ser EEG for Predicting Early Neurodevelopment in Preterm Infants: An Observational Cohort Study By pediatrics.aappublications.org Published On :: 2012-09-03T00:07:28-07:00 Previous studies suggest that abnormal findings on conventional EEG during the neonatal period are associated with death or severe brain injury in preterm infants. However, large cohort studies on preterm EEG for predicting later neurodevelopmental outcome remain scarce.This study demonstrates precise prognostic values of conventional EEG for predicting neurodevelopmental outcome in the current perinatal care setting. Additionally, its prognostic values are independent of severe injury on neuroimaging and clinical risk factors. (Read the full article) Full Article
ser Evaluation of Interobserver Agreement of Apgar Scoring in Preterm Infants By pediatrics.aappublications.org Published On :: 2012-09-24T00:07:06-07:00 The Apgar score is a convenient method to rapidly assess the clinical status of the newborn infant. Recent literature suggests Apgar scores vary widely in preterm infants.The Apgar signs for respiratory effort, grimace, and muscle tone demonstrated considerable disagreement in preterm infants ≤28 weeks’ gestation. Disagreement exists despite the level of respiratory intervention, continuous positive airway pressure, or intubation, and is likely independent of gestational age. (Read the full article) Full Article
ser Incidence of Serious Injuries Due to Physical Abuse in the United States: 1997 to 2009 By pediatrics.aappublications.org Published On :: 2012-10-01T00:07:26-07:00 National data from child protective services agencies have shown a 55% decrease in the incidence of substantiated cases of physical abuse from 1992 to 2009, but no study has tracked the occurrence of serious injuries due to physical abuse.Using national data from hospitalized children, we found a statistically significant increase in the incidence of serious injuries due to physical abuse from 1997 to 2009. These results are in sharp contrast to data from child protective services. (Read the full article) Full Article
ser Mental Health Services Use by Children Investigated by Child Welfare Agencies By pediatrics.aappublications.org Published On :: 2012-10-08T00:07:35-07:00 Children investigated for alleged maltreatment have considerable physical, mental health (MH), developmental, and educational needs and often do not receive services to address these needs. The prevalence/correlates of MH services use in the current challenging financial environment is unknown.This study demonstrates the importance of medical providers and schools for receipt of MH services for these children, but shows disparities in MH service use between white and nonwhite children. Unlike earlier findings, MH service use declined over the follow-up. (Read the full article) Full Article
ser Variations in Children's Dental Service Use Based on Four National Health Surveys By pediatrics.aappublications.org Published On :: 2012-10-15T00:08:06-07:00 Oral health researchers and policy makers primarily use 4 national surveys to examine use of dental services among US children. Estimates from the surveys may vary, posing a challenge to population-based monitoring.The authors of this study compared estimates of dental service use and delayed dental care obtained from 4 commonly used health surveys to appraise their utility for guiding pediatric oral health research and policy. (Read the full article) Full Article
ser Part C Early Intervention for Infants and Toddlers: Percentage Eligible Versus Served By pediatrics.aappublications.org Published On :: 2012-12-24T00:06:40-08:00 Part C early intervention serves ~2.8% of US children who are younger than 3 years old; however, there is evidence that substantial numbers of infants and toddlers with developmental delays receive no early intervention services.Broad eligibility criteria can classify children who have no delays or minimal delays as candidates for Part C services. Despite this, no jurisdiction provides Part C services to all children who have substantial delays. (Read the full article) Full Article
ser Plate Size and Children's Appetite: Effects of Larger Dishware on Self-Served Portions and Intake By pediatrics.aappublications.org Published On :: 2013-04-08T00:06:51-07:00 Research has shown that dishware size influences self-served portion sizes and meal intake in adults. In children, larger bowls led children to request more food, but whether larger dishware affects children’s self-served portions or intake at meals is not known.We assessed the effect of increasing dishware size on self-served portions and intake in young children. Larger plates and bowls resulted in larger self-served portions, and indirectly promoted greater intake, emphasizing the importance of age-appropriate dishware. (Read the full article) Full Article
