Synthèse totale de la pactamycine et d’une sélection d’analogues, progrès vers la synthèse totale de la daphniglaucine C et brève étude d’une transposition allylique réductrice

Il y a plus de cinquante ans, la pactamycine a été isolée en tant qu’agent antitumoral potentiel. Il a été réalisé plus tard qu’il s’agissait en fait d’un agent antibactérien capable d’inhiber la synthèse de protéines lors du procédé de traduction. Récemment, il a même été démontré que certains de ses analogues possèdent des propriétés antiprotozoaires prometteuses. La présente thèse détaille la première synthèse totale de la pactamycine, entreprise au sein du groupe Hanessian, ainsi que la préparation d’une sélection d’analogues testés pour leurs propriétés biologiques. En outre, la daphniglaucine C appartient à une vaste famille de composés naturels isolés des feuilles du daphniphyllum au cours des dix dernières années. Bien que relativement peu d’information soit connue par rapport à l’activité biologique de la daphniglaucine C, la synthèse de celle-ci représente certainement un défi intéressant pour un chimiste organicien. Au passage, nos efforts vers la synthèse totale du composé cible auront permis d’explorer l’emploi de plusieurs méthodes en vue de la formation de centres quaternaires. De plus, un réarrangement réductif atypique, catalysé au palladium à partir d’alcools allyliques non-activés, a été étudié et employé afin de générer une sélection de pyrrolidines polysubstituées.

Caractérisation des unités de soins aigus chirurgicaux au sein des départements de chirurgie générale au Canada

Introduction : The acute care surgery (ACS) units are dedicated to the prompt management of surgical emergencies. It is a systemic way of organizing on-call services to diminish conflict between urgent care and elective obligations. The aim of this study was to define the characteristics of an ACS unit and to find common criteria in units with reported good functioning. Methods : As of July 1st 2014, 22 Canadian hospitals reported having an ACS unit. A survey with questions about the organization of the ACS units, the population it serves, the number of emergencies and trauma cases treated per year, and the satisfaction about the implementation of this ACS unit was sent to those hospitals. Results : The survey’s response rate was 73%. The majority of hospitals were tertiary or quaternary centers, served a population of more than 200 000 and had their ACS unit for more than three years. The median number of surgeons participating in an ACS unit was 8.5 and the majority were doing seven day rotations. The median number of operating room days was 2.5 per week. Most ACS units (85%) had an estimated annual volume of more than 2500 emergency consultations (including both trauma and non-trauma) and 80% operated over 1000 cases per year. Nearly all the respondents (94%) were satisfied with the implementation of the ACS unit in their hospital. Conclusion : Most surgeons felt that the implementation of an ACS unit resulted in positive outcomes. However, there should be a sizeable catchment population and number of surgical emergencies to justify the resulting financial and human resources.

Catalytic Enantioselective alpha-Arylation of Carbonyl Compounds

Enantioselective creation of benzylic quaternary centers still is a continuous challenge to many synthetic organic chemists. Among the existing methods for installation of this type of center, the direct asymmetric alpha-arylation of carbonyl compounds is very attractive due to the ready availability of the coupling substrates. Herein, we present some new tools to the catalytic asymmetric alpha-arylation of carbonyl compounds that overcame many of the drawbacks posted in previous methods for this type of reaction.

Caractérisation des unités de soins aigus chirurgicaux au sein des départements de chirurgie générale au Canada

Introduction : The acute care surgery (ACS) units are dedicated to the prompt management of surgical emergencies. It is a systemic way of organizing on-call services to diminish conflict between urgent care and elective obligations. The aim of this study was to define the characteristics of an ACS unit and to find common criteria in units with reported good functioning. Methods : As of July 1st 2014, 22 Canadian hospitals reported having an ACS unit. A survey with questions about the organization of the ACS units, the population it serves, the number of emergencies and trauma cases treated per year, and the satisfaction about the implementation of this ACS unit was sent to those hospitals. Results : The survey’s response rate was 73%. The majority of hospitals were tertiary or quaternary centers, served a population of more than 200 000 and had their ACS unit for more than three years. The median number of surgeons participating in an ACS unit was 8.5 and the majority were doing seven day rotations. The median number of operating room days was 2.5 per week. Most ACS units (85%) had an estimated annual volume of more than 2500 emergency consultations (including both trauma and non-trauma) and 80% operated over 1000 cases per year. Nearly all the respondents (94%) were satisfied with the implementation of the ACS unit in their hospital. Conclusion : Most surgeons felt that the implementation of an ACS unit resulted in positive outcomes. However, there should be a sizeable catchment population and number of surgical emergencies to justify the resulting financial and human resources.

