Syndrome-specific standardized growth curves are not currently available for non–growth hormone–treated subjects with Prader-Willi syndrome and are required for monitoring growth and development in this rare obesity-related disorder.

Standardized growth curves were useful in monitoring growth and development in these subjects with Prader-Willi syndrome and for the management of growth hormone treatment of both genders, particularly those aged 3 to 18 years. (Read the full article)

Previous trials reported no significant effect of triamcinolone acetonide aqueous nasal spray on growth velocity of children with perennial allergic rhinitis. However, they did not conform to Food and Drug Administration guidelines for evaluating effects of intranasal corticosteroids on growth.

This is the first published study consistent with the 2007 Food and Drug Administration–recommended study design evaluating growth velocity in children aged 3–9 years with perennial allergic rhinitis treated with triamcinolone acetonide or placebo for 12 months. (Read the full article)

The number of nurse practitioner graduates in the United States has nearly doubled over the past 2 decades. However, the number of pediatric nurse practitioner (PNP) graduates has remained relatively flat, although the demand for PNPs is expected to increase.

This study estimates the best-case shortage of PNPs over the next 25 years. We propose possible policy interventions to address key areas of the PNP workforce system and we compute their impact on the forecasted PNP shortage. (Read the full article)

Studies on the consequences of abnormal prenatal hemoglobin (Hb) concentration have focused on maternal morbidities and adverse birth outcomes. To date, very little is known about the association between prenatal Hb concentration and infant cognitive and motor functions.

There is an inverted U-shaped relationship between maternal Hb concentration and infant gross motor function. Hb concentration between 90 and 110 g/L appears to be optimal for early gross motor function of children. (Read the full article)

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)

Two prospective studies of children with septic arthritis have shown that the addition of dexamethasone to antibiotic therapy contributes to clinical and laboratory improvement. Nevertheless, the mainstay of treatment remains antibiotics alone.

This study, which was conducted outside a randomized controlled trial, demonstrates that children with septic arthritis treated early with a short course of adjuvant dexamethasone show earlier improvement in clinical and laboratory parameters than children treated with antibiotics alone. (Read the full article)

Apple is thought to be planning a merger of its app platforms, which means a developer can develop an app once and have it automatically run on iPhone, iPad, and Mac without any extra work. The initiative is called 'Marzipan.'

In a 5-4 decision, the Supreme Court sided with four iPhone owners who contend the company has been inflating the prices on the App Store. Current antitrust laws allow the plaintiffs to recover three times the amount of damages.

Sick of the same-old on-screen keyboard you get with iOS? Download and install a new one and experience keyboard nirvana.

Afraid someone might be able to access your phone and get to your files and pictures? Add an extra layer of security with these apps.

Under a fifth of South Africans over the age of 60 are receiving private pensions, a new report has shown.

A Fin24 reader nearing retirement wants to know if he can access his retirement annuity now while still employed or only after officially retiring.

A health expert discusses what late joiner penalties are and how to avoid them.

A Fin24 reader under debt consolidation is left with less than R3 000 per month, finding it impossible to make ends meet. A finance expert responds.

A Fin24 reader currently under debt wants to know how lockdown will affect his monthly debt repayment order.

A South African working abroad, able to save R36 000 per month, hopeful that he will continue these earnings, seeks the best investment strategy. Investment expert Elian Wiener responds.

A Fin24 reader who bought a property in December 2019 sent his registration papers off just before the lockdown was announced, which was unfortunately too late. A property law expert responds.

A Fin24 reader heading into retirement seeks the opinion of an expert on investing during the uncertainty of Covid-19.

Due to markets and festivals closing until the end of June, a Fin24 reader will have no source of income and wants to know if there will be a payment holiday period. A debt expert responds.

A Fin24 reader whose son is a student at Stellenbosch University and stays at a private residence near the campus wants to know what his options are in requesting a rental payment holiday.

Investment consultant, Andre Tuck, tackles the question of investment strategy.

Even the most promising education innovations often struggle to gain traction. In a new paper, New Classrooms CEO Joel Rose identifies three barriers to innovation and what to do about them.

Source: www.reuters.com - Saturday, May 09, 2020
Little Richard, the self-proclaimed "architect of rock 'n' roll" who built his ground-breaking sound with a boiling blend of boogie-woogie, rhythm and blues and gospel, died on Saturday at the age of 87, Rolling Stone magazine reported.

Is $349 still too pricey for a OnePlus 2? Enter our contest and you could get one for free.

A training session designed to improve players' ability in one-on-one and two-on-two situations.

The Valencia CF starlet gives you his formula for finishing when running in on goal.

FC Barcelona's talisman tells us about his appetite for goals.

Recreate a classic goal from the Manchester United star's unforgettable Old Trafford debut.

High-quality professional learning is difficult to provide in education, principal Jasmine Kullar writes. Here's a solution.

Like many in Angola, Tchipangu did not have the financial means for an education. But this changed when a company decided to invest in her.

It took rickshaw driver Mohammad Rasheed a year to save 300 rupees to buy his daughter a bike, so when he found three billion rupees ($22.5 million) had passed through an unused bank account in his name, he was stunned ... and scared.

Indonesia was rattled by more than 11 500 earthquakes last year, almost double the annual average of the past decade, according to the nation’s meteorological agency.

Trees, shrubs and woody vines are among the top food sources for honey bees in urban environments, according to an international team of researchers. By using honey bees housed in rooftop apiaries in Philadelphia, the researchers identified the plant species from which the honey bees collected most of their food, and tracked how these food resources changed from spring to fall. The findings may be useful to homeowners, beekeepers and urban land managers who wish to sustain honey bees and other bee and pollinator species.

Burundi escapó de una guerra civil y años de terror. Hoy se supone que vive en democracia, pero eso está por verse. Ante las próximas elecciones de mayo, y con el panorama de violencia política que asuela el país, parece imposible que éstas se celebren pacíficamente y bajo el paraguas de la democracia.

Después de 28 años bajo el gobierno de Paul Biya, Camerún se encuentra en una situación de inestabilidad grave que no sólo podría echar a perder las próximas elecciones presidenciales en 2011, sino que también pone en riesgo su papel como principal pilar de estabilidad en África Central.

Extreme poverty and armed conflict in the diamond-rich areas of the Central African Republic (CAR) put thousands of lives in danger and demand urgent reform of the mining sector.

Rising piracy in the Gulf of Guinea, which supplies around 40 per cent of Europe’s oil and 29 per cent of the U.S.’s, demands effective regional security cooperation and better economic governance to prevent the region becoming another Gulf of Aden.

La imagen de Camerún como una isla de paz en medio de una región tumultuosa terminó en 2013, cuando la violencia de Boko Haram cruzó la frontera nigeriana. Este grupo está afiliado al llamado Estado Islámico o Daesh, e incluso se rebautizó como Estado Islámico de África Occidental a principios de este año. Pero la forma brutal de yihadismo africano que representa difícilmente se explica por el auge del Estado Islámico en Irak y Siria. De hecho, es en parte una consecuencia del cambiante panorama religioso africano, que afecta y no poco a Camerún.

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

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Background: Intensive care unit (ICU) patients may experience ceftriaxone underexposure but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes amongst ICU patients without central nervous system (CNS) infection.

Methods: A retrospective study of ICU patients receiving intravenous, empiric ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 grams of ceftriaxone daily for ≥72 hours were included and categorized as receiving ceftriaxone 1 gram or 2 grams daily. The primary, composite outcome was treatment failure: inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving ceftriaxone 2 grams daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort.

Results: A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 gram and 2 grams daily, respectively (p=0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 gram dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio=0.190; 95% confidence interval: 0.059 – 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR 1.440, 95% CI 1.254 – 1.653) and creatinine clearance at 72 hours from ceftriaxone initiation (aOR 0.980, 95% CI (0.971 – 0.999).

Conclusions: Ceftriaxone 2 grams daily when used as appropriate antimicrobial coverage may be appropriate for ICU patients with lower mortality risk.

The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxA^Y144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target.

Antibiotic resistance is a global concern; however, data on antibiotic-resistant Ureaplasma spp. and Mycoplasma hominis are limited in comparison to similar data on other microbes. A total of 492 Ureaplasma spp. and 13 M. hominis strains obtained in Hangzhou, China, in 2018, were subjected to antimicrobial susceptibility testing for levofloxacin, moxifloxacin, erythromycin, clindamycin, and doxycycline using the broth microdilution method. The mechanisms underlying quinolone and macrolide resistance were determined. Meanwhile, a model of the topoisomerase IV complex bound to levofloxacin in wild-type Ureaplasma spp. was built to study the quinolone resistance mutations. For Ureaplasma spp., the levofloxacin, moxifloxacin and erythromycin resistance rates were 84.69%, 51.44% and 3.59% in U. parvum and 82.43%, 62.16% and 5.40% in U. urealyticum, respectively. Of the 13 M. hominis strains, 11 were resistant to both levofloxacin and moxifloxacin, and five strains showed clindamycin resistance. ParC S83L was the most prevalent mutation in levofloxacin-resistant Ureaplasma strains, followed by ParE R448K. The two mutations GyrA S153L and ParC S91I were commonly identified in quinolone-resistant M. hominis. A molecular dynamics-refined structure revealed that quinolone resistance-associated mutations inhibited the interaction and reduced affinity with gyrase or topoisomerase IV and quinolones. The novel mutations S21A in the L4 protein and G2654T and T2245C in 23S rRNA and ermB gene were identified in erythromycin-resistant Ureaplasma spp. Fluoroquinolone resistance in Ureaplasma spp. and Mycoplasma hominis remains high in China, the rational use of antibiotics needs to be further enhanced.

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.

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

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 bla_CTX-M genes were identified, with bla_CTX-M-65, bla_CTX-M-123, bla_CTX-M-14, bla_CTX-M-79, and bla_CTX-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.

Staphylococcus aureus osteomyelitis is a debilitating infection of bone. Treatment of osteomyelitis is impaired by the propensity of invading bacteria to induce pathologic bone remodeling that may limit antibiotic penetration to the infectious focus. The nonsteroidal anti-inflammatory drug diflunisal was previously identified as an osteoprotective adjunctive therapy for osteomyelitis, based on the ability of this compound to inhibit S. aureus quorum sensing and subsequent quorum-dependent toxin production. When delivered locally during experimental osteomyelitis, diflunisal significantly limits bone destruction without affecting bacterial burdens. However, because diflunisal's "quorum-quenching" activity could theoretically increase antibiotic recalcitrance, it is critically important to evaluate this adjunctive therapy in the context of standard of care antibiotics. The objective of this study is to evaluate the efficacy of vancomycin to treat osteomyelitis during local diflunisal treatment. We first determined that systemic vancomycin effectively reduces bacterial burdens in a murine model of osteomyelitis, and identified a dosing regimen that decreases bacterial burdens without eradicating infection. Using this dosing scheme, we found that vancomycin activity is unaffected by the presence of diflunisal in vitro and in vivo. Similarly, locally-delivered diflunisal still potently inhibits osteoblast cytotoxicity in vitro and bone destruction in vivo in the presence of sub-therapeutic vancomycin. However, we also found that the resorbable polyurethane foams used to deliver diflunisal serve as a nidus for infection. Taken together, these data demonstrate that diflunisal does not significantly impact standard of care antibiotic therapy for S. aureus osteomyelitis, but also highlight potential pitfalls encountered with local drug delivery.