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Changing the future of migration by investing in food security and rural development

Migration has always existed. It has been a means to reunite with family, to find better jobs, to have a new experience or to start a better life. In 2015, the number of people migrating was up to 1 out of every 7 people in the world.   When it is a choice, migration can be a good way to spread [...]




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Empowering rural women is key to ensuring food security

When approaching the small house, Hanen can be seen laughing with her family in the yard. Hanen is a 25-year-old biologist living in Ouled Taleb, Siliana, one of several areas in North West Tunisia that are particularly hard-hit by unemployment, low income and high rates of migration. Hanen comes from a poor rural family, who invested in their children’s education [...]




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7 success factors to empowering rural women through ICTs

The digital revolution has changed the way we work, access information and connect with each other. It offers opportunities to those who can use the new technologies, but also presents new challenges for those who are left behind. Often referred to collectively as Information and Communications Technologies or ICTs, these technologies are any method of electronically sharing or storing data: telephones, [...]




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Ethiopia's youth find hope in agricultural entrepreneurship

27-year-old Amiat Ahmed and her two-year-old son live with Amiat’s parents in the South Wollo Zone of Amhara Region, Ethiopia. Like many other young people in her region, Amiat used to feel that there were limited opportunities to earn income in her village, which led to her decision to migrate to Saudi Arabia.  




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How COVID-19 Is Affecting the Cultural World

Museum closures and event cancellations abound as officials rush to contain the new coronavirus' spread




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http://digg.com/submit?url=http://www.edge.org/conversation/a-cultural-history-of-physics




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At 67 Million Years Old, Oldest Modern Bird Ever Found Is Natural 'Turducken'

Remarkable fossil hints at the traits birds evolved just before an asteroid wiped their nonavian dinosaur kin




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68 Cultural, Historical and Scientific Collections You Can Explore Online

Tour world-class museums, read historic cookbooks, browse interactive maps and more




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As COVID-19 Reshapes the World, Cultural Institutions Collect Oral Histories

Universities, libraries and museums are among the organizations seeking personal stories about the pandemic's effects on daily life




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Rural living complicates access to Real ID




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See How Artists Have Turned Farm Silos Into Stunning Giant Murals

The projects are helping Australia's drought-stricken rural towns find new life as outdoor art galleries




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Saskatchewan to have higher than normal fire conditions this summer: Natural Resources Canada

Fire scientist say that Saskatchewan say Canadian Forest Service is updating their interactive maps every month from May to September this year so people can check the fire map in their region. Saskatchewan is one of the highest chances of fire this year.



  • News/Canada/Saskatchewan

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“The Arts” and Kenyon Cox: A Mural in the Thomas Jefferson Building

The following is a post by Kristi Finefield, Reference Specialist in the Prints & Photographs Division, and member of the Picture This blog team. As the Library of Congress marks its 220th year, we take the opportunity to explore one example of its efforts to sustain and celebrate the arts in its physical spaces. Above […]




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Cultural CRM-ization

You can reduce the story of CRM to a lot of things, especially its many component parts. Social networking, cloud computing and analytics are mentioned often. We don't need an exhaustive list, but if we stop there I think we miss a lot. To me CRM isn't about the parts, although like most people following the industry, I get a modicum of joy when a vendor adds something new to the toolbox.




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Bomb scare at Windsor cultural centre turns out to be forgotten ghost-hunting device

It turns out a small black box with a dangling red wire and little blue light investigated by Windsor's bomb squad Tuesday isn't actually dangerous — at least to the living.



  • News/Canada/Windsor

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Designing and Troubleshooting Immunopanning Protocols for Purifying Neural Cells

Purifying and culturing cells from the central nervous system (CNS) has proved to be an incredibly powerful tool for dissecting fundamental neuron and glial properties, and especially powerful in understanding neuronal–glial interactions. In a series of detailed protocols, we have provided step-by-step instructions for purifying and culturing specific types of neurons, glia, and vascular cells from the CNS by immunopanning. This article discusses common pitfalls and errors as well as important design considerations for the immunopanning procedure.




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Perform Abaqus High-End Simulations from Home with Structural Mechanics Engineer

Structural Mechanics Engineer on the cloud-based 3DEXPERIENCE platform enables SOLIDWORKS users to solve any finite element analysis (FEA) problem with confidence.

Author information

Nicolas Tillet
Product Portfolio Manager at DS SOLIDWORKS Corp.