ser Resource Utilization for Observation-Status Stays at Children's Hospitals By pediatrics.aappublications.org Published On :: 2013-05-13T00:07:01-07:00 Hospitalizations under observation status are presumed to be shorter and less resource-intensive, but utilization for pediatric observation-status stays has not been studied.Children’s hospitals use observation status with great variation. Resource utilization for pediatric patients under observation status overlaps substantially with inpatient-status utilization, calling into question the utility of segmenting pediatric patients according to billing status. (Read the full article) Full Article
ser Serum Uric Acid and Blood Pressure in Children at Cardiovascular Risk By pediatrics.aappublications.org Published On :: 2013-06-17T01:07:30-07:00 Uric acid (UA) is associated with hypertension in children, after body weight adjustment. Whether the whole spectrum of variables, such as visceral adiposity, insulin resistance, puberty, and renal function, influence the relationship between UA and blood pressure is unknown.In a cohort of children at relatively high cardiovascular risk, the association between UA and blood pressure levels is independent of several well-known factors implicated in the development of hypertension, such as insulin resistance, pubertal status, and renal function. (Read the full article) Full Article
ser Racial and Ethnic Differences in Subspecialty Service Use by Children With Autism By pediatrics.aappublications.org Published On :: 2013-06-17T01:07:30-07:00 Racial and ethnic differences exist in age at diagnosis and early access to mental and behavioral health services among children with autism spectrum disorders (ASDs). ASDs are also associated with increased rates of other medical comorbidities that may require specialty care.Significant racial and ethnic differences in use of specialty care and specialty procedures exist among children with documented ASD. (Read the full article) Full Article
ser Changes in Language Services Use by US Pediatricians By pediatrics.aappublications.org Published On :: 2013-07-08T00:07:25-07:00 Language barriers adversely affect health care access, utilization, outcomes, and patient safety. Trained formal interpreters can improve care quality and safety, but many patients and families with limited English proficiency do not receive appropriate language services during health care encounters.Despite continued growth of the US population with limited English proficiency, federal language use standards, and enhanced education about appropriate use of language services, there has been only modest improvement over time in pediatricians’ use of language services. (Read the full article) Full Article
ser Randomized Controlled Trial of a Car Safety Seat Insert to Reduce Hypoxia in Term Infants By pediatrics.aappublications.org Published On :: 2013-07-15T00:07:09-07:00 Brief periods of low oxygen saturation are common in infants while restrained in car safety seats. There is some evidence that an insert that allows the infant head to rest in a neutral position in sleep may reduce hypoxic episodes.This randomized controlled study shows that the insert reduced numbers of obstructive apneas and the severity of desaturation events but did not significantly reduce the overall rate of moderate desaturations. (Read the full article) Full Article
ser Pneumococcal Meningitis in Children: Epidemiology, Serotypes, and Outcomes From 1997-2010 in Utah By pediatrics.aappublications.org Published On :: 2013-08-26T00:07:47-07:00 The incidence of pediatric pneumococcal meningitis has declined after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). It is unknown whether the frequency of severe neurologic sequelae and adverse outcomes has changed in the era of widespread PCV7 use.Pneumococcal meningitis continues to be associated with substantial mortality and long-term morbidity. Sixty-three percent of survivors had neurologic sequelae. More than one-half of the children who were eligible for PCV7 were unimmunized at the time that they developed pneumococcal meningitis. (Read the full article) Full Article
ser Gunshot Injuries in Children Served by Emergency Services By pediatrics.aappublications.org Published On :: 2013-10-14T00:07:21-07:00 Gunshot injuries are an important cause of preventable injury and mortality in children, with emergency services often providing the initial care for patients. However, there is little recent population-based research to guide public health, injury prevention, and health policy efforts.Gunshot injuries are uncommon in children, but cause greater injury severity, need for major surgery, mortality, and costs compared with other injury mechanisms. There is also large variation in the population-adjusted incidence of pediatric gunshot injuries between regions. (Read the full article) Full Article
ser Serum Tocopherol Levels in Very Preterm Infants After a Single Dose of Vitamin E at Birth By pediatrics.aappublications.org Published On :: 2013-11-11T00:07:46-08:00 Preterm infants are born with low serum levels and low body stores of tocopherol. Serum levels ≥0.5 mg/dL are required for protection against lipid peroxidation. Previous studies have shown good intestinal absorption of vitamin E given intragastrically to preterm infants.Serum α-tocopherol increases after a single 50-IU/kg dose of vitamin E as dl-α-tocopheryl acetate given intragastrically to very preterm infants soon after birth; however, 30% of infants still have serum α-tocopherol level <0.5 mg/dL 24 hours after dosing. (Read the full article) Full Article
