Africa without Qaddafi: The Case of Chad
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Towards harmonization of voriconazole CLSI and EUCAST breakpoints for Candida albicans using a validated in vitro pharmacokinetic/pharmacodynamic model [Susceptibility]
Background. CLSI and EUCAST susceptibility breakpoints for voriconazole and C. albicans differ by one dilution (≤0.125 and ≤0.06 mg/l, respectively) whereas the epidemiological cutoff values (ECOFF/ECV) with both methodologies are the same (0.03 mg/L). We therefore determined the pharmacokinetic-pharmacodynamic (PK/PD) breakpoints of voriconazole against C. albicans for both methodologies with an in vitro PK/PD model, which was validated using existing animal PK/PD data.
Methods. Four clinical wild-type and non-wild-type C. albicans isolates (voriconazole MICs 0.008-0.125 mg/l) were tested in an in vitro PK/PD model. For validation purposes, mouse PK were simulated and in vitro PD were compared with in vivo outcome. Human PK were simulated and the exposure-effect relationship fAUC0-24/MIC was described for EUCAST and CLSI24/48h methods. PK/PD breakpoints were determined using the fAUC0-24/MIC associated with half-maximal activity (EI50) and Monte Carlo simulation analysis.
Results. The in vitro 24h-PD EI50 of voriconazole against C. albicans were 2.5-5 (1.5-17) fAUC/MIC. However, the 72h-PD were higher, 133 (51-347) fAUC/MIC for EUCAST and 94 (35-252) fAUC/MIC for CLSI. The mean (95% confidence interval) probability of target attainment (PTA) was 100(95-100)%, 97(72-100)%, 83(35-99)%, and 49(8-91)% and 100(97-100)%, 99(85-100)%, 91(52-100)% and 68(17-96)% for EUCAST and CLSI MICs 0.03, 0.06, 0.125, and 0.25 mg/L, respectively. Significantly, >95% PTAs were found for EUCAST/CLSI MICs ≤0.03 mg/ll. For MICs 0.06-0.125 mg/l trough levels 1-4 mg/ll would be required.
Conclusion. A PK/PD breakpoint of C. albicans voriconazole at the ECOFF/ECV of 0.03 mg/L was determined for both EUCAST/CLSI methods, indicating the need for breakpoint harmonization for the reference methodologies.
Development of probiotic formulations for oral candidiasis prevention: Gellan gum as a carrier to deliver Lactobacillus paracasei 28.4 [Experimental Therapeutics]
Probiotics might provide an alternative approach for the control of oral candidiasis. However, studies on the antifungal activity of probiotics in the oral cavity are based on the consumption of yogurt or other dietary products, and there is a necessary to use appropriate biomaterials and specific strains to obtain probiotic formulations targeting local oral administration. In this study, we impregnated gellan gum, a natural biopolymer used as a food-additive, with a probiotic and investigated its antifungal activity against Candida albicans. Lactobacillus paracasei 28.4, a strain recently isolated from the oral cavity of a caries-free individual, was incorporated in several concentrations of gellan gum (0.6% to 1%). All tested concentrations could incorporate L. paracasei cells while maintaining bacterial viability. Probiotic/gellan formulations were stable for 7 days when stored at room temperature or 4°C. Long-term storage of bacteria-impregnated gellan gum was achieved when L. paracasei 28.4 was lyophilized. The probiotic/gellan formulations provided a release of L. paracasei cells over 24 hours that was sufficient to inhibit the growth of C. albicans with effects dependent on the cell concentrations incorporated into gellan gum. The probiotic/gellan formulations also had inhibitory activity against Candida spp. biofilms by reducing the number of Candida spp. cells (p < 0.0001), decreasing the total biomass (p = 0.0003), and impairing hyphae formation (p = 0.0002), compared to the control group which received no treatment. Interestingly, probiotic formulation of 1% w/v gellan gum provided an oral colonization of L. paracasei in mice with approximately 6 log of CFU/mL after 10 days. This formulation inhibited the C. albicans growth (p < 0.0001), prevented the development of candidiasis lesions (p = 0.0013), and suppressed inflammation (p = 0.0006) when compared to the mice not treated in the microscopic analysis of the tongue dorsum. These results indicate that gellan gum is a promising biomaterial and can be used as a carrier system to promote oral colonization for probiotics that prevent oral candidiasis.