Product Portfolio Manager for SOLIDWORKS Simulation

The post Perform Abaqus High-End Simulations from Home with Structural Mechanics Engineer appeared first on The SOLIDWORKS Blog.




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Cross-cultural pioneers

OM team in Hong Kong breaks cross-cultural ground, learning how to reach out to the ethnic minority, largely ignored by the Chinese population.




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Pope Francis speaks up for ‘harshly exploited’ agricultural workers

Vatican City, May 6, 2020 / 05:30 am (CNA).- The coronavirus crisis can be an opportunity to recenter work on the dignity of each person, Pope Francis said in an appeal at the end of his general audience broadcast on Wednesday. 

“On May 1, I received several messages about the world of work and its problems. I was particularly struck by that of the agricultural workers, among them many migrants, who work in the Italian countryside. Unfortunately, many are very harshly exploited,” Pope Francis said May 6.

“It is true that the current crisis affects everyone, but people's dignity must always be respected. That is why I add my voice to the appeal of these workers and of all exploited workers. May the crisis give us the opportunity to make the dignity of the person and of work the center of our concern,” he said. 

Amid fears of a food shortage, the Italian government is currently discussing whether to legalize some undocumented migrant workers. These workers are particularly vulnerable to exploitation with illegal contracts that can pay less than half of Italy’s minimum wage for the agricultural sector.

May 1 is recognized as Labor Day in Italy and many countries throughout Europe, however it is not an official holiday in the Vatican, which instead celebrates the feast of St. Joseph the Worker, established by Pope Pius XII in 1955.

On the feast day, the pope asked St. Joseph to help Catholics fight for dignified work. He prayed that “no one might be without work and all might be paid a just wage.”

Pope Francis said in his Wednesday audience that prayer is “a cry that comes for the heart of those who believe and entrust themselves to God.” The pope began a new cycle of weekly catechesis on May 6 focused on prayer. 

“Not only do Christians pray, they share the cry of prayer with all men and women. But the horizon can still be widened. Paul says that the whole creation ‘groans and suffers the pains of childbirth,’” he said, quoting St. Paul’s letter to the Romans.

“The Catechism states that ‘humility is the foundation of prayer,’” the pope said. “Prayer … comes from our precarious state, from our continuous thirst for God.”

Pope Francis focused his catechesis on the Gospel account of Bartimaeus, the blind beggar from Jericho.

Bartimaeus “uses the only weapon in his possession: his voice. He starts shouting: ‘Son of David, Jesus, have mercy on me,’” the pope explained.

“And Jesus listens to his cry. Bartimaeus' prayer touches his heart, the heart of God, and the doors of salvation are opened for him,” he said. “He recognizes in that poor, helpless, despised man, all the power of his faith, which attracts the mercy and power of God.”

“Stronger than any argument, there is a voice in the human heart that calls out. We all have this voice inside. A voice that comes out spontaneously, without anyone commanding it, a voice that questions the meaning of our journey down here, especially when we are in the dark: ‘Jesus, have mercy on me! Jesus, have mercy on me!’ This is a beautiful prayer,” Pope Francis said.




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Coronavirus: Home working 'could help revive Scotland's rural communities'

SCOTLAND’S workers could stay put in rural communities in the post-lockdown world - boosting countryside economies and cutting commuter traffic, a Holyrood cabinet secretary has suggested.




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Culturally Responsive Teaching Is Promising. But There's a Pressing Need for More Research

The evidence that culturally responsive teaching can fix the nation's schools for children of color is promising, but woefully incomplete, writes Heather C. Hill.




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Culturally Supportive Program for Black Boys Boosts On-Time Graduation Rates

The California district rolled out a culturally-specific program to support black male students, and the program has led to positive outcomes for students who had an opportunity to participate.




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How and Why to Teach Rural Entrepreneurship

Rural advocates say developing youth entrepreneurs is one way to spark economic development, and a new Rural Entrepreneurship Teaching Unit gives educators a template for teaching students about that issue.




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Q & A: Rural Children Are a Marginalized Population

Laurie Baker says the rural population should be considered a special population when considering education reforms.




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Culturally Supportive Program for Black Boys Boosts On-Time Graduation Rates

The California district rolled out a culturally-specific program to support black male students, and the program has led to positive outcomes for students who had an opportunity to participate.




