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Background Although Southeast Asia is one of the most leptospirosis afflicted regions, little is known about the diversity and molecular epidemiology of the causative agents of this widespread and emerging zoonotic disease. Methodology/Principal findings We used whole genome sequencing to examine genetic variation in 75 Leptospira strains isolated from patients in the Lao PDR (Laos) between 2006 and 2017. Eleven serogroups from 4 Leptospira species and 43 cgMLST-defined clonal groups (CGs) were identified. The most prevalent CG was CG272 (n = 18, 26.8%), composed of L. interrogans serogroup Autumnalis isolates. This genotype was recovered throughout the 12-year period and was associated with deaths, and with a large outbreak in neighbouring Thailand. Genome analysis reveals that the CG272 strains form a highly clonal group of strains that have, for yet unknown reasons, recently spread in Laos and Thailand. Additionally, accessory genes clearly discriminate CG272 strains from the other Leptospira strains. Conclusions/Significance The present study reveals a high diversity of Leptospira genotypes in Laos, thus extending our current knowledge of the pan- and core-genomes of these life-threatening pathogens. Our results demonstrate that the CG272 strains belong to a unique clonal group, which probably evolved through clonal expansion following niche adaptation. Additional epidemiological studies are required to better evaluate the spread of this genotype in Southeast Asia. To further investigate the key factors driving the virulence and spread of these pathogens, more intense genomic surveillance is needed, combining detailed clinical and epidemiological data., Author summary Pathogenic Leptospira are the causative agents for leptospirosis, a neglected and emerging zoonosis occurring worldwide. In this study, we investigated the genetic diversity of Leptospira strains isolated from patients over a 12-year period in Lao PDR. Our genome analysis revealed a high diversity of Leptospira genotypes in this endemic country for leptospirosis, including a group of clonal strains which was responsible for a large outbreak in neighboring Thailand. Further progress in our understanding of the epidemiology of Leptospira circulating genotypes should contribute to the implementation of prevention and intervention measures to reduce the risk of leptospirosis transmission.

Objective To analyze the differences in characteristics and prognosis between alcoholic and nonalcoholic patients with Wernicke encephalopathy (WE). Patients and Methods A retrospective observational cohort of 468 patients diagnosed with WE with at least 2 Caine criteria was selected from all patients discharged with a diagnosis of WE from 21 medical centers in Spain from January 1, 2000, through December 31, 2012. Demographic, clinical, and outcome variables were described. Results Among the 468 patients, the most common risk factor was alcoholism (n=434 [92.7%]). More than one-third of patients (n=181 [38.7%]) had the classic WE triad of symptoms (ocular signs, cerebellar dysfunction, and confusion). Among 252 patients for whom magnetic resonance imaging data were available, 135 (53.6%) had WE-related lesions and 42 (16.7%) had cerebellar lesions. Of the 468 patients, 25 (5.3%) died during hospitalization. Alcoholic patients presented more frequently than nonalcoholic patients with cerebellar signs ( P =.01) but less frequently with ocular signs ( P =.02). Alcoholic patients had a significantly higher frequency of hyponatremia ( P =.04) and decreased platelet count ( P =.005) compared with nonalcoholics. Alcoholic patients were diagnosed earlier than nonalcoholics (median time to diagnosis, 1 vs 4 days; P =.001) and had shorter hospitalizations (13 vs 23 days; P =.002). Conclusion Compared with nonalcoholic patients, alcoholic patients with WE are more likely to present with cerebellar signs and less likely to have ocular signs. Diagnosis may be delayed in nonalcoholic patients. Mortality in the present series was lower than described previously.

The conformational and electronic characteristics of the polar O(9)═C(8)-X(10) moiety in the anticonvulsant valproic acid (Vpa) drug and some of their amides and ester derivatives are analyzed at the B3LYP level using the 6-31+G(d,p) and 6-311++G(d,p) 6d,10f basis sets. Exploring the delocalization of the electron density of the O(9)═C(8)-X(10) moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O(9)═C(8)-X(10) is accompanied by a three-dimensional arrangement of donor and acceptor proton units closing nearly planar pseudorings of four, five, and six members arising from stabilizing interactions around the O(9)═C(8)-X(10) backbone. From the structure-property relationship analysis, we explain the origin of the change in the structural parameters and atomic charges in the polar moiety.

