Alors qu’une tentative de coup d’Etat contre Pierre Nkurunziza, émanant de l’ex-chef d’état-major, Godefroid Niyombaré, est en cours au Burundi, Thierry Vircoulon chercheur à l'International Crisis Group, explique qui est le général putschiste et analyse, plus généralement, l'appareil sécuritaire du Burundi.

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤10⁶ CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., bla_PAO and bla_OXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empiric treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been investigated in a phase 3 trial in patients with complicated urinary tract infections or acute pyelonephritis. This study examined pharmacokinetic-pharmacodynamic (PK-PD) relationships of enmetazobactam, in combination with cefepime, for ESBL-producing isolates of Klebsiella pneumoniae in 26-hour murine neutropenic thigh infection models. Enmetazobactam dose fractionation identified time above a free threshold concentration (fT > C_T) as the PK-PD index predictive of efficacy. Nine ESBL-producing isolates of K. pneumoniae, resistant to cefepime and piperacillin-tazobactam, were included in enmetazobactam dose-ranging studies. The isolates encoded CTX-M-type, SHV-12, DHA-1 and OXA-48 β-lactamases and covered a cefepime-enmetazobactam MIC range from 0.06 to 2 μg/ml. Enmetazobactam restored the efficacy of cefepime against all isolates tested. Sigmoid curve fitting across the combined set of isolates identified enmetazobactam PK-PD targets for stasis and for a 1-log₁₀ bioburden reduction of 8% and 44% fT > 2 μg/ml, respectively, with a concomitant cefepime PK-PD target of 40 – 60% fT > cefepime-enmetazobactam MIC. These findings support clinical dose selection and breakpoint setting for cefepime-enmetazobactam.

Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics such as bedaquiline and imipenem although in vitro data have questioned this combination. We report that the efficacy of the bedaquiline plus imipenem treatment relies essentially on the activity of bedaquiline in a C3HeB/FeJ mice model of infection with a rough variant of M. abscessus. The addition of imipenem contributed at clearing the infection in the spleen.

Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUC_ELF:AUC_plasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia.

Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy, and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (NFX) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than that in BZ-treated mice. These results were associated with an increase in the number of eosinophils and reticulocytes and level of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the LXA₄ receptor antagonist, Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of acute phase of Chagas disease that are beneficial for chronic patients.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

BACKGROUND AND OBJECTIVES:

Annual incidence of venous thromboembolism (VTE) including postoperative VTE in hospitalized children is rising significantly. A growing body of evidence supports the role of red blood cells (RBCs) in pathologic thrombosis. In this study, we examined the association of perioperative RBC transfusion with postoperative VTE in pediatric patients.

Are you unhappy with your credit provider? Have you been given more debt than you can afford to pay back? Help is at hand, and it’s just an SMS away.

Credit card fraud increased to 19.47% as at the end of March 2019, compared to 12.2% reported at the beginning of January 2019.

Automated EFT payments enabled by technology from fintech company Ozow may be a secure alternative method to transact than card payments.

Allegations of maladministration by banks accounted for 39% of cases completed by the Ombudsman for Banking Services so far this year.

Bogotá, Colombia, Apr 3, 2020 / 04:04 am (CNA).- Diana María Toro Vélez was kidnapped on a September day, as she drove home from Mass in the Colombian city where she lived. She spent 453 days in captivity. And she says that God’s grace kept her hope alive during the ordeal.

“I left Mass one Thursday and was driving home in my car and when I got home they assaulted me. They asked me a few questions and took me away. They sold me to the guerrillas,” Toro told ACI Prensa, CNA’s Spanish language news partner.

Toro, the mother of three, told ACI Prensa that during her captivity, she was sometimes forced to march a lot, one time for up to 15 days in a row.

“I clung to God. I cried and prayed a lot. I really held fast to God. I taught the kidnappers how to read and write. We prayed. There was a certain coexistence, and good things came out of the bad,” she said.

Toro, 41, was kidnapped Sept. 27, 2018, in Amagá, about an hour’s drive from Medellin. Her captors were criminals, members of a gang called “The Sorcerers,” who handed her over to Marxist guerrillas from the the National Liberation Army (ELN) for 48M pesos, about $12,000. The ELN reportedly asked 3 billion pesos, about $745,000 for her return.

