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The Guiana Shield, a small region of South America, is currently one of the main hotspots of malaria transmission on the continent. This Amazonian area is characterised by remarkable socioeconomic, cultural, health, and political heterogeneity and a high degree of regional and cross-border population mobility, which has contributed to the increase of malaria in the region in the past few years. In this context, regional cooperation to control malaria represents both a challenge and an indispensable initiative. This Viewpoint advocates for the creation of a regional cooperative mechanism for the elimination of malaria in the Guiana Shield. This strategy would help address operational and political obstacles to successful technical cooperation in the region and could contribute to reversing the regional upsurge in malaria incidence through creating a functional international control and elimination partnership., Competing Interests: Declaration of interests We declare no competing interests. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In French Guiana, life expectancy is between 2 and 3 years below that of France, reflecting differences in mortality rates that are largely sensitive to primary healthcare and thus preventable. However, because poverty affects half of the population in French Guiana, global measurements of life expectancy presumably conflate at least two distinct situations: persons who have similar life expectancies as in mainland France and persons living in precariousness who have far greater mortality rates than their wealthier counterparts. We thus aimed to synthesize what is known about statistical regularities regarding exposures and sketch typical French Guiana exposomes in relation to health outcomes. We conducted a narrative review on common exposures in French Guiana and made comparisons between French Guiana and mainland France, between rich and poor in French Guiana, and between urban and rural areas within French Guiana. The most striking fact this panorama shows is that being a fetus or a young child in French Guiana is fraught with multiple threats. In French Guiana, poverty and poor pregnancy follow-up; renouncing healthcare; wide variety of infectious diseases; very high prevalence of food insecurity; psychosocial stress; micronutrient deficiencies; obesity and metabolic problems; and frequent exposure to lead and mercury in rural areas constitute a stunningly challenging exposome for a new human being to develop into. A substantial part of the population's health is hence affected by poverty and its sources of nutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nacher, Basurko, Douine, Lambert, Rousseau, Michaud, Garlantezec, Adenis, Gomes, Alsibai, Sabbah, Lambert, Epelboin, Sukul, Terlutter, Janvier and Hcini.)

In 2020, food shortages occurred at the beginning of the confinement period that was supposed to curb the COVID-19 pandemic. In French Guiana, where a major part of the population lives under the poverty line, health workers voiced major concerns. Alongside massive food aid distributions, a first transversal study was carried out in August 2020 targeting poor neighborhoods in Cayenne. The results were particularly worrying. More than 80% of households had been suffering from hunger during that month, with a median decrease of 46% in revenue. Two other investigations followed in February and then in August of 2021. With the relaxing of the health measures, the situation improved in the Cayenne region, but two out of three were still affected, showing signs of quantitative deficiencies and insufficient food diversity. The situation seemed particularly grave for children. In light of this situation, we propose to create an observatory of food insecurity in Guiana, while maintaining this topic as a health priority. In addition, the fight against food insecurity cannot be limited to multi-sectorial material and strategic aide. It must be thought about in a more global manner, including health and social questions, territorial management policies, access to land and water, access to rights and social inclusion. Targeted actions helping the most exposed and vulnerable people is also an important stake, independent of the administrative situation and residency rights of the concerned people.

