ses Status update on Abington, Brandywine and Great Valley campuses By news.psu.edu Published On :: Wed, 25 Mar 2020 22:07 -0400 With Pennsylvania Gov. Tom Wolf’s March 25 “Stay at Home” order, Penn State is updating the status of its Abington, Brandywine and Great Valley campuses. Full Article
ses Students Build Tiny Houses to Bring Geometry Lessons to Life By feedproxy.google.com Published On :: Tue, 30 Apr 2019 00:00:00 +0000 At Battle High School in Columbia, Mo., students in geometry class have swapped their compasses and protractors for hammers and hard hats. And they're doing it for a good cause. Full Article Mathematics
ses Supreme Court Hears Three Cases on Rights Of LGBT Employees By feedproxy.google.com Published On :: Tue, 22 Oct 2019 00:00:00 +0000 On the first week of its new term, the U.S. Supreme Court held two hours of intense arguments about whether the main federal job-discrimination law protects gay, lesbian, and transgender employees. Full Article Gender
ses Penn College alumna uses gaming for goodwill By news.psu.edu Published On :: Tue, 25 Feb 2020 10:09 -0500 Anna-Maree Manciet is one of the estimated 164 million adult gamers. But for the Pennsylvania College of Technology alum, gaming is much more than entertainment. It’s a source of goodwill, both for herself and countless others. Since graduating from Penn College in 2013, Manciet’s video game prowess has led to personal healing, a thriving career and nearly $88,000 raised for St. Jude Children’s Research Hospital in Memphis, Tennessee. Full Article
ses Penn College offers discounted Building Operator Certification courses By news.psu.edu Published On :: Tue, 10 Mar 2020 16:39 -0400 The National Sustainable Structures Center of Pennsylvania College of Technology, the mid-Atlantic administrator of the Building Operator Certification, will offer two BOC Level I courses at a 75% discount made possible by a grant from the Pennsylvania Department of Environmental Protection. Full Article
ses Kudzu Bricks, Tiny Homes, and Glow-in-the-Dark Horseshoes: Innovation in Rural Kentucky Schools By feedproxy.google.com Published On :: Fri, 13 Sep 2019 00:00:00 +0000 In rural Kentucky, teachers and students are awarded innovation grants to solve a challenge facing their community or classroom. Full Article Professionaldevelopment
ses Score a Nikon DSLR Camera, Two Lenses For Less Than $600 By www.pcmag.com Published On :: This bundle normally sells for $1,149.95 but is available right now for just $596.95, and it will arrive before Christmas with Prime. Full Article
ses Canon Releases Details on Flagship EOS-1D X Mark III SLR By www.pcmag.com Published On :: Canon is lifting the lid on the tech inside its upcoming EOS-1D X Mark III SLR. It's a fully pro, and fully loaded camera, with 20fps Raw imaging and 5.5K Raw video capture. Full Article
ses Fin24.com | WATCH: How would Saudi Arabia retaliate if US imposes sanctions? By www.fin24.com Published On :: Tue, 16 Oct 2018 10:38:46 +0200 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. Full Article
ses Fin24.com | OPINION | Beer for health workers, fashion face masks: How businesses innovate during Covid-19 By www.fin24.com Published On :: Mon, 04 May 2020 17:44:02 +0200 Where businesses are fighting to survive, agility is the name of the game, says Mignon Reynecke. Full Article
ses U.S. Department of Education OKs Modified Texas Assessment By feedproxy.google.com Published On :: Tue, 14 Jul 2009 00:00:00 +0000 Texas has become the first state to have its "alternate assessment aligned to modified academic-achievement standards" pass the U.S. Department of Education's peer-review process. Full Article Assessment+Accountability+Achievement
ses Is It Time for the American Approach to Assessment to Change? By feedproxy.google.com Published On :: Wed, 05 Sep 2018 00:00:00 +0000 The U.S. tests its students more than most nations, but is the deluge of data providing the information schools need? Full Article Assessment+Accountability+Achievement
ses Accountability and Assessment Systems By feedproxy.google.com Published On :: Sun, 20 Oct 2013 00:00:00 +0000 Helen Janc Malone introduces this week's blog theme, "accountability and assessment systems." She writes that at the heart of the current accountability debate is a fundamental question, What is the purpose of all the collected assessment data? Are they an end game or a starting point to educational Full Article Assessment+Accountability+Achievement
ses Throwback Thursday: Achievement, Assessment, and Accountability By feedproxy.google.com Published On :: Thu, 14 Aug 2014 00:00:00 +0000 If we continue to focus on student growth and improvement as learners, keep track of that progress, and watch its impact on standard test results, will we be able to know if what we are doing is helping students develop as learners and thinkers. Full Article Assessment+Accountability+Achievement