Species Distribution and Comparison between EUCAST and Gradient Concentration Strips Methods for Antifungal Susceptibility Testing of 112 Aspergillus Section Nigri Isolates [Susceptibility]
Aspergillus niger, the third species responsible for invasive aspergillosis has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri. However little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The Minimum Inhibitory Concentrations (MICs) of itraconazole, voriconazole, posaconazole, isavuconazole and amphotericin B were determined by both the EUCAST and gradient concentration strips methods. Aspergillus tubingensis (n=51, 45.5%) and A. welwitschiae (n=50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n=7). The MICs of azoles drugs were higher for A. tubingensis than for A. welwitschiae. The MIC of amphotericin B was 2 mg/L or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by gradient concentration strips methods, these latter being lower than the former (Spearman's rank correlation tests ranging - depending on the antifungal agent - from 0.01 to 0.25; p>0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri. The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and gradient concentration strips methods require further investigation.
Effect of the Lysin, Exebacase, on Cardiac Vegetation Progression in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus (MRSA) Endocarditis as Determined by Echocardiography [Pharmacology]
Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).
Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.
Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).
Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).
Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE.
Casio ProTrek WSD-F30
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Statue of Christ carrying the cross will process Holy Wednesday in Caracas
CNA Staff, Apr 2, 2020 / 02:50 pm (CNA).- The statue of the Nazarene of Saint Paul will be processed April 8 through the streets of Caracas to help the faithful observe Holy Week.
It will be atop a popemobile used by St. John Paul II when he visited the country in 1985.
According to local tradition, the striking image was brought to Caracas from Seville in 1674. The wooden sculpture depicts Christ dressed in an ornately embroidered purple robe carrying his cross.
According to accounts, the image was processed in the city with prayers during a plague that broke out in Caracas in 1696, and the devotional act was credited with ending the pestilence.
The image was originally kept in a church dedicated to Saint Paul the Hermit, whose intercession was attributed to ending a plague in 1579. The wooden sculpture is now reserved in Saint Teresa Basilica, as Saint Paul’s church was demolished and replaced with a municipal theater by an anticlerical president in 1881.
The procession is held annually on Holy Wednesday.
Cardinal Baltazar Enrique Porras Cardozo, Archbishop of Merida and apostolic administrator of Caracas, said the “route will cover a great part of the city for veneration by its devotees,” and asked for understanding as the route itself has not yet been finalized and will be announced later.
According to local media, the prelate said in a letter that the image should be transported in accordance with safety and hygiene regulations to avoid spreading the coronavirus.
Porras said that the image should not be carried by people but transported by vehicle only and there should be another vehicle for a priest and assistant along with sound equipment for the prayers.
The archdiocese said that parishes can join the initiative and organize such a procession in their own areas as long as they observe the proper health precautions.
Finally, the archdiocese asked the faithful devotees of the Nazarene of Saint Paul to offer their prayers from their homes and to wait for the end of the coronavirus lockdown to visit the image in Saint Teresa Basilica.
Brazilian Supreme Court to consider legalizing abortion in Zika cases
Rio de Janeiro, Brazil, Apr 20, 2020 / 09:25 am (CNA).- On Friday, Brazil’s Federal Supreme Court will hold a virtual hearing to consider whether to decriminalize abortion for pregnant women infected with the Zika virus.
The legal intervention, called “Direct Action on Unconstitutionality-ADI 5581,” was filed with Brazil’s highest court by the National Association of Public Defenders. Supreme Court Justice Cármen Lúcia Antunes Rocha will present the legal action to the court, whose 11 members will have until April 30 to vote on the issue.
Several pro-life organizations have come out strongly against efforts to expand abortion, which is illegal in Brazil but is considered a “non-punishable crime” in cases of rape, a proven risk to life of the mother and, as of 2012, babies diagnosed with anencephaly.
“It’s a usurpation of powers because the Supreme Court does not have competency to rule on this matter,” said jurist José Miranda de Siqueira, president of the National Association of Citizens for Life. “This is a crime against the Federal Constitution of Brazil which in Article V guarantees the inviolability of the right to life.”
“We’re working with the Union of Catholic Jurists of Rio de Janeiro and will soon issue a strong statement on the issue,” continued Miranda, who is also a bioethics professor and authored a book on euthanasia, “O Poder sobre a Vida” (The Power over Life), which specifically addresses ADI 5581.
“Life is a preeminent right in the legal world. I’m asking people to pray and publicize this serious situation which is going on,” the lawyer added.
In an open letter to all Brazilians, the National Network for the Defense of Life and Family argued that the court challenge is “part of a strategy to introduce abortion in case of disabilities in general, or even abortion on demand, with the weak justification that the pregnant woman would be in a state of distress.”
“Eugenic abortion carries an enormous burden of prejudice and discrimination towards people with disabilities, sending an unseemly message that it would be better if they did not exist,” the pro-life organization added.
The Zika virus garnered international attention in 2015 after areas of Brazil noted a spike in cases of the birth defect microcephaly – a condition marked by abnormally small heads, brains, and developmental delays – following a recent outbreak of the virus in areas of northeastern Brazil.