Objectives: French Guiana, the least-vaccinated French territory, also has the lowest COVID-19 vaccination coverage in Latin America. We aimed to estimate how many deaths, hospitalizations and costs the vaccines had and could have avoided., Methods: We calculated the Number Needed to Vaccinate to prevent one death per year, 1 standard hospitalization, 1 Intensive Care Unit admission given the mean incidence numbers of the past 6 months, and divided the number of persons vaccinated to estimate how many deaths and hospitalizations had been avoided in French Guiana at that time., Results: The crude number needed to vaccinate to prevent one death per year, the crude number needed to vaccinate to prevent one hospitalization per 6 months were computed Based on our observed incidence and ICU admission rate, the crude number needed to vaccinate to prevent one ICU admission per 6 months.After 6 months with an incidence exceeding 400 per million inhabitants, and 148 observed deaths, we estimate that vaccination avoided 46 deaths (IC95%=43.5-48.7). If the number of vaccinated persons had reached the same proportion as mainland France, 141 deaths per year could have been prevented (IC95%=131.9-147.6).With 2085 hospitalization and 370 ICU admissions during the same period, we estimate that the current albeit low vaccination rate avoided 300 hospital (IC95%=280-313) and 77 (IC95%=72-81) ICU admissions. With the same vaccination rates as mainland France, we estimate that 900 hospitalizations and 231 ICU admissions would have been avoided.Similarly, there would have been 139 ICU admission (instead of 370)., Conclusions: In sparsely populated French Guiana these numbers are quite substantial and framing the vaccine benefits and wasted opportunities using such concrete numbers may help convincing undecided persons to get vaccinated., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European territory in Amazonia, surrounded by the Brazilian giant and the little-known Suriname, Ariane 6 rockets are launched from Kourou while 50% of the population lives below the poverty line. This paradoxical situation is a source of health problems specific to this territory, whether they be infectious diseases with unknown germs, intoxications or chronic pathologies.Some infectious diseases such as Q fever, toxoplasmosis, cryptococcosis or HIV infection are in common with temperate countries, but present specificities leading to sometimes different management and medical reasoning. In addition to these pathologies, many tropical diseases are present in an endemic and / or epidemic mode such as malaria, leishmaniasis, Chagas disease, histoplasmosis or dengue. Besides, Amazonian dermatology is extremely varied, ranging from rare but serious pathologies (Buruli ulcer, leprosy) to others which are frequent and benign such as agouti lice (mites of the family Trombiculidae) or papillonitis. Envenomations by wild fauna are not rare, and deserve an appropriate management of the incriminated taxon. Obstetrical, cardiovascular and metabolic cosmopolitan pathologies sometimes take on a particular dimension in French Guiana that must be taken into account in the management of patients. Finally, different types of intoxication are to be known by practitioners, especially due to heavy metals.European-level resources offer diagnostic and therapeutic possibilities that do not exist in the surrounding countries and regions, thus allowing the management of diseases that are not well known elsewhere.Thanks to these same European-level resources, research in Guyana occupies a key place within the Amazon region, despite a smaller population than in the surrounding countries. Thus, certain pathologies such as histoplasmosis of the immunocompromised patient, Amazonian toxoplasmosis or Q fever are hardly described in neighboring countries, probably due to under-diagnosis linked to more limited resources. French Guiana plays a leading role in the study of these diseases.The objective of this overview is to guide health care providers coming to or practicing in French Guiana in their daily practice, but also practitioners taking care of people returning from French Guiana., (Copyright © 2023 SFMTSI.)

