Assessing risks of multiple sclerosis therapies.

Over the last two decades, thanks to the discovery of several pharmaceutical agents, multiple sclerosis (MS) has been transformed into a treatable disorder although the degree of therapeutic response may vary considerably. As more medications find their entry into the MS market, a clinician faces a mounting challenge of comparing risk and benefit profiles of various agents in an attempt to find the best treatment approach for each individual patient. In this review, we aim to summarize the available data on safety profiles of available MS therapies while focusing mostly on serious medication specific potential adverse events without discussing the teratogenic potential of each agent (unless there is a black box warning) or hypersensitivity reactions. Our goal is to provide a clinician with guidance on assuring the appropriate safety monitoring for patients treated with one of the agents discussed. We also comment on the future of risk management in MS and discuss possible enhancements to the current model of drug approval process and general strategies to improve the patient safety.

Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5.

Genomic rearrangements at chromosome 13q31.3q32.1 have been associated with digital anomalies, dysmorphic features, and variable degree of mental disability. Microdeletions leading to haploinsufficiency of miR17∼92, a cluster of micro RNA genes closely linked to GPC5 in both mouse and human genomes, has recently been associated with digital anomalies in the Feingold like syndrome. Here, we report on a boy with familial dominant post-axial polydactyly (PAP) type A, overgrowth, significant facial dysmorphisms and autistic traits who carries the smallest germline microduplication known so far in that region. The microduplication encompasses the whole miR17∼92 cluster and the first 5 exons of GPC5. This report supports the newly recognized role of miR17∼92 gene dosage in digital developmental anomalies, and suggests a possible role of GPC5 in growth regulation and in cognitive development.

Diabetes mellitus, a microRNA-related disease?

Diabetes mellitus is a complex disease resulting in altered glucose homeostasis. In both type 1 and type 2 diabetes mellitus, pancreatic β cells cannot secrete appropriate amounts of insulin to regulate blood glucose level. Moreover, in type 2 diabetes mellitus, altered insulin secretion is combined with a resistance of insulin-target tissues, mainly liver, adipose tissue, and skeletal muscle. Both environmental and genetic factors are known to contribute to the development of the disease. Growing evidence indicates that microRNAs (miRNAs), a class of small noncoding RNA molecules, are involved in the pathogenesis of diabetes. miRNAs function as translational repressors and are emerging as important regulators of key biological processes. Here, we review recent studies reporting changes in miRNA expression in tissues isolated from different diabetic animal models. We also describe the role of several miRNAs in pancreatic β cells and insulin-target tissues. Finally, we discuss the possible use of miRNAs as blood biomarkers to prevent diabetes development and as tools for gene-based therapy to treat both type 1 and type 2 diabetes mellitus.

The investigation of deaths in custody: a qualitative analysis of problems and prospects.

The right to be treated humanely when detained is universally recognized. Deficiencies in detention conditions and violence, however, subvert this right. When this occurs, proper medico-legal investigations are critical irrespective of the nature of death. Unfortunately, the very context of custody raises serious concerns over the effectiveness and fairness of medico-legal examinations. The aim of this manuscript is to identify and discuss the practical and ethical difficulties encountered in the medico-legal investigation following deaths in custody. Data for this manuscript come from a larger project on Death in Custody that examined the causes of deaths in custody and the conditions under which these deaths should be investigated and prevented. A total of 33 stakeholders from forensic medicine, law, prison administration or national human rights administration were interviewed. Data obtained were analyzed qualitatively. Forensic experts are an essential part of the criminal justice process as they offer evidence for subsequent indictment and eventual punishment of perpetrators. Their independence when investigating a death in custody was deemed critical and lack thereof, problematic. When experts were not independent, concerns arose in relation to conflicts of interest, biased perspectives, and low-quality forensic reports. The solutions to ensure independent forensic investigations of deaths in custody must be structural and simple: setting binding standards of practice rather than detailed procedures and relying on preexisting national practices as opposed to encouraging new practices that are unattainable for countries with limited resources.

Il laudario dei battisti di Modena... : Con una tavola fuori testo / pubblicato a cura di Giulio Bertoni...