I. Synthetic Studies Toward the Total Synthesis of Polycyclic Natural Products – Communesin F, Perophoramidine and Ineleganolide. II. Nickel Catalyzed Intramolecular C–O Bond Formation

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Finally, a previously unknown mild and efficient deprotection protocol for the o-nitrobenzyl group is disclosed – this serendipitous discovery permitted a concise endgame for the formal syntheses of both communesin F and perophoramidine.

In addition, the atroposelective synthesis of PINAP ligands has been accomplished via a palladium-catalyzed C–P coupling process through dynamic kinetic resolution. These catalytic conditions allow access to a wide variety of alkoxy- and benzyloxy-substituted PINAP ligands in high enantiomeric excess.

An efficient and exceptionally mild intramolecular nickel-catalyzed carbon–oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. This operationally simple method allows direct access to cyclic vinyl ethers in high yields in a single step.

Finally, synthetic studies toward polycyclic ineleganolide are described. The entire fragmented carbon framework has been constructed from this work. Highly (Z)-selective olefination was achieved by the method by the Ando group.

Organocatalytic domino reaction of cyanosulfones: access to complex cyclohexane systems with quaternary carbon centers

When ε-nitro-a,β-unsaturated esters are added to conjugated cyanosulfones in the presence of a bifunctional thiourea catalyst, a highly stereoselective domino reaction occurs to generate complex cyclohexanes with up to four stereogenic centers, one of which is quaternary in nature. Therefore, it is demonstrated that, like nitro compounds, sulfones can undergo an asymmetric intramolecular conjugate addition to r,β- unsaturated esters in the presence of a bifunctional organocatalyst.

Interactions between Late Quaternary volcanic and sedimentary processes in the Naples Bay, Southern Tyrrhenian sea

The interactions between Late Quaternary volcanic and sedimentary processes in the Naples Bay, Southern Tyrrhenian sea, are here discussed through the results of the marine geological survey at the scale 1:25.000. The example of the geological map n. 465 “Isola di Procida”, herein presented, has put in evidence the stratigraphy of marine Quaternary deposits and related volcanic seismic units. The volcanic deposits cropping out in the Procida island have been explained as the result of eruptions of local eruptive centres. The geological survey carried out onshore indicates the occurrence of several pyroclastic units linked to the eruptive activity of the Ischian and Phlegrean volcanic complexes, interstratified with the products erupted by local volcanic centres. The occurrence in the pyroclastic sequences of Ischia and Procida islands of several marker horizons and their stratigraphic correlations have allowed to reconstruct the volcanological evolution of the two islands and the interactions with sedimentary processes at the scale of the whole Tyrrhenian margin. Four geological maps at the scale 1:25.000 covering the whole Naples Bay have been reconstructed based on the interpretation of marine geological and geophysical data. The stratigraphic relationships between the seismic units and the eruptive deposits have testified the activity of several monogenetic volcanic centers, whose products are interstratified with marine and continental deposits of the Late Quaternary depositional sequence.

Variables Associated With The Performance Of Centers For Dental Specialties In Brazil.

The aim of this study was to evaluate the performance of the Centers for Dental Specialties (CDS) in the country and associations with sociodemographic indicators of the municipalities, structural variables of services and primary health care organization in the years 2004-2009. The study used secondary data from procedures performed in the CDS to the specialties of periodontics, endodontics, surgery and primary care. Bivariate analysis by χ2 test was used to test the association between the dependent variable (performance of the CDS) with the independents. Then, Poisson regression analysis was performed. With regard to the overall achievement of targets, it was observed that the majority of CDS (69.25%) performance was considered poor/regular. The independent factors associated with poor/regular performance of CDS were: municipalities belonging to the Northeast, South and Southeast regions, with lower Human Development Index (HDI), lower population density, and reduced time to deployment. HDI and population density are important for the performance of the CDS in Brazil. Similarly, the peculiarities related to less populated areas as well as regional location and time of service implementation CDS should be taken into account in the planning of these services.

Oral health in Brazil - Part II: Dental Specialty Centers (CEOs)

The concepts of health promotion, self-care and community participation emerged during the 1970s and, since then, their application has grown rapidly in the developed world, showing evidence of effectiveness. In spite of this, a major part of the population in the developing countries still has no access to specialized dental care such as endodontic treatment, dental care for patients with special needs, minor oral surgery, periodontal treatment and oral diagnosis. This review focuses on a program of the Brazilian Federal Government named CEOs (Dental Specialty Centers), which is an attempt to solve the dental care deficit of a population that is suffering from oral diseases and whose oral health care needs have not been addressed by the regular programs offered by the SUS (Unified National Health System). Literature published from 2000 to the present day, using electronic searches by Medline, Scielo, Google and hand-searching was considered. The descriptors used were Brazil, Oral health, Health policy, Health programs, and Dental Specialty Centers. There are currently 640 CEOs in Brazil, distributed in 545 municipal districts, carrying out dental procedures with major complexity. Based on this data, it was possible to conclude that public actions on oral health must involve both preventive and curative procedures aiming to minimize the oral health distortions still prevailing in developing countries like Brazil.