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The Natural Course of Infantile Spinal Muscular Atrophy With Respiratory Distress Type 1 (SMARD1)

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a progressive, inherited neuromuscular disease manifesting with diaphragmatic paralysis in the first year of life. All patients need mechanical ventilation.

We describe the natural course of SMARD1, developed a scoring system, and defined prognostic values. The clinical outcome of the patients was heterogeneous, and residual enzymatic activity of the IGHMBP2 protein was associated with a more benign disease course. (Read the full article)




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Intrapartum Temperature Elevation, Epidural Use, and Adverse Outcome in Term Infants

Previous observational studies and randomized trials have reported an association between the use of epidural analgesia for pain relief in labor and intrapartum maternal fever. Studies have also reported an increase in adverse neonatal outcomes with intrapartum maternal fever.

Among low-risk women receiving epidural analgesia, intrapartum maternal temperature >99.5°F was associated with adverse neonatal outcomes, with the rate of adverse outcomes increasing directly with maximum maternal temperature. Without temperature elevation, epidural use was not associated with adverse neonatal outcomes. (Read the full article)




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Incidence and Cost of Injury Among Youth in Agricultural Settings, United States, 2001-2006

Several studies have analyzed fatal or nonfatal youth injury incidence in US agricultural settings, but none have combined those estimates to form an overall picture. The only detailed study of costs related to such injuries is restricted to nonfatal injury.

This study provides a comprehensive analysis of the annual incidence and cost of agricultural youth injuries in the United States. It analyzes them from different perspectives: fatal versus nonfatal, at work versus not at work, and requiring hospitalization versus not requiring hospitalization. (Read the full article)




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Birth Asphyxia: A Major Cause of Early Neonatal Mortality in a Tanzanian Rural Hospital

The presumed causes of neonatal deaths globally have remained unchanged over the past decade and include infections (~30%), prematurity (~30%), and asphyxia (~25%). Great uncertainty surrounds these estimates and, in addition, cases are likely misclassified as stillbirths.

These observational findings indicate that asphyxia accounts for a much higher percentage (60% of early deaths). Prematurity (18%), low birth weight (8%), and overt infection are much less common. The 5-minute Apgar score is an unreliable indicator of birth asphyxia. (Read the full article)




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Risk Factors for Hospitalization With Lower Respiratory Tract Infections in Children in Rural Alaska

Rural Alaska children have high rates of hospitalization with lower respiratory tract infections from a variety of pathogens. Past studies of risk factors for respiratory syncytial virus infection associated medically high-risk status, household crowding, and infant feeding practices with hospitalization.

This study reveals the importance of medically high-risk status and infant feeding practices as important factors in respiratory hospitalization. In addition, we identified woodstove use and the absence of 2 or more sinks in household as risk factors for hospitalization. (Read the full article)




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Culturally Tailored, Family-Centered, Behavioral Obesity Intervention for Latino-American Preschool-aged Children

Childhood obesity is already prevalent by preschool age, particularly among Latinos. Parents have tremendous influence on factors that contribute to childhood obesity (eg, diet, physical activity); thus, family plays a crucial role in pediatric obesity prevention.

This randomized controlled trial examined the effect of a behavioral intervention involving Latino-American parent–preschool-aged child dyads. The intervention resulted in reductions in absolute BMI across the 3-month study period, with patterns suggesting the largest effect for obese children. (Read the full article)




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Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence

Despite the dramatic rise in prevalence of metabolic syndrome (MetS) among children and adolescents, and that MetS is associated with cognitive and brain impairments among adults, no data on the impact of MetS on the brain exist in children.

It provides the first data on the impact of MetS on brain in adolescence. We show reductions in cognitive function and brain structural integrity in nondiabetic adolescents with MetS, thus suggesting that even pre-clinical metabolic illness may give rise to brain complications. (Read the full article)




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Hospitalization of Rural and Urban Infants During the First Year of Life

Patients living in rural versus urban counties encounter different health care environments. Whether these differences result in different health care utilization for rural versus urban infants is not known.

In this study, infants living in rural California counties were hospitalized less often than infants living in urban counties. Among those hospitalized, infants living in rural counties were hospitalized for fewer cumulative days than infants residing in urban counties. (Read the full article)




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Effect of Iron Deficiency Anemia in Pregnancy on Child Mental Development in Rural China

In humans, the brain growth spurt begins in the last trimester of pregnancy and extends through the first 2 years of life. Studies show poor cognitive and motor development among children who have iron deficiency anemia in infancy.