Purpose: The border between the State of Amapa, Brazil, and French Guiana is mostly primary forest. In the Oyapock basin, socioeconomic circumstances have fueled sex work, gold mining and the circulation of sexually transmitted infections. Given the lack of comprehensive data on this border area, we describe the different sexually transmitted infections along the Brazil/French Guiana border and the testing and care activity., Methods: We conducted a review of the available scientific and technical literature on sexually transmitted infections in this complex border area. Temporal trends were graphed and for Human Immunodeficiency Virus (HIV) we estimated incidence using the European Center for prevention and Disease Control modeling tool., Results: Until 2019, 26 of the 46 HIV-infected patients followed and treated in Saint Georges de l'Oyapock were residing on the Brazilian side in Oiapoque. Virological suppression was only achieved for 75% of treated patients; but dropped to 62% during the COVID-19 epidemic. In 2019, cooperation efforts allowed HIV care in Oiapoque, resulting in the transfer of Brazilian patients previously followed on the French side and a substantial increase in the number of patients followed in Oiapoque. The average yearly HIV serological testing activity at the health center in Saint Georges was 16 tests per 100 inhabitants per year; in Camopi it was 12.2 per 100 inhabitants. Modeling estimated the number of persons living with HIV around 170 persons, corresponding to a prevalence of 0.54% and about 40 undiagnosed infections. The model also suggested that there were about 12 new infections per year in Saint Georges and Oiapoque, representing an HIV incidence rate of 3.8 cases per 10,000 per year. HPV prevalence in Saint Georges ranges between 25 and 30% and between 35 and 40% in Camopi. Testing activity for other sexually transmitted infections markedly increased in the past 5 years; the introduction of PCR for chlamydiasis and gonorrhea also had a substantial impact on the number of diagnoses., Conclusions: The ongoing cooperation between multiple partners on both sides of the border has led to remarkable progress in primary prevention, in testing efforts, in treatment and retention on both sides of the border. In a region with intense health professional turnover, nurturing cooperation and providing accurate assessments of the burden of sexually transmitted infections is essential to tackle a problem that is shared on both sides of the border., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nacher, Divino, Leborgne, Correa, Rabier, Lucarelli, Rhodes, Gaillet, Malafaia, Rousseau, Sanna, Gomes, Adenis, Peiter and Michaud.)

Context: There is a general health decline among farmers and the leading cause of death in this population remains cardiovascular (CV) diseases. The situation is similar in the Guianese general population, with a preoccupying increase in CV diseases. However, there are no data on farmers' health., Methods: A cross-sectional study analyzed data from the "Novembre Vert" action conducted in 2018 in French Guiana. Beneficiaries and farmers affiliated to the Mutualité Sociale Agricole who completed the survey were included. The objective was to assess their CV risk., Results: 603 farmers were included. The sex-ratio was 1.6 and the median age was 52. Over 70% of the participants had a Body Mass Index ≥ 25, with a greater risk of obesity in the female population. High blood pressure (HBP) affected 53.1% of farmers and 80.1% were diagnosed during screening. About 13.5% had diabetes. Overall, 27% of participants were at high or very high CV risk. CV risk was 3 times greater in men., Conclusion: HBP (53.1%), obesity (30.3%) and diabetes (13.5%) prevalence are particularly worrying and underline the importance of policies to reduce cardiovascular morbimortality among farmers.

Since the first cases of SARS-CoV-2 infection in Wuhan in December 2019, this RNA virus gave rise to different viral lineages with different virological, epidemiological and immunological properties. Here we describe the dynamics of circulation of SARS-CoV-2 lineages in an Amazonian South American French overseas territory, French Guiana (FG). The data analyzed are based on the general epidemic course, and genomic surveillance data come from whole genome sequencing (WGS) as well as typing PCRs. From March 2020 to October 2021, four COVID-19 epidemic waves were observed in FG with an evolution of viral lineages influenced by virus introductions from continental France and above all by land-based introductions from neighbouring countries. The third epidemic wave from March to June 2021 was driven by a predominant Gamma introduced from Brazil and a less frequent Alpha introduced from France. This coexistence was completely substituted by Delta that initiated the fourth epidemic wave., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The Maroni basin -delineating the border between Suriname and French Guiana- presents sociocultural, geographical and economic circumstances that have been conducive to the circulation of sexually transmitted infections and to delays in diagnosis and care. Given the scarcity of published data, we aimed to describe different sexually transmitted infections along the Maroni and to gain a broader understanding of the epidemiologic situation., Methods: We conducted a scoping review of the efforts to approach the problem of sexually transmitted infections in this complex border area. Temporal trends were plotted and crude numbers were divided by local population numbers., Results: For HIV, despite increasing testing efforts, most patients still present at the advanced HIV stage (median CD4 count at diagnosis is < 20 per mm 3 ), and 25% of patients in Saint Laurent du Maroni were lost to follow-up within 6 years. However, progress on both sides has led to a decline in AIDS cases and mortality. Despite a rapid increase in the 1990's along the Maroni, the current HIV prevalence seemed lower (0.52%) in the rural villages than in coastal urban centers (> 1%). High risk HPV infection prevalence among women reaches 23.3%. The incidence of gonorrhea was 4.2 per 1,000 population aged 15-59. For chlamydiasis it was 3.4 per 1,000 population aged 15-59. For syphilis, the incidence was 2.5 per 1,000 population aged 15-59. Gonorrhea, chlamydiasis, hepatitis B detection increased over time with greater testing efforts and new diagnostic tests. Since the COVID-19 epidemic, congenital syphilis has dramatically increased in Saint Laurent du Maroni reaching 808 per 100,000 live births., Conclusion: Sexually transmitted infections seemed more prevalent in Saint Laurent du Maroni -the sole urban center-than in the remote villages along the Maroni. The syndromic approach and the heterogeneity of diagnostic platforms presumably overlook most infections in the region. Therefore, a concerted approach and a shared diagnostic upgrade with molecular diagnosis and rapid diagnostic tests seem necessary to reduce the burden of sexually transmitted infections on both sides of the Maroni. Congenital syphilis resulting from COVID-19 disruption of health services requires urgent attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nacher, Koendjbiharie, Michaud, Rabier, Leborgne, Rousseau, Lucarelli, Thorey, Gonzales, Terlutter, Thomas, Gastel, Biacabe, Eer, Vreden, Hcini and Woittiez.)

