oni Global and Regional Burden of Isoniazid-Resistant Tuberculosis By pediatrics.aappublications.org Published On :: 2015-06-01T06:07:56-07:00 Fifteen percent of tuberculosis cases globally are resistant to the drug isoniazid. Isoniazid resistance puts patients with tuberculosis at risk for poor treatment outcomes and threatens the effectiveness of isoniazid preventive therapy in people with latent tuberculosis infection.We present the first global and regional estimates of the proportion of children with tuberculosis who have isoniazid-resistant disease, showing large geographic variations in risk of resistance. We estimate the number of annual incident cases of isoniazid-resistant tuberculosis in children. (Read the full article) Full Article
oni Antibiotic Choice for Children Hospitalized With Pneumonia and Adherence to National Guidelines By pediatrics.aappublications.org Published On :: 2015-06-22T00:06:54-07:00 The 2011 national guidelines for the management of pediatric community-acquired pneumonia recommended narrow-spectrum antibiotic therapy (eg, ampicillin) for most children hospitalized with pneumonia. Before the release of the guidelines, the use of broader-spectrum antibiotics (eg, third-generation cephalosporins) was much more common.After release of the guidelines, third-generation cephalosporin use declined and penicillin/ampicillin use increased among children hospitalized with pneumonia. Changes were most apparent among institutions that proactively disseminated the guidelines, underscoring the importance of local efforts for timely guideline implementation. (Read the full article) Full Article
oni Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome By pediatrics.aappublications.org Published On :: 2015-07-27T00:08:19-07:00 Stevens-Johnson syndrome (SJS) is a rare and severe immunologic phenomenon characterized by rash and mucous membrane disease. SJS may be triggered by medications and, less commonly, by infections such as Mycoplasma pneumoniae (Mp). Outbreaks of SJS are exceedingly rare.We describe the largest SJS outbreak reported in children, which was also Mp-associated. In the first case-control study of this disease, we identify predictors of Mp-associated SJS versus non–Mp-associated SJS, including fewer skin lesions, pneumonia, and elevated erythrocyte sedimentation rate. (Read the full article) Full Article
oni Psychosocial Factors Associated With Adolescent Electronic Cigarette and Cigarette Use By pediatrics.aappublications.org Published On :: 2015-07-27T00:08:18-07:00 Electronic cigarette (e-cigarette) use in adolescence is increasing. E-cigarette use has been associated with cigarette use, but there has been little study of other psychosocial risk factors for e-cigarette use and their relationship with cigarette use.Approval and use of e-cigarettes and cigarettes among friends and family were strongly associated with cigarette and e-cigarette use in a cohort of adolescents in southern California. (Read the full article) Full Article
oni Outcome of Patients Initiating Chronic Peritoneal Dialysis During the First Year of Life By pediatrics.aappublications.org Published On :: 2015-08-24T00:07:08-07:00 Historically, children with end-stage renal disease who initiated chronic dialysis during the first year of life were far less likely to survive or successfully receive a kidney transplant compared with those who initiated chronic dialysis at older ages.In recent years, survival has improved markedly among children who initiate chronic peritoneal dialysis at <1 year of age. Among those infants who initiate dialysis after the neonatal period and later undergo kidney transplantation, graft survival has improved as well. (Read the full article) Full Article
oni High School Students' Use of Electronic Cigarettes to Vaporize Cannabis By pediatrics.aappublications.org Published On :: 2015-09-07T00:07:57-07:00 Electronic cigarette use among youth is rising exponentially. Among other concerns, modified electronic cigarettes can be used to vaporize cannabis. However, no scientific data have been published on the rates of using electronic cigarettes to vaporize cannabis among youth.This study presents rates of vaporizing cannabis among a sample of high school students (N = 3847). Rates of vaporizing cannabis were high among lifetime e-cigarette users (18.0%), lifetime cannabis users (18.4%), and lifetime dual cannabis and e-cigarette users (26.5%). (Read the full article) Full Article
