United States President Donald Trump told CBS’s 60 Minutes that he would added pressure on Saudi Arabia, vowing "severe punishment" should the kingdom’s leaders be linked to the disappearance of Washington Post columnist Jamal Khashoggi.

Saudi Arabia has begun an internal investigation into the disappearance of a prominent journalist at its Istanbul consulate and could hold people accountable if the evidence warrants it, according to a Saudi official.

US President Donald trump has suggested that 'rogue killers' may be behind the disappearance of journalist Jamal Khashoggi in Turkey.

An op-ed in Saudi-owned Al Arabiya news has warned of repercussions should the US impose sanctions on Saudi Arabia over the disappearance of journalist Jamal Khashoggi.

Los conflictos en los países pequeños suelen agravarse debido a la indiferencia internacional. Sin embargo, en el caso de la República Centroafricana (RCA), el problema es ligeramente distinto. Hay una importante presencia internacional en este Estado, pero los actores principales han decidido mantenerse al margen y esperar en vez de intervenir activamente en la crisis.

L’image de havre de paix dans une région en proie aux conflits dont bénéficiait le Cameroun a volé en éclats depuis l’irruption de Boko Haram en 2013 au nord du pays. Ce mouvement, devenu l’Etat islamique en Afrique de l’Ouest en mars 2015, revendique son affiliation à Daech. Néanmoins, l’apparition brutale et sanglante de ce djihadisme africain est moins liée à l’essor de Daech en Irak et en Syrie qu’aux bouleversements du paysage religieux de l’Afrique en général et du Cameroun en particulier.

QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC₅₀ range 1-3 nM) and carbapenemases such as KPC (IC₅₀ 2.9±0.4 nM) as well as class C P99 (IC₅₀ of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC₅₀ range 1-2 nM) as well as MBLs such as NDM-1 (IC₅₀ 55±25 nM), VIM-1 (IC₅₀ 14±4 nM) and IMP-1 (IC₅₀ 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k₂/K ranging from of 6.3 x 10⁴ (for P99) to 9.9 x 10⁵ M^-1 s^-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with K_is of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1_LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.

Malaria parasites invade and replicate within red blood cells (RBCs), extensively modifying their structure and gaining access to the extracellular environment by placing the plasmodial surface anion channel (PSAC) into the RBC membrane. Expression of members of the cytoadherence linked antigen gene 3 (clag3) family is required for PSAC activity, a process that is regulated epigenetically. PSAC is a well-established route of uptake for large, hydrophilic antimalarial compounds and parasites can acquire resistance by silencing clag3 gene expression, thereby reducing drug uptake. We found that exposure to sub-IC50 concentrations of the histone methyltransferase inhibitor chaetocin caused substantial changes in both clag3 gene expression and RBC permeability, reversing acquired resistance to the antimalarial compound blasticidin S that is transported through PSAC. Chaetocin treatment also altered progression of parasites through their replicative cycle, presumably by changing their ability to modify chromatin appropriately to enable DNA replication. These results indicate that targeting histone modifiers could represent a novel tool for reversing epigenetically acquired drug resistance in P. falciparum.

Continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRNI-A/FGKGS/T pfdhfr/pfdhps haplotypes including the pfdhps A581G and A613S/T mutations was high at delivery among post-SP treatment isolates (18.2%) compared to those of first-antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP); 6.1%; p = 0.03). Regarding the pfk13 marker gene, two non-synonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast-Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance on additional mutations associated with increased SP resistance as well as emergence of resistance against artemesinin derivatives.

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.

The rapid evolution of resistance in the malaria parasite to every single drug developed against it calls for the urgent identification of new molecular targets. Using a stain specific for the detection of intracellular amyloid deposits in live cells we have detected the presence of abundant protein aggregates in Plasmodium falciparum blood stages and female gametes cultured in vitro, in the blood stages of mice infected by Plasmodium yoelii, and in the mosquito stages of the murine malaria species Plasmodium berghei. Aggregated proteins could not be detected in early rings, the parasite form that starts the intraerythrocytic cycle. A proteomics approach was followed to pinpoint actual aggregating polypeptides in functional P. falciparum blood stages, which resulted in the identification of 369 proteins, with roles particularly enriched in nuclear import-related processes. Five aggregation-prone short peptides selected from this protein pool exhibited different aggregation propensity according to Thioflavin-T fluorescence measurements, and were observed to form amorphous aggregates and amyloid fibrils in transmission electron microscope images. The results presented suggest that generalized protein aggregation might have a functional role in malaria parasites. Future antimalarial strategies based on the upsetting of the pathogen's proteostasis and therefore affecting multiple gene products could represent the entry to new therapeutic approaches.

Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log₁₀ colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r²) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log₁₀ CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae.

The off-label use of third generation cephalosporin (3GC) during in ovo vaccination or vaccination of newly hatched chicks, was a common practice worldwide. CMY-2-producing Escherichia coli have been disseminated among broiler production. The objectives of this study were to determine the epidemiological linkage of bla_CMY-2-positive plasmids among broilers both within and outside Japan because grandparent stock and parent stock were imported in Japan. We examined the whole genome sequences of 132 3GC-resistant E. coli isolates collected from healthy broilers during 2002-2014. The predominant 3GC-resistance gene was bla_CMY-2, which was detected in the plasmids of 87 (65.9%) isolates. The main plasmid replicon types were IncI1-I (n=21; 24.1%), IncI (n=12; 13.8%), IncB/O/K/Z (n=28; 32.2%), and IncC (n=22; 25.3%). Those plasmids were subjected to gene clustering and network analyses and plasmid multi-locus sequence typing (pMLST). The chromosomal DNA of isolates was subjected to MLST and single nucleotide variant (SNV)-based phylogenetic analysis.

MLST and SNV-based phylogenetic analysis revealed high diversity of E. coli isolates. ST429 harboring bla_CMY-2-positive IncB/O/K/Z was closely related to isolates from broiler in Germany harboring bla_CMY-2-positive IncB/O/K/Z. pST55-IncI and pST12-IncI1-I and pST3-IncC were prevalent in western Japan. pST12-IncI1-I and pST3-IncC were closely related to those detected in E. coli isolates from chicken in American continent, whereas 26 IncB/O/K/Z were related to those in Europe. These data will be useful to reveal the whole picture of transmission of CMY-2-producing bacteria in and out of Japan.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Developed by physicians and neuroscientists, Apollo isn't the sleekiest of wearables—you might mistake it for a court-ordered ankle bracelet—but it put a little pep in my step, and is an interesting talking point, if nothing else.

The DnaBand sits on your wrist, scans the barcodes on food, compares it to your DNA, and flashes red if the food is a bad choice and green if it's a healthier option. It's only available in the UK right now, but co-founder Chris Toumazou has his sights set on LA.

Jessica L. Barrington-Trimis
May 1, 2020; 145:e20191652-e20191652
ARTICLES

Andrea T. Cruz
Apr 8, 2020; 0:peds.2020-0834v2-e20200834
COMMENTARY

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...

The 10,700-capacity Pabellón Príncipe Felipe in Zaragoza will host the UEFA Futsal Cup finals in April involving Spain's Inter FS and Barcelona plus Portugal's Sporting CP and Győr of Hungary.

People travelling to the UK will be quarantined for two weeks upon arrival as part of measures to prevent a second peak of the coronavirus pandemic.

Marcia E. Herman-Giddens
Apr 1, 1997; 99:505-512
ARTICLES

The National Council on Teacher Quality has found that the number of elementary programs teaching scientifically based reading instruction is increasing.

Nearly every state in the nation has experienced enrollment declines, with some states seeing steep declines of more than 50 percent.

The National Council on Teacher Quality has found that the number of elementary programs teaching scientifically based reading instruction is increasing.

CNA Staff, Mar 31, 2020 / 06:01 pm (CNA).- Local media in Nicaragua are reporting that despite the nation’s bishops’ conference suspending Mass and prohibiting large gatherings, the mayor of Granada is going ahead with an annual pilgrimage that the bishops had canceled.

For more than 150 years, Catholics in Nicaragua have venerated an image of Jesus del Rescate (Jesus of the Rescue) in Popoyuapa, near the city of Rivas. The image represents the crowning of thorns and the flogging of Christ.

Normally there is an annual pilgrimage to the image, which pilgrims make by wagon and on foot, during the "Week of Sorrows" that marks "the final stretch" of the time of Lent, according to ACI Prensa, CNA’s Spanish language news partner.

However, the bishops have said that this year it will not be possible to carry it out in the traditional way, given the coronavirus (COVID-19) pandemic.