ses Education Week: Assessment, Accountability, Achievement By feedproxy.google.com Published On :: Sun, 16 Feb 2020 20:01:04 +0000 Full Article Assessment+Accountability+Achievement
ses Assessment, Accountability, Achievement By feedproxy.google.com Published On :: Fri, 02 Nov 2012 00:00:00 +0000 Full Article Assessment+Accountability+Achievement
ses Assessment of drug resistance during phase 2b clinical trials of presatovir in adults naturally infected with respiratory syncytial virus [Antiviral Agents] By aac.asm.org Published On :: 2020-02-18T08:15:40-08:00 Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes. Full Article
ses Biochemical Characterization of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo-Beta-Lactamases [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-09T08:34:13-07:00 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 Kis 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. Full Article
ses ZN148 - a modular synthetic metallo-{beta}-lactamase inhibitor reverses carbapenem-resistance in Gram-negative pathogens in vivo [Experimental Therapeutics] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound. Full Article
ses Metronidazole-Treated Porphyromonas gingivalis Persisters Invade Human Gingival Epithelial Cells and Perturb Innate Responses [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-23T08:47:35-07:00 Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. Porphyromonas gingivalis as a ‘keystone' periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis, and critically contributes to the pathogenesis of periodontitis. Persisters are a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and notably metronidazole-tolerant P. gingivalis persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated P. gingivalis persisters (M-PgPs) with human gingival epithelial cells (HGECs). P. gingivalis cells (ATCC 33277) at stationary phase were treated with lethal dosage of metronidazole (100 μg/ml, 6 hours) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling and qPCR. We demonstrated that the overall morphology and ultra-cellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade into HGECs. Moreover, M-PgPs significantly suppressed pro-inflammatory cytokine expression in HGECs at a comparable level with the untreated P. gingivalis cells, through the thermo-sensitive components. The present study reveals that P. gingivalis persisters induced by lethal treatment of antibiotics could maintain their capabilities to adhere to and invade into human gingival epithelial cells, and perturb the innate host responses. Novel strategies and approaches need to be developed for tackling P. gingivalis and favourably modulating the dysregulated immuno-inflammatory responses for oral/periodontal health and general wellbeing. Full Article
ses Spectrum of Beta-Lactamase Inhibition by the Cyclic Boronate QPX7728, an Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases: Enhancement of Activity of Multiple Antibiotics Against Isogenic Strains Expressing Single {beta} By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development. Full Article
ses The Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. [Mechanisms of Resis By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics. Full Article
ses Ceftazidime-avibactam resistance mediated by the N346Y substitution in various AmpC {beta}-lactamases [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-06T08:49:26-07:00 Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa. The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn346 of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N346Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI). The aim of this study was to phenotypically and biochemically characterize the consequences of the N346Y substitution in various AmpC backgrounds. Introduction of N346Y into Enterobacter cloacae AmpC (AmpCcloacae), plasmid-mediated DHA-1, and P. aeruginosa PDC-5, led to 270-, 12,000-, and 79-fold decreases in the inhibitory efficacy (k2/Ki) of avibactam, respectively. The kinetic parameters of AmpCcloacaeand DHA-1 for ceftazidime hydrolysis were moderately affected by the substitution. Accordingly, AmpCcloacaeand DHA-1 harboring N346Y conferred CAZ-AVI resistance (MIC of ceftazidime of 16 µg/ml in the presence of 4 µg/ml of avibactam). In contrast, production of PDC-5 N346Y was associated with a lower MIC (4 µg/ml) since this β-lactamase retained a higher inactivation efficacy by avibactam in comparison to AmpCcloacaeN346Y. For FOX-3, the I346Y substitution did not reduce the inactivation efficacy of avibactam and the substitution was highly deleterious for β-lactam hydrolysis, including ceftazidime, preventing CAZ-AVI resistance. Since AmpCcloacaeand DHA-1 display substantial sequence diversity, our results suggest that loss of hydrogen interaction between Asn346 and avibactam could be a common mechanism of acquisition of CAZ-AVI resistance. Full Article