Infrared spectra at 300 and 77 K and Raman spectra at 300 K of the valpromide (Vpd), N-substituted derivatives, N-ethylvalpromide (Etvpd), N-isopropylvalpromide (Ipvpd) and the N,N-disubstituted derivative, N,N-dimethylvalpromide (Dmvpd) with antiepileptic activity, have been measured and analyzed with results derived from computational chemistry calculation. In agreement with theoretical predictions, experimental data indicate that while in Etvpd, Dmvpd and Ipvpd there are four different conformational co-existing components (Etvpd: TTCG+, TCCG−, TTTC, G+G+C G+; Dmvpd: TTCC, G−TTA+, G+A−TC, G+A−C A+; Ipvpd: TTCT, TCCT, TCCC, G− TTT) in the Vpd there are only three distinct stable conformations of C1 symmetry group: TTC, TCT, G+G+T. Based on the accuracy of the B3LYP calculation, with the 6-31 + G** basis set estimated by comparison between the predicted values of the vibrational modes and the available experimental data, we performed a structural and vibrational study of the amide group in the Vpd and their derivatives. We found that small nonplanarity deviations of C(O)N backbone induce significant changes on the structural and spectroscopic properties. These are not compatible with the decreasing of the resonance effect as it is produced when the twisting around the C(O)N increases. From the Natural Bond Orbital (NBO) analysis the existence of stabilizing electrostatic interactions of type CH···O/N and CH···HN/C, which induce significant structural changes and a complex electronic redistribution of charge on the π-system in those structures becomes evident. We view this as a consequence of the filled electron density change Lewis-type NBOs type lpO1, 2, lpN1, σ(CH)Nacyl and empty non-Lewis NBOs type σ*(CH)Nacyl, σ*NH. Copyright © 2009 John Wiley & Sons, Ltd.

In this work, we present results of the conformational and vibrational properties of valpromide (Vpd), an amide with antiepileptic activity, studied by IR and Raman spectroscopy at 300 and 77 K, and 300 K, respectively. Experimental data are compared against ab initio calculations performed at B3LYP level with the inclusion of solvatation effects. Experimental results, reinforced by theoretical calculations, point out that Vpd has three conformers on the potential energy surface, with different structures that can be identified in the CO and NH spectral regions. These conformers are defined by different angular arrays of the dihedral angles formed with the CO, CN and C〈H, CC of the aliphatic chain bonds. The existence of different conformations and structures are discussed on the basis of results derived from electronic localization function (ELF) and natural orbital bond (NBO) analysis. Copyright © 2008 John Wiley & Sons, Ltd.

[ESP] Dentro del nuevo marco normativo, respaldado por la ley 25/2009 “ley ómnibus”, donde las exigencias técnicas residen en competencias y no sólo en atribuciones, cabe destacar la función del Ingeniero de Organización Industrial como profesional capacitado para la gestión técnica del conocimiento y su presentación ante los impulsores del sector industrial. Estas necesidades se presentan no sólo en la fase tradicional de actuación, esto es, en la realidad de procesos, plantas industriales y empresas ya implantadas donde el Ingeniero de Organización Industrial podía acometer mejoras de innovación, ahorro y eficiencia en base a las correcciones del sistema implantado, sino también en las fases previas de proyecto donde la realidad exige entornos de trabajo multidisciplinares orientados a un mismo fin. Cada vez más los promotores del sector industrial, y con especial hincapié en épocas de difícil situación económica, buscan implementar el máximo del ahorro antes de acometer la ejecución de un proyecto. Por otra parte la elaboración de un proyecto, tanto si es básico como de ejecución, conlleva el respaldo de un compromiso firmado entre el promotor y la empresa proyectista. El objetivo de esta comunicación es analizar un caso práctico a través de una auditoría real presentada y realizada por un grupo multidisciplinar de Ingeniería de Organización Industrial.