Pediatric obstructive sleep apnea syndrome (OSAS) has been associated with decreased health-related quality of life (QoL). Observational studies suggest that adenotonsillectomy for pediatric OSAS improves QoL, but these studies did not use a randomized study design or a control group of children with OSAS managed nonsurgically.

A prospective, randomized controlled study of adenotonsillectomy for pediatric OSAS showed significantly greater QoL and symptom improvements in children undergoing adenotonsillectomy than in the nonsurgical control arm. The extent of improvement was not appreciably influenced by baseline OSAS severity or obesity. (Read the full article)

Increased central adrenergic activity occurs with opiate withdrawal. Clonidine is an effective drug as an adjunct to morphine in the treatment of neonatal abstinence syndrome. It is unclear whether clonidine is effective as single-drug therapy.

Clonidine, a α₂-adrenergic agonist, seems to be as effective as morphine when used as a single-drug therapy for neonatal abstinence syndrome. Its administration results in improvement in neurobehavioral performance. (Read the full article)

In adults, adverse drug events account for 5% to 25% of all hospital admissions and 12% of emergency department (ED) visits of which 50% to 70% are preventable. There remains a significant gap in our understanding of the magnitude and impact of medication-related ED visits in pediatrics.

This study is the largest and most rigorous study performed evaluating the impact of medication-related visits to the ED in pediatrics and provides important information regarding the magnitude of this problem in our health care system. (Read the full article)

Obstructive sleep apnea syndrome (OSAS) is associated with significant comorbidity: behavioral problems, sleepiness, and impaired quality of life. However, the utility of OSAS symptoms versus polysomnography in the prediction of comorbidities or response to treatment is not well known.

Among children with OSAS, the Pediatric Sleep Questionnaire, a well-validated, simple 1-page symptom inventory, predicts key adenotonsillectomy-responsive OSAS comorbidities and their improvement after adenotonsillectomy. In contrast, polysomnographic results do not offer similar predictive value. (Read the full article)

Concern exists about the ability of new general pediatricians to find jobs that match their career goals.

A large majority of new pediatricians secure positions consistent with their career goals and desired responsibilities. (Read the full article)

Diabetic ketoacidosis (DKA) is a common and serious first manifestation of diabetes mellitus in children. During initial evaluation, the venous blood pH is frequently used to make the diagnosis and classify the severity of DKA.

This study demonstrates that the serum bicarbonate concentration is a simple and accurate predictor of DKA and its severity and can be used in lieu of venous pH measurement, especially in resource-poor settings where access to pH measurement is limited. (Read the full article)

Use of a standard treatment protocol with stringent weaning guidelines for infants with neonatal abstinence syndrome supports improved outcomes including shorter duration of opioid exposure and length of hospital stay.

We demonstrate generalizability of a protocol-driven weaning strategy for improvement in hospital outcomes for neonatal abstinence syndrome. After adoption, adherent protocol-adopting centers improved outcomes and eliminated differences in outcomes compared with centers with preexisting stringent weaning protocols. (Read the full article)

Infants with neonatal abstinence syndrome are hospitalized for longer after birth and are more likely to be from highly vulnerable families. Determining long-term outcomes is difficult because this is a large and chaotic population.

(Read the full article)

Research demonstrates that substance use, beliefs about use, and influence from family and friends can put young adults at risk for DUI and RWDD. Much of this research is cross-sectional and focuses on risk factors identified in young adults.

This longitudinal study emphasizes the importance of prevention efforts in early adolescence at multiple levels to reduce high school DUI/RWDD, because marijuana beliefs and marijuana use by peers and family members during middle school were associated with high school DUI/RWDD. (Read the full article)

The impact of neonatal abstinence syndrome is of concern because the number of newborns showing symptoms of withdrawal after intrauterine drug exposure is increasing worldwide. Newborns developing neonatal abstinence syndrome require prolonged medical treatment and longer hospital admission after birth.

This first randomized controlled trial presents data on newborns with neonatal abstinence syndrome treated with laser acupuncture. The findings suggest that adjuvant laser acupuncture has the potential to reduce duration of morphine therapy and length of hospital stay. (Read the full article)

It was far too easy to accidentally start an app subscription if you own an iPhone with Touch ID. Apple just solved the problem with a pop-up.

The Government Accountability Office finds that parents often have a hard time initiating complaints about special education services, but that these barriers don't affect all parents in the same way.

Report of the Subsidiary Body for Scientific and Technological Advice on its forty-seventh session, held in Bonn from 6 to 15 November 2017.

Adaptation in human settlements: key findings and way forward. Report by the secretariat.

Provisional agenda and annotations. Note by the Executive Secretary.

Initial draft of the technology framework. Informal document by the Chair

Informal document containing the draft elements of the draft decision on the work programme under the framework for non-market approaches referred to in Article 6, paragraph 8, of the Paris Agreement. Informal document by the Chair.

Informal document containing the draft elements of the rules, modalities and procedures for the mechanism established by Article 6, paragraph 4, of the Paris Agreement. Informal document by the Chair.