Context: Tropical areas and small islands are identified as highly vulnerable to climate change, and already experiencing shifts in their temperature distribution. However, the knowledge on the health impacts of temperatures under tropical marine climate is limited. We explored the influence of temperature on mortality in four French overseas regions located in French Guiana, French West Indies, and in the Indian Ocean, between 2000 and 2015., Method: Distributed lag non-linear generalized models linking temperature and mortality were developed in each area, and relative risks were combined through a meta-analysis. Models were used to estimate the fraction of mortality attributable to non-optimal temperatures. The role of humidity was also investigated., Results: An increased risk of mortality was observed when the temperature deviated from median. Results were not modified when introducing humidity. Between 2000 and 2015, 979 deaths [confidence interval (CI) 95% 531:1359] were attributable to temperatures higher than the 90th percentile of the temperature distribution, and 442 [CI 95% 178:667] to temperature lower than the 10th percentile., Discussion: Heat already has a large impact on mortality in the French overseas regions. Results suggest that adaptation to heat is relevant under tropical marine climate., (© 2022. The Author(s) under exclusive licence to International Society of Biometeorology.)

Background: French Guiana (FG) is an ultra-peripheral European region in the Amazon, and the COVID-19 epidemic has had very different kinetics from both its giant neighbors, Brazil or mainland France., Methods: This study summarized the epidemics of COVID-19 in FG., Results: The tropical climate, multiethnicity, and remoteness of the population forced healthcare providers to accordingly adapt the management of the epidemic. Incidence and mortality have been lower than that in Europe and Latin America due to a combination of prevalence of the youth in the population and highly developed healthcare system., Conclusions: Currently, vaccine hesitancy hinders the rapid expansion of vaccine coverage.

Cyclodextrins (CDs) are cyclic oligosaccharides used in many fields. Grafting polymers onto CDs enables new structures and applications to be obtained. Polylactide (PLA) is a biobased, biocompatible aliphatic polyester that can be grafted onto CDs by -OH-initiated ring-opening polymerization. Using 4-dimethylaminopyridine (DMAP) as an organocatalyst, a quantitative functionalization is reached on native α-, β-, γ- and 2,3-dimethyl- β-cyclodextrins. Narrow molecular weight distributions are obtained with the native CDs (dispersity < 1.1). The DMAP/β-CD combination is used as a case study, and the formation of an inclusion complex (1/1) is shown for the first time in the literature, which is fully characterized by NMR. The inclusion of DMAP into the cavity occurs via the secondary rim of the β-CD and the association constant (K a ) is estimated to be 88.2 M -1 . Its use as an initiator for ring-opening polymerization leads to a partial functionalization efficiency, and thus a more hydrophilic β-CD-PLA conjugate than that obtained starting from native β-CD. Polymerization results including also the use of the adamantane/β-CD inclusion complex as an initiator suggest that inclusion of the DMAP catalyst into the CD may not occur during polymerization reactions. Rac -lactide does not form an inclusion complex with β-CD.

