Pneumococcal conjugate vaccine implementation in middle-income countries

Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs

Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary experience

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by NOTCH3 mutations. It is characterized by migraine, with or without aura, ischemic events, psychiatric and cognitive disturbances. There is no approved treatment for migraine prophylaxis in CADASIL, but acetazolamide has been anecdotally reported to be effective. We retrospectively reviewed our database of patients with a genetic diagnosis of CADASIL to identify how many of them were treated with acetazolamide for the prophylaxis of migraine. The efficacy and the tolerability of this treatment were checked looking at the clinic reports. Acetazolamide was prescribed in seven patients; the mean duration of treatment was 6 months, and the daily dose ranged from 125 to 500 mg. Three patients had a total and sustained remission, while in two patients a reduction in attacks and an improvement of the headache intensity were recorded. In one of these, acetazolamide was deliberately taken only during the migraine attack and the beneficial effect started 1 h after administration. In two patients, the drug did not produce any beneficial effect. Mild side effects were recorded in two patients. Our preliminary experience expands previous reports and confirms the possible efficacy of acetazolamide in CADASIL migraine. Based on these data, a randomized controlled trial seems worthy to be carried out to test the efficacy and safety of this drug

Mechanical properties of the compass depressors of the sea-urchin Paracentrotus lividus (Echinodermata, Echinoidea) and the effects of enzymes, neurotransmitters and synthetic tensilin-like protein

The compass depressors (CDs) of the sea-urchin lantern are ligaments consisting mainly of discontinuous collagen fibrils associated with a small population of myocytes. They are mutable collagenous structures, which can change their mechanical properties rapidly and reversibly under nervous control. The aims of this investigation were to characterise the baseline (i.e. unmanipulated) static mechanical properties of the CDs of Paracentrotus lividus by means of creep tests and incremental force-extension tests, and to determine the effects on their mechanical behaviour of a range of agents. Under constant load the CDs exhibited a three-phase creep curve, the mean coefficient of viscosity being 561±365 MPa.s. The stress-strain curve showed toe, linear and yield regions; the mean strain at the toe-linear inflection was 0.86±0.61; the mean Young's modulus was 18.62±10.30 MPa; and the mean tensile strength was 8.14±5.73 MPa. Hyaluronidase from Streptomyces hyalurolyticus had no effect on creep behaviour, whilst chondroitinase ABC prolonged primary creep but had no effect on secondary creep or on any force-extension parameters; it thus appears that neither hyaluronic acid nor sulphated glycosaminoglycans have an interfibrillar load transfer function in the CD. Acetylcholine, the muscarinic agonists arecoline and methacholine, and the nicotinic agonists nicotine and 1-[1-(3,4-dimethyl-phenyl)-ethyl]-piperazine produced an abrupt increase in CD viscosity; the CDs were not differentially sensitive to muscarinic or nicotinic agonists. CDs showed either no, or no consistent, response to adrenaline, L-glutamic acid, 5-hydroxytryptamine and γ-aminobutyric acid. Synthetic echinoid tensilin-like protein had a weak and inconsistent stiffening effect, indicating that, in contrast to holothurian tensilins, the echinoid molecule may not be involved in the regulation of collagenous tissue tensility. We compare in detail the mechanical behaviour of the CD with that of mammalian tendon and highlight its potential as a model system for investigating poorly understood aspects of the ontogeny and phylogeny of vertebrate collagenous tissues.(undefined)info:eu-repo/semantics/publishedVersio

Systemic and neuronal inflammatory markers in a mouse model of mevalonate kinase deficiency: a strain-comparative study

BACKGROUND/AIM: There is a lack of reliable animal models for the study of the rare auto-inflammatory disease mevalonate kinase deficiency (MKD). The one most frequently used is a biochemical model, obtained by treating BALB/c mice in order to block the mevalonate pathway, thus attempting to reproduce the inflammatory pattern presented in patients. This study aims to assess the role played in pathology by the inflammasome and the reliability of this model. MATERIALS AND METHODS: We mimicked MKD using two different mice strains (BALB/c and C57BL/6), evaluating typical inflammatory markers of MKD and inflammasome modulation. RESULTS: Without significant differences, both strains exhibited a general MKD-like inflammation, including the modulation of the molecular platform inflammasome, mimicking the characteristics observed in human patients. CONCLUSION: Although with some limitations, the mouse model appears robust and suitable for studying MKD. Results do not seem to vary with the mouse strain used, and appear to be treatment-dependent. Finally, in vivo inflammasome activation was assessed for the first time here