Informal document containing the draft elements of guidance on cooperative approaches referred to in Article 6, paragraph 2, of the Paris Agreement. Informal document by the Chair.

Outcomes of work under the Nairobi work programme on impacts, vulnerability and adaptation to climate change since May 2016. Synthesis report by the secretariat.

La rechute est le risque majeur des pays post-conflit et l'une des principales raisons de cette rechute s'appelle la corruption.

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.

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

Multidrug resistant strains belonging to the Enterobacter cloacae complex (ECC) group, and especially those belonging to clusters C-III, C-IV and C-VIII, have increasingly emerged as a leading cause of healthcare-associated infections, with colistin used as one of the last line of treatment. However, colistin-resistant ECC strains have emerged. The aim of this study was to prove that MgrB, the negative regulator of PhoP/PhoQ two-component regulatory system, is involved in colistin resistance in ECC of cluster C-VIII, formerly referred to as Enterobacter hormaechei subsp. steigerwaltii. An in vitro mutant (Eh22-Mut) was selected from a clinical isolate of Eh22. The sequencing analysis of its mgrB gene showed the presence of one nucleotide deletion leading to the formation of a truncated protein of six instead of 47 amino acids. Wild-type mgrB gene from Eh22, as well as that of a clinical strain of Klebsiella pneumoniae used as controls, were cloned and the corresponding recombinant plasmids were used for complementation assays. Results showed a fully restored susceptibility to colistin, and confirmed for the first time that mgrB gene expression plays a key role in acquired resistance to colistin in ECC strains.

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

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 (AmpC_cloacae), plasmid-mediated DHA-1, and P. aeruginosa PDC-5, led to 270-, 12,000-, and 79-fold decreases in the inhibitory efficacy (k₂/K_i) of avibactam, respectively. The kinetic parameters of AmpC_cloacaeand DHA-1 for ceftazidime hydrolysis were moderately affected by the substitution. Accordingly, AmpC_cloacaeand 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 AmpC_cloacaeN³⁴⁶Y. 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 AmpC_cloacaeand 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.

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.

HubSpot CRM does a great job delivering a high-quality CRM for small business customers. With a fast-growing portfolio of new platforms and features, HubSpot might also evolve into an end-to-end martech ecosystem for many customers.

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

While we wait for Apple Arcade to launch for iOS devices, Google is preparing its own app/game subscription service for Android called Play Pass.

Comixology Unlimited lets you dive into more than 20,000 digital comics for just $5.99 per month. Make the most of your subscription by starting with these 10 titles.

The Government Accountability Office finds that parents often have a hard time initiating complaints about special education services, but that these barriers don't affect all parents in the same way.

THE SPFL were tonight criticised for giving Scotland’s clubs hope that league reconstruction was a possibility in their controversial end-of-season resolution.

PARTICK Thistle today branded the SPFL a "disgrace" for failing to inform them that league reconstruction had been abandoned and revealed they are "deeply angered" by Ladbrokes Premiership clubs scuppering the plans.

Former Hearts chairman Leslie Deans has urged the club to take legal action against the SPFL as well as those who voted to end the season early, effectively relegating the Jambos.

Vinod K. Bhutani
Jan 1, 1999; 103:6-14
ARTICLES

"This is a very values-oriented generation—they seek to work with purpose and passion, and without that, they'll leave," an education leader at Microsoft said about Generation Z teachers.

Penn State Health St. Joseph opened a curbside, chest X-ray service at the medical center’s main entrance at 2500 Bernville Road on May 4. This new service is part of its continued efforts to increase patient safety during the coronavirus pandemic.

The cable is capable of delivering 72Tbps of bandwidth to South America and will be reserved for Gmail, YouTube, Search, and Google Cloud data transmission.

The official UEFA EURO 2016 website has been nominated for two categories in the sixth Annual Lovie Awards which honour the best of the European internet.

Anyone with an organization, a small business, or just a passion needs a website to share it with the world. These are the best website builders we've tested for making it easy to create full-featured, mobile-compatible sites on a budget and with no coding required.

Source: www.thestar.com - Friday, May 08, 2020
The unemployment rate jumped 5.2 points in April to 13 per cent in the first full month of economic restrictions.

038 - Romanian club handed deferred sanction

042 - Decisions made after Beşiktaş JK and Fenerbahçe SK appeal initial decision

053 - UEFA Club Financial Control Body investigatory chamber takes measures

Source: www.youtube.com - Saturday, February 29, 2020

South African banks are holding off on any further layoffs as they prepare to help the shrinking economy survive a potential jobs bloodbath.

The horse racing authority is pleading for a partial restart of the industry under Level 4 of the lockdown, warning that a prolonged suspension of activity could lead to massive financial impact and job losses.

The Chinese government is getting local ISPs and cloud service providers to practice taking websites offline quickly when they are deemed harmful.

Governor Jack Markell, Delaware State Housing Authority, and their partners are pleased to announce the launch of a free housing locator website providing information about rental housing across the First State.