An outbreak of Legionnaires' disease affected 18 people in Montpellier, a town of the south of France, between December 2016 and July 2017. All cases were diagnosed by a positive urinary antigen test. No deaths were reported. Epidemiological, environmental and genomic investigations (nested Sequence-Based Typing (nSBT) and whole genome sequencing) were undertaken. For the cases for which we had information, four had a new isolate (ST2471), one had a different new isolate (ST2470), one had a genomic pattern compatible with the ST2471 identified by nSBT ( fla A = 3), and one had a genomic pattern not compatible with two previous identified STs ( pil E = 6). The analysis conducted on the pool of an aquatic therapy center revealed seven isolates of Legionella pneumophila . Whole genome analysis confirmed the link between the environmental and clinical isolates for both ST2470 and ST2471. As the outbreak occurred slowly, with several weeks between new cases, it was not possible to immediately identify a common source. The sixth case was the first to report having aquatic therapy care. Of the 18 cases, eight had attended the aquatic therapy center and the other 10 were inhabitants who lived, worked or walked close to the center. The main cause for this outbreak was the lack of facility maintenance. This investigation highlights the risk to public health of aquatic therapy centers for users and nearby populations, and emphasizes the need for risk reduction measures with specific guidelines to improve health and safety in aquatic facilities.

Oropouche fever is a zoonotic dengue-like syndrome caused by Oropouche virus. In August-September 2020, dengue-like syndrome developed in 41 patients in a remote rainforest village in French Guiana. By PCR or microneutralization, 23 (82.1%) of 28 tested patients were positive for Oropouche virus, documenting its emergence in French Guiana.

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty.

Background: The COVID 19 epidemic submerged many health systems in the Amazon. The objective of the present study was to focus on the epidemic curves of the COVID 19 epidemic in different centers, and to look at testing and mortality data. Methods: Publicly available datasets were used. The log 10 of the daily cumulated number of cases starting from the day the territory reached 100 cumulated cases was plotted to compare the magnitude, shape and slope of the different curves. The maximum daily testing efforts were plotted for each territory in relation to the maximum daily number of diagnoses. The case fatality rate was computed by dividing the number of COVID 19 deaths by the number of confirmed cases. Results: In the Amazonian regions in general the speed of growth was generally lower than in Europe or the USA, or Southern Brazil. Whereas, countries like South Korea or New Zealand "broke" the curve relatively rapidly the log linear trajectory seemed much longer with signs of a decline in growth rate as of early July 2020. After a very slow start, French Guiana had the lowest slope when compared to other Amazonian territories with significant epidemics. The Amazonian states of Roraima, Amazonas, Parà, and Amapà had among the highest number of cases and deaths per million inhabitants in the world. French Guiana had significantly fewer deaths relative to its number of confirmed cases than other Amazonian territories. French Guiana had a late epidemic surge with intense testing scale-up often exceeding 4,000 persons tested daily per million inhabitants. Brazil was an outlier with low daily testing levels in relation to the number of daily diagnoses. Conclusions: There were marked heterogeneities mortality rates suggesting that socioeconomic, political factors, and perhaps ethnic vulnerability led to striking outcome differences in this Amazonian context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nacher, Rousseau, Succo, Andrieu, Gaillet, Michaud, Servas, Douine, Schaub, Adenis, Demar, Abboud, Epelboin and Djossou.)

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic continues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the widespread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologically fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: The authors have declared that no competing interests exist.