ses A genotype-phenotype correlation study of SHV {beta}-lactamases - new insight into SHV resistance profiles [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-13T08:15:31-07:00 The SHV β-lactamases (BLs) have undergone strong allele diversification that changed their substrate specificities. Based on 147 NCBI entries for SHV alleles, in silico mathematical models predicted five positions as relevant for the β-lactamase inhibitor (BLI) resistant (2br) phenotype, 12 as relevant for the extended-spectrum BL (ESBL) (2be) phenotype, and two positions were related to solely the narrow spectrum (2b) phenotype. These positions and additional 6 positions described in other studies (including one promoter mutation), were systematically substituted and investigated for their substrate specificities in a BL-free E. coli background, representing, to our knowledge, the most comprehensive substrate and substitution analysis for SHV alleles to date. An in vitro analysis confirmed the essentiality of the positions 238 and 179 for the 2be phenotype and 69 for the 2br phenotype. The substitutions E240K and E240R, which do not occur alone in known 2br SHV variants, led to a 2br phenotype, indicating a latent BLI-resistance potential of these substitutions. The substitutions M129V, A234G, S271I and R292Q conferred latent resistance to cefotaxime. In addition, 7 positions that were found to be not always associated with the ESBL phenotype resulted in increased resistance to ceftaroline. We also observed that coupling of a strong promoter (IS26) to a A146V mutant with the 2b phenotype resulted in a highly increased resistance to BLIs, cefepime and ceftaroline but not to 3rd generation cephalosporins, indicating that SHV enzymes represent an underestimated risk for empirical therapies that use piperacillin/tazobactam or cefepime to treat different infectious diseases caused by gram-negatives. Full Article
ses Epidemiological study on prevalence, serovar diversity, multi-drug resistance and CTX-M-type extended-spectrum {beta}-lactamases of Salmonella spp. from patients with diarrhea, food of animal origin, and pets in several provinces of China [Epidemiology an By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 A total of 2,283 Salmonella spp. isolates were recovered from 18,334 samples including patients with diarrhea, food of animal origin and pets across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistant to ≥ 1 antimicrobial and 56.4% were multi-drug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), 200 of which were CTX-M-type that were mostly detected from chicken meat and turtle fecal. Overall, eight blaCTX-M genes were identified, with blaCTX-M-65, blaCTX-M-123, blaCTX-M-14, blaCTX-M-79, and blaCTX-M-130 being the most prevalent. Totally, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (and S80I), whilst the PMQR-encoding genes oqxA/B, qepA, and qnrB/S were detected in almost all isolates. Of the fifteen sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in the number of isolates. Our study revealed considerable serovars diversity, high prevalence of co-occurrence of MDR determinants, including CTX-M-type ESBLs, QRDRs mutations and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDRs mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in the health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M Salmonella spp. isolates. Full Article
ses Mutation of kvrA causes OmpK35/36 porin downregulation and reduced meropenem/vaborbactam susceptibility in KPC-producing Klebsiella pneumoniae. [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 Meropenem/vaborbactam resistance in Klebsiella pneumoniae is associated with loss of function mutations in the OmpK35 and OmpK36 porins. Here we identify two previously unknown loss of function mutations that confer cefuroxime resistance in K. pneumoniae. The proteins lost were NlpD and KvrA; the latter is a transcriptional repressor controlling capsule production. We demonstrate that KvrA loss reduces OmpK35 and OmpK36 porin production, which confers reduced susceptibility to meropenem/vaborbactam in a KPC-3 producing K. pneumoniae isolate. Full Article
ses Advanced quantification methods to improve the 18b dormancy model for assessing the activity of tuberculosis drugs in vitro. [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-27T08:14:57-07:00 One of the reasons for the lengthy tuberculosis (TB) treatment is the difficult to treat non-multiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our pre-clinical drug development pipeline. In most available dormancy models it takes a long time to create a dormant state and it is difficult to identify and quantify this non-multiplying condition.The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes non-multiplying after 10 days of streptomycin starvation, but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetic model to assess the difference in the activity of isoniazid, rifampicin, moxifloxacin and bedaquiline against log-phase growth compared to the non-multiplying M. tuberculosis subpopulation by CFU counting including a novel AUC-based approach as well as time-to-positivity (TTP) measurements.We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampicin and high dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value as it identifies a specific mycobacterial subpopulation that is non-culturable on solid media.In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline. Full Article