oni Weight Gain, Executive Functioning, and Eating Behaviors Among Girls By pediatrics.aappublications.org Published On :: 2015-09-21T00:07:36-07:00 Executive functioning and excess weight have been associated in both cross-sectional and prospective studies, but mechanisms explaining this relationship are unclear.Impulsivity and planning at age 10 predicted age 10 to 16 BMI changes, and age 12 binge-eating tendencies mediated the relation between impulsivity at age 10 and changes in BMI change through age 16. (Read the full article) Full Article
oni Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life By pediatrics.aappublications.org Published On :: 2015-09-21T00:07:35-07:00 Neurodevelopmental outcomes after cardiac surgery in early life provide critical information for understanding and improving care. Studies show these children are at risk for arterial ischemic stroke and acquired brain injury; further characterization of motor impairment is needed.This study focuses on the presence of chronic neuromotor disabilities including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery, providing information on the frequency, characteristics, and predictors that may assist in prevention. (Read the full article) Full Article
oni Hospital Use in the Last Year of Life for Children With Life-Threatening Complex Chronic Conditions By pediatrics.aappublications.org Published On :: 2015-10-05T00:07:47-07:00 Children with life-threatening complex chronic conditions (LT-CCCs) experience high hospital use.Hospital use in the last year of life for these children varies by type and number of LT-CCCs. Most children with ≥3 LT-CCCs are admitted to the hospital for more than 2 months in the last year of life. (Read the full article) Full Article
oni Voronin's shooting guide By www.uefa.com Published On :: Thu, 01 Mar 2012 07:13:00 GMT FC Dinamo Moskva's Ukrainian forward star Andriy Voronin offers you his shooting tips. Full Article
oni Struggle for a Functioning Congo By feedproxy.google.com Published On :: Thu, 03 Aug 2006 22:00:00 GMT Full Article
oni Francophonie : aller ou ne pas aller à Kinshasa By feedproxy.google.com Published On :: Sun, 01 Jul 2012 22:00:00 GMT François Hollande semble hésiter à se rendre à Kinshasa en octobre pour le sommet de la francophonie. Il serait bien inspiré de ne pas offrir au président, Joseph Kabila, une telle occasion de s’afficher réconcilié avec les démocraties après les élections présidentielle et législative calamiteuses en République démocratique du Congo (RDC) qui privent le régime d’une véritable légitimité démocratique. En se rendant à Kinshasa, François Hollande enverrait un message plus que trouble aux pays d’Afrique où la démocratisation est encore une lutte quotidienne que l’on paie au prix du sang. Full Article
oni In Vitro and In Vivo Characterization of Potent Antileishmanial Methionine Aminopeptidase-1 Inhibitors [Experimental Therapeutics] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 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 MetAP1LM 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. Full Article
oni MK-571, a cysteinyl leukotriene receptor-1 antagonist, inhibits hepatitis C virus (HCV) replication [Antiviral Agents] By aac.asm.org Published On :: 2020-03-16T08:17:37-07:00 The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC50 of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log10. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle. Full Article
oni Impact of KPC-production and high-level meropenem resistance on all-cause mortality of ventilator-associated pneumonia in association with Klebisella pneumoniae [Clinical Therapeutics] By aac.asm.org Published On :: 2020-03-23T08:47:35-07:00 Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used. Full Article
oni 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
oni Towards harmonization of voriconazole CLSI and EUCAST breakpoints for Candida albicans using a validated in vitro pharmacokinetic/pharmacodynamic model [Susceptibility] By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 Background. CLSI and EUCAST susceptibility breakpoints for voriconazole and C. albicans differ by one dilution (≤0.125 and ≤0.06 mg/l, respectively) whereas the epidemiological cutoff values (ECOFF/ECV) with both methodologies are the same (0.03 mg/L). We therefore determined the pharmacokinetic-pharmacodynamic (PK/PD) breakpoints of voriconazole against C. albicans for both methodologies with an in vitro PK/PD model, which was validated using existing animal PK/PD data.Methods. Four clinical wild-type and non-wild-type C. albicans isolates (voriconazole MICs 0.008-0.125 mg/l) were tested in an in vitro PK/PD model. For validation purposes, mouse PK were simulated and in vitro PD were compared with in vivo outcome. Human PK were simulated and the exposure-effect relationship fAUC0-24/MIC was described for EUCAST and CLSI24/48h methods. PK/PD breakpoints were determined using the fAUC0-24/MIC associated with half-maximal activity (EI50) and Monte Carlo simulation analysis.Results. The in vitro 24h-PD EI50 of voriconazole against C. albicans were 2.5-5 (1.5-17) fAUC/MIC. However, the 72h-PD were higher, 133 (51-347) fAUC/MIC for EUCAST and 94 (35-252) fAUC/MIC for CLSI. The mean (95% confidence interval) probability of target attainment (PTA) was 100(95-100)%, 97(72-100)%, 83(35-99)%, and 49(8-91)% and 100(97-100)%, 99(85-100)%, 91(52-100)% and 68(17-96)% for EUCAST and CLSI MICs 0.03, 0.06, 0.125, and 0.25 mg/L, respectively. Significantly, >95% PTAs were found for EUCAST/CLSI MICs ≤0.03 mg/ll. For MICs 0.06-0.125 mg/l trough levels 1-4 mg/ll would be required.Conclusion. A PK/PD breakpoint of C. albicans voriconazole at the ECOFF/ECV of 0.03 mg/L was determined for both EUCAST/CLSI methods, indicating the need for breakpoint harmonization for the reference methodologies. Full Article
oni Proteomic changes of Klebsiella pneumoniae in response to colistin treatment and crrB mutation-mediated colistin resistance [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance. Full Article
oni Pharmacodynamics of Cefepime Combined with the Novel Extended-Spectrum Beta Lactamase (ESBL) Inhibitor Enmetazobactam for Murine Pneumonia caused by ESBL-Producing Klebsiella pneumoniae [Pharmacology] By aac.asm.org Published On :: 2020-04-06T08:49:25-07:00 Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUCELF:AUCplasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia. Full Article
oni Imipenem population pharmacokinetics: therapeutic drug monitoring data collected in critically ill patients with or without extracorporeal membrane oxygenation [Pharmacology] By aac.asm.org Published On :: 2020-04-06T08:49:26-07:00 Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens. Full Article
oni Therapeutic efficacy of a mixed formulation of conventional and PEGylated liposomes containing meglumine antimoniate, combined with allopurinol, in dogs naturally infected with Leishmania infantum [Experimental Therapeutics] By aac.asm.org Published On :: 2020-04-13T08:15:31-07:00 Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis. Full Article
oni Genetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis in Mongolia [Epidemiology and Surveillance] By aac.asm.org Published On :: 2020-04-20T08:36:47-07:00 Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations. The GenoType® MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType® MTBDRplus assay, 127 (31.1%) were resistant to rifampicin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and two (0.5%) strains had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 trains with any inhA mutation, 290 (98.0%) had a C–15T mutation. The proportion of isoniazid-resistant strains with katG mutations was 25.3% among new cases and 36.2% among retreatment cases (p=0.03), as well as 17.0% among rifampicin-susceptible strains and 52.8% among rifampicin-resistant strains (p<0.01). Rifampicin resistance was significantly associated with the katG mutation (adjusted odds ratio 5.36, 95% CI 3.3–8.67, p<0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than that among new cases, and that in cases with rifampicin resistance was higher than that in cases without rifampicin resistance. Full Article
oni 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
oni 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
oni RHSU Classic: How Education Philanthropy Can Accidentally Promote Groupthink and Bandwagonism By feedproxy.google.com Published On :: Mon, 17 Feb 2020 00:00:00 +0000 In number 10 in our countdown, I tried to offer a few thoughts to funders as they embraced new agendas and looked to avoid repeating yesterday's missteps. Full Article Philanthropy