Collection : Beihefte zur Zeitschrift für romanische Philologie ; 20

Review of the genus Chalcolepidius Eschscholtz, 1829 (Coleoptera, Elateridae, Agrypninae)

The genus Chalcolepidius is revised. Type specimens of 65 nominal species, except C. costatus Pjatakowa, 1941, C. fleutiauxi Pjatakowa, 1941 and C. viriditarsus Schwarz, 1906, are examined. Eighty five species are studied, of which 34 are synonymyzed and 12 new species described; three species, C. alicii Pjatakowa, 1941, C. haroldi Candèze, 1878 and C. unicus Fleutiaux, 1910, formely included in this genus, are not congeneric and are removed; C. validus Candèze, 1857 is revalidated. The genus is now formed by 63 species. Redescriptions, illustrations and a key for the examined species, and a cladistic analysis for groups of species are also included. New synonyms established: C. apacheanus Casey, 1891 = C. simulans Casey, 1907 syn. nov. = C. acuminatus Casey, 1907 syn. nov. = C. nobilis Casey, 1907 syn. nov.; C. approximatus Erichson, 1841 = C. aztecus Casey, 1907 syn. nov. = C. niger Pjatakowa, 1941 syn. nov.; C. attenuatus Erichson, 1841 = C. cuneatus Champion, 1894 syn. nov. = C. tenuis Champion, 1894 syn. nov.; C. aurulentus Candèze, 1874 = C. candezei Dohrn, 1881 syn. nov. = C. grossheimi Pjatakowa, 1941 syn. nov.; C. bomplandii Guérin, 1844 = C. humboldti Candèze, 1881 syn. nov.; C. chalcantheus Candèze, 1857 = C. violaceous Pjatakowa, 1941 syn. nov.; C. cyaneus Candèze, 1881 = C. scitus Candèze, 1889 syn. nov. = C. abbreviatovittatus Pjatakowa, 1941 syn. nov.; C. desmarestii Chevrolat, 1835 = C. brevicollis Casey, 1907 syn. nov.; C. gossipiatus Guérin, 1844 = C. erichsonii Guérin-Méneville, 1844 syn. nov. = C. lemoinii Candèze, 1857 syn. nov.; C. inops Candèze, 1886 = C. murinus Champion, 1894 syn. nov.; C. jansoni Candèze, 1874 = C. mucronatus Candèze, 1889 syn. nov.; C. lacordairii Candèze, 1857 = C. exquisitus Candèze, 1886 syn. nov. = C. monachus Candèze, 1893 syn. nov.; C. lenzi Candèze, 1886 = C. behrensi Candèze, 1886 syn. nov.; C. oxydatus Candèze, 1857 = C. jekeli Candèze, 1874 syn. nov.; C. porcatus (Linnaeus, 1767) = C. peruanus Candèze, 1886 syn. nov. = C. flavostriatus Pjatakowa, 1941 syn. nov. = C. herbstii multistriatus Golbach, 1977 syn. nov.; C. rugatus Candèze, 1857 = C. amictus Casey, 1907 syn. nov.; C. smaragdinus LeConte, 1854 = C. ostentus Casey, 1907 syn. nov. = C. rectus Casey, 1907 syn. nov.; C. sulcatus (Fabricius, 1777) = C. herbstii Erichson, 1841 syn. nov; C. virens (Fabricius, 1787) = C. perrisi Candèze, 1857 syn. nov.; C. virginalis Candèze, 1857 = C. championi Casey, 1907 syn. nov.; C. viridipilis (Say, 1825) = C. debilis Casey, 1907 syn. nov.; C. webbi LeConte, 1854 = C. sonoricus Casey, 1907 syn. nov.; C. zonatus Eschscholtz, 1829 = C. longicollis Candèze, 1857 syn. nov. New species described: C. albisetosus sp. nov. (Ecuador), C. albiventris sp. nov. (Mexico: Veracruz), C. copulatuvittatus sp. nov. (Venezuela), C. extenuatuvittatus sp. nov. (Venezuela), C. fasciatus sp. nov. (Mexico: Durango), C. ferratuvittatus sp. nov. (Ecuador), C. proximus sp. nov. (Mexico: Sinaloa), C. serricornis sp. nov. (Mexico: Veracruz), C. spinipennis sp. nov. (Mexico: Veracruz), C. supremus sp. nov. (Venezuela), C. truncuvittatus sp. nov. (Mexico: Tamaulipas) and C. virgatipennis sp. nov. (Mexico: Durango). Redescribed species: C. angustatus Candèze, 1857, C. apacheanus Casey, 1891, C. approximatus Erichson, 1841, C. attenuatus Erichson, 1841, C. aurulentus Candèze, 1874, C. bomplandii Guérin-Méneville, 1844, C. boucardi Candèze, 1874, C. chalcantheus Candèze, 1857, C. corpulentus Candèze, 1874, C. cyaneus Candèze, 1881, C. desmarestii Chevrolat, 1835, C. dugesi Candèze, 1886, C. erythroloma Candèze, 1857, C. eschscholtzi Chevrolat, 1833, C. exulatus Candèze, 1874, C. fabricii Erichson, 1841, C. forreri Candèze, 1886, C. fryi Candèze, 1874, C. gossipiatus Guérin-Méneville, 1844, C. inops Candèze, 1886, C. jansoni Candèze, 1874, C. lacordairii Candèze, 1857, C. lafargi Chevrolat, 1835, C. lenzi Candèze, 1886, C. limbatus (Fabricius, 1777), C. mexicanus Castelnau, 1836, C. mniszechi Candèze, 1881, C. mocquerysii Candèze, 1857, C. morio Candèze, 1857, C. obscurus Castelnau, 1836, C. oxydatus Candèze, 1857, C. porcatus (Linnaeus, 1767), C. pruinosus Erichson, 1841, C. rodriguezi Candèze, 1886, C. rostainei Candèze, 1889, C. rubripennis LeConte, 1861, C. rugatus Candèze, 1857, C. silbermanni Chevrolat, 1835, C. smaragdinus LeConte, 1854, C. sulcatus (Fabricius, 1777), C. tartarus Fall, 1898, C. validus Candèze, 1857, reval., C. villei Candèze, 1878, C. virens (Fabricius, 1787), C. virginalis Candèze, 1857, C. viridipilis (Say, 1825), C. webbi LeConte, 1854, C. zonatus Eschscholtz, 1829.