ses Population Pharmacokinetic Analyses for Omadacycline Using Phase 1 and 3 Data [Pharmacology] By aac.asm.org Published On :: 2020-04-27T08:14:56-07:00 Omadacycline, a novel aminomethylcycline antibiotic with activity against Gram-positive and -negative organisms, including tetracycline-resistant pathogens, received FDA approval in October, 2018 for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). A previously-developed population pharmacokinetic (PK) model based on Phase 1 intravenous and oral PK data was refined using data from infected patients. Data from 10 Phase 1 studies used to develop the previous model were pooled with data from three additional Phase 1 studies, a Phase 1b uncomplicated urinary tract infection study, one Phase 3 CABP study, and two Phase 3 ABSSSI studies. The final population PK model was a three-compartment model with first-order absorption using transit compartments to account for absorption delay following oral dosing and first-order elimination. Epithelial lining fluid (ELF) concentrations were modeled as a sub-compartment of the first peripheral compartment. A food effect on oral bioavailability was included in the model. Sex was the only significant covariate identified, with 15.6% lower clearance for females relative to males. Goodness-of-fit diagnostics indicated a precise and unbiased fit to the data. The final model, which was robust in its ability to predict plasma and ELF exposures following omadacycline administration, was also able to predict the central tendency and variability in concentration-time profiles using an external Phase 3 ABSSSI dataset. A population PK model, which described omadacycline PK in healthy subjects and infected patients, was developed and subsequently used to support pharmacokinetic-pharmacodynamic (PK-PD) and PK-PD target attainment assessments. Full Article
ses Combination Therapy Using Benznidazole and Aspirin During the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase [Clinical Therapeutics] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 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. Full Article
ses Fin24.com | JSE erases earlier gains as global economy exhibits more strain By www.fin24.com Published On :: Thu, 30 Apr 2020 18:14:24 +0200 The local bourse had managed to open firmer following a rally in Asian stocks in earlier trading. Full Article
ses Fin24.com | Oil rises for a fifth day with output cuts easing glut concern By www.fin24.com Published On :: Tue, 05 May 2020 09:15:12 +0200 Oil was headed for the longest run of daily gains in more than nine months on signs the worst of the supply glut may be over as production cuts start to take effect. Full Article
ses Fin24.com | Stocks rise despite record US job losses By www.fin24.com Published On :: Fri, 08 May 2020 18:25:47 +0200 The rand strengthened against the greenback as it peaked at a session high of R18.30 before it was recorded trading 1.41% firmer at R18.32/$ at 17.00 Full Article
ses Virtual tutoring and parent sessions available for local school district By news.psu.edu Published On :: Mon, 04 May 2020 15:42 -0400 Community and university leaders collaborate to help students and parents residing in the McKeesport Area School District. Full Article
ses Fitness instructors lead virtual classes during remote learning By news.psu.edu Published On :: Fri, 01 May 2020 21:28 -0400 Penn State Campus Recreation is now offering a library of more than 50 workouts online through YouTube as well as live classes that are held every business day on the Penn State Campus Recreation Instagram. Group fitness instructor Alexis "Lexi" Neimeyer talked about her experience on the transition to virtual fitness classes. Full Article
ses Student nurses are even more motivated to serve during COVID-19 By news.psu.edu Published On :: Tue, 05 May 2020 11:42 -0400 As the COVID-19 pandemic continues to spread across the nation, nurses worldwide are coming to the frontlines of health care to help patients every day. Penn State student nurses, Megan Lucas and Lorrie Youngs, are among the ones helping those in need and their experiences have reinforced their passions about becoming a nurse in the first place. Full Article
ses WD Teases Super-Fast 8TB Portable SSD, New Game Drives By www.pcmag.com Published On :: The 8TB SSD prototype includes SuperSpeed USB 20Gbps support; WD also showed off a portable Luxe drive with USB-C and five WD_Black drives for console and PC gamers Full Article