Sea urchins and mechanically adaptable connective tissues: alternative sources for biomaterial design

Sea urchins, as all echinoderms (starfish, sea cucumber, etc.), possess connective tissues that undergo drastic changes in their mechanical properties (Mutable Collagenous Tissues: MCTs). Mammalian connective tissues rarely undergo significant changes within a physiological timescale, the only major exception being the destiffening then restiffening of the mammalian uterine cervix at the end of pregnancy. In contrast, MCT can switch reversibly between stiff and compliant conditions in timescales of seconds to minutes following nervous stimulation. Considering this, MCT could be an inspiration for new matrices capable of changing their molecular and structural conformation in response to external stimuli. Furthermore, elucidating the molecular mechanism underlying MCT mutability could have implications for veterinary and biomedical science, particularly regarding the pathological plasticization or stiffening of connective tissue structures. The MIMESIS (Marine Invertebrate Models & Engineered Substrates for Innovative bio-Scaffolds) project has being developed within this scientific context. This contribution presents a review of the distinctive features of MCT together with the first results aimed to the production of MCT-derived matrices as cell culture /tissue regeneration substrates

The smart connective tissue of echinoderms: a materializing promise for biotech applications

Echinoderm Mutable Collagenous Tissues (MCTs) undergo nervously mediated, drastic and reversible changes in their passive mechanical properties. MCT mutability is involved in autotomy,posture maintenance and motility, and, as a consequence, it influences all aspects of echinoderm biology (nutrition, reproduction, habitat selection, self-defense and predatory behavior) representing a key-factor for the ecological success of the phylum. Besides this, MCT performance represents a topic of remarkable interest for many different applied fields. A biomimetic research route looks at MCTs as a source of inspiration for the development of smart and innovative biomaterials with great potential for in vitro and in vivo applications when controlled and reversible plasticization and/or stiffening of the extracellular matrix is required. The MIMESIS (Marine Invertebrates Models & Engineered Substrates for Innovative bio-Scaffolds) project has been developed within this scientific context. The selected echinoderm model is the common sea urchin Paracentrotus lividus. This project is based on a multidisciplinary approach combining functional biology with biomaterial engineering. A brief review of recent morphological, biomolecular, biomechanical and biochemical results on P.lividus MCTs are here presented in a biotechnological perspective, taking into account also a promising application regarding the use of MCT-derived substrata for cell culture studies

Effects of enzymes on the creep behaviour of <i>P. lividus</i> CDs.

<p>The numbers of values in the primary and secondary creep groups are shown respectively in parentheses. Means sharing the same superscript letter are significantly different (^a<i>P</i> = 0.001; ^b<i>P</i> = 0.005; Mann-Whitney tests). There were no other statistically significant differences between enzyme-treated CDs and corresponding control (PBS- or Tris-ASW-treated) CDs.</p><p>Effects of enzymes on the creep behaviour of <i>P. lividus</i> CDs.</p

Effect of tensilin-like protein (TLP) on the creep behaviour of <i>P</i>. <i>lividus</i> CDs.

<p>(A) Recording of a response to 3.0 μg ml^-1 TLP; vertical scalebar, 0.2 mm; horizontal scalebar, 60 s. (B, C) Effect of TLP on relative viscosity. CDs were treated with TLP at concentrations of 1.5 μg ml^-1 and 3.0 μg ml^-1; separate DEB-PPASW and PPASW controls were used for each concentration. (B) Mean relative viscosities for the time period 15–75 s after the start of TLP treatment. (C) Mean relative viscosities for the time period 5–6 min after the start of TLP treatment. Error bars are standard deviations and numbers of CDs in each group are shown above error bars.</p