The current political crisis has reopened the wounds of Burundi’s past. Hardliners now dominant in the government brutally stifle dissent, fuel ethnic hatred, and undermine the Arusha accord that framed Burundi’s peace for the past decade. The international community should push toward real dialogue, and prepare to intervene if violence escalates.

Le 1er juin dernier à Mugamba (province de Bururi), Pierre Nkurunziza a lancé un ultimatum. « Du haut d’une camionnette, micro à la main, sous très haute protection de l’armée et de la police », rapporte l’AFP, le président burundais a ordonné aux insurgés de cette commune du Sud du pays de déposer les armes dans les quinze jours : « Téléphonez à vos frères qui ont pris les armes, dites-leur que nous leur donnons quinze jours pour qu’ils y renoncent […] Quinze jours, pas plus. Dites-leur cela ». Hasard ou préméditation, la fin de cet ultimatum devrait coïncider avec la reprise prévue des discussions à Arusha, en Tanzanie, entre le gouvernement et l’opposition.

Burundi’s year-long crisis has not gone away. It started with President Pierre Nkurunziza’s determination to claim a third term, trampling over the constitutional arrangements that ended a decade-long civil war. Press freedom is a major casualty of the new strife; but the turmoil has also transformed the way in which Burundians get information. For better or worse, social media has filled the vacuum left by the shutting down of the most popular radio stations and forcing out of many of the country’s professional journalists.

This article, published ahead of print on 28 July 2008, has been withdrawn by the authors. Although moderate synergy between P2-RANTES and C peptides can be observed with high statistical significance in cell fusion assays, this synergy was not able to be verified in HIV viral assays. The authors regret the overstatement of synergy and will revise the paper for publication at a later date.

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the current study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1 in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

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 fAUC_0-24/MIC was described for EUCAST and CLSI24/48h methods. PK/PD breakpoints were determined using the fAUC_0-24/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.

KBP-7072 is a semi-synthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens including multidrug resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (IV) administration of single and multiple doses were investigated in animal models including during fed and fasted states and also evaluated the protein binding and excretion characteristics. In Sprague-Dawley (SD) rats, Beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after administration of single oral and IV and multiple oral doses. Oral bioavailability ranged from 12% to 32%. Mean T_max ranged from 0.5 to 4 hours, and mean half-life ranged from approximately 6 to 11 hours. Administration of oral doses in the fed state resulted in a marked reduction in C_max and AUC compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies.

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.

Drug repositioning is the only feasible option to address the COVID-19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects.

BACKGROUND:

Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan indications.

BACKGROUND:

For children who cannot be discharged from the emergency department, definitive care has become less frequent at most hospitals. It is uncertain whether this is true for common conditions that do not require specialty care. We sought to determine how the likelihood of definitive care has changed for 3 common pediatric conditions: asthma, croup, and gastroenteritis.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

India, this magical land, has irresistibly captivated crowds of visitors because of definite motives: incredible Indian charms, numerous residues of past ages, and various sacred points for pilgrimage. Tourism in India has always been among the most full-blown spheres of the state's politics. India tourism allows traveling to all the most famous places, you may wish to visit. Among them, there are illustrious palaces and groves, forts built in both oriental and English colonial manners, and...

Today you can save up to 30 percent on select laptops, networking devices, and storage drives at Amazon. Also, the highly anticipated game Cyberpunk 2077 is $10 off when you pre-order it.

A survey of educators around the country found that many reported looking up interventions on their own, when they really wanted more formal training, a survey found.

Arizona's ambitious expansion of its school voucher program has officially been put on hold after opponents filed enough signatures to at least temporarily block the new law.

Already home to a thriving ecosystem of private school choice, the state’s lawmakers want vouchers for thousands of new students.

Tamara D. Simon
Oct 1, 2010; 126:647-655
ARTICLES

Teacher performance pay may soon be coming to the Cornhusker State.

Penn State Brandywine students who have impacted the campus through their leadership and service have been honored with student leadership awards. The annual awards program highlights the achievements of students involved with clubs, student government and campus programs

If warming continues unabated in the Midwest, in 50 years we can expect the best conditions for corn and soybean production to have shifted from Iowa and Illinois to Minnesota and the Dakotas, according to Penn State researchers.

Dylan Fredricey, a senior majoring in rehabilitation and human services, has been chosen as the recipient of the Outstanding Adult Learner of the Year award for Penn State Wilkes-Barre.

Thank you Marissa Bufalini, Trisha Everhart, Donald Natale, Vickie Clauer, Holly Seidel, Deb Sam and Jill Blonski — and to everyone who helps make Penn State such an incredible community. We Are!

Student Wellness Project offers help and support to Penn State York students during time away from campus, and remote learning.