Toro was released from captivity on Christmas Eve, 2019.

The Catholic Church in Colombia had appealed for her release, and the release appeared to be a goodwill gesture toward achieving some kind of peace agreement between the ELN and the country’s government. Public officials credited the Church with arranging the release.

Speaking to ACI Prensa, the young mom said that she was “very devoted to Our Lady of Guadalupe. When I was kidnapped I made a rosary and prayed it every day, praying a lot to the Virgin that she would allow me to be returned to my children. And God heard me, because I was released on Dec. 24, 2019.”

It was difficult, Toro said, to be “separated from my three children, one of them 3, another 4 and one 14 years old. Separated from my husband, my parents, my siblings, my family members, relatives and friends.”

“These were 453 days of anxiety, grief, sadness and despair. 453 days of living in the middle of the jungle, sleeping under a canopy, on branches, with snakes, scorpions, mosquitos and many other animals around,” she said.

Toro told ACI Prensa she subsisted on parrot, pasta, cooked banana, and rice. She had only two sets of clothes and infrequently bathed. 

“These were really hard days without knowing anything about my family, just with the certainty that God was with me, filling me daily with his strength and fortitude and firmly believing that if I woke up okay, my family was okay too,” she said.

“And God brought me out of that really hard situation. I saw that his glory and his mercy are immense.”

Toro said the ordeal has filled her with gratitude.

“I want to tell those people who in these times feel alone or in despair because of the situation we’re going through in Colombia and the entire world, that God is with us, he never has left us alone, especially now.”

“Let’s pray the rosary, let’s pray as a family. The power of prayer is immense,” she added.

 

This story was first published by ACI Prensa, CNA's Spanish-language news partner. It has been translated and adapted by CNA.

 

Villavicencio, Colombia, Apr 7, 2020 / 12:00 am (CNA).- The president of the Colombian bishops’ conference, Óscar Urbina, suspended 15 priests of his archdiocese from ministry who have been accused of sexual abuse. Other jurisdictions in the country have removed four other priests.

Archbishop Óscar Urbina of Villavicencio told Colombian media that the accused priests represent 15% of the city’s priests.

The priests are accused of committing sexual abuse in Colombia, Italy and the United States, Caracol Radio reported.

Fr. Carlos Villabón, communications director and chancellor for the archdiocese of Villavicencio, told ACI Prensa, CNA’s Spanish language news partner, that the 15 priests were suspended while a canonical investigation proceeds at the Vatican.

“On March 16, 2020 these 15 priests were notified after a preliminary investigation was carried out. They are neither convicted nor acquitted by this suspension, only asked to relinquish their parish duties, cease celebrating the Eucharist and cease their ministerial service while the complete investigation is conducted,” the priest explained.

The results of the preliminary investigation “are now being sent to the Congregation for the Doctrine of the Faith at the Vatican, and there they will determine the gravity of the facts and what the Church calls a penal canonical process will be conducted,” Villabón said.

“It’s unknown how much time the canonical process will take, but the idea is that it proceed as quickly as possible, considering that in Italy and in many parts of the world there’s a quarantine because of the coronavirus,” the communications director added.
Caracol Radio published a list of the 19 priests, but Villabón told ACI Prensa that the archdiocese would neither confirm nor deny the names reported.

 “According to a witness under protection by the prosecutor’s office, the 19 priests apparently formed a network of abusers, Caracol Radio reported.

In an April 3 statement, the archdiocese of Villavicencio announced that an accusation was received Feb. 14, 2020 concerning “acts against sexual morality by some priests of this archdiocese.”

“Having as a priority the alleged victim, we expressed to him our deep pain and solidarity and have offered him psychological and spiritual accompaniment. We reaffirm our commitment to act with clarity and transparency for his good and that of the Church,” the statement said.

Following the protocols of the Archdiocesan Commission for the Protection of Minors, once the abuse was reported, the regional prosecutor’s office was notified and “we made ourselves completely available to cooperate in the investigations taking place in this case,” the statement said.

The archdiocese said that it has taken steps “to eradicate the terrible evil of abuse within and outside our institution. We ask to be informed of any situations where one of our members has finally betrayed his vocation of service and dedication to the Lord and the community.”

A version of this story was first reported by ACI Prensa, CNA's Spanish-language news partner. It has been translated and adapted by CNA.

