Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis.

Cortical lesions are common in multiple sclerosis and are associated with disability and progressive disease. We asked whether cortical lesions continue to form in people with stable white matter lesions and whether the association of cortical lesions with worsening disability relates to pre-existing or new cortical lesions. Fifty adults with multiple sclerosis and no new white matter lesions in the year prior to enrolment (33 relapsing-remitting and 17 progressive) and a comparison group of nine adults who had formed at least one new white matter lesion in the year prior to enrolment (active relapsing-remitting) were evaluated annually with 7 tesla (T) brain MRI and 3T brain and spine MRI for 2 years, with clinical assessments for 3 years.

Cortical lesions uniquely predict motor disability accrual and form rarely in the absence of new white matter lesions in multiple sclerosis.

Background And Objectives: Cortical lesions (CL) are common in multiple sclerosis (MS) and associate with disability and progressive disease. We asked whether CL continue to form in people with stable white matter lesions (WML) and whether the association of CL with worsening disability relates to pre-existing or new CL.

Methods: A cohort of adults with MS were evaluated annually with 7 tesla (T) brain magnetic resonance imaging (MRI) and 3T brain and spine MRI for 2 years, and clinical assessments for 3 years.

Experience with ultrasound use in central venous catheterization (jugular-femoral) in pediatric patients in an intensive care unit.

Objective: Describe ultrasound-guided central venous catheterization use comparing the number of attempts (1 versus 2 or more attempts) in relation to catheters placed in the internal jugular vein (IJV) versus the femoral vein (FV).

Material And Methods: Descriptive, prospective study of central venous catheters (CVCs) inserted via ultrasound-guided puncture in patients aged 1 month to 18 years. A multivariate regression model was done considering the primary endpoint, first puncture success in relation to the insertion site (IJV versus FV), and predictors of success.

Intermediate-Intensity Autologous Hematopoietic Stem Cell Transplantation Reduces Serum Neurofilament Light Chains and Brain Atrophy in Aggressive Multiple Sclerosis.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.

Cortical lesion hotspots and association of subpial lesions with disability in multiple sclerosis.

Background: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course.

Objective: Characterize cortical lesions by 7 tesla (T) T-/T-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability.

Methods: Sixty-four adults with MS (45 relapsing-remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing.

Navigator-Guided Motion and B0 Correction of T2*-Weighted Magnetic Resonance Imaging Improves Multiple Sclerosis Cortical Lesion Detection.

Background: Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations.

Purpose: The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T2*w magnetic resonance imaging.

Inversion Recovery Susceptibility Weighted Imaging With Enhanced T2 Weighting at 3 T Improves Visualization of Subpial Cortical Multiple Sclerosis Lesions.

Objectives: Cortical demyelination is common in multiple sclerosis (MS) and can be extensive. Cortical lesions contribute to disability independently from white matter lesions and may form via a distinct mechanism. However, current magnetic resonance imaging methods at 3 T are insensitive to cortical, and especially subpial cortical, lesions.

Impact of autologous haematopoietic stem cell transplantation on disability and brain atrophy in secondary progressive multiple sclerosis.

Background: Autologous haematopoietic stem cell transplantation (aHSCT) is a valuable option in aggressive relapsing-remitting multiple sclerosis (MS), but its efficacy in secondary progressive (SP)-MS is still controversial.

Objective: Assessing efficacy of aHSCT in SP-MS by clinical-radiological outcomes.

Methods: Open-label monocentric retrospective study enrolling consecutive SP-MS patients treated with BEAM-aHSCT in the period 1999-2016.

Intravital microscopy of osteolytic progression and therapy response of cancer lesions in the bone.

Intravital multiphoton microscopy (iMPM) in mice provides access to cellular and molecular mechanisms of metastatic progression of cancers and the underlying interactions with the tumor stroma. Whereas iMPM of malignant disease has been performed for soft tissues, noninvasive iMPM of solid tumor in the bone is lacking. We combined miniaturized tissue-engineered bone constructs in nude mice with a skin window to noninvasively and repetitively monitor prostate cancer lesions by three-dimensional iMPM.

Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women.