ser Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis By pediatrics.aappublications.org Published On :: 2013-12-09T00:06:36-08:00 Individuals with autism spectrum disorders have a higher comorbidity burden than the general pediatric population, including higher rates of seizures, psychiatric illness, and gastrointestinal disorders.Comorbidities do not occur evenly. Our clustering analysis reveals subgroups characterized by seizure, psychiatric disorders, and complex multisystem disorders including auditory and gastrointestinal disorders. Correlations between seizure, psychiatric disorders, and gastrointestinal disorders are validated on a sample from a second hospital. (Read the full article) Full Article
ser Vitamin D During Pregnancy and Infancy and Infant Serum 25-Hydroxyvitamin D Concentration By pediatrics.aappublications.org Published On :: 2013-12-16T00:07:05-08:00 A serum 25-hydroxyvitamin D (25(OH)D) concentration of 20 ng/mL meets the requirements of at least 97.5% of the population older than 1 year. A recommended dietary intake to achieve this serum 25(OH)D concentration has not been established during infancy.Daily maternal (during pregnancy) and then infant vitamin supplementation with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL during infancy with the higher dose sustaining this increase for longer. (Read the full article) Full Article
ser Predicting Service Use for Mental Health Problems Among Young Children By pediatrics.aappublications.org Published On :: 2014-05-12T00:06:51-07:00 A large majority of preschool and young school age children with mental health problems do not receive services and little is known about the determinants of service use in this age group.Behavioral, not emotional, disorders increase service use but only if impairment is present. Such impairment may operate via increased parental burden and parent and caregiver problem recognition. Low socioeconomic status has an independent effect increasing service use. (Read the full article) Full Article
ser Duration of Protection After Infant Hepatitis B Vaccination Series By pediatrics.aappublications.org Published On :: 2014-05-19T00:07:01-07:00 Duration of protection among children and adolescents who have received the recombinant hepatitis B (HB) vaccination series is known to be long. Less is known about duration of protection of the vaccination series after being administered during infancy.A robust response to a challenge dose of HB vaccine among adolescents indicates prolonged duration of protection against disease; the addition of a booster dose of HB vaccine to the routine immunization schedule for adolescents appears unnecessary. (Read the full article) Full Article
ser An Innovative Nonanimal Simulation Trainer for Chest Tube Insertion in Neonates By pediatrics.aappublications.org Published On :: 2014-08-04T00:06:56-07:00 Practitioners caring for critically ill infants need to acquire competence in insertion of chest tubes for pneumothorax. Ethical and logistic concerns inhibit the use of animals, and there are no realistic simulation models available for neonatal chest tube insertion training.An inexpensive, nonanimal chest tube insertion model can be easily constructed and used effectively to train interns and residents to improve their knowledge, clinical skills, and comfort levels to perform the chest tube insertion procedure in infants. (Read the full article) Full Article
ser Behavioral Health Services Following Implementation of Screening in Massachusetts Medicaid Children By pediatrics.aappublications.org Published On :: 2014-09-15T00:06:27-07:00 Behavioral health (BH) screening is known to increase identification of children with BH issues, but in small-scale studies, rates of follow-up after screening have been reported to be low.This study examines the relationship between BH screening and the receipt of BH services in Massachusetts Medicaid children. Nearly 60% of children identified with BH problems received BH services, but only 30% of newly identified children received BH services. (Read the full article) Full Article
ser Prenatal and Newborn Screening for Critical Congenital Heart Disease: Findings From a Nursery By pediatrics.aappublications.org Published On :: 2014-10-06T00:06:22-07:00 The detection of critical congenital heart disease by fetal echocardiography or neonatal physical examination can have limitations. The addition of pulse oximetry screening in the newborn nursery increases the rate of diagnosis of these conditions before hospital discharge.In a tertiary-care center with comprehensive fetal echocardiography, nearly all newborns with critical congenital heart disease are diagnosed prenatally. Pulse oximetry will identify more infants from settings with lower prenatal detection. Improving access to and training in fetal echocardiography should also improve detection of these conditions. (Read the full article) Full Article