ses Rangers vice-chairman John Bennett criticises 'cynical tactics' of SPFL and insists issue not just Gers vs governing body By www.heraldscotland.com Published On :: Sat, 09 May 2020 11:32:31 +0100 Rangers vice-chairman John Bennett has criticised the SPFL for their 'cynical tactics' over their labelling of the club's dossier as a "smoking gun" - and insists the issue is not merely Gers vs the governing body. Full Article
ses Video showcases Penn State Berks’ impact on community By news.psu.edu Published On :: Wed, 29 Apr 2020 09:01 -0400 Watch Penn State Berks’ new video titled “One Community Impacting Many,” which showcases the depth and breadth of the college’s positive effects on the surrounding region. Full Article
ses The Efficacy of Bacillus Calmette-Guerin Vaccination of Newborns and Infants in the Prevention of Tuberculosis: Meta-Analyses of the Published Literature By pediatrics.aappublications.org Published On :: 1995-07-01 Graham A. ColditzJul 1, 1995; 96:29-35ARTICLES Full Article
ses Secondary Sexual Characteristics and Menses in Young Girls Seen in Office Practice: A Study from the Pediatric Research in Office Settings Network By pediatrics.aappublications.org Published On :: 1997-04-01 Marcia E. Herman-GiddensApr 1, 1997; 99:505-512ARTICLES Full Article
ses Blood Pressure Responses to Psychosocial Stress in Young Adults With Very Low Birth Weight: Helsinki Study of Very Low Birth Weight Adults By pediatrics.aappublications.org Published On :: 2009-01-26 Young adults born prematurely with very low birth weight (≤1500 g) have higher blood pressure than do their counterparts born at term. We tested whether they also have higher blood pressure reactivity to psychosocial stress, which may be a more-specific predictor of long-term cardiovascular morbidity. Systolic and diastolic blood pressure levels for 44 very low birth weight adults (mean age: 23.1 years; SD: 2.3 years) and 37 control subjects (mean age: 23.6 years; SD: 2.0 years) were measured through noninvasive finger photoplethysmography during a standardized psychosocial stress challenge (Trier Social Stress Test). Baseline and task values and their difference (ie, reactivity) served as outcome variables. In comparison with the control group, the very low birth weight group had 7.9 mm Hg higher diastolic blood pressure during the task and 4.8 mm Hg higher diastolic reactivity, with adjustment for gender and age, height, and BMI at testing. A similar trend was seen for systolic blood pressure during the baseline period and the task, but the group differences were not statistically significant. Our results indicate that very low birth weight is associated with elevated blood pressure reactivity to psychosocial stress and, therefore, may increase the risk of cardiovascular morbidity. Full Article
ses Amazon Teases Prime Day Deals on Speakers, Tablets, TVs, More By www.pcmag.com Published On :: On the tech front, expect deals on Alexa smart speakers and displays, Fire TV media streamers, Fire tablets, Kindle ebook readers, home security devices, TVs, gaming gear, printers, and more. Full Article
ses L.A. Proposes Linking Teacher Pay to Tests By feedproxy.google.com Published On :: Wed, 22 Mar 2000 00:00:00 +0000 The Los Angeles school district wants to pay teachers based on how much they improve their students' scores on standardized tests, an idea that has provoked a negative reaction from the teachers' union. Full Article Payforperformance
ses Abington offers 200+ online summer courses By news.psu.edu Published On :: Fri, 03 Apr 2020 09:55 -0400 Catch up or get ahead on credits by taking online courses at Penn State Abington this summer. Three sessions are offered and class sizes are small. Full Article
ses Penn State Extension extends free online courses offer through May 10 By news.psu.edu Published On :: Mon, 04 May 2020 11:06 -0400 Penn State Extension is extending its free online courses offer through May 10. Full Article
ses Barron discusses Penn State’s response to pandemic and actions for trustees By news.psu.edu Published On :: Fri, 08 May 2020 13:22 -0400 As the world continues to face the ongoing impacts of the global coronavirus pandemic, Penn State President Eric Barron outlined Friday the University’s actions over the past five months to address the challenges, protect the health and safety of the University community, and prepare for the future. Full Article
ses Brazilian Supreme Court to consider legalizing abortion in Zika cases By feedproxy.google.com Published On :: Mon, 20 Apr 2020 09:25:00 -0600 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. Full Article Americas
ses Argentine archbishop proposes measures to open country's churches amid coronavirus pandemic By feedproxy.google.com Published On :: Tue, 21 Apr 2020 15:15:00 -0600 Denver Newsroom, Apr 21, 2020 / 03:15 pm (CNA).- An Argentine archbishop has proposed 13 measures that would aim to allow churches to reopen churches during the coronavirus pandemic while reducing the risk of contagion. The proposal is an effort to balance safety and the need for Catholics to receive the Eucharist, Archbishop Víctor Fernández of La Plata said this week. In response to the pandemic, Argentina has been under lockdown since March 20. According to John Hopkins University, there are 3,031 confirmed cases of COVID-19 with 145 deaths in the country. Fernández said that although the Church is providing material sustenance to those hardest hit by the pandemic “when we think about sustaining the interior life of the faithful and encouraging its growth, we find ourselves in the serious difficulty of seeing them deprived of the Eucharist for a long time, and we can also foresee that this situation could last for several months.” In a letter dated April 19 and addressed to the conference’s executive committee, the bishop said the Second Vatican Council teaches that “no Christian community is built up if it is not rooted and centered on the celebration of the Holy Eucharist,” and that Saint John Paul II emphasized that the Mass “rather than an obligation, should be felt as a requisite deeply inscribed in Christian existence.” Fernández said the letter he sent puts together the suggestions of several bishops and that it is understandable “that many of the faithful are calling on us to find some way to make the Eucharist accessible again.” “We tell them that they can experience other forms of prayer, and they do, but as Saint John Chrysostom has said “’You can also pray in your home, however, you cannot pray the same way you do in church where the brethren are gathered together.’” Fernández noted that Pope Francis “teaches that God ‘in the culmination of the mystery of the Incarnation, chose to reach our intimate depths through a fragment of matter.’ It’s good that our faithful have learned that and so it’s not the same thing for them,” he said, adding that Catholics are eager “the food of the love that is the source of supernatural life.” “It won’t be easy to prove that this situation is lasting too long, nor can we simply wait till the pandemic is completely over,” the prelate noted. “We know that exposing yourself to infection is irresponsible especially because it involves exposing others to infection and indirectly could lead to a public health crisis that we don’t want to see in our country,” he said. Aiming to send “a clear message to our People of God to show that we’re truly concerned and that we intend to take some steps that would allow us to resolve this situation as soon as possible,” without neglecting “the health concerns of the authorities” Fernández proposed a series of obligatory measures to celebrate the Eucharist publicly: 1) Keep a distance of two meters between people to the side, front and back. This will require removing or closing off half the pews in the church. 2) No more than two people per pew. 3) Once the pews are occupied in that manner, no more people are to be allowed to enter the church. 4) In the churches where there is usually a lot of people in attendance, the number of Masses should be increased so the faithful can spread themselves out over Saturday and Sunday at different times. Given the prevalence and closeness of churches this will not involve using transportation. 5) Mass should not be celebrated publicly at the most frequently visited shrines due to the difficulty of establishing appropriate controls. 6) There should be no line for communion, instead the Eucharistic ministers should go to the people positioned at the ends of the pews and place the Eucharist in the hand. 7) Every Eucharistic minister should wash his hands with soap before and after and apply alcohol gel. 8) The sign of peace and any physical contact should be omitted. 9) Mass should last no more than 40 minutes. 10) People should leave the church progressively, not all at once, and avoid greeting each other. 11) No intentions should be taken at Mass time, only those previously received by phone, mail or messages. 12) Those people who because of their age are prevented from attending may receive Communion at home. 13) The dispensation from the Sunday obligation should be temporarily maintained so that people who prefer to exercise extreme caution don’t feel obliged to attend. The archbishop also pointed out in his letter that “if the economic impact has to be foreseen, it’s also appropriate to place a value on those things that provide consolation and strength to people during hard times.” A version of this story was first published by ACI Prensa, CNA's Spanish-language news partner. It has been translated and adapted by CNA. Full Article Americas
ses Brazil’s Supreme Court rejects effort to legalize abortion in Zika cases By feedproxy.google.com Published On :: Mon, 27 Apr 2020 16:35:00 -0600 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. Full Article Americas
ses Coronavirus Closes Apple's China-Based Retail Stores, Corporate Offices By www.pcmag.com Published On :: Retail stores, corporate offices, and contact centers in China are closed through February 9 as the coronavirus spreads globally. Apple's online store will remain open, though. Full Article