Screening and risk factors for cervical cancer among survivors of sexual violence in conflict settings, in Eastern Democratic Republic of Congo.

This study assesses the risk that rape survivors have of developing cervical cancer in the context of conflict. A cross-sectional and descriptive study conducted in Bunyakiri and Kavumu, a conflict region in the east of the Democratic Republic of the Congo during the period from September 1 to 10, 2022, including 47 women survivors of sexual violence, 41 of whom were selected on the basis of certain criteria with age ranging from 18 to 50 years. Speculum examination was performed with visual inspection with acetic acid (VIA). After collecting data, the latter were encoded in the Excel file and grouped in the form of tables then analyzed after calculating the percentage. Ages of 21-30 years was the most represented, i.e., 56%. Among them, 34.1% were married and 31.7% were abandoned. Majority was in secondary school (46.3%) and illiterates (34.1%). 36.5% complained of pelvic pain and 36.5% reported first sexual intercourse at the age range of 13-15 years, of which 25 cases, i.e., 61% were sexually active. 39% reported having had 3 sexual partners in their life. VIA was negative in 97.5% of cases. It should be mentioned in this study that the environment of conflict zone, the circumstances of rape and the risky sexual behavior of survivors are an ecosystem that predisposes them to cervical cancer.

Cette étude évalue le risque qu'ont les survivantes de viol de développer un cancer du col de l'utérus dans un contexte de conflit. Une étude transversale et descriptive menée à Bunyakiri et Kavumu, région de conflit à l'est de la République Démocratique du Congo durant la période du 1er au 10 septembre 2022, incluant 47 femmes survivantes de violences sexuelles, dont 41 ont été sélectionnées sur la base de certains critères avec un âge allant de 18 à 50 ans. L'examen au spéculum a été réalisé avec inspection visuelle à l'acide acétique (VIA). Après collecte des données, ces dernières ont été encodées dans le fichier Excel et regroupées sous forme de tableaux puis analysées après calcul du pourcentage. La tranche d'âge de 21 à 30 ans était la plus représentée, soit 56 %. Parmi eux, 34,1% étaient mariés et 31,7% étaient abandonnés. La majorité était scolarisée dans le secondaire (46,3%) et analphabète (34,1%). 36,5% se plaignaient de douleurs pelviennes et 36,5% rapportaient leurs premiers rapports sexuels entre 13 et 15 ans, dont 25 cas, soit 61% étaient sexuellement actifs. 39 % déclarent avoir eu 3 partenaires sexuels dans leur vie. VIA était négatif dans 97,5 % des cas. Il convient de mentionner dans cette étude que l'environnement de la zone de conflit, les circonstances du viol et le comportement sexuel à risque des survivantes constituent un écosystème qui les prédispose au cancer du col de l'utérus.

Bioelectrocatalytic CO2 Reduction by Mo-Dependent Formylmethanofuran Dehydrogenase.

Massive efforts are invested in developing innovative CO2 -sequestration strategies to counter climate change and transform CO2 into higher-value products. CO2 -capture by reduction is a chemical challenge, and attention is turned toward biological systems that selectively and efficiently catalyse this reaction under mild conditions and in aqueous solvents. While a few reports have evaluated the effectiveness of isolated bacterial formate dehydrogenases as catalysts for the reversible electrochemical reduction of CO2 , it is imperative to explore other enzymes among the natural reservoir of potential models that might exhibit higher turnover rates or preferential directionality for the reductive reaction. Here, we present electroenzymatic catalysis of formylmethanofuran dehydrogenase, a CO2 -reducing-and-fixing biomachinery isolated from a thermophilic methanogen, which was deposited on a graphite rod electrode to enable direct electron transfer for electroenzymatic CO2 reduction. The gas is reduced with a high Faradaic efficiency (109±1 %), where a low affinity for formate prevents its electrochemical reoxidation and favours formate accumulation. These properties make the enzyme an excellent tool for electroenzymatic CO2 -fixation and inspiration for protein engineering that would be beneficial for biotechnological purposes to convert the greenhouse gas into stable formate that can subsequently be safely stored, transported, and used for power generation without energy loss.