ser Serum Bilirubin and Bilirubin/Albumin Ratio as Predictors of Bilirubin Encephalopathy By pediatrics.aappublications.org Published On :: 2014-10-20T00:06:38-07:00 Jaundiced newborns without additional risk factors rarely develop kernicterus if the total serum bilirubin is <25 mg/dL. Measuring the bilirubin/albumin ratio might improve risk assessment, but the relationships of both indicators to advancing stages of neurotoxicity are poorly documented.Both total serum bilirubin and bilirubin/albumin ratio are strong predictors of advancing stages of acute and post-treatment auditory and neurologic impairment. However, bilirubin/albumin ratio, adjusted to the same sensitivity, does not improve prediction over total serum bilirubin alone. (Read the full article) Full Article
ser College Health Service Capacity to Support Youth With Chronic Medical Conditions By pediatrics.aappublications.org Published On :: 2014-10-27T00:06:33-07:00 The population of youth with chronic medical conditions is growing and many attend college. Yet we know little about US colleges’ capacity to identify and care for these youth, nor how transition guidelines and financing models should incorporate college health.This is the first study to find that although many colleges can provide some clinical care for youth with chronic conditions, few colleges have systems to identify and track these students, elucidating gaps that pediatricians and institutions need to address. (Read the full article) Full Article
ser Identifying Autism in a Brief Observation By pediatrics.aappublications.org Published On :: 2015-01-12T00:05:26-08:00 Behavioral observations influence a clinician’s decision to diagnose or refer, and may even override formal screening results. In the case of autism spectrum disorder, an expected rate of atypical behavior during the span of a medical visit is unknown.We are the first to quantify the high base rates of typical behavior in young children who have autism and language delay. When observation times are brief, the preponderance of typical behaviors may negatively impact referral decision accuracy. (Read the full article) Full Article
ser Family Hardships and Serum Cotinine in Children With Asthma By pediatrics.aappublications.org Published On :: 2015-01-12T00:05:26-08:00 Poverty is prevalent among children in the United States, and it has a clear association with negative health outcomes. Smoking and passive smoke exposure are both more common among socioeconomically disadvantaged populations and are associated with asthma morbidity.Reported family hardships were common among children admitted for asthma or wheezing, and most were associated with detectable tobacco smoke exposure. The cumulative number of hardships was also associated with greater odds of tobacco smoke exposure. (Read the full article) Full Article
ser Discrepancies Between Transcutaneous and Serum Bilirubin Measurements By pediatrics.aappublications.org Published On :: 2015-01-19T00:05:32-08:00 In most previous studies, transcutaneous bilirubin measurement has been found to provide an accurate estimate of total serum bilirubin levels. However, most of these studies were conducted in settings that optimized accuracy.This study provides a "real-world" assessment of the accuracy of transcutaneous bilirubin measurements in multiple clinical settings and identification of sources of discrepancy between transcutaneous and total serum bilirubin measurements. (Read the full article) Full Article
ser Medication-Related Emergency Department Visits in Pediatrics: a Prospective Observational Study By pediatrics.aappublications.org Published On :: 2015-02-02T00:05:27-08:00 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) Full Article
ser First Use of a Serogroup B Meningococcal Vaccine in the US in Response to a University Outbreak By pediatrics.aappublications.org Published On :: 2015-04-27T00:05:19-07:00 Outbreaks of serogroup B meningococcal disease occur at universities and other organizations. Until October 2014, options for control of serogroup B outbreaks were limited by the absence of a licensed vaccine for serogroup B meningococcal disease in the United States.We describe a serogroup B outbreak at a university in 2013 and the campaign with investigational serogroup B vaccine held in response. This was the first use of a serogroup B vaccine as an outbreak response in the United States. (Read the full article) Full Article
ser Effects of Physician-Based Preventive Oral Health Services on Dental Caries By pediatrics.aappublications.org Published On :: 2015-06-29T00:07:57-07:00 The US Preventive Services Task Force recommends primary care clinicians apply fluoride varnish to the teeth of all young children, but no studies have examined the effect of comprehensive preventive oral health services on children’s clinical oral health status.Comprehensive preventive oral health services delivered by primary care clinicians can help improve the oral health of Medicaid-enrolled children, but more work is needed to link medical and dental offices to ensure the continuity of dental care for these children. (Read the full article) Full Article
ser Use of Serum Bicarbonate to Substitute for Venous pH in New-Onset Diabetes By pediatrics.aappublications.org Published On :: 2015-07-20T00:07:27-07:00 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) Full Article
ser Home Foreclosure and Child Protective Services Involvement By pediatrics.aappublications.org Published On :: 2015-07-20T00:07:27-07:00 Prior studies have found a positive relationship between macro-level indicators of home foreclosure and child maltreatment rates. The extent to which home foreclosure may be associated with child protective services involvement at the micro level is largely unknown.Foreclosure filings are positively associated with child protective services involvement. However, this is true of the periods before and after a filing, which are characterized by economic and other stress, which may drive this association more than the filing itself. (Read the full article) Full Article
ser Congenital Heart Defects and Receipt of Special Education Services By pediatrics.aappublications.org Published On :: 2015-08-17T00:06:44-07:00 Poor neurocognitive outcomes are associated with some types of congenital heart defects (CHDs). Guidelines for developmental screening for children with CHDs have been published. Population-based information on special education services needed among children with CHDs is limited.Children in metropolitan Atlanta with congenital heart defects (CHDs) received special education services more often than children without birth defects. These findings highlight the need for special education services and the importance of developmental screening for all children with CHDs. (Read the full article) Full Article
ser Laser Acupuncture for Neonatal Abstinence Syndrome: A Randomized Controlled Trial By pediatrics.aappublications.org Published On :: 2015-10-26T00:07:20-07:00 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) Full Article
ser This Tool Can Help Identify 'STEM Deserts.' But It Needs Your Feedback By feedproxy.google.com Published On :: Fri, 03 May 2019 00:00:00 +0000 The National Math and Science Initiative's new tool aims to help the field look for patterns in STEM data, so educators and policy folks can fill in holes. Full Article Mathematics
ser Half-Life Game Series Will Finally Return With VR-Based Project By www.pcmag.com Published On :: Valve's tweet describes the upcoming title Half-Life: Alyx as the company's 'flagship VR game.' So you'll probably need a virtual headset to play it. The company will reveal more details on Thursday. Full Article
ser Netflix Series Reignites 'The Witcher 3' Interest on Steam By www.pcmag.com Published On :: The Witcher 3 is more popular on Steam today than at its launch in May 2015, thanks in large part to the Netflix series based on the popular book series. Full Article
ser Civil engineering student’s success earned through service By news.psu.edu Published On :: Fri, 01 May 2020 09:13 -0400 Penn State senior Abigail Cowser was recently named one of 10 American Society of Civil Engineers "2020 New Faces of Civil Engineering - College Edition." Full Article
ser Free dental services for veterans, active military and dependents By news.psu.edu Published On :: Wed, 11 Mar 2020 11:57 -0400 Pennsylvania College of Technology dental hygiene students and volunteer dental professionals will provide free dental hygiene services to veterans, members of the armed services, and their dependents on Saturday, April 4. Full Article
ser As dating apps try to pivot to virtual events, some users are trying to get people to violate social distancing rules By feedproxy.google.com Published On :: Sat, 09 May 2020 12:50:00 GMT Source: www.businessinsider.com - Saturday, May 09, 2020 Dating apps like Tinder, Bumble, and Hinge have reported increased use amid the coronavirus pandemic, while touting virtual dating alternatives for users instead of meeting up in person. Swaths of users are still encouraging matches to break quarantine to have sex and go on dates, despite social distancing guidelines and fines to comply with them. An illustrator on Instagram has been collecting screenshots of these situations, and told Business Insider that users will brand themselves as "badasses," dispute the effectiveness of isolating, and lash out in anger and hurl abusive language when they're rejected. Spokespeople for Grindr, Tinder and Bumble told Business Insider they've informed users to adhere to social-distancing guidelines, but did not respond to inquiries about actions they're taking against users in places where violating lockdown orders can be against the law. Visit Business Insider's homepage for more stories . As millions remain confined to their homes to prevent the spread of coronavirus, the desire for human contact and connection has risen dramatically and led some to search for ways to break those social distancing rules. Popular dating apps — including Tinder , Bumble , and Hinge — have reported significant increases during the outbreak of swiping activity, matches between users, and messages exchanged. It's also led to the introduction of a breed of users who are interested in shirking lockdown orders, anAll Related Full Article
ser Stuckeman School graduate student earns Alumni Association Dissertation Award By news.psu.edu Published On :: Fri, 24 Apr 2020 09:51 -0400 Stuckeman School graduate student Debora Verniz, who is a doctoral candidate in architecture, has been awarded the 2020 Alumni Association Dissertation Award from the Graduate School at Penn State for her research work in planning affordable housing structures in low-income areas. Full Article
ser Les élections seront-elles l’étincelle qui mettra le feu au Burundi ? By feedproxy.google.com Published On :: Wed, 03 Jun 2015 22:00:00 GMT Tous les éléments d’une confrontation violente sont en place en Burundi. En observant les derniers développements, il semble que les éléments qui ont conduit par le passé à des massacres et à une longue guerre civile au début des années 1990 se remettent en place. Full Article
ser Biochemical Characterization of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo-Beta-Lactamases [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-09T08:34:13-07:00 QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC50 range 1-3 nM) and carbapenemases such as KPC (IC50 2.9±0.4 nM) as well as class C P99 (IC50 of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC50 range 1-2 nM) as well as MBLs such as NDM-1 (IC50 55±25 nM), VIM-1 (IC50 14±4 nM) and IMP-1 (IC50 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k2/K ranging from of 6.3 x 104 (for P99) to 9.9 x 105 M-1 s-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with Kis of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics. Full Article
ser The Als3 cell wall adhesin plays a critical role in human Serum amyloid A1 (SAA1)-induced cell death and aggregation in Candida albicans [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-23T08:47:35-07:00 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. Full Article
ser Spectrum of Beta-Lactamase Inhibition by the Cyclic Boronate QPX7728, an Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases: Enhancement of Activity of Multiple Antibiotics Against Isogenic Strains Expressing Single {beta} By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development. Full Article
ser The Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. [Mechanisms of Resis By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics. Full Article
ser Epidemiological study on prevalence, serovar diversity, multi-drug resistance and CTX-M-type extended-spectrum {beta}-lactamases of Salmonella spp. from patients with diarrhea, food of animal origin, and pets in several provinces of China [Epidemiology an By aac.asm.org Published On :: 2020-04-20T08:36:46-07:00 A total of 2,283 Salmonella spp. isolates were recovered from 18,334 samples including patients with diarrhea, food of animal origin and pets across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistant to ≥ 1 antimicrobial and 56.4% were multi-drug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), 200 of which were CTX-M-type that were mostly detected from chicken meat and turtle fecal. Overall, eight blaCTX-M genes were identified, with blaCTX-M-65, blaCTX-M-123, blaCTX-M-14, blaCTX-M-79, and blaCTX-M-130 being the most prevalent. Totally, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (and S80I), whilst the PMQR-encoding genes oqxA/B, qepA, and qnrB/S were detected in almost all isolates. Of the fifteen sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in the number of isolates. Our study revealed considerable serovars diversity, high prevalence of co-occurrence of MDR determinants, including CTX-M-type ESBLs, QRDRs mutations and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDRs mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in the health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M Salmonella spp. isolates. Full Article
ser Google's Advanced Protection Expands to Phone-Only Users By www.pcmag.com Published On :: Google has made it easier to join the company's Advanced Protection Program, which is designed to stop the most sophisticated hackers from breaking into your Gmail account. Before you needed two security keys to enroll. Now you just need a smartphone. Full Article
ser Bad Flaw in Windows 10 Also Affects Chrome Browser By www.pcmag.com Published On :: Security researchers are demonstrating how you can use the Windows 10 flaw, CVE-2020-0601, to spoof the trusted digital certificates for official website domains on Google's Chrome browser. These same certificates can warn you about hacking attempts. Full Article
ser Avast Defends Data Harvesting, Plans to Get Users to Agree to It By www.pcmag.com Published On :: On Tuesday, Avast responded to a PCMag-Motherboard investigation into the company's browser history collection practices, saying it was entirely legal. Avast users should expect to see a prompt from the antivirus products, asking them to consent to the data harvesting. Full Article