Research on the virus suggested a link between Zika virus infection during pregnancy and severe neurological birth defects, including microcephaly and incomplete brain development.
A CitizenGo petition addressed to the Supreme Court justices called for the case to be removed from the docket and for the lives of the unborn to be respected. The petition was launched April 16. Within 24 hours, it had garnered 35,000 signatures and as of April 20 has 85,000.
Brazil’s Supreme Court rejects effort to legalize abortion in Zika cases
Rio de Janeiro, Brazil, Apr 27, 2020 / 04:35 pm (CNA).- A majority of Brazil’s Supreme Federal Tribunal has voted against an intervention seeking to decriminalize abortion for expectant mothers diagnosed with the Zika virus.
The judges convened a virtual plenary session April 24 to hear arguments for and against the “Direct Action on Unconstitutionality-ADI 5581,” a legal intervention filed with the court by the National Association of Public Defenders.
While the court has until April 30 to vote on the matter, 7 of its 11 members have already voted in opposition, effectively rejecting the measure.
Abortion is illegal in Brazil but previous Supreme Court rulings have declared it a “non-punishable crime” in cases of rape, a proven risk to life of the mother and, as of 2012, babies diagnosed with anencephaly.
The Zika virus garnered international attention in 2015 after areas of Brazil noted a spike in cases of the birth defect microcephaly – a condition marked by abnormally small heads, brains, and developmental delays – following a recent outbreak of the virus in areas of northeastern Brazil.
Research on the virus suggested a link between Zika virus infection during pregnancy and severe neurological birth defects, including microcephaly and incomplete brain development.
However, some experts criticized what they described as technical and scientific flaws of the premise behind ADI 5581.
The Union of Catholic Jurists of Rio de Janeiro issued an official statement arguing that a causal relationship was never established between Zika virus and the microcephaly outbreak that occurred in Brazil.
Raphael Câmara, an obstetrician at the Federal University of Rio de Janeiro, said that when an attempt was made in 2016 to allow abortion in Zika cases, little was known about the virus.
“Since then, we have answers to many of the issues raised in ADI-5581 in support of allowing abortion,” Câmara said. “The first fact is that recent studies show that fetuses of infected mothers are affected only 5 to 14% of the time, with the majority having mild problems, as shown by research from the Centers for Disease Control and Prevention.”
“In addition, a study recently released by the CDC showed that 73% of Brazilian labs have a low accuracy rate for diagnosing the Zika virus, so the request is meaningless because we cannot talk about someone 'infected with Zika', but rather 'maybe infected by Zika.’ Is it based on this inaccuracy that we will kill fetuses?” the obstetrician continued.
Ahead of the Supreme Court ruling, pro-life groups in Brazil had spoken out against efforts to expand abortion in the country. A CitizenGo petition against the legal action drew more than 184,000 online signatures.
The Brazilian Bishops’ Conference had also opposed the attempt, calling on Catholics to defend life and oppose abortion. The conference wrote an open letter and also wrote privately to the Supreme Court, reiterating the duty to value the inviolable gift of life.
In 2017, the conference stated, “It does not belong to any public authority to selectively recognize the right to life or who will live or die. This discrimination is evil and exclusionary.”
This article was originally published by our sister agency, ACI Digital. It has been translated and adapted by CNA.
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Wintrust Financial Corporation Announces Cash Dividends, Increasing Quarterly Common Stock Dividend Rate 12%
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Life Sentence for 2017 Murder in New Castle
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New Castle man convicted of murder
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Racketeering Judgment Against Massage Parlor Owner; Murder Conviction in 2012 Cold Case
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State Sen. Nicole Poore visits the New Castle Court House Museum to celebrate accreditation by the American Alliance of Museums
Delaware Division of Historical and Cultural Affairs to replace roof of Academy building in New Castle
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Underground Railroad exhibit to open at the New Castle Court House Museum on Feb. 23, 2019
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Negro Travelers’ Green Book program at the New Castle Court House Museum on March 16, 2019
Program on the travel and vacation guidebook for people of color during the segregation era
“Separation—Freedom for Delaware” at the New Castle Court House Museum on June 9, 2019
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Ron Whittington to portray Hall of Famer William “Judy” Johnson at the New Castle Court House Museum on July 20, 2019
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“Caesar Rodney in His Own Words” Historical play at the New Castle Court House Museum on Sept. 22, 2019
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“William Penn Day” at Delaware’s New Castle Court House Museum on Oct. 26, 2019
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Parker’s Dairy Palace in New Castle, Del. added to the National Register of Historic Places
Delaware Valley Archaeology and History Symposium at the Arsenal in New Castle, Del. on Dec. 7, 2019
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