 

Microsoft originally sought to become a 'carbon neutral' company, meaning it could generate carbon emissions as long as it offset them through other means, but "in short, neutral is not enough to address the world's needs," says Microsoft President Brad Smith.

NATURE BOOK

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.

The Raspberry Pi Foundation is the educational partner for 'Shaun the Sheep Movie 2: Farmageddon,' which hits theaters today. We spoke to Raspberry Pi Foundation CEO Philip Colligan to get the backstory on these low-cost PCs built for tinkerers.

Fortino struck twice after Sergio Romano had opened the scoring to seal a 3-0 victory for Italy in their third-place play-off against Colombia, who lost goalkeeper Juan Lozano to a red card.

Colombia has been selected to stage the eighth FIFA Futsal World Cup in 2016 with Bogota, Villavicencio, Bucaramanga, Cucuta, Ibaque and Neiva proposed as the host cities.

Portugal, Russia, Italy, Ukraine, Kazakhstan, Azerbaijan and Spain are representing Europe in the FIFA Futsal World Cup: we look at the challengers in Colombia.

Roombas, Echo and Ring Alarm devices, and the Apple Watch Series 5 are all still discounted. There's also a great Nintendo Switch deal that includes $20 in Nintendo eShop credit.

The Apple Watch Series 4 smartwatch is back at $359, matching its Prime Day price. Plus, Dell is offering an extra 15 percent off select XPS laptops. Finally, the Roomba 891 is just $380.

Alex Carey chose Shikhar Dhawan over Rohit Sharma to open along with Australian cricketer David Warner.

The Bombay toasty is a special sandwich sold on the streets of Bombay which is made with lots of fresh vegetables, mint chutney and butter.

Salman Khan's Radhe is still in the post-production stage

OMB accepting public input on agency regulations through December 1.

Governor Markell ordered flags to be lowered between April 16 and 22 as a mark of respect for the victims of the April 15 bombings in Boston, Massachusetts.

The Office of Management and Budget (OMB) is currently accepting comments and will hold a series of public hearings on three OMB regulations in accordance with the regulatory review provisions of HB 147 of the 148th General Assembly. Comments will be accepted through November 1 for the following regulations: • 4102 Regulations for the Annual […]

A finance ministry official said some other state governments have also shown interest in borrowing from their respective state CAMPA funds, but refused to name them.

The plea pointed out that on the same day the Union government issued an advisory asking all private and public firms not to reduce salaries or sack employees due to the pandemic.

January serves as National Slavery and Human Trafficking Awareness Month, culminating in the annual observation of National Freedom Day on February 1. For many, this month presents an opportunity to refocus efforts to slow, and ultimately stop, human trafficking around the globe, but especially here in the United States. The [...]

The post Analytics can help combat the horrors of human trafficking appeared first on Government Data Connection.

People snapped grouping together at popular spots in Milan, defying social-distancing rules just days after the city eased its lockdown, have prompted an Italian virologist to compare it to a ticking coronavirus infection ‘bomb.’
Read Full Article at RT.com

Resolution details the country's 2018 adoption of UN system

Manufacturers have been told to commence production before July 31, 2020.

The Centre has released Rs 11,092 crore as the first instalment in FY21 to State Disaster Response Mitigation Fund of 28 states.

The Marrakech film festival, which was held from November 29 to December 7, had Gitanjali Rao’s hand-painted animated film Bombay Rose vying for the festival's top prize, the Golden Star.

Recently, Team India captain Virat Kohli had also called upon people to "stay safe and vigilant" in the midst of the coronavirus outbreak.

Voice AI apps can help in prevention, detection and treatment of hundreds of patients at the same time, thus helping mitigate the shortage of doctors

Helyxon’s two solutions—OXY-2 and 98.6 Fever Watch—equipped with geo-fencing tracking alerts, keep a tab on the patient’s vital parameters and inform the medical staff about any aberration.

The researchers believe that a future phase 3 trial will confirm or refute the usefulness of this candidate drug as a backbone treatment for COVID-19.

1 Seychellois Rupee = 226.9616 Colombian Peso

1 Trinidad and Tobago Dollar = 576.6126 Colombian Peso

1 Swedish Krona = 398.7454 Colombian Peso