Late Quaternary drainage dynamics in northern Brazil based on the study of a large paleochannel from southwestern Marajó Island

Marajó Island shows an abundance of paleochannels easily mapped in its eastern portion, where vegetation consists mostly of savannas. SRTM data make possible to recognize paleochannels also in western Marajó, even considering the dense forest cover. A well preserved paleodrainage network from the adjacency of the town of Breves (southwestern Marajó Island) was investigated in this work combining remote sensing and sedimentological studies. The palimpsest drainage system consists of a large meander connected to narrower tributaries. Sedimentological studies revealed mostly sharp-based, fining upward sands for the channelized features, and interbedded muds and sands for floodplain areas. The sedimentary structures and facies successions are in perfect agreement with deposition in channelized and floodplain environments, as suggested by remote sensing mapping. The present study shows that this paleodrainage was abandoned during Late Pleistocene, slightly earlier than the Holocene paleochannel systems from the east part of the island. Integration of previous studies with the data available herein supports a tectonic origin, related to the opening of the Pará River along fault lineaments. This would explain the disappearance of large, north to northeastward migrating channel systems in southwestern Marajó Island, which were replaced by the much narrower, south to southeastward flowing modern channels.

The Southern Brazilian shelf: general characteristics, quaternary evolution and sediment distribution

Extending from latitude 34ºS to 22ºS the Southern Brazilian shelf constitutes the only part of the Brazilian shelf with a subtropical to temperate environment. The studies on the different geological aspects of the area began in the 1960's and have recently been reassessed after studies related to the determination of the Economic Exclusive Zone. In terms of morphology, the Southern Brazilian shelf may be divided into three sectors, the São Paulo Bight, the Florianópolis-Mostardas Sector and the Rio Grande Cone, characterized by conspicuous differences in terms of geological determining factors, bathymetry, declivities and the presence of canyons and channels. Despite the existence of hundreds of radiocarbon datings the sea level changes curve of southern Brazil during the Last Glacial Cycle is still a matter of debate. A recent controversy on the Middle and late Holocene sea level changes curve raised the question of the amplitude of the oscillations which occurred in the period. Also, a few but relatively consistent radiocarbon datings suggest the occurrence of a high sea level during Isotope Stage 3. In terms of sedimentary cover the Southern Brazilian shelf exhibits a very strong hydrodynamic control, both latitudinal and bathymetrical. The sector southward from 25ºS is characterized by the influence of the plume of water carrying sediments originating from the Río de La Plata. Actually its presence is conspicuous up to 28ºS, with the area between this latitude and 25ºS constituting a transitional zone. In terms of bathymetry the outer shelf is marked by the "floor-polisher" effect of the Brazil Current, which is responsible for the maintenance of a relict facies in areas deeper than 100 meters.

Paleoproductivity changes during the Late Quaternary in the southeastern Brazilian upper continental margin of the Southwestern Atlantic

Changes in the Brazilian continental margins oceanic productivity and circulation over the last 27,000 years were reconstructed based on sedimentological and microfaunal analyses. Our results suggest that oceanic paleoproductivity and the supply of terrigenous sediments to the Brazilian continental margin were higher during the Last Glacial Maximum (LGM) than during the Holocene. These changes may have been primarily influenced by significant sea level fluctuations that have occurred since the late Pleistocene. During the LGM, the lower sea level, higher productivity and lower sea-surface paleotemperatures may have been the result of the offshore displacement of the main flow of the Brazil Current. However, during the Holocene, the warm waters of the Brazil Current were displaced toward the coast. This displacement contributed to the increase in water temperature and prevented an increase in oceanic productivity. The decrease in terrigenous supply since the LGM could be related to the increase of the extension of the continental shelf and/or drier climatic conditions.

Estimating HIV-1 incidence using the serologic testing algorithm for recent HIV infections at HIV counseling and testing centers in the city of São Paulo, Brazil

The network of HIV counseling and testing centers in São Paulo, Brazil is a major source of data used to build epidemiological profiles of the client population. We examined HIV-1 incidence from November 2000 to April 2001, comparing epidemiological and socio-behavioral data of recently-infected individuals with those with long-standing infection. A less sensitive ELISA was employed to identify recent infection. The overall incidence of HIV-1 infection was 0.53/100/year (95% CI: 0.31-0.85/100/year): 0.77/100/year for males (95% CI: 0.42-1.27/100/year) and 0.22/100/ year (95% CI: 0.05-0.59/100/year) for females. Overall HIV-1 prevalence was 3.2% (95% CI: 2.8-3.7%), being 4.0% among males (95% CI: 3.3-4.7%) and 2.1% among females (95% CI: 1.6-2.8%). Recent infections accounted for 15% of the total (95% CI: 10.2-20.8%). Recent infection correlated with being younger and male (p = 0.019). Therefore, recent infection was more common among younger males and older females.