A Structural View of Alkyl-Coenzyme M Reductases, the First Step of Alkane Anaerobic Oxidation Catalyzed by Archaea.

Microbial anaerobic oxidation of alkanes intrigues the scientific community by way of its impact on the global carbon cycle, and its biotechnological applications. Archaea are proposed to degrade short- and long-chain alkanes to CO2 by reversing methanogenesis, a theoretically reversible process. The pathway would start with alkane activation, an endergonic step catalyzed by methyl-coenzyme M reductase (MCR) homologues that would generate alkyl-thiols carried by coenzyme M. While the methane-generating MCR found in methanogens has been well characterized, the enzymatic activity of the putative alkane-fixing counterparts has not been validated so far. Such an absence of biochemical investigations contrasts with the current explosion of metagenomics data, which draws new potential alkane-oxidizing pathways in various archaeal phyla. Therefore, validating the physiological function of these putative alkane-fixing machines and investigating how their structures, catalytic mechanisms, and cofactors vary depending on the targeted alkane have become urgent needs. The first structural insights into the methane- and ethane-capturing MCRs highlighted unsuspected differences and proposed some explanations for their substrate specificity. This Perspective reviews the current physiological, biochemical, and structural knowledge of alkyl-CoM reductases and offers fresh ideas about the expected mechanistic and chemical differences among members of this broad family. We conclude with the challenges of the investigation of these particular enzymes, which might one day generate biofuels for our modern society.

Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity.

Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (Teff) and T regulatory (Treg) CD4+Foxp3+ cells. In vivo Teff are present in all immune organs, whereas the TPO-specific Treg are present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of Teff and the depletion of Treg via activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.

Endovascular treatment for acute ischemic stroke at a primary stroke center: First results of the Perpignan center.

INTRODUCTION: Converting a high-volume primary stroke center (PSC) into a stroke center that can perform emergency endovascular treatment (EVT) could reduce the time to thrombectomy. We report the first results of a newly established EVT facility at the Perpignan PSC and their comparison with the targets defined by the established guidelines. PATIENTS AND METHOD: For this comprehensive observational study, data of patients with acute ischemic stroke (AIS) due to proximal large vessel occlusion (LVO) and treated by EVT at the Perpignan PSC from December 5, 2019 to September 15, 2020 were extracted from an ongoing prospective database. RESULTS: During the study period, 37 patients underwent EVT at the Perpignan PSC. The median (range) symptom-onset to recanalization time was 262min (100-485min). The median (range) intra-hospital times were: 20min (2-58min) for door-to-imaging, 57min (30-155min) for imaging-to-puncture, 55min (15-180min) for puncture-to-recanalization, and 137min (59-319min) for door-to-recanalization. At 3 months post-AIS, the favorable outcome (modified Ranking Score: 0-2) rate was 50% and the mortality rate was 19.4%. These results are comparable to those of previous clinical trials, and meet the targets defined by the current consensus statements for EVT. DISCUSSION AND CONCLUSION: Our results show the feasibility and safety of EVT in a PSC for patients with AIS due to LVO. The implementation of this strategy may be important for shortening the time to thrombectomy.

Is off-label thrombolysis safe and effective in a real-life primary stroke center? A retrospective analysis of data from a 5-year prospective database.

BACKGROUND: Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC). METHODS: This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event. RESULTS: Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P<0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P<0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P<0.0001) at admission. CONCLUSIONS: "Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.

Legacy and emerging organic contaminants: Levels and profiles in top predator fish from the western Indian Ocean in relation to their trophic ecology.

Tuna and billfish are large pelagic fish of ecological importance in open oceans. As top predators with a long lifespan, they are prone to exposure to various contaminants such as persistent organic pollutants (POPs) and contaminants of emerging concern. In this study, three pollutant families were investigated, including polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and perfluoroalkyl substances (PFASs), including perfluorooctane sulfonate (PFOS) and perfluorocarboxylic acids (PFCAs). Contamination was investigated in individuals from three tropical tuna species, namely bigeye (Thunnus obesus), skipjack (Katsuwonus pelamis) and yellowfin (Thunnusalbacares) tunas and the billfish swordfish (Xiphias gladius), collected from various areas of the western Indian Ocean (WIO) in 2013-2014. Contamination levels and profiles were examined in fish muscle, together with biological parameters (fish length / age, sex, lipid content) and ecological tracers (carbon and nitrogen stable isotopes). POP levels were low in all species in comparison to other locations worldwide, revealing a low impact of anthropogenic organic contaminants in the WIO. A predominance of OCPs (especially DDTs) versus PCBs was highlighted in all species; PFASs were predominant over chlorinated POPs in tunas. Among the studied PFASs, long-chain PFCAs were found to prevail over PFOS in all species. Organic contaminant profiles differed across species according to their foraging habitat; swordfish and bigeye tuna, which both feed in deep oceanic layers, showed similarities in their contaminant profiles. Geographically, the distinct DDT profiles of fish from the Mozambique Channel suggested an exposure to different DDT sources, in line with regional use of this insecticide and coupled with an extended residence time of fish in the Channel. To our knowledge, the data presented here are among the first obtained for legacy and emerging organic contaminants in various species of large pelagic predators from the WIO.

Shewanella decolorationis LDS1 Chromate Resistance.

The genus Shewanella is well known for its genetic diversity, its outstanding respiratory capacity, and its high potential for bioremediation. Here, a novel strain isolated from sediments of the Indian Ocean was characterized. A 16S rRNA analysis indicated that it belongs to the species Shewanella decolorationis It was named Shewanella decolorationis LDS1. This strain presented an unusual ability to grow efficiently at temperatures from 24°C to 40°C without apparent modifications of its metabolism, as shown by testing respiratory activities or carbon assimilation, and in a wide range of salt concentrations. Moreover, S. decolorationis LDS1 tolerates high chromate concentrations. Indeed, it was able to grow in the presence of 4 mM chromate at 28°C and 3 mM chromate at 40°C. Interestingly, whatever the temperature, when the culture reached the stationary phase, the strain reduced the chromate present in the growth medium. In addition, S. decolorationis LDS1 degrades different toxic dyes, including anthraquinone, triarylmethane, and azo dyes. Thus, compared to Shewanella oneidensis, this strain presented better capacity to cope with various abiotic stresses, particularly at high temperatures. The analysis of genome sequence preliminary data indicated that, in contrast to S. oneidensis and S. decolorationis S12, S. decolorationis LDS1 possesses the phosphorothioate modification machinery that has been described as participating in survival against various abiotic stresses by protecting DNA. We demonstrate that its heterologous production in S. oneidensis allows it to resist higher concentrations of chromate.IMPORTANCEShewanella species have long been described as interesting microorganisms in regard to their ability to reduce many organic and inorganic compounds, including metals. However, members of the Shewanella genus are often depicted as cold-water microorganisms, although their optimal growth temperature usually ranges from 25 to 28°C under laboratory growth conditions. Shewanella decolorationis LDS1 is highly attractive, since its metabolism allows it to develop efficiently at temperatures from 24 to 40°C, conserving its ability to respire alternative substrates and to reduce toxic compounds such as chromate or toxic dyes. Our results clearly indicate that this novel strain has the potential to be a powerful tool for bioremediation and unveil one of the mechanisms involved in its chromate resistance.

Anaesthetic management during intracranial mechanical thrombectomy: systematic review and meta-analysis of current data.

OBJECTIVE: Our aim was to compare the clinical outcome of patients with ischaemic stroke with anterior large vessel occlusion treated with stent retrievers and/or contact aspiration mechanical thrombectomy (MT) under general anaesthesia (GA) or conscious sedation non-GA through a systematic review and meta-analysis. METHODS: The literature was searched using PubMed, Embase and Cochrane databases to identify studies reporting on anaesthesia and MT. Using fixed or random weighted effect, we evaluated the following outcomes: 3-month mortality, modified Rankin Score (mRs) 0-2, recanalisation success (thrombolysis in cerebral infarction (TICI) ≥2b) and symptomatic intracerebral haemorrhagic (sICH) transformation. RESULTS: We identified seven cohorts (including three dedicated randomised controlled trials), totalling 1929 patients (932 with GA). Over the entire sample, mortality, mRs 0-2, TICI≥2b and sICH rates were, respectively 17.5% (99% CI 9.7% to 29.6%; Q-value: 60.1; I2: 93%, 1717 patients), 42.1% (99% CI 33.3% to 51.7%; Q-value: 41.3; I2: 87.9%), 82.9% (99% CI 74.0% to 89.1%; Q-value: 20.7; I2: 80.6%, 1006 patients) and 5.5% (99% CI 2.8% to 10.8%; Q-value: 18.6; I2: 78.5%). MT performed in non-GA patients was associated with better 3-month functional outcome (pooled OR, 1.35; 99% CI 1.04 to 1.76; Q-value: 24.0; I2: 9.2%, 1845 patients) and lower 3-month mortality rate (pooled OR, 0.70; 99% CI 0.49 to 0.98; Q-value: 1.4; I2: 0%, 1717 patients; fixed weighted effect model) compared with GA. MT performed under conscious sedation non-GA had significantly shorter onset-to-recanalisation and onset-to-groin delay compared with GA, and recanalisation success and sICH were similar. CONCLUSION: Non-GA during MT for anterior acute ischaemic stroke with current-generation stent retriever/aspiration devices is associated with better 3-month functional outcome and lower mortality rates. These unadjusted estimates are subject to biases and should be interpreted with caution.

Quantitative in Situ SEM High Cycle Fatigue: The Critical Role of Oxygen on Nanoscale-Void-Controlled Nucleation and Propagation of Small Cracks in Ni Microbeams.

This Letter presents a quantitative in situ scanning electron microscope (SEM) nanoscale high and very high cycle fatigue (HCF/VHCF) investigation of Ni microbeams under bending, using a MEMS microresonator as an integrated testing machine. The novel technique highlights ultraslow fatigue crack growth (average values down to ∼10-14 m/cycle) that has heretofore not been reported and that indicates a discontinuous process; it also reveals strong environmental effects on fatigue lives that are 3 orders of magnitude longer in a vacuum than in air. This ultraslow fatigue regime does not follow the well documented fatigue mechanisms that rely on the common crack tip stress intensification, mediated by dislocation emission and associated with much larger crack growth rates. Instead, our study reveals fatigue nucleation and propagation mechanisms that mainly result from room temperature void formation based on vacancy condensation processes that are strongly affected by oxygen. This study therefore shows significant size effects governing the bending high/very high cycle fatigue behavior of metals at the micro- and nanoscales, whereby the stress concentration effect at the tip of a growing small fatigue crack is assumed to be greatly reduced by the effect of the bending-induced extreme stress gradients, which prevents any significant cyclic crack tip opening displacement. In this scenario, ultraslow processes relying on vacancy formation at the subsurface or in the vicinity of a crack tip and subsequent condensation into voids become the dominant fatigue mechanisms.

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

BACKGROUND: Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. METHODS: ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. RESULTS: ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. CONCLUSIONS: This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of concept for ATR-101 as a novel agent for the treatment of endocrine disorders like Cushing's syndrome in humans.

Burden and spectrum of bacterial infections among sickle cell disease children living in Cameroon.

BACKGROUND: Although sickle cell disease (SCD) children are highly susceptible to bacterial infections (BIs), there is a dreadful lack of data related to the burden and spectrum of BIs in sub-Saharan Africa (SSA), the highest affected region with SCD. This study aimed to determine the burden and spectrum of BIs among SCD children hospitalized in a pediatric reference hospital in Cameroon, a SSA country. METHODS: We conducted a retrospective analysis of records of children hospitalized from November 2012 to August 2015 in the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, Cameroon. We enrolled all known SCD children aged 15 years or less, hospitalized for a suspicion of BI and who presented a positive culture of a body specimen. RESULTS: A total of 987 SCD children were hospitalized during the study period. Cultures were positive for 96 patients (9.7%) among whom 60.4% males. Ages ranged from 6 to 192 months with a median of 53 (Interquartile range (IQR) 21-101) months. For children no more covered by the Expanded Programme on Immunization, only 13 (18.8%) had received the Pneumo 23® and Meningo A&C® antigens, and 12 (17.4%), the Typhim vi® and the Haemophilus influenzae type b antigens; 58 children (84.1%) had received no vaccine. The specimen yielding positive cultures were: blood (70.7%), urine (13.1%), pus (9.1%), synovial fluid (4.1%), cerebrospinal fluid (2.0%), and bone fragment (1.0%). The different types of infection included: urinary tract infections (13.5%), myositis (8.3%), arthritis (6.3%), osteomyelitis (4.2%), and meningitis (2.1%); the site of infection was unidentified in 65.6% of cases. The main bacteria included: Salmonella sp. (28.1%), Staphylococcus sp. (18.8%), Klebsiella pneumoniae (17.7%), Escherichia coli (10.4%), Enterobacter sp. (5.2%), Acinetobacter sp. (4.2%), Streptococcus sp. (4.2%) and Serratia sp. (4.2%). CONCLUSION: This retrospective analysis revealed 9.7% cases of BIs, mainly caused by Salmonella sp. (28.1%), Staphylococcus sp. (18.8%), Klebsiella pneumoniae (17.7%), and Escherichia coli (10.4%).

Tissue-specific distribution and maternal transfer of polybrominated diphenyl ethers (PBDEs) and their metabolites in adult common sole (Solea solea L.) over an entire reproduction cycle.

Tissue-specific accumulation and distribution of polybrominated diphenyl ethers (PBDEs) and their debrominated metabolites were studied in common sole (Solea solea) over an entire reproduction cycle. The fish were dietary-exposed to selected PBDEs in laboratory-controlled conditions for one year. Fish of both sexes were sampled throughout the reproduction cycle and their muscle, liver, viscera, carcass, skin and gonads (female) were analysed for total lipid content, PBDEs and their debrominated metabolites. On a wet weight basis, the concentrations of most spiked congeners showed an increase at the end of the exposure time in the whole body of fish of both sexes. Conversely, BDE-99 and BDE-209 - the two most highly metabolized congeners - did not show a similar increase, while their debrominated metabolites exhibited a linear increase over time. Biomagnification factors (BMFs) calculated in whole body were > 1 for all PBDEs except BDE-99 (0.89 ± 0.22) and BDE-209 (0.013 ± 0.006). BMFs were strongly correlated to apparent assimilation efficiencies, which ranged from 1.6% ± 0.7% (BDE-209) to 88% ± 11% (BDE-100). Fish carcass was the most predominant storage compartment for all PBDEs except BDE-209 in both male and female fish, followed by skin, muscle, female gonads, liver and visceral tissue. BDE-209 showed a different distribution and was stored more predominantly in the liver, viscera and female gonads than other congeners, probably due to its transport with lipoproteins. All PBDEs except BDE-209 showed equilibrium partitioning between the liver and other studied compartments, while BDE-209 showed a higher affinity with blood-enriched tissues, leading to higher liver / carcass, skin and muscle concentration ratios. Visceral tissue and liver exhibited the most pronounced differences in terms of concentration variations between sexes and over time. In females, both tissues showed a significant decrease in most PBDE concentrations (ww) and TLC in March during the spawning season, with low inter-individual variability, reflecting the striking utilisation of lipids by females for reproduction at this time. In males, no differences were found in concentrations in these compartments over time and a high inter-individual variability was observed. Maternal transfer of PBDEs from gonad to eggs was constant, regardless of spawn rank in the spawning season. Egg / gonad PBDE concentration ratios (in lw) were 1.3 ± 0.7 for all congeners and 2.6 ± 0.3 for BDE-209, suggesting a higher transfer of this congener from gonads to eggs.

Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening.

OBJECTIVE: To determine the effects of a 1-year quality-improvement (QI) process to reduce door-to-needle (DTN) time in a secondary general hospital in which multimodal MRI screening is used before tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke (AIS). METHODS: The QI process was initiated in January 2015. Patients who received intravenous (iv) tPA<4.5h after AIS onset between 26 February 2015 to 25 February 2016 (during implementation of the QI process; the "2015 cohort") were identified (n=130), and their demographic and clinical characteristics and timing metrics compared with those of patients treated by iv tPA in 2014 (the "2014 cohort", n=135). RESULTS: Of the 130 patients in the 2015 cohort, 120 (92.3%) of them were screened by MRI. The median DTN time was significantly reduced by 30% (from 84min in 2014 to 59min; P<0.003), while the proportion of treated patients with a DTN time≤60min increased from 21% to 52% (P<0.0001). Demographic and baseline characteristics did not significantly differ between cohorts, and the improvement in DTN time was associated with better outcomes after discharge (patients with a 0-2 score on the modified rankin scale: 59% in the 2015 cohort vs 42.4% in the 2014 cohort; P<0.01). During the 1-year QI process, the median DTN time decreased by 15% (from 65min in the first trimester to 55min in the last trimester; P≤0.04) with a non-significant 1.5-fold increase in the proportion of treated patients with a DTN time≤60min (from 41% to 62%; P=0.09). CONCLUSION: It is feasible to deliver tPA to patients with AIS within 60min in a general hospital, using MRI as the routine screening modality, making this QI process to reduce DTN time widely applicable to other secondary general hospitals.

Transcriptome responses of an ungrafted Phytophthora root rot tolerant avocado (Persea americana) rootstock to flooding and Phytophthora cinnamomi.

BACKGROUND: Avocado (Persea americana Mill.) is a commercially important fruit crop worldwide. A major limitation to production is the oomycete Phytophthora cinnamomi, which causes root rot leading to branch-dieback and tree death. The decline of orchards infected with P. cinnamomi occurs much faster when exposed to flooding, even if flooding is only transient. Flooding is a multifactorial stress compromised of several individual stresses, making breeding and selection for tolerant varieties challenging. With more plantations occurring in marginal areas, with imperfect irrigation and drainage, understanding the response of avocado to these stresses will be important for the industry. RESULTS: Maintenance of energy production was found to be central in the response to flooding, as seen by up-regulation of transcripts related to glycolysis and induction of transcripts related to ethanolic fermentation. Energy-intensive processes were generally down-regulated, as evidenced by repression of transcripts related to processes such as secondary cell-wall biosynthesis as well as defence-related transcripts. Aquaporins were found to be down-regulated in avocado roots exposed to flooding, indicating reduced water-uptake under these conditions. CONCLUSIONS: The transcriptomic response of avocado to flooding and P. cinnamomi was investigated utilizing microarray analysis. Differences in the transcriptome caused by the presence of the pathogen were minor compared to transcriptomic perturbations caused by flooding. The transcriptomic response of avocado to flooding reveals a response to flooding that is conserved in several species. This data could provide key information that could be used to improve selection of stress tolerant rootstocks in the avocado industry.

Active transposable elements recover species boundaries and geographic structure in Madagascan coffee species.