In this work, we aimed to understand the biological activity and the mechanism of action of three polymer-'ruthenium-cyclopentadienyl' conjugates (RuPMC) and a low molecular weight parental compound (Ru1) in cancer cells. Several biological assays were performed in ovarian (A2780) and breast (MCF7, MDA-MB-231) human cancer derived cell lines as well as in A2780cis, a cisplatin resistant cancer cell line. Our results show that all compounds have high activity towards cancer cells with low IC 50 values in the micromolar range. We observed that all Ru-PMC compounds are mainly found inside the cells, in contrast with the parental low molecular weight compound Ru1 that was mainly found at the membrane. All compounds induced mitochondrial alterations. PMC3 and Ru1 caused F-actin cytoskeleton morphology changes and reduced the clonogenic ability of the cells. The conjugate PMC3 induced apoptosis at low concentrations comparing to cisplatin and could overcame the platinum resistance of A2780cis cancer cells. A proteomic analysis showed that these compounds induce alterations in several cellular proteins which are related to the phenotypic disorders induced by them. Our results suggest that PMC3 is foreseen as a lead candidate to future studies and acting through a different mechanism of action than cisplatin. Here we established the potential of these Ru compounds as new metallodrugs for cancer chemotherapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

BackgroundClusters of dengue cases have recently become more frequent in areas of southern France colonised by the vector mosquito Aedes albopictus . In July 2015, a 2-month outbreak of dengue virus serotype 1 (DENV-1) was reported in Nîmes. Aim: We conducted a serosurvey in the affected area at the end of the vector activity period to determine the true extent of dengue transmission. Methods: We collected capillary blood from consenting household members, and information on their medical and travel histories, and exposure to mosquito bites. Recent infections were identified using IgM and IgG anti-DENV ELISA, followed, when positive, by plaque reduction neutralisation tests on serum against DENV 1-4 and West Nile virus. The prevalence estimator was calibrated on reference demographic data. We quantified the spatial clustering of dengue cases within the affected community and inferred the transmission tree. Results: The study participation rate was 39% (564/1,431). Three of 564 participants tested positive for DENV-1 infection (after marginal calibration, 0.41%; 95% confidence interval: 0.00-0.84). The spatial analysis showed that cases were clustered at the household level. Most participants perceived the presence of mosquitos as abundant (83%) and reported frequent mosquito bites (57%). We incidentally identified six past West Nile virus infections (0.9%; 95% CI: 0.2-1.6). Conclusion: This serosurvey confirms the potential for arboviral diseases to cause outbreaks - albeit limited for now - in France and Europe.

In August and September 2015, seven locally acquired cases of dengue virus type 1 (DENV-1) were detected in Nîmes, south of France, where Aedes albopictus has been established since 2011. Epidemiological and entomological investigations allowed to steer vector control measures to contain transmission. An imported case from French Polynesia with onset fever on 4 July was identified as primary case. This outbreak occurred from 8 August to 11 September in a 300 m radius area. Six sprayings to control mosquitos were performed in the affected area. We describe the first considerable dengue outbreak in mainland France where only sporadic cases of autochthonous dengue were recorded previously (2010, 2013 and 2014). The 69 day-period between the primary case and the last autochthonous case suggests multiple episodes of mosquito infections. The absence of notification of autochthonous cases during the month following the primary case's symptoms onset could be explained by the occurrence of inapparent illness. Recurrence of cases every year since 2013, the size of the 2015 outbreak and continuing expansion of areas with presence of Ae. albopictus highlight the threat of arboviral diseases in parts of Europe. Thus, European guidelines should be assessed and adjusted to the current context.

d-glucose end-capped polylactide ruthenium cyclopentadienyl complex (RuPMC) was newly synthesized by a straightforward method. RuPMC was tested against human MCF7 and MDAMB231 breast and A2780 ovarian adenocarcinoma revealing IC50 values in the micromolar range. A pH dependent hydrolysis is advanced by preliminary UV-visible spectroscopy. Cellular distribution studies showed that RuPMC is predominantly found in the nucleus and in the membrane. Data suggest potential application of RuPMC as a new drug delivery system for Ru(II)Cp compounds., (© 2013.)