Objectives: The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera.

Methods: Maternal and cord sera collected at baseline and at delivery from vaccine and placebo recipients during a double-blind placebo-controlled Phase II study (www.

Examination of the foreign body response to biomaterials by nonlinear intravital microscopy.

Implanted biomaterials often fail because they elicit a foreign body response (FBR) and concomitant fibrotic encapsulation. To design clinically relevant interference approaches, it is crucial to first examine the FBR mechanisms. Here, we report the development and validation of infrared-excited nonlinear microscopy to resolve the three-dimensional (3D) organization and fate of 3D-electrospun scaffolds implanted deep into the skin of mice, and the following step-wise FBR process.

Nutritional Characterization and Phenolic Profiling of Moringa oleifera Leaves Grown in Chad, Sahrawi Refugee Camps, and Haiti.

Moringa oleifera is a plant that grows in tropical and subtropical areas of the world. Its leaves are rich of nutrients and bioactive compounds. However, several differences are reported in the literature.

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments.

A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX) is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS) fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed.

Investigating the immunodominance of carbohydrate antigens in a bivalent unimolecular glycoconjugate vaccine against serogroup A and C meningococcal disease.

Multicomponent constructs, obtained by coupling different glycans to the carrier protein, have been proposed as a way to co-deliver multiple surface carbohydrates targeting different strains of one pathogen and reduce the number of biomolecules in the formulation of multivalent vaccines. To assess the feasibility of this approach for anti-microbial vaccines and investigate the potential immunodominance of one carbohydrate antigen over the others in these constructs, we designed a bivalent unimolecular vaccine against serogroup A (MenA) and C (MenC) meningococci, with the two different oligomers conjugated to same molecule of carrier protein (CRM197). The immune response elicited in mice by the bivalent MenAC construct was compared with the ones induced by the monovalent MenA and MenC vaccines and their combinations.

Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model.

Next generation vaccine adjuvants include Toll like receptor agonists, which are mostly extracted from microorganisms, but synthetic small molecule TLR agonists have also been identified. However, their delivery systems have not been optimized for effective administration in conjunction with antigens. Here, we describe a novel approach in which a small molecule TLR agonist was directly conjugated to antigen to ensure effective co-delivery.

Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X.

Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in the African meningitis belt, and has a high associated mortality. The meningococcal serogroups A, W, and X have been responsible for epidemics and almost all cases of meningococcal meningitis in the meningitis belt over the past 12 y. Currently no vaccine is available against meningococcal X (MenX).

Immunoactivity of protein conjugates of carba analogues from Neisseria meningitidis a capsular polysaccharide.

Neisseria meningitidis type A (MenA) is a Gram-negative encapsulated bacterium that is a major cause of epidemic meningitis, especially in the sub-Saharan region of Africa. The development and manufacture of a liquid glycoconjugate vaccine against MenA are hampered by the poor hydrolytic stability of its capsular polysaccharide (CPS), consisting of (1→6)-linked 2-acetamido-2-deoxy-α-d-mannopyranosyl phosphate repeating units. The replacement of the ring oxygen with a methylene group to generate a carbocyclic analogue leads to enhancement of its chemical stability.

Breast cancer genes: beyond BRCA1 and BRCA2.

Breast cancer (BC) is a heterogeneous disease. The majority of breast cancer cases (about 70 percent) are considered sporadic. Familial breast cancer (about 30 percent of patients), often seen in families with a high incidence of BC, has been associated with a number of high-, moderate-, and low-penetrance susceptibility genes.

Synergy between stents and extracorporeal membrane oxygenation in multitrauma patients with inferior vena cava injury.

Despite the lack of evidence in the literature, we report the case of a 25-year-old man involved in a road traffic accident, who had an inferior vena cava (IVC) injury and severe lung contusion with parenchymal bleeding requiring an extracorporeal membrane oxygenation (ECMO). An emergency procedure to implant a stent graft was successful in repairing the IVC injury. Moreover, we think that ECMO, in addition to providing oxygenation, reduced bleeding by creating a negative pressure along the injured IVC.

[Continuous infusion of vancomycin in pediatric critical care].

Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof.