scholarly journals Low Prevalence of Pfcrt Resistance Alleles among Patients with Uncomplicated Falciparum Malaria in Niger Six Years after Chloroquine Withdrawal

2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Adamou Salissou ◽  
Halima Zamanka ◽  
Brigitte Biyghe Binze ◽  
Taiana Rivière ◽  
Magalie Tichit ◽  
...  
Keyword(s):  
Public Health ◽  
Sequence Data ◽  
Ex Vivo ◽  
Significant Decline ◽  
Wild Type ◽  
Blood Samples ◽  
Few Data ◽  
Low Prevalence ◽  
First Time ◽  
Resistant Genotypes

Chloroquine (CQ) resistance is widespread in Africa, but few data are available for Niger. Pfcrt haplotypes (aa 56–118) and ex vivo responses to CQ and amodiaquine were characterized for 26 isolates collected in South Niger from children under 15 years of age suffering from uncomplicated falciparum malaria, six years after the introduction of artemisinin-based combinations and the withdrawal of CQ. The wild-type Pfcrt haplotype CVMNK was found in 22 of the 26 isolates, with CVIET sequences observed in only three of the samples. We also describe for the first time a new CVINT haplotype. The ex vivo responses were better for CVMNK than for CVIET parasites. Pfcrt sequence data were compared with those obtained for 26 additional parasitized blood samples collected in Gabon, from an area of CQ resistance used as a control. Our findings suggest that there has been a significant decline in CQ-resistant genotypes since the previous estimates for Niger were obtained. No such decline in molecular resistance to CQ was observed in the subset of samples collected in similar conditions from Gabon. These results have important implications for public health and support the policy implemented in Niger since 2005, which aims to increase the efficacy and availability of antimalarial drugs whilst controlling the spread of resistance.

scholarly journals Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Christine Landlinger ◽  
Lenka Tisakova ◽  
Vera Oberbauer ◽  
Timo Schwebs ◽  
Abbas Muhammad ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Bactericidal Activity ◽  
High Selectivity ◽  
Ex Vivo ◽  
Vaginal Microbiome ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Promising Alternative ◽  
First Time

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.

Abstract P283: Parkin Mediates Mitophagy in Cardioprotection

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Allen M Andres ◽  
Chengqun Huang ◽  
Eric P Ratliff ◽  
Genaro Hernandez ◽  
Pamela Lee ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Wild Type ◽  
Simulated Ischemia ◽  
Selective Targeting ◽  
Cardioprotective Effects ◽  
Mitochondrial Turnover ◽  
First Time

Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining cellular homeostasis. However, the mechanisms that govern the selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown to be essential for the selective clearance of damaged mitochondria. Parkin is expressed in the heart, yet its function has not been investigated in the context of cardioprotection. We previously reported that autophagy is required for cardioprotection by ischemic preconditioning (IPC). In the present study, we used simulated ischemia in vitro and IPC in hearts (in vivo and ex vivo) to investigate the role of Parkin in mediating cardioprotection. In HL-1 cells, simulated ischemia induced Parkin translocation to mitochondria and mitochondrial elimination. Mitochondrial loss was blunted in Atg5-deficient cells, revealing the requirement for autophagy in mitochondrial elimination. Consistent with previous reports implicating p62/SQSTM1 in mitophagy, we found that downregulation of p62 attenuated mitophagy and exacerbated cell death in HL-1 cardiomyocytes subjected to simulated ischemia. While wild type mice showed p62 translocation to mitochondria after IPC, Parkin knockout mice exhibited attenuated translocation of p62 to mitochondria. Importantly, ablation of Parkin in mice abolished the cardioprotective effects of IPC. These results reveal for the first time the crucial role of Parkin and mitophagy in cardioprotection.

scholarly journals What Is the Appropriate Meropenem MIC for Screening of Carbapenemase-Producing Enterobacteriaceae in Low-Prevalence Settings?

2015 ◽  
Vol 60 (3) ◽  
pp. 1556-1559 ◽  
Author(s):  
Ramzi Fattouh ◽  
Nathalie Tijet ◽  
Allison McGeer ◽  
Susan M. Poutanen ◽  
Roberto G. Melano ◽  
...  
Keyword(s):  
Public Health ◽  
Escherichia Coli ◽  
Treatment Options ◽  
Large Set ◽  
Wild Type ◽  
Content Type ◽  
The Public ◽  
E Coli ◽  
Low Prevalence ◽  
Screening Approaches

Infection with carbapenemase-producingEnterobacteriaceae(CPE) has been shown to cause significant illness among hospitalized patients. Given the paucity of treatment options, there is a critical need to stop the spread of CPE. However, screening for the presence of CPE in laboratory settings has been challenging. In order to assess the effectiveness of current CPE detection guidelines, we analyzed the meropenem MIC distribution for a large set of clinicalEnterobacteriaceaeisolates. A total of 1,022 isolates submitted to the Public Health Ontario Laboratories (PHOL) from January 2011 to March 2014 were examined. Only isolates displaying a meropenem or ertapenem MIC of ≥0.25 or ≥1 μg/ml, respectively, were included. Carbapenemase-positive isolates were identified by multiplex PCR. We identified 189 isolates positive for carbapenemases, which primarily comprised NDM, KPC, and OXA-48-like carbapenemases, and these isolates were largelyKlebsiellaspp.,Escherichia coli, andEnterobacterspp. Interestingly, 14 to 20% of these isolates displayed meropenem MICs within the susceptible range on the basis of CLSI and EUCAST breakpoint interpretive criteria. While the majority of meropenem-susceptible CPE isolates were observed to beE. coli, meropenem susceptibility was not exclusive to any one species/genus or carbapenemase type. Application of CLSI screening recommendations captured only 86% of carbapenemase-producing isolates, whereas application of EUCAST recommendations detected 98.4% of CPE isolates. In a region with a low carbapenemase prevalence, meropenem-based screening approaches require a cutoff MIC near the epidemiological wild-type threshold in order to achieve nearly optimal CPE identification.

scholarly journals Identification and molecular characterization of novel viruses in Ugandan cattle

2022 ◽  
Author(s):  
Stephen Balinandi ◽  
Juliette Hayer ◽  
Harindranath Cholleti ◽  
Julius Lutwama ◽  
Michelle Wille ◽  
...  
Keyword(s):  
Public Health ◽  
Geographical Location ◽  
Zoonotic Diseases ◽  
Virus Family ◽  
Blood Samples ◽  
Molecular Approaches ◽  
Reservoir Hosts ◽  
First Time ◽  
Family Rhabdoviridae

The risk for the emergence of novel viral zoonotic diseases in animals and humans in Uganda is high given its geographical location with high biodiversity. We aimed to identify and characterize viruses in 175 blood samples from cattle selected in Uganda using molecular approaches. We identified 8 viral species belonging to 4 families (Flaviviridae, Peribunyaviridae, Reoviridae and Rhabdoviridae) and 6 genera (Hepacivirus, Pestivirus, Orthobunyavirus, Coltivirus, Dinovernavirus and Ephemerovirus). Four viruses were novel and tetantively named as Zikole virus (Family: Flaviviridae), Zeboroti virus (Family: Reoviridae), Zebtine virus (Family: Rhabdoviridae) and Kokolu virus (Family: Rhabdoviridae). In addition, Bovine hepacivirus, Obodhiang virus, Aedes pseudoscutellaris reovirus and Schmallenberg virus were identified for the first time in Ugandan cattle. We report a broad range of viruses including novel ones in the blood of cattle likely as reservoir hosts for emergence of novel viruses with serious public health implications.

The CARE Telematics Network for the Surveillance of Influenza in Europe

1995 ◽  
Vol 34 (05) ◽  
pp. 518-522 ◽  
Author(s):  
M. Bensadon ◽  
A. Strauss ◽  
R. Snacken
Keyword(s):  
Public Health ◽  
Early Warning ◽  
Early Warning Systems ◽  
Warning Systems ◽  
Surveillance Networks ◽  
Spanish Flu ◽  
The 1950S ◽  
National Networks ◽  
First Time

Abstract:Since the 1950s, national networks for the surveillance of influenza have been progressively implemented in several countries. New epidemiological arguments have triggered changes in order to increase the sensitivity of existent early warning systems and to strengthen the communications between European networks. The WHO project CARE Telematics, which collects clinical and virological data of nine national networks and sends useful information to public health administrations, is presented. From the results of the 1993-94 season, the benefits of the system are discussed. Though other telematics networks in this field already exist, it is the first time that virological data, absolutely essential for characterizing the type of an outbreak, are timely available by other countries. This argument will be decisive in case of occurrence of a new strain of virus (shift), such as the Spanish flu in 1918. Priorities are now to include other existing European surveillance networks.

Monitoring of r-Hirudin Anticoagulation during Cardiopulmonary Bypass – Assessment of the Whole Blood Ecarin Clotting Time

1997 ◽  
Vol 77 (05) ◽  
pp. 0920-0925 ◽  
Author(s):  
Bernd Pötzsch ◽  
Katharina Madlener ◽  
Christoph Seelig ◽  
Christian F Riess ◽  
Andreas Greinacher ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Whole Blood ◽  
Heart Surgery ◽  
Ex Vivo ◽  
Open Heart Surgery ◽  
Clotting Time ◽  
Blood Samples ◽  
Alternative Approach ◽  
Ecarin Clotting Time

SummaryThe use of recombinant ® hirudin as an anticoagulant in performing extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices requires a specific and easy to handle monitoring system. The usefulness of the celite-induced activated clotting time (ACT) and the activated partial thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo blood samples obtained from eight patients treated with r-hirudin during open heart surgery. The very poor relationship between the prolongation of the ACT and APTT values and the concentration of r-hirudin as measured using a chromogenic factor Ila assay indicates that both assays are not suitable to monitor r-hirudin anticoagulation. As an alternative approach a whole blood clotting assay based on the prothrombin-activating snake venom ecarin has been tested. In vitro experiments using r-hirudin- spiked whole blood samples showed a linear relationship between the concentration of hirudin added and the prolongation of the clotting times up to a concentration of r-hirudin of 4.0 µg/ml. Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the accuracy of the ecarin clotting time (ECT) assay. Differences in the interindividual responsiveness to r-hirudin were analyzed on r-hirudin- spiked blood samples obtained from 50 healthy blood donors. CV- values between 1.8% and 6% measured at r-hirudin concentrations between 0.5 and 4 µg/ml indicate remarkably slight differences in r-hirudin responsiveness. ECT assay results of the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of r-hirudin. Moreover, assay results were not influenced by treatment with aprotinin or heparin. These findings together with the short measuring time with less than 120 seconds warrant the whole blood ECT to be a suitable assay for monitoring of r-hirudin anticoagulation in cardiac surgery.

Who Did the Audit? Audit Quality and Disclosures of Other Audit Participants in PCAOB Filings

2014 ◽  
Vol 90 (5) ◽  
pp. 1939-1967 ◽  
Author(s):  
Carol Callaway Dee ◽  
Ayalew Lulseged ◽  
Tianming Zhang
Keyword(s):  
Audit Quality ◽  
Market Reaction ◽  
Audit Fees ◽  
Discretionary Accruals ◽  
Multivariate Model ◽  
Significant Decline ◽  
Earnings Response Coefficients ◽  
Absolute Value ◽  
Earnings Response ◽  
First Time

ABSTRACT We empirically test whether audit quality is affected when part of an SEC issuer's audit is outsourced to auditors other than the principal auditor (“participating auditors”). We find a significantly negative market reaction and a significant decline in earnings response coefficients (ERCs) for experimental issuers disclosed for the first time as having participating auditors involved in their audits. However, we find no market reaction and no decline in ERCs for a matching sample of issuers that are not disclosed as using participating auditors, nor for issuers disclosed for the second or third time as using participating auditors. We also find actual audit quality as measured by absolute value of performance-matched discretionary accruals is lower for the experimental issuers, although we find no difference in audit fees paid by the experimental and matching issuers in a multivariate model. Our findings suggest that the PCAOB's proposed rule requiring disclosure of the use of other auditors in addition to the principal auditor would provide information useful to investors in assessing audit quality for SEC issuers.

scholarly journals Challenges in evaluating the use of viral sequence data to identify HIV transmission networks for public health

2020 ◽  
Vol 12 (s1) ◽  
Author(s):  
Rami Kantor ◽  
John P. Fulton ◽  
Jon Steingrimsson ◽  
Vladimir Novitsky ◽  
Mark Howison ◽  
...  
Keyword(s):  
Public Health ◽  
United States ◽  
Hiv Transmission ◽  
Sequence Data ◽  
The United States ◽  
Viral Sequence ◽  
Transmission Networks ◽  
New Methods ◽  
Hiv Epidemic ◽  
The World

AbstractGreat efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential. In this paper, we recognize challenges associated with such evaluation, and make the case that overcoming these challenges is key to the use of HIV sequence data in routine public health actions to disrupt HIV transmission networks.

scholarly journals Predicting chromosome damage in astronauts participating in international space station missions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Feiveson ◽  
Kerry George ◽  
Mark Shavers ◽  
Maria Moreno-Villanueva ◽  
Ye Zhang ◽  
...  
Keyword(s):  
International Space Station ◽  
Dose Response ◽  
Ex Vivo ◽  
Space Station ◽  
Space Radiation ◽  
Blood Samples ◽  
International Space ◽  
Significant Difference ◽  
Subject Specific

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

scholarly journals NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 147
Author(s):  
Romuald Brice Babou Kammoe ◽  
Gilles Kauffenstein ◽  
Julie Pelletier ◽  
Bernard Robaye ◽  
Jean Sévigny
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Smooth Muscle Contraction ◽  
Receptor Activation ◽  
Nucleoside Triphosphate ◽  
Nucleotide Receptors ◽  
Nerve Terminals ◽  
Wild Type ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Bladder Contraction

Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.

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