oni Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND AND OBJECTIVES: Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED). METHODS: We performed a prospective cohort study of children (ages 3 months–18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7–15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription. RESULTS: Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45–2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures. CONCLUSIONS: Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription. Full Article
oni Efficacy of Melatonin in Children With Postconcussive Symptoms: A Randomized Clinical Trial By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND: Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo. METHODS: We conducted a randomized, double-blind trial of 3 or 10 mg of melatonin compared with a placebo (NCT01874847). We included youth (ages 8–18 years) with PPCS at 4 to 6 weeks after mild traumatic brain injury. Those with significant medical or psychiatric histories or a previous concussion within the last 3 months were excluded. The primary outcome was change in the total youth self-reported Post-Concussion Symptom Inventory score measured after 28 days of treatment. Secondary outcomes included change in health-related quality of life, cognition, and sleep. RESULTS: Ninety-nine children (mean age: 13.8 years; SD = 2.6 years; 58% girls) were randomly assigned. Symptoms improved over time with a median Post-Concussion Symptom Inventory change score of –21 (95% confidence interval [CI]: –16 to –27). There was no significant effect of melatonin when compared with a placebo in the intention-to-treat analysis (3 mg melatonin, –2 [95% CI: –13 to 6]; 10 mg melatonin, 4 [95% CI: –7 to 14]). No significant group differences in secondary outcomes were observed. Side effects were mild and similar to the placebo. CONCLUSIONS: Children with PPCS had significant impairment in their quality of life. Seventy-eight percent demonstrated significant recovery between 1 and 3 months postinjury. This clinical trial does not support the use of melatonin for the treatment of pediatric PPCS. Full Article
oni Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma By pediatrics.aappublications.org Published On :: 2020-04-01T01:00:57-07:00 BACKGROUND AND OBJECTIVES: The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. METHODS: We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A P value <.05 was considered significant. RESULTS: A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .001). CONCLUSIONS: BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization. Full Article
oni Campaign Monitor By www.pcmag.com Published On :: Campaign Monitor is a satisfactory marketing tool, especially with email marketing features and analytics, but it trails the competition in areas like direct online support. Full Article
oni Deals: Lenovo Flex 14, Dell Gaming Monitor, New Nintendo Switch By www.pcmag.com Published On :: Today you can save $120 on the Lenovo Flex 14 2-in-1 laptop. Also, the 24-inch Dell S2419HGF 1080p monitor dropped is now just $149.99. Finally, the new Nintendo Switch, featuring improved battery life, is now available. Full Article
oni Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia By pediatrics.aappublications.org Published On :: 2020-04-01 Matthew J. LipshawApr 1, 2020; 145:e20193138-e20193138ARTICLES Full Article
oni Coronavirus May Disrupt TV, Laptop, and PC Monitor Production By www.pcmag.com Published On :: Research firm IHS Markit expects the display panel factories in Wuhan, China, to struggle to resume full production when the Chinese New Year holiday ends on Feb. 2. As a result, supplies for panels for TVs and PCs are expected to be tight in the ensuing months. Full Article
oni Veteran's Day Deals: Netgear Router, Apple AirPods, Dell Monitor By www.pcmag.com Published On :: The popular Netgear Nighthawk R6700 wireless router is just $68 right now. Plus, you can save on a 32-inch Dell monitor and Apple AirPods with the wireless charging case. Full Article
oni Is Chronic Lung Disease in Low Birth Weight Infants Preventable? A Survey of Eight Centers By pediatrics.aappublications.org Published On :: 1987-01-01 Mary Ellen AveryJan 1, 1987; 79:26-30ARTICLES Full Article
oni Children With Complex Chronic Conditions in Inpatient Hospital Settings in the United States By pediatrics.aappublications.org Published On :: 2010-10-01 Tamara D. SimonOct 1, 2010; 126:647-655ARTICLES Full Article
oni Abington nutritionist shares science behind nutrition By news.psu.edu Published On :: Fri, 10 Apr 2020 11:16 -0400 Despite what people may read or hear from friends and family, there are no magical foods or pills that are guaranteed to protect against COVID-19, according to Wendy Richman, who teaches nutrition at Penn State Abington. Full Article
oni European football stands united against COVID-19 crisis: North Macedonia By www.uefa.com Published On :: Fri, 17 Apr 2020 23:28:26 GMT National team and staff raise money for health service Full Article national association
oni SideTrak Portable Monitor By www.pcmag.com Published On :: The cleverly designed SideTrak Portable Monitor gives you a second screen that can stay attached to your laptop, even while traveling. Full Article
oni Deals: 32-Inch Monitor, 2TB Seagate Drive, Arlo Pro 2 By www.pcmag.com Published On :: A popular 32-inch Dell 1080p IPS monitor is back at $150, the 2TB Seagate expansion is only $55, and the Netgear Arlo Pro 2 four-camera kit is just $400. Full Article
oni Deals: Samsung Monitors, Tablets, Dell XPS 15, Nintendo Switch By www.pcmag.com Published On :: Amazon is offering up to 34 percent off Samsung monitors and tablets today. Plus, you can save on the Dell XPS 15 and pre-order Nintendo Switch Animal Crossing: New Horizons Edition. Full Article
oni ViewSonic Elite XG270QG By www.pcmag.com Published On :: ViewSonic's Elite XG270QG gaming monitor delivers everything that 1440p gamers could want, and a bunch more. It's a premium panel that, despite the price, still packs tremendous value for serious high-speed play. Full Article
oni The Best Computer Monitors for 2020 By www.pcmag.com Published On :: The right display will help you make the most of your movies, your games, or your work. Here's everything you need to know when shopping for a new one. Plus, see the best monitors we've tested at a variety of sizes and price levels, backed by hundreds of deep-dive reviews. Full Article
oni The Best Gaming Monitors for 2020 By www.pcmag.com Published On :: Elevate your game with a gaming monitor that plays as hard as you do. These are the key things to look for in a gaming display, along with our top-ranked models. We've got deep-dive reviews of the best gaming monitors on the market. Full Article
oni The Best 4K Monitors for 2020 By www.pcmag.com Published On :: Fast becoming staples on the desks of gamers and creative pros, 4K monitors are falling in price—but getting more complicated to buy. Here's how to shop for an ultra-high-definition (UHD) display, plus our top picks, backed by deep-dive reviews. Full Article
oni Dell 27 USB-C Monitor (P2720DC) By www.pcmag.com Published On :: The Dell 27 USB-C Monitor (P2720DC) offers a broad port selection, a range of ergonomic features, and bright, realistic-looking colors. Its practically automatic daisy-chaining to a second display is a bonus. Full Article
oni Westinghouse 32-Inch Ultra HD Home/Office Monitor By www.pcmag.com Published On :: Westinghouse's 32-Inch Ultra HD Home/Office Monitor has some color-accuracy shortfalls and a limited feature set, but it does get you a large-screen 4K display at an affordable price. Full Article
oni The Best Portable Monitors for 2020 By www.pcmag.com Published On :: Whether you're a traveling exec, a gamer, or a graphic designer, a portable second monitor can add both screen room and an extra dimension to your work or play. We tested most of the majors on the market. Full Article
oni The Best Computer Monitors for Business in 2020 By www.pcmag.com Published On :: Tasked with buying a squadron of desktop LCD monitors for your employees, or just one for a special task? Here's what you need to know, along with our top-rated, lab-tested picks all across the price spectrum. Full Article
oni Lucy Calkins, Creator of Reading Workshop, Responds to 'Phonics-Centric People' By feedproxy.google.com Published On :: Wed, 27 Nov 2019 00:00:00 +0000 One of the giants of the literacy world is grappling with the recent push for the "science of reading"—and responding to critics who say her early reading program doesn't align to evidence-based practice. Full Article Reading
oni ViewSonic Elite XG270 By www.pcmag.com Published On :: Another new monitor and another win for ViewSonic, the Elite XG270 shares much of its DNA with the Editors' Choice XG270QG, and helps to move the entire category of gaming displays forward with screaming speeds and beautiful picture quality. Full Article