The completion of the genome assembly for the economically important coffee plant Coffea canephora (Rubiaceae) has allowed the use of bioinformatic tools to identify and characterize a diverse array of transposable elements (TEs), which can be used in evolutionary studies of the genus. An overview of the copy number and location within the C. canephora genome of four TEs is presented. These are tested for their use as molecular markers to unravel the evolutionary history of the Millotii Complex, a group of six wild coffee (Coffea) species native to Madagascar. Two TEs from the Gypsy superfamily successfully recovered some species boundaries and geographic structure among samples, whereas a TE from the Copia superfamily did not. Notably, species occurring in evergreen moist forests of eastern and southeastern Madagascar were divergent with respect to species in other habitats and regions. Our results suggest that the peak of transpositional activity of the Gypsy and Copia TEs occurred, respectively, before and after the speciation events of the tested Madagascan species. We conclude that the utilization of active TEs has considerable potential to unravel the evolutionary history and delimitation of closely related Coffea species. However, the selection of TE needs to be experimentally tested, since each element has its own evolutionary history. Different TEs with similar copy number in a given species can render different dendrograms; thus copy number is not a good selection criterion to attain phylogenetic resolution.

Intracranial Aneurysms: Recurrences More than 10 Years after Endovascular Treatment-A Prospective Cohort Study, Systematic Review, and Meta-Analysis.

PURPOSE: To assess the efficacy of endovascular treatment (EVT) of intracranial aneurysms for recurrence, bleeding, and de novo aneurysm formation at long-term follow-up (> 10 years after treatment) with magnetic resonance (MR) angiography and to identify risk factors for recurrence through a prospective study and a systematic review of the literature. MATERIALS AND METHODS: Clinical examinations and 3-T MR angiography were performed prospectively 10 years after EVT of intracranial aneurysms in a single institution. Ethics committee approval and informed consent were obtained. PubMed, EMBASE, and Cochrane databases were searched to identify studies in which authors reported bleeding and/or aneurysm recurrence rates in patients who received follow-up more than 10 years after EVT. Univariate and multivariate subgroup analyses were performed to identify risk factors (midterm MR angiographic results, aneurysm characteristics, retreatment within 5 years). RESULTS: In the prospective study, sac recanalization occurred between midterm and long-term MR angiography in 16 of 129 (12.4%) aneurysms. Grade 2 classification on the Raymond scale at midterm MR angiography (relative risk [RR], 4.16; 99% confidence interval [CI]: 2.12, 8.14) and retreatment within 5 years (RR, 4.67; 99% CI: 1.55, 14.03) were risk factors for late recurrence. In the systematic review (15 cohorts, 2773 patients, 2902 aneurysms), bleeding, aneurysm recurrence, and de novo lesion formation rates were, respectively, 0.7% (99% CI: 0.2%, 2.7%; I(2), 0%; one of 694 patients), 11.4% (99% CI: 7.0%, 18.0%; I(2), 21.6%), and 4.1% (99% CI: 1.7, 9.4%; I(2), 54.1%). Raymond grade 2 initial result (RR, 7.08; 99% CI: 1.24, 40.37; I(2), 82.6%) and aneurysm size greater than 10 mm (RR, 4.37; 99% CI: 1.83, 10.44; I(2), 0%) were risk factors for late recurrence. CONCLUSION: EVT of intracranial aneurysm is effective for prevention of long-term bleeding, but recurrences occur in a clinically relevant percentage of patients, a finding that may justify follow-up of selected patients for 10 years or more, such as patients with aneurysms larger than 10 mm or classified as Raymond grade 2 at midterm MR angiography.

The Acute Chest Syndrome in Cameroonian children living with sickle cell disease.

BACKGROUND: Although sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. METHODS: This was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization. RESULTS: Twenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9% with a mean of 14.6% (6.0%). The three main symptoms at admission were fever (90.5%), cough (81%) and chest pains (28.6%). Two patients (9.5%) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm(3), 23476 (11543.7)/mm(3), 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5%). Treatment associated broad-spectrum antibiotics (100%), hydration (100%), analgesics (43.2%), whole blood transfusion (66.7%), and oxygen supplementation (33.3%). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05). CONCLUSION: ACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients' parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.