Prevalence of Human T-Cell Lymphotropic Virus (HTLV-1/2) in Individuals from Public Health Centers in Mozambique

The prevalence of human T-cell lymphotropic viruses types 1 and 2 (HTLV-1/2) in Mozambique is not known. The present study examined blood samples from 208, 226, and 318 individuals from Northern, Central, and Southern Mozambique, respectively, of all socioeconomic and demographic strata attending public health centers in Mozambique for HTLV-1/2-specific antibodies. Serum samples were assessed for HIV- and HTLV-1/2-specific antibodies by using enzyme immunoassays, and infections with HTLV-1 and -2 were confirmed by using Western blot. An overall HTLV-1/2 prevalence of 2.3% (2.9% in female and 1.1% in male subjects) was observed, and the prevalence of infection increased with age. Regional variation in the prevalence of HIV and HTLV-1/2 was observed; 32.2%, 65.5%, and 44% of individuals tested HIV positive in Northern, Central, and Southern Mozambique, respectively, and 2.4%, 3.9%, and 0.9% tested HTLV-1/2 positive in the same regions. HTLV-1 infection was confirmed in these individuals. No association between HTLV-1 infection and socio-demographic variables or HIV status was detected, although the low number of HTLV-1-positive cases did not allow robust statistical analyses. The results obtained suggest different risk factors and epidemiologic correlates of HIV and HTLV-1 transmission in Mozambique. Furthermore, our results suggested that North and Central Mozambique should be considered endemic regions for HTLV-1 infection. As no cases of HTLV-2 were detected, HTLV-2 appears to have not been introduced into Mozambique.

Facies, delta(13)C, delta(15)N and C/N analyses in a late Quaternary compound estuarine fill, northern Brazil and relation to sea level

The present work integrates sedimentary facies, (14)C dating, delta(13)C, delta(15)N, and C/N with geologic and geomorphologic data available from literature. The aim was to characterize the depositional settings of a late Quaternary estuary in northeastern Marajo Island and analyze its evolution within the context of relative sea level fluctuations. The data derive from four continuous cores along a proximal-to-distal transect of a paleoestuary, previously recognized using remote sensing information. Fifteen sediment samples recorded ages ranging from 42,580 +/- 1430 to 3184 +/- 37 (14)C yr B.P. Fades analysis indicated fine- to coarse-grained sands with parallel lamination or cross stratification, massive or laminated muds and heterolithic deposits. delta(13)C (-28.1 parts per thousand to -19.7 parts per thousand, mean = -23.0 parts per thousand), delta(15)N (+ 14.8 parts per thousand to + 4.7 parts per thousand, mean = + 9.2 parts per thousand) and C/N (14.5 to 1.5, mean = 7.9) indicate mostly marine and freshwater phytoplankton sources for the organic matter. The results confirm a large late Quaternary paleoestuary in northeastern Marajo Island. The distribution of delta(13)C, delta(15)N, and C/N, together with fades associations, led to identify depositional settings related to fluvial channel, floodplain, tidal channel/tidal flat, central basin, tidal delta, and tidal inlet/sand barrier. These deposits are consistent with a wave-dominated estuary. Variations in stratigraphy and geochemistry are controlled by changes in relative sea level, revealing a main transgression from an undetermined time around 42,000 (14)C yr B.P. and 29,340 (+/- 200) (14)C yr B.P., which is synchronous to the overall drop in sea level after the last interglacial. Following this period, and probably until 9110 +/- 37 (14)C yr B.P., i.e., during a time interval encompassing two glacial episodes including the Last Glacial and the Younger Dryas, there was a pronounced drop in sea level, recorded by the development of a major erosional discontinuity due to valley re-incision. Sea level rose again until 5464 +/- 40 (14)C yr B.P, just before the main worldwide mid-Holocene transgressive peak. Mid to late Holocene coastal progradation ended the Marajo paleoestuarine history, and promoted the establishment of continental conditions throughout the island. The divergence comparing the Marajo sea level behavior with the eustatic curve allows hypothesizing that post-rifting tectonics along the Brazilian Equatorial margin influenced the sedimentary evolution of the studied paleoestuary. Considering that sedimentary facies in estuarine settings are highly variable both laterally and vertically, the present integration of facies with isotope and elemental analyses was crucial to provide a more precise interpretation of the Late Pleistocene and Holocene Marajo paleoestuary, and analyze its sea level history within the eustatic and tectonic context. (C) 2010 Elsevier B.V. All rights reserved.