Prenatal iron deficiency anemia in the third trimester affects child mental development. Prenatal micronutrient supplementation with sufficient iron protects child mental development even when the woman’s iron deficiency anemia is not properly corrected during pregnancy. (Read the full article)




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Natural History of Stuttering to 4 Years of Age: A Prospective Community-Based Study

Stuttering is extremely common, with 8.5% of children affected by age 3 years in a prospective community-ascertained cohort of Australian children. The natural history and comorbidities of early stuttering are uncertain at the population level.

The cumulative incidence of stuttering was 11% by 4 years. Stuttering children were similar in temperament and social-emotional development but had better verbal and nonverbal skills than their peers. Recovery from stuttering was low; 6.3% 12 months after onset. (Read the full article)




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Telemedicine Consultations and Medication Errors in Rural Emergency Departments

Medication errors occur frequently among pediatric patients, particularly those treated in rural emergency departments (EDs). Although telemedicine has been proposed as a potential solution, there are few data supporting its clinical effectiveness and its effect on medication errors.

The use of telemedicine to provide pediatric critical care consultations to rural EDs is associated with less frequent physician-related ED medication errors among seriously ill and injured children. Therefore, this model of care may improve patient safety in rural hospital EDs. (Read the full article)




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Postural Orthostatic Tachycardia Syndrome (POTS) and Vitamin B12 Deficiency in Adolescents

Studies have shown dysfunction in the baroreflex mechanism and the autonomic nervous system, particularly in the sympathetic nervous system, in the pathophysiology of chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and syncope.

Vitamin B12 deficiency is associated with postural orthostatic tachycardia syndrome in adolescence. (Read the full article)




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The Natural History of Jaundice in Predominantly Breastfed Infants

Newborn infants who are predominantly breastfed are much more likely to develop prolonged hyperbilirubinemia than those fed formula, but the prevalence of prolonged hyperbilirubinemia in a largely white, North American, breastfed population is unknown.

Practitioners can be reassured that it is normal for 20% to 30% of predominantly breastfed infants to be jaundiced at age 3 to 4 weeks and for 30% to 40% of these infants to have bilirubin levels ≥5 mg/dL. (Read the full article)




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Subdural Hemorrhage and Hypoxia in Infants With Congenital Heart Disease

Asymptomatic neonatal subdural hemorrhage (SDH) is common, resolves within 4 weeks, and is typically infratentorial or posterior when supratentorial. Subdural hemorrhages may occur after cardiac surgery in infancy. Some hypothesize a causal relationship between hypoxia and SDH in infancy.

Asymptomatic neonatal SDH is often supratentorial and over the convexities. Small infratentorial SDHs may persist for ≤90 days. In young infants with congenital heart disease, an association between hypoxia and SDH could not be demonstrated. (Read the full article)




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Cognitive-Behavioral Counseling for Exclusive Breastfeeding in Rural Pediatrics: A Cluster RCT

Exclusive breastfeeding until 6 months of an infant’s age is described as the safest, most powerful and cost-effective intervention to reduce infant morbidity and mortality globally. In developing countries, only ~25% of infants are exclusively breastfed for 6 months.

We developed a psycho-educational intervention combining education with techniques of cognitive-behavioral therapy, integrated it into the routine work of community health workers, which increased the rate and duration of exclusive breastfeeding until 6 months of an infant’s age. (Read the full article)




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Risk of Sensorineural Hearing Loss and Bilirubin Exchange Transfusion Thresholds

High bilirubin levels are associated with sensorineural hearing loss. Exchange transfusions are recommended when bilirubin levels reach certain thresholds. However, the relative and excess risks of hearing loss in infants with bilirubin levels at/above exchange transfusion thresholds are unknown.

In this Northern California population of term and late preterm infants, elevated bilirubin levels were not associated with an increased risk of sensorineural hearing loss unless the levels were at least 10 mg/dL above exchange transfusion thresholds. (Read the full article)




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Response: 'Challenges Are a Natural Part of Mathematics'

Makeda Brome, Pia Hansen, Linda Gojak, Marian Small, Kenneth Baum and David Krulwich share their thoughts on the biggest challenges facing math teachers.




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SB 12-02 Agricultural Holdings (Amendment)(Scotland) Bill

9 January 2012This briefing details the development of the Agricultural Holdings (Amendment)(Scotland) Bill and the changes proposed by the Bill.