The effect of a (2,5)B boat conformation on xyloside reactivity has been investigated by studying the hydrolysis and glycosylation of a series of synthetic xyloside analogues based on a 2-oxabicyclo[2.2.2]octane framework, which forces the xylose analogue to adopt a (2,5)B conformation. The locked β-xylosides were found to hydrolyze 100-1200 times faster than methyl β-D-xylopyranoside, whereas the locked α-xylosides hydrolyzed up to 2×10(4) times faster than methyl α-D-xylopyranoside. A significant rate enhancement was also observed for the glycosylation reaction. The high reactivity of these conformers can be related to the imposition of a (2,5)B conformation, which approximates a transition state (TS) boat conformation. In this way, the energy penalty required to go from the chair to the TS conformation is already paid. These results parallel and support the observation that the GH-11 xylanase family force their substrate to adopt a (2,5)B conformation to achieve highly efficient enzymatic glycosidic bond hydrolysis., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A method for selective monofunctionalition of readily available cyclodextrin diols (2(A-F),3(A-F),6(B,C,E,F)-hexadeca-O-benzyl-alpha-cyclodextrin and 2(A-G),3(A-G),6(B,C,E-G)-nonadeca-O-benzyl-beta-cyclodextrin) by regioselective nucleophilic opening of their cyclic sulfates is presented. Although the A and D products are nonequivalent in beta-cyclodextrin, only the A product is formed.

Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well as chemzymes that catalyze conjugate additions, cycloadditions, and self-replicating processes. The focus will be mainly on cyclodextrin-based chemzymes since they have shown to be good candidate structures to base an enzyme model skeleton on. In addition hereto, other molecules that encompass binding properties will also be presented.

6A,6D-Di-O-(propan-2-on-1,3-diyl) alpha-cyclodextrin-6A,6D-dicarboxylate (2alpha) and 6A,6D-di-O-(propan-2-on-1,3-diyl) beta-cyclodextrin-6A,6D-dicarboxylate (2beta) were found to catalyze the oxidation of aromatic amines in the presence of hydrogen peroxide. The products were the corresponding nitro compounds or in some cases azo-, azoxy-, or other dimerization products. The catalysis was found to follow enzyme kinetics giving a rate increase (kcat/kuncat) of up to 1100 in the best case.

alpha- and beta-Cyclodextrin 6(A),6(D)-diacids (1 and 2), beta-cyclodextrin-6-monoacid (14), beta-cyclodextrin 6(A),6(D)-di-O-sulfate (16) and beta-cyclodextrin-6-heptasulfate (19) were synthesised. Acids 1, 2 and 14 were made from perbenzylated alpha- or beta-cyclodextrin, by diisobutylaluminum hydride (DIBAL)-promoted debenzylation, oxidation and deprotection. Addition of molecular sieves was found to improve the debenzylation reaction. Sulfates 16 and 19 were made by sulfation of the appropriately partially protected derivatives and deprotection. Catalysis of 4-nitrophenyl glycoside cleavage by these cyclodextrin derivatives was studied. Compounds 1, 2 and 16 were found to catalyse the reaction, with the catalysis following Michaelis-Menten kinetics and depending first order on the phosphate concentration. In a phosphate buffer (0.5 M, 59 degrees C, pH 8.0), K(M) varied from 2-10 mM and the k(cat)/k(uncat) ratio from 80-1000 depending on the stereochemistry of the substrate and the catalyst, with 2 being the best catalyst and with the sulfated 16 also displaying catalytic ability. The monoacid 14 and the heptasulfate 19 were not catalytic.

(6AR,6DR)-6A,6D-di-C-cyano-beta-cyclodextrin (3) was synthesized and shown to catalyze hydrolysis of nitrophenyl glycosides with the reaction following Michaelis-Menten kinetics. At pH 7.4 and 25 degrees C, hydrolysis of 4-nitrophenyl-beta-glucopyranoside (2) was catalyzed with KM = 15 mM, kcat = 8.2 x 10-6 s-1, and kcat/kuncat = 1217. Catalysis was observed with concentration of 3 as low as 10 muM. Hydrolysis of the corresponding alpha-glucoside, alpha-galactoside, alpha-mannoside, and 2-nitrophenyl-beta-galactoside was also catalyzed by 3, with kcat/kuncat ranging from 283 to 2147. A series of analogues of 3 was prepared and investigated for catalysis of the hydrolysis of 2: (6AR,6DR)-6A,6D-di-C-propyl-beta-cyclodextrin (9) was not catalytic, while 6A,6D-di-C-cyano-6A,6D-dideoxy-beta-cyclodextrin (12) had a low catalytic activity (kcat/kuncat = 4). A kcat/kuncat = 48 was found for 6A,6D-dialdehydo-beta-cyclodextrin dihydrate (11). It was proposed that 3 acts by general acid catalysis on the bound substrate.

Three cyclodextrine derivatives (6A,6D-di-O-(prop-2-one-1,3-dienyl)-alpha-cyclodextrin (1), 6-O-(prop-2-one-1-yl)-alpha-cyclodextrin (2) and 6A,6D-di-O-(prop-2-one-1,3-dienyl)-beta-cyclodextrin (3)) were synthesised and investigated as epoxidation catalysts. The three compounds were synthesised from the corresponding perbenzylated cyclodextrins which were mono- or didebenzylated in the 6-position using Sinaÿ's method. Reaction with NaH and methallyl chloride in the case of 2, or methallyl dichloride in the case of 1 and 3, followed by dihydroxylation, periodate cleavage and protection group removal gave the target compounds. All three compounds catalysed, in the presence of oxone, the epoxidation of a series of alkenes. Epoxidation was compared to the reaction catalysed by simple ketones and inhibition was studied.

[reaction: see text] An efficient procedure for the stereoselective synthesis of aryl alpha-C-glycosides is presented. The key step of the method is the intramolecular delivery of the aryl group from a 2-O-aryldialkylsilyl substituent to the anomeric carbon by an electrophilic ipso-desilylation; this process leads exclusively to the product having the 1,2-cis configuration.

The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study. The steady-state mean minimum plasma amprenavir concentration (C(min,ss)) was 1.92 microg/ml for patients who received amprenavir and ritonavir without an NNRTI and 1.36 microg/ml for patients who received amprenavir and ritonavir plus efavirenz. For patients who received amprenavir-ritonavir without an NNRTI, the steady-state mean peak plasma amprenavir concentration (C(max,ss)) was 7.12 microg/ml, the area under the concentration-time curve from 0 to 10 h (AUC(0-10)) was 32.06 microg. h/ml, and the area under the concentration-time curve over a dosing interval (12 h) at steady-state (AUC(ss)) was 35.74 microg. h/ml. Decreases in the mean values of C(min,ss) (29%), C(max,ss) (42%), AUC(0-10) (42%), and AUC(ss) (40%) for amprenavir occurred when efavirenz was coadministered with amprenavir-ritonavir. No unexpected side effects were observed. As expected, coadministration of amprenavir with ritonavir resulted in an amprenavir C(min,ss) markedly higher than those previously reported for the marketed dose of amprenavir. When amprenavir-ritonavir was coadministered with efavirenz, amprenavir-ritonavir maintained a mean amprenavir C(min,ss) above the mean 50% inhibitory concentration of amprenavir previously determined for both wild-type HIV-1 isolates and HIV-1 strains isolated from PI-experienced patients. These data support the use of low-dose ritonavir to enhance the level of exposure to amprenavir and increase the efficacy of amprenavir.