt). Autophagy-lysosomal degradation of Htt aggregates may protect the neurons in HD. HD patients eventually manifest parkinsonian-like symptoms, which underlie defects in the dopaminergic system.

Celecoxib inhibits proliferation and survival of chronic myelogeous leukemia (CML) cells via AMPK-dependent regulation of β-catenin and mTORC1/2.

CML is effectively treated with tyrosine kinase inhibitors (TKIs). However, the efficacy of these drugs is confined to the chronic phase of the disease and development of resistance to TKIs remains a pressing issue. The anti-inflammatory COX2 inhibitor celecoxib has been utilized as anti-tumour drug due to its anti-proliferative activity.

Microencapsulated bitter compounds (from reduce daily energy intakes in humans.

Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter ingredient (EBI) with a core of bitter root extract and a coating of ethylcellulose-stearate was developed and included in a vanilla microencapsulated bitter ingredient-enriched pudding (EBIP).

Physico-chemical properties of Mn complexes formed with cis- and trans-DO2A: thermodynamic, electrochemical and kinetic studies.

Mn complexes formed with cis- and trans-DO2A (DO2A=1,4,7,10-tetraazacyclododecane-1,4 (or 1,7) -diacetic acid) chelators were investigated by pH-potentiometry, H relaxometry, UV-vis spectrophotometry and cyclic voltammetry. The physico-chemical characteristics of Mn complexes of these structure isomers do not differ dramatically, however the cis-DO2A platform has better potential for further development. Manganese (Mn) is a promising alternative to gadolinium (Gd) as a magnetic resonance imaging (MRI) agent.

Structure and Function of Iron-Loaded Synthetic Melanin.

We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure-property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions.

Interdomain interactions rearrangements control the reaction steps of a thermostable DNA alkyltransferase.

Background: Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs.

Tools and Checklists Used for the Evaluation of Hospital Disaster Preparedness: A Systematic Review.

Hospitals need to be fully operative during disasters. It is therefore essential to be able to evaluate hospital preparedness. However, there is no consensus of a standardized, comprehensive and reliable tool with which to measure hospital preparedness.

The Association of Bifidobacterium breve BR03 and B632 is Effective to Prevent Colics in Bottle-fed Infants: A Pilot, Controlled, Randomized, and Double-Blind Study.

Goals: To assess the effectiveness of Bifidobacterium breve B632 and BR03 association in the reduction of infants crying over time. The second endpoint was to observe the effect of the same strains on daily evacuations and on the number of regurgitations and vomits.

Background: Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause.

A Synthetic Disaccharide Analogue from Neisseria meningitidis A Capsular Polysaccharide Stimulates Immune Cell Responses and Induces Immunoglobulin G (IgG) Production in Mice When Protein-Conjugated.

Some new phosphonoester-linked oligomers, stabilized analogues of the corresponding phosphate-bridged oligomers of Neisseria meningitidis A (MenA) capsular polysaccharide (CPS), were conjugated to human serum albumin (HSA), as a protein carrier model, and studied for immunological activities. We determined (i) in vitro, their biocompatibility (CAM test) and activity in inducing both T cell proliferation (CFSE method) and IL-2 release (ELISA), and (ii) in vivo, their ability to stimulate specific IgG antibody production (ELISA). All HSA-conjugated compounds induce T cell proliferation (40% of proliferation at 10(2) μM), whereas only the phosphonodisaccharide was effective (28% of proliferation at 10(2) μM) among the unconjugated forms.

Prognostic sub-classification of intermediate-stage hepatocellular carcinoma: a multicenter cohort study with propensity score analysis.

There is significant heterogeneity in the clinicopathological characteristics of intermediate hepatocellular carcinoma (IHCC). This also translates to treatment as transarterial chemoembolization (TACE) is used as first-line therapy for patients with IHCC; however, in Asia liver resection (LR) is preferred. Prognostic tools are required to help guide clinicians in deciding treatment options.

Clinical features of migraine aura: Results from a prospective diary-aided study.

Background A detailed evaluation of migraine aura symptoms is crucial for classification issues and pathophysiological discussion. Few studies have focused on the detailed clinical aspects of migraine aura. Methods We conducted a prospective diary-based study of migraine aura features including presence, quality, laterality, duration of each aura symptom, their temporal succession; presence of headache and its temporal succession with aura.

Unraveling the Decomposition Process of Lead(II) Acetate: Anhydrous Polymorphs, Hydrates, and Byproducts and Room Temperature Phosphorescence.

Lead(II) acetate [Pb(Ac)2, where Ac = acetate group (CH3-COO(-))2] is a very common salt with many and varied uses throughout history. However, only lead(II) acetate trihydrate [Pb(Ac)2·3H2O] has been characterized to date. In this paper, two enantiotropic polymorphs of the anhydrous salt, a novel hydrate [lead(II) acetate hemihydrate: Pb(Ac)2·(1)/2H2O], and two decomposition products [corresponding to two different basic lead(II) acetates: Pb4O(Ac)6 and Pb2O(Ac)2] are reported, with their structures being solved for the first time.