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Kudzu Bricks, Tiny Homes, and Glow-in-the-Dark Horseshoes: Innovation in Rural Kentucky Schools

In rural Kentucky, teachers and students are awarded innovation grants to solve a challenge facing their community or classroom.




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College of Agricultural Sciences stays connected with alumni during pandemic

Penn State’s College of Agricultural Sciences is staying connected to alumni during the COVID-19 pandemic by moving its monthly Alumni Society board meetings and other alumni activities online.




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Assessment of drug resistance during phase 2b clinical trials of presatovir in adults naturally infected with respiratory syncytial virus [Antiviral Agents]

Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.

Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.

Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.

Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes.




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Antimicrobial resistance in clinical Ureaplasma spp. and Mycoplasma hominis and structural mechanisms underlying the quinolone resistance [Mechanisms of Resistance]

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.




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Structural recognition of spectinomycin by resistance enzyme ANT(9) from Enterococcus faecalis [Mechanisms of Resistance]

Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is the modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT (9) family or by the dual-specificity ANT(3") (9) family that also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3") (9) AadA from Salmonella enterica. ANT (9) from Enterococcus faecalis adenylates the 9-hydroxyl of spectinomycin. We here present the first structures of spectinomycin bound to an ANT enzyme. Structures were solved for ANT (9) in apo form, in complex with ATP, spectinomycin and magnesium or in complex with only spectinomycin. ANT (9) shows similar overall structure as AadA with an N-terminal nucleotidyltransferase domain and a C-terminal α-helical domain. Spectinomycin binds close to the entrance of the interdomain cleft, while ATP is buried at the bottom. Upon drug binding, the C-terminal domain rotates by 14 degrees to close the cleft, allowing contacts of both domains with the drug. Comparison with AadA shows that spectinomycin specificity is explained by a straight α5 helix and a shorter α5-α6 loop that would clash with the larger streptomycin substrate. In the active site, we observe two magnesium ions, one of them in a previously un-observed position that may activate the 9-hydroxyl for deprotonation by the catalytic base Glu-86. The observed binding mode for spectinomycin suggests that also spectinamides and aminomethyl spectinomycins, recent spectinomycin analogues with expansions in position 4 of the C ring, will be subjected to modification by ANT (9) and ANT(3") (9) enzymes.




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Structural basis of reduced susceptibility to ceftazidime-avibactam and cefiderocol in Enterobacter cloacae due to AmpC R2 loop deletion [Mechanisms of Resistance]

Ceftazidime–avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. Here we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant Enterobacter cloacae clinical strain (Ent385) was found to be resistant to ceftazidime–avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpCEnt385) contained an alanine–proline deletion at positions 294–295 (A294_P295del) in the R2 loop. AmpCEnt385 conferred reduced susceptibility to ceftazidime–avibactam and cefiderocol when cloned into Escherichia coli TOP10. Purified AmpCEnt385 showed increased hydrolysis of ceftazidime and cefiderocol compared with AmpCEnt385Rev, in which the deletion was reverted. Comparisons of crystal structures of AmpCEnt385 and AmpCP99, the canonical AmpC of E. cloacae, revealed that the two-residue deletion in AmpCEnt385 induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in ampC to confer reduced susceptibility to both ceftazidime–avibactam and cefiderocol requires close monitoring.

Importance Ceftazidime–avibactam and cefiderocol are newly approved β-lactam agents that possess broad spectrum activity against multidrug-resistant (MDR) Gram-negative bacteria. We show here that a two amino-acid deletion in the chromosomal AmpC β-lactamase, identified in a clinical strain of Enterobacter cloacae, confers reduced susceptibility to both agents. By crystallographic studies of free and drug-bound forms of enzyme, we demonstrate that this deletion in AmpC induces slanting of the H-9 helix that is directly connected with the R2 loop, and disappearance of the H-10 helix, is directly responsible for increased hydrolysis of ceftazidime and cefiderocol. These findings provide novel insights into how MDR Gram-negative bacteria may evolve their β-lactamases to survive selective pressure from these newly developed β-lactam agents.




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Therapeutic efficacy of a mixed formulation of conventional and PEGylated liposomes containing meglumine antimoniate, combined with allopurinol, in dogs naturally infected with Leishmania infantum [Experimental Therapeutics]

Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis.