Various clinical and demographic factors are associated with sudden infant death syndrome (SIDS), and an association between altitude of residence and SIDS has been questioned but not yet demonstrated in any large observational studies.

This study demonstrates an association between altitude and SIDS, with higher SIDS rates observed at high elevation (>8000 feet) than at the more moderate elevations (<6000 feet). (Read the full article)

Almost half of NICUs include low birth weight (<2.5 kg) as an inclusion criterion for car seat tolerance screening (CSTS), formerly car seat challenges. However, little is known about incidence and risk factors for failure in this group.

This is the largest study to date evaluating the incidence and predictors of CSTS failure in full-term low birth weight neonates. Epidemiologic data are provided to help guide future CSTS policies and protocol development for this group. (Read the full article)

Street youth demonstrate elevated mortality compared with the general adolescent and young adult population. Suicide is a leading cause of death among street youth. Many street youth have experienced childhood maltreatment, including abuse and neglect.

In this prospective cohort of street youth, self-reported attempted suicide and history of childhood maltreatment were common. Individuals who experienced childhood physical abuse, emotional abuse, or emotional neglect were at highest risk of attempting suicide. (Read the full article)

Selective eating is a common, burdensome eating pattern in young children. A significant subset remain selective eaters at least until adolescence and, for some, adulthood. The question is whether selective eating is a serious enough developmental pattern to warrant intervention.

This study examines whether selective eating, at 2 levels of severity, is associated with current and future psychological problems. Because moderate levels of selective eating were associated with impairment, selective eating falls within the diagnosis of avoidant/restrictive food intake disorder. (Read the full article)

Increasing percentages of youth are living with chronic medical conditions. Although adolescents face peak risks for onset and intensification of alcohol and marijuana use, we know little about these behaviors and their associations with treatment adherence among chronically ill youth.

This study quantifies alcohol and marijuana use behaviors among a heterogeneous sample of chronically ill youth in aggregate and by condition, and measures associations between alcohol use/binge drinking and knowledge about alcohol interactions with medications/laboratory tests and also treatment nonadherence. (Read the full article)

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)

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)

Strictly-defined pediatric bipolar I disorder (BP-I) is a serious condition. Although lithium is a benchmark treatment and has shown effectiveness in adults for decades, no definitive efficacy or long-term safety studies had been performed in pediatric patients with BP-I.

This study provides evidence to support the efficacy of lithium in the acute treatment of youths with BP-I who are currently in a manic or mixed state. Lithium had an adverse effect profile that was acceptable for most patients. (Read the full article)

Continuous conventional EEG video is currently gold standard for identifying neonatal seizures and a substantial proportion of neonatal seizures are electrographic. Currently there is no direct evidence that EEG monitoring, seizure identification, or treatment impacts long-term outcomes.

In neonates with hypoxic ischemic encephalopathy, EEG monitoring and treatment of electrographic seizures results in significant reduction in seizure burden. Increasing seizure burden is associated with more severe brain injury and significantly lower performance scores on Bayley Scales of Infant Development III. (Read the full article)

National guidelines recommend testing and prophylaxis for chlamydia, gonorrhea, and pregnancy for adolescent sexual assault victims. Little is known about rates of testing and prophylaxis in adolescent victims of sexual assault evaluated in pediatric emergency departments.

There is significant variation in testing and prophylaxis practices in the pediatric emergency department evaluation of adolescent victims of sexual assault. Adolescents cared for in emergency departments with clinical pathways are more likely to receive recommended prophylaxis. (Read the full article)

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.

Ashkan Negahban, assistant professor of engineering management, and Satish Srinivasan, assistant professor of information science, will lead projects that help address the COVID-19 crisis, thanks to seed grants from the Huck Institutes of the Life Sciences.

Lisa Dahlkvist's penalty won Sweden an Olympic shoot-out against favourites the United States, and Germany forged on, but France did not make it to the last four.

The United States beat the Netherlands to retain the trophy in Lyon while Sweden pipped England to bronze.

Source: www.brooklynpaper.com - Saturday, May 09, 2020
The owner of the iconic Park Slope events venue Grand Prospect Hall, Michael Halkias, died from COVID-19 on Wednesday. He was 82. Halkias’ death sent shockwaves throughout Brooklyn, where community leaders and friends remember him as a passionate, generous figure. “ He was a Brooklyn character for sure in the best sort of way,” said Randy Peers, president and CEO of the Brooklyn Chamber of Commerce. “He was larger than life.” Halkias and his wife Alice bought Grand Prospect Hall in 1984 and turned the extravagant Prospect Avenue building into an opulent catering hall. The space became a New York icon because of the its long-running, popular commercials, where Alice Halkias declares in a Greek accent, “We make your dreams come true!” Saturday Night Live spoofed the famous commercial in February of 2019, and the pair appeared on Jimmy Kimmel Live in October to remake the ad with Mets player Pete Alonso. Grand Prospect Hall, a Victorian banquet hall built in 1892, attracted big names such as dancer Fred Astaire and mafioso Al Capone during its heyday in the early 20th century — and boasted some of the borough’s oldest treasures, such as Brooklyn’s first reported elevator, which functions to this day. But by the 1980s, the landmarked building had fallen into disrepair: its walls had been painted black, molding had been stripped off the walls, and the chandeliers were gone, Halkias told Brooklyn Paper in 2004. The couple spent 20 yea

A student-centered approach to teaching mathematics enables students to develop conceptual understanding and to grow as confident mathematicians.

If you're shopping for a gamer, especially if you can pin down their preferred platform, these cheap but fun accessories are guaranteed winners.

Quantum machine learning, an emerging field that combines machine learning and quantum physics, is the focus of research to discover possible treatments for COVID-19, according to Penn State researchers, who believe that this method could be faster and more economical than the current methods used for drug discovery.

So, how do we manage? What do we do when consistently engaging in the difficult discussion about rape culture is hard on our hearts, but helpful for our students?

Former Tottenham Hotspur FC manager David Pleat analyses FC Barcelona's winning formation from 2009.

Valor Collegiate Academies has been in the top 5 percent of Tennessee schools on growth and achievement every year since it started in 2014. But Tom visited Valor because of the well-regarded Valor Compass, a holistic human-development program.

Penn State and the Palmer Museum of Art mourn the loss of dear friend, generous donor, and loyal champion John P. Driscoll, who died from complications due to COVID-19 on Friday, April 10. Driscoll, owner of Driscoll Babcock Galleries in New York, was a longtime friend and supporter of the Palmer Museum and will be remembered for his role as a leader, gracious mentor and trusted adviser, as well as for the expansive gifts he made to the collection and to his alma mater, Penn State.

Stokvels are an important strategy for financial survival, so it's crucial to find a way to make them work during the pandemic, says Dr Norman Chivasa.

While the prospect of Guinea's return to constitutional rule after its recent election is cause for hope, the recent resurgence of military takeovers in Africa may not yet have run its full course.

Renewed oil interest in the Democratic Republic of the Congo (DRC) could nurture communal resentments, exacerbate deep-rooted conflict dynamics and weaken national cohesion.

​Religious intolerance is a growing but seriously underestimated risk in Cameroon, both between and inside the major faiths. To halt the spread of violent extremism in the country, Cameroon needs to bring all sects into a new social compact and within the bounds of a charter for religious tolerance.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Antimicrobial peptides and proteins play critical roles in the host defense against invading pathogens. We recently discovered that recombinantly expressed human and mouse serum amyloid A1 (rhSAA1 and rmSAA1) proteins have potent antifungal activities against the major human fungal pathogen Candida albicans. At high concentrations, rhSAA1 disrupts C. albicans membrane integrity and induces rapid fungal cell death. In the current study, we find that rhSAA1 promotes cell aggregation and targets the C. albicans cell wall adhesin Als3. Inactivation of ALS3 in C. albicans leads to a striking decrease in cell aggregation and cell death upon rhSAA1 treatment, suggesting that Als3 plays a critical role in SAA1 sensing. We further demonstrate that deletion of the transcriptional regulators controlling the expression of ALS3, such as AHR1, BCR1, and EFG1 in C. albicans results in similar effects to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling indicates that rhSAA1 has a discernible impact on the expression of cell wall- and metabolism-related genes, suggesting that rhSAA1 treatment could lead to a nutrient starvation effect on C. albicans cells.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, an early step in the conserved glycosylphosphotidyl inositol (GPI) post-translational modification pathway of surface proteins in eukaryotic cells. Inhibition of inositol acylation by MGX results in pleiotropic effects including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some strains of Mucorales. Here we assessed the in vivo activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two Rhizopus arrhizus strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-live of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 post infection when compared to placebo. In addition, administration of fosmanogepix resulted in a 1-2 log reduction in both lung and kidney fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first in class treatment for invasive mucormycosis.

Telacebec (Q203) is a new anti-tubercular drug with extremely potent activity against Mycobacterium ulcerans. Here, we explored the treatment-shortening potential of Q203 alone or in combination with rifampin (RIF) in a mouse footpad infection model. The first study compared Q203 at 5 and 10 mg/kg doses alone and with rifampin. Q203 alone rendered most mouse footpads culture-negative in 2 weeks. Combining Q203 with rifampin resulted in relapse-free cure 24 weeks after completing 2 weeks of treatment, compared to a 25% relapse rate in mice receiving RIF+clarithromycin, the current standard of care, for 4 weeks.

The second study explored the dose-ranging activity of Q203 alone and with RIF, including the extended activity of Q203 after treatment discontinuation. The bactericidal activity of Q203 persisted for ≥ 4 weeks beyond the last dose. All mice receiving just 1 week of Q203 at 2-10 mg/kg were culture-negative 4 weeks after stopping treatment. Mice receiving 2 weeks of Q203 at 0.5, 2 and 10 mg/kg were culture-negative 4 weeks after treatment. RIF did not increase the efficacy of Q203. A pharmacokinetics sub-study revealed that Q203 doses of 2-10 mg/kg in mice produce plasma concentrations similar to those produced by 100-300 mg doses in humans, with no adverse effect of RIF on Q203 concentrations.

These results indicate the extraordinary potential of Q203 to reduce the duration of treatment necessary for cure to ≤ 1 week (or 5 doses of 2-10 mg/kg) in our mouse footpad infection model and warrant further evaluation of Q203 in clinical trials.

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.

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.

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant Enterococcus (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against E. faecalis and E. faecium isolates using a dynamic in vitro bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing (E. faecalis MIC_50/90 32/64 μg/mL; E. faecium MIC_50/90 64/128 μg/mL). Sixteen isolates (including E. faecalis ATCC 29212 and E. faecium ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, E. faecium demonstrated greater growth restriction in SHU compared to E. faecalis (E. faecium maximal growth 5.8 ± 0.6 log₁₀ CFU/mL; E. faecalis 8.0 ± 1.0 log₁₀ CFU/mL). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and two-doses given daily with low urinary exposure. Simulated concentrations closely matched the target (bias 2.3%). E. faecalis isolates required greater fosfomycin exposure for 3 log₁₀ kill from the starting inoculum compared with E. faecium. The fAUC_0-72/MIC and f%T > MIC_0-72 for E. faecalis was 672 and 70%, compared to 216 and 51% for E. faecium, respectively. There was no rise in fosfomycin MIC post-exposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log₁₀ kill) in the majority of isolates.

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

Tedizolid has demonstrated its efficacy and safety in clinical trials, however, data concerning its tolerability in long-term treatments is scarce. The aim of the study was to assess the indications and to describe the long-term safety profile of tedizolid.

A multicentric, retrospective study of patients who received tedizolid for more than 6-days was conducted. Adverse events (AEs) were identified from patients' medical records and laboratory data. The World Health Organization causality categories were used to discern AEs probably associated with tedizolid.

Eighty-one patients, treated with tedizolid 200mg once-daily for a median (IQR) duration of 28 (14-59) days, were included, 36 (44.4%) had previously received linezolid. Most common reasons for selecting tedizolid were to avoid linezolid potential toxicities or interactions (53.1%) or due to previous linezolid-related toxicities (27.2%). Most common indications were off-label, including prosthetic joint infections, osteomyelitis and respiratory infections (77.8%). Overall, 9/81 patients (11.1%) experienced a probably associated AE. Two patients (2.5%) developed gastrointestinal disorders, 1 (1.2%) anemia and 6 thrombocytopenia (7.4%) after a median (IQR) duration of treatment of 26.5 (17-58.5) days. Four (5%) patients discontinued tedizolid due to AEs. Among 23 patients with chronic renal failure (CRF) the rate of mielotoxicity was 17.4% and only 8.7% had to stop tedizolid and 20 out of 22 with previous linezolid-associated toxicity had no AE.

Long-term tedizolid treatments had good tolerance with rates of gastrointestinal AE and hematological toxicity lower than those reported with linezolid, particularly in patients with CRF and in those with a previous history of linezolid-associated toxicity.

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-lactam antibiotics have emerged as a potential option for combination therapy with VAN/DAP that may meet an unmet therapeutic need for MRSA BSI. Ceftaroline (CPT), the only commercially available β-lactam in the United States with intrinsic in vitro activity against MRSA, has been increasingly studied in the setting of VAN and DAP failures. Novel combinations of first-line agents (VAN and DAP) with β-lactams have been the subject of many recent investigations due to in vitro findings such as the "see-saw effect", where β-lactam susceptibility may be improved in the presence of decreased glycopeptide and lipopeptide susceptibility. The combination of CPT and DAP, in particular, has become the focus of many scientific evaluations, due to intrinsic anti-MRSA activities and potent in vitro synergistic activity against various MRSA strains. This article reviews the available literature describing these innovative therapeutic approaches for MRSA BSI, focusing on preclinical and clinical studies, and evaluates the potential benefits and limitations of each strategy.

The currently unfolding coronavirus pandemic threatens health systems and economies worldwide....

A case of M. leprae rifampicin resistance after irregular anti-leprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampicin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Exploring different ways of minimising linezolid toxicity without compromising efficacy is a major quest in the treatment of drug resistant tuberculosis (TB)....

We thank Kim and colleagues for their interest in our study....

Deep losses were recorded across most European benchmarks except the FTSE 100 which managed to trade relatively flat on the day.

Benetech, a Palo Alto, Calif. based software company, is embarking on is third 5-year award with the U.S. Department of Education to create books for students with print disabilities.

Penn State Health has enrolled its first COVID-19 patient into an experimental treatment program called convalescent plasma therapy.

The shooting death of a 10-year-old spectator at a high school football game exposes a critical vulnerability and crucial responsibility for schools: keeping people safe at events outside school buildings.

A signature program at Penn State Greater Allegheny, implemented to give students, faculty and staff the digital skills to communicate, solve problems and create new knowledge, is front and center in the University’s remote learning period.

Dedication to student print journalism paid off for several Penn State Greater Allegheny student reporters and designers.

Campus Recreation, a unit of Penn State Student Affairs, is hosting the first ever “We Are Penn State Virtual 5K,” with the opportunity to benefit the Penn State Student Care and Advocacy Student Emergency Fund.

RANGERS vice-chairman John Bennett last night dismissed a claim that Ibrox chairman Douglas Park had threatened SPFL chief executive Neil Doncaster as “unfounded”.