Factor analysis of the North American Spine Society outcome assessment instrument: a study based on a spine registry of patients treated with lumbar and cervical disc arthroplasty.

BACKGROUND CONTEXT: Studies involving factor analysis (FA) of the items in the North American Spine Society (NASS) outcome assessment instrument have revealed inconsistent factor structures for the individual items. PURPOSE: This study examined whether the factor structure of the NASS varied in relation to the severity of the back/neck problem and differed from that originally recommended by the developers of the questionnaire, by analyzing data before and after surgery in a large series of patients undergoing lumbar or cervical disc arthroplasty. STUDY DESIGN/SETTING: Prospective multicenter observational case series. PATIENT SAMPLE: Three hundred ninety-one patients with low back pain and 553 patients with neck pain completed questionnaires preoperatively and again at 3 to 6 and 12 months follow-ups (FUs), in connection with the SWISSspine disc arthroplasty registry. OUTCOME MEASURES: North American Spine Society outcome assessment instrument. METHODS: First, an exploratory FA without a priori assumptions and subsequently a confirmatory FA were performed on the 17 items of the NASS-lumbar and 19 items of the NASS-cervical collected at each assessment time point. The item-loading invariance was tested in the German version of the questionnaire for baseline and FU. RESULTS: Both NASS-lumbar and NASS-cervical factor structures differed between baseline and postoperative data sets. The confirmatory analysis and item-loading invariance showed better fit for a three-factor (3F) structure for NASS-lumbar, containing items on "disability," "back pain," and "radiating pain, numbness, and weakness (leg/foot)" and for a 5F structure for NASS-cervical including disability, "neck pain," "radiating pain and numbness (arm/hand)," "weakness (arm/hand)," and "motor deficit (legs)." CONCLUSIONS: The best-fitting factor structure at both baseline and FU was selected for both the lumbar- and cervical-NASS questionnaires. It differed from that proposed by the originators of the NASS instruments. Although the NASS questionnaire represents a valid outcome measure for degenerative spine diseases, it is able to distinguish among all major symptom domains (factors) in patients undergoing lumbar and cervical disc arthroplasty; overall, the item structure could be improved. Any potential revision of the NASS should consider its factorial structure; factorial invariance over time should be aimed for, to allow for more precise interpretations of treatment success.