Nevertheless, Julia Mena, mayor of Granada, has organized and funded a group of pilgrims to do the pilgrimage, providing them with food and personal hygiene supplies, according to the Nicaraguan news website Confidencial. The priest at the shrine told Confidencial that he has “no plans to receive the pilgrimage.”

The Nicaraguan Episcopal Conference has not commented publicly on the matter.

Nicaragua has five confirmed cases of COVID-19. The government has not yet decreed any kind of alert or emergency regarding the pandemic, nor has it ordered a suspension of classes, Confidencial reports.

The country’s Ministry of Health has maintained that the internal movements of travelers arriving from countries with outbreaks of coronavirus would not be restricted, La Prensa reports.

President Daniel Ortega has been president of Nicaragua since 2007, and oversaw the abolition of presidential term limits in 2014.

The Church had suggested that elections, which are not scheduled until 2021, be held this year, but Ortega has ruled this out.

Ortega was a leader in the Sandinista National Liberation Front, which had ousted the Somoza dictatorship in 1979 and fought US-backed right-wing counterrevolutionaries during the 1980s. Ortega was also leader of Nicaragua from 1979 to 1990.

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.

Google has said that privacy and security are the focus for Android Q and many of its other releases this year, but Senior Security Analyst Max Eddy explains that a company built on mapping and sorting data can't deliver perfect privacy.

Tara Laubenstine comes from a long line of Penn Staters. When she began her college search, she knew exactly where she would apply and eagerly wait to be accepted. This week, she will graduate with her bachelor’s degree in business with a minor in psychology, after which she will pursue a career in human resource management. She made the most of her college experience by becoming involved, and with graduation on the horizon, Laubenstine sat down to speak about her college experience and offer advice to the incoming class.

Türkiye devleti ile uluslararası alanda terör örgütü olarak kabul edilen PKK arasındaki çözüm sürecinin çökmesi, Temmuz 2015’te çatışmaların yeniden başlaması ve daha sonra derinleşen şiddet sarmalı, yeni bir çözüm sürecinin inşasını hiç olmadığı kadar gerekli kılıyor.

Source: www.bitsandpieces.us - Friday, May 08, 2020
via

Don't rely on Facebook's self-regulation to save us from election interference in this year's critical elections. In fact, despite a PR push to the contrary, the company is doubling down on the access it sells to would-be meddlers.

Source: www.youtube.com - Wednesday, May 06, 2020

A tweet from the former president about education's role in addressing inequality and lack of opportunities drew split reactions and a chance to review his record and where K-12 stands in the political sphere.

As the wife of former President George H.W. Bush, she used the bully pulpit of her office as first lady to advance the issue on behalf of both for children and parents.

Relaxed travel begins at home. This also includes the correct packing of your luggage.

Sitting the second-generation CineBeam Laser 4K project two inches away from a wall allows for a 90-inch display to be projected. However, increasing the wall distance to seven inches allows the screen size to grow to 120-inches. Expect to see it on display at CES 2019.

Internal documents reveal Amazon sees this as a health and wellness product that's voice-activated and controlled via a smartphone app.

With designer brands like Michael Kors and Puma unveiling their first fitness-centric smartwatches, it's clear athleisure was the trend in Berlin this year.

Apple reported a whopping $65 billion in revenue in Q3. The tech giant's growth is largely due to its Apple Watch and AirPods sales, along with recurring subscriptions from its ever-expanding portfolio of services.

Amid rumors of Apple's upcoming AR glasses, head-mounted displays are looking to be the highest-growth category.

With Penn State Scranton students now into their sixth week of stay-at-home restrictions due to the COVID-19 pandemic, Campus Counselor Katherine Stefanelli offers some tips on how to deal with the stress, anxiety and loneliness that some may be feeling.

Even in this extraordinary #MeToo era, ordinary women who've experienced harassment or assault at work are often reluctant to share their stories publicly. Arianna Prothero found that to be just as true as she reported on sexual harassment and assaults in schools and other K-12 workplaces.

A new study shows that teachers with negative parental interactions are more likely to have such experiences. How can teachers deal with parental harassment?

A Maryland woman who caused a fatal crash while driving under the influence of drugs has been sentenced to prison. Deputy Attorneys General Barzilai Axelrod and William Leonard secured the sentence for Michelle Park, 35, of Earlville. In March 2018, with her 2-year-old child in the car, Park failed to negotiate a curve while driving […]