Members of a Holyrood Committee have visited the shipyard where two overdue and over-budget vessels to serve the Clyde and Hebrides ferries network are being built.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

JooYoung Seo, a doctoral candidate in the College of Education’s Learning, Design, and Technology program, has secured a highly competitive internship with RStudio that will allow him to help people just like himself — those with severe visual impairments.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

Cleaning up after class turns into a moment of sharing between an OM worker and two North African women.

While reaching out to Turks in France, one long-term worker feels like Apostle Paul: preaching in house churches and getting kicked out of a mosque.

When parents or guardians hope for a miracle for their child who is critically ill, ethical and professional challenges can arise. Often, although not always, the parent or guardian’s hope for a miracle entails a request for continued life-sustaining interventions. Striking a balance between the pediatrician’s conception of good medicine and the parent or guardian’s authority requires a response that is sensitive, practical, and ethically sound. In this article, we recommend 3 cumulative steps that promote such a response. First, we recommend ways of exploring essential issues through open inquiry, interdisciplinary dialogue, and self-reflection. As part of this exploration, pediatricians will discover that parents or guardians often have unique ideas about what a miracle might be for their child. The second step includes analyzing this diversity and seeking understanding. We classify the hope for a miracle into 3 distinct categories: integrated, seeking, and adaptive. After the pediatrician has categorized the parent or guardian’s hope, they can consider specific recommendations. We detail context-specific responses for each kind of hope. By attending to these nuances, not only will the parent or guardian’s perspective be heard but also the pediatrician’s recommendation can strike a balance between advocating for their conception of good medicine and respecting the parent or guardian’s beliefs.

Source: www.youtube.com - Friday, May 08, 2020

Calls to fully fund the nation's main special education law resound on the campaign trail, but a complex array of factors make that an elusive goal.

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

A man thought he understood how life worked until he had a conversation with OM workers in Bangladesh. Then Jesus changed his life.

An executive order signed this week is meant to address concerns of anti-Semitism on college and university campuses. But the legal underpinnings of that order apply to elementary and secondary schools, too.

Doron's experience on Logos Hope shows him God's faithfulness and uncovers leadership abilities he is using today in a new role.

Defying the notion that business-focused smartphones need to be clunky and thick, Samsung's Galaxy XCover Pro is thin, light, and durable. Use it as a walkie-talkie, a mobile point-of-sale (POS) system, and however you get work done.

Minister of Public Enterprises Pravin Gordhan would not have committed to the framework of his 'Leadership Compact' if he did not know where the money would come from, the Labour Court heard.

The House appropriations committee voted Wednesday to advance a bill providing a slight funding increase for the U.S. Department of Education, bringing overall funding to about $71 billion.

Downtown revitalization efforts in Wilmington, Dover and Seaford continue to gain momentum, with new projects in all three counties slated to receive funding from Delaware’s Downtown Development Districts program.

$4.5 million in grant funding for 11 projects will leverage $130 million in private investment DOVER, DE — Building on progress in Delaware’s downtowns, Governor Jack Markell and the Delaware State Housing Authority announced on Monday that 11 new downtown revitalization projects in Wilmington, Dover and Seaford will receive $4.5 million in grant funding through […]

$3.6 million in grant funding for 16 projects to leverage $38.6 million in private investment MILFORD – Building on progress in Delaware’s downtowns, Governor Jack Markell and the Delaware State Housing Authority announced on Tuesday that sixteen new downtown revitalization projects in Harrington, Milford, Dover, Smyrna and Wilmington will receive $3.56 million in grant funding […]

WILMINGTON (January 28, 2019) – Delaware State Housing Authority (DSHA) and Federal Home Loan Bank of Pittsburgh (FHLBank Pittsburgh) announced today $1.2 million in Home4Good funding awarded to programs across the state working to reduce homelessness. DSHA provided $500,000 toward the effort, and FHLBank Pittsburgh provided $700,000. The funding will be used to address four key […]

SMYRNA – Building on progress in Delaware’s downtowns, Governor John Carney and the Delaware State Housing Authority (DSHA) announced today that eight new downtown revitalization projects in Milford, Dover and Wilmington will receive $4.6 million in rebate funding through Delaware’s Downtown Development Districts (DDD) program. Established in May 2014, the DDD program was created to […]

DOVER – Twelve downtown revitalization projects in Milford, Smyrna and Wilmington have been selected to receive funding through Delaware’s Downtown Development Districts (DDD) program, with $5.5 million in rebates leveraging $103 million in total investment, Governor John Carney and the Delaware State Housing Authority (DSHA) announced today. Established in May 2014, the DDD program was […]

DOVER – Delaware State Housing Authority (DSHA) and Federal Home Loan Bank of Pittsburgh (FHLBank Pittsburgh) announced today $1.2 million in Home4Good funding awarded to programs across the state working to reduce homelessness. DSHA provided $500,000 toward the effort, and FHLBank Pittsburgh provided $700,000. The funding will be used to address four key areas: homelessness […]