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Judge Dismisses Concussion Lawsuit Against Illinois High School Association

An Illinois judge has dismissed the nation's first class-action lawsuit against a state high school association over its handling of concussions, ruling that it had made strides in that regard since the filing of the lawsuit.




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Illinois Gov. Apologizes for Calling Chicago Teachers 'Illiterate'

Illinois Gov. Bruce Rauner said that half of Chicago teachers were "illiterate" in a 2011 email, recently released to a city newspaper.




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Latino Vote Implications for Trump, the GOP, and Bilingual Education

Californians are expected to reinstate bilingual education. The vote is likely to be a milestone in the rise of Latino voting power. Bad news for Donald Trump; worse news for the GOP.




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Fish-Oil Fat Emulsion Supplementation May Reduce the Risk of Severe Retinopathy in VLBW Infants

Docosahexaenoic acid is important for fetal brain development and visual acuity in infants. Infants born prematurely are at particular risk for docosahexaenoic acid insufficiency because they may not have benefited from a full trimester of the mother's lipid stores.

This is the first study in which the administration of fish-oil lipid emulsion in very low birth weight infants from the first day of life is described. The influence of fish-oil lipid emulsion on the regression of retinopathy seems to be worthy of further investigation. (Read the full article)




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Impact of a Transcutaneous Bilirubinometry Program on Resource Utilization and Severe Hyperbilirubinemia

Predischarge serum or transcutaneous bilirubinometry (TcB) measurements are recommended as appropriate screening options for identifying infants at risk for neonatal hyperbilirubinemia (NH). Visual inspection for jaundice is not reliable at identifying infants with NH in the community.

When compared with visual inspection alone, coordinated TcB screening for NH in acute-care and community settings is associated with significant improvements in laboratory utilization, patient care, convenience, and safety. (Read the full article)




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Human Rhinoviruses in Severe Respiratory Disease in Very Low Birth Weight Infants

Human rhinovirus infections are common in children. Although historically associated with upper respiratory tract illness, rhinoviruses are increasingly recognized for their role in the exacerbation of asthma. Their role in bronchiolitis and severe lung disease in premature infants is unclear.

The authors of this study prospectively explore the role of rhinoviruses in premature infants using molecular techniques and identify these agents as the most frequent cause of hospitalization in this population. (Read the full article)




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Early Childhood Family Intervention and Long-term Obesity Prevention Among High-risk Minority Youth

The evidence base for obesity prevention is extremely limited. Although minority youth are at higher risk of obesity, and early childhood is a critical period for prevention, only 1 program has demonstrated sustained effects on obesity in young minority children.

Among youth at high risk for obesity based on income, minority status, and child behavior problems, early intervention that promotes effective parenting led to meaningful differences in obesity in preadolescence. Early family intervention is an innovative and promising approach. (Read the full article)




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Medication Adherence Among Latino and Non-Latino White Children With Asthma

Asthma disparities exist, with Latino children of Caribbean descent at risk for poor disease control. Controller medications reduce symptoms; however, medication adherence remains suboptimal. Identifying what factors predict poor medication adherence in at-risk groups could identify important treatment targets.

This study is the first to assess objective rates of medication use among children with asthma in Puerto Rico. Findings suggest that interventions incorporating family resources and addressing parental beliefs about medications may be of benefit across cultural groups. (Read the full article)




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Preeclampsia and Retinopathy of Prematurity in Preterm Births

Preterm infants are at a high risk for retinopathy of prematurity (ROP). Several postnatal factors are well known to be associated with ROP. However, the relationships between antenatal or maternal risk factors and ROP are poorly understood.

This study used a large cohort database to study the influence of maternal gestational hypertension and preeclampsia on ROP in preterm infants. The results showed that preeclampsia, but not gestational hypertension, was associated with a reduced risk of ROP in preterm births. (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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Physical Activity During School in Urban Minority Kindergarten and First-Grade Students

Physical inactivity is one of the major modifiable factors contributing to the growing national epidemic of childhood obesity. There is lack of literature on pedometer-determined physical activity (PA) during the school day in US minority kindergarten and first-grade students.

This is the first study to assess school-day PA in US urban minority kindergarten and first-grade students. Higher grade level, participation in physical education class, and outdoor recess were found to be independent predictors of PA. (Read the full article)




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Chronic Acetaminophen Exposure in Pediatric Acute Liver Failure

Children with acute liver failure due to a single-dose acetaminophen exposure have a characteristic liver biochemistry profile of low conjugated bilirubin and high alanine aminotransferase, which is associated with a favorable clinical outcome when treated with N-acetylcysteine.

Children with acute liver failure associated with chronic acetaminophen exposure also have a similar liver biochemistry profile, but for unknown reasons, they have a poorer clinical outcome than patients with single-dose acetaminophen exposure. (Read the full article)




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Pediatrician Identification of Latino Children at Risk for Autism Spectrum Disorder

Latino children are diagnosed with autism spectrum disorders (ASDs) less often and later than white children. Primary care pediatricians (PCPs) may play an important role in early ASD identification for Latinos.

PCPs find it more difficult to assess for ASDs in Latinos with Spanish primary language, view Latino parents as less knowledgeable about ASDs, and experience frequent barriers to ASD diagnosis in Latino patients. Many PCPs do not offer recommended screenings in Spanish. (Read the full article)




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Nurse and Physician Agreement in the Assessment of Minor Blunt Head Trauma

Effective implementation of Pediatric Emergency Care Applied Research Network head trauma rules depends on their early application. As the registered nurse (RN) is often the first to evaluate children with blunt head trauma, initial RN assessments will be an important component of this strategy.

We demonstrated fair to moderate agreement between RN and physician providers in the application of the Pediatric Emergency Care Applied Research Network head trauma rules. Effective implementation strategies may require physician verification of RN predictor assessments before computed tomography decision-making. (Read the full article)




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Human Rhinovirus and Disease Severity in Children

Human rhinovirus has been known as the common cold agent. Recently, studies have reported that this virus is responsible for severe infections of the lower respiratory tract in children. Reports of factors that increase disease severity have been contradictory.

This study identifies some of the factors involved in disease severity in HRV infections in children. We expect that children at risk for developing severe disease could be identified sooner and appropriate measures could be taken. (Read the full article)




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Early-Onset Basal Cell Carcinoma and Indoor Tanning: A Population-Based Study

Indoor tanning has gained widespread popularity among adolescents and young adults. Incidence rates of early-onset basal cell carcinoma also appear to be rising. Scant evidence exists on the impacts of early exposure and whether it leads to early occurrence of this malignancy.

In a US population-based study, indoor tanning was associated with an elevated risk of basal cell carcinomas occurring at or before the age of 50 years, with an increasing trend in risk with younger age at exposure among adolescents and young adults. (Read the full article)




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Pediatricians' Communication About Weight With Overweight Latino Children and Their Parents

Little is known about how pediatricians communicate with overweight Latino children and their parents regarding overweight and obesity.

Findings suggest that many overweight Latino children and their parents do not receive direct communication that the child is overweight, weight-management plans, culturally relevant dietary recommendations, or follow-up visits. (Read the full article)




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Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract.

In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. (Read the full article)




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Intranasal Triamcinolone and Growth Velocity

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

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




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Trisomy 21 and Risk of Retinopathy of Prematurity

It is known that trisomy 21 decreases the risk of (nonocular) angiogenic-mediated disorders, such as solid tumors. It is not known whether trisomy 21 decreases the risk of ocular angiogenic-mediated disorders such as retinopathy of prematurity.

This study shows that trisomy 21 decreases the risk of retinopathy of prematurity (ROP), thus unmasking a potentially identifiable genetic component to ROP risk. This study paves the way for the future development of a laboratory-based ROP screening tool. (Read the full article)




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High Stakes for Schools If 2020 Census Undercounts Latino Families

For communities with significant numbers of Latino and immigrant residents, the barriers to an accurate 2020 Census count are high—and so are the stakes for their schools, which could lose hundreds of millions of dollars if counts are inaccurate.




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In Vitro and In Vivo Characterization of Potent Antileishmanial Methionine Aminopeptidase-1 Inhibitors [Experimental Therapeutics]

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.




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Evaluation of the efficacy of antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa in automated time-lapse microscopy and static time-kill experiments [Clinical Therapeutics]

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤106 CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., blaPAO and blaOXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.




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Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, An Aminomethylcycline Antibiotic in Animal Models [Pharmacology]

KBP-7072 is a semi-synthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens including multidrug resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (IV) administration of single and multiple doses were investigated in animal models including during fed and fasted states and also evaluated the protein binding and excretion characteristics. In Sprague-Dawley (SD) rats, Beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after administration of single oral and IV and multiple oral doses. Oral bioavailability ranged from 12% to 32%. Mean Tmax ranged from 0.5 to 4 hours, and mean half-life ranged from approximately 6 to 11 hours. Administration of oral doses in the fed state resulted in a marked reduction in Cmax and AUC compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies.




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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

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.




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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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In vitro and in vivo study on the synergistic effect of minocycline and azoles against pathogenic fungi [Susceptibility]

In vitro and in vivo interactions of minocycline and azoles including itraconazole, voriconazole, and posaconazole against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus, 7 strains of A. flavus, 16 strains of Exophiala dermatitidis, 10 strains of Fusarium solani and 3 strain s of F. oxysporum. The results revealed that minocycline individually did not exhibit any significant antifungal activity against all tested strains. However, favorable synergy of minocycline with itraconazole, voriconazole, or posaconazole were observed against 34 (61%), 28 (50%), and 38 (69%) isolates, respectively, including azole resistant A. fumigatus and Fusarium spp. with inherently high MICs of azoles. Synergistic combinations resulted in 4 fold to 16-fold reduction of effective MICs of minocycline and azoles. No antagonism was observed. In vivo effect of minocycline-azole combinations were evaluated by survival assay in Galleria mellonella model infected with E. dermatitidis strain BMU00034, F. solani strain FS9, A. fumigatus strain AF293, AFR1 and AFR2 . Minocycline acted synergistically with azoles and significantly increased larvae survival in all isolates (P<0.001), including azole resistant A. fumigatus and azole-inactive Fusarium spp.. In conclusion, the results suggested that minocycline combined with azoles may help to enhance the antifungal susceptibilities of azoles against pathogenic fungi and had the potential to overcome azole resistance issues.




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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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Repurposing the antiamoebic drug diiodohydroxyquinoline for treatment of Clostridioides difficile infections [Experimental Therapeutics]

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.




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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.




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PAGI-associated CrpP-like fluoroquinolone-modifying enzymes among Pseudomonas aeruginosa clinical isolates in Europe [Mechanisms of Resistance]

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.




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Clinically relevant epithelial lining fluid concentrations of meropenem with ciprofloxacin provide synergistic killing and resistance suppression of hypermutable Pseudomonas aeruginosa in a dynamic biofilm model [Pharmacology]

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MICciprofloxacin 0.25 mg/L, MICmeropenem 2 mg/L) and CW44 (MICciprofloxacin 0.5 mg/L, MICmeropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log10 CFU/mL) and biofilm (>8log10 CFU/cm2) bacteria at 120h (MICciprofloxacin up to 8 mg/L, MICmeropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log10 CFU/mL and ≤6log10 CFU/cm2 at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.




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Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment




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Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), A Randomized, Controlled Trial. I: Primary Outcomes

The STOP-ROP Multicenter Study Group
Feb 1, 2000; 105:295-310
ARTICLES




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Let Minority-Serving Colleges Be a Model for Teacher Prep, Report Says

Teacher-preparation programs need to better prepare teachers, and especially white teachers, to serve students and communities of colors more effectively, the report says.




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Entrepreneurship and innovation minor graduates record number of students

The intercollege minor in entrepreneurship and innovation (ENTI) continues to spread its influence as it graduates its largest number of students this spring with 153 across eight clusters.




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Pandemic may revive Islamic State and hurt Iraq’s minorities, say NGOs

Rome Newsroom, Apr 22, 2020 / 12:00 pm (CNA).- For Iraqi Christian and Yazidi communities still recovering from the destruction wreaked by the Islamic State, the coronavirus poses significant risks, NGOs have said in a joint statement. 

“The public health system in Sinjar and the wider Nineveh Governorate was decimated by ISIS during its brutal occupation and genocidal campaign in Iraq, beginning in 2014,” the letter stated.

“An impending humanitarian and security disaster looms large in Iraq. … There is a significant attendant threat to global security if ISIS uses this opportunity to regroup and return, but it does not have to be this way. Iraqi authorities and the United Nations must act now,” it continued.

Twenty-five NGOs working in northern Iraq issued a joint statement April 16 calling on the World Health Organization to undertake an assessment mission in the area, where testing has been limited, and urging Iraqi authorities to prevent the Islamic State from regrouping.

Signed by the Iraqi Christian Relief Council, Free Yezidi Foundation, Genocide Alert, and the Religious Freedom Institute, the statement described how the pandemic is exacerbating existing security, humanitarian, and health risks among displaced and rebuilding Iraqi minority communities. It highlighted, in particular, the global risk of a potential resurgence of the Islamic State.

Security threat

“COVID-19 and the precipitous drop in oil prices have caused the Iraqi economy to collapse, leaving a dangerous security vacuum for ISIS to exploit. Indeed, the resultant political turmoil and social strife recall the very conditions that earlier incarnations of ISIS and its supporters capitalized on during its initial surge almost a decade ago,” it stated.

“According to International Crisis Group, ISIS in its weekly newsletter Al-Naba called on its fighters to attack and weaken its enemies while they are distracted by the pandemic,” it added.

U.S. military officials have expressed concern that the Islamic State could use adverse conditions to its advantage in it recruitment efforts.

“COVID-19 has also hastened the departure of some coalition forces from Iraq, weakening counter-terrorism operations, while some ISIS detainees have recently escaped prison in Syria,” the letter stated.

On March 30, Islamic State fighters imprisoned in northwestern Syria revolted. The rioting prisoners took over one wing of the prison before Kurdish forces intervened.

“There is an urgent need for reform in the civilian security sector, in order to integrate regional militias into a unified Federal Police that upholds the rule of law and protects all citizens, regardless of religion or clan affiliation,” the letter said.

Health infrastructure needs

The economic strain has also hindered Iraqi minorities’ efforts to rebuild their communities, including medical infrastructure needs.

“Many Yazidis (Ezidis/Yezidis) want to return to Sinjar, but security, reconstruction and basic services are still lacking to allow a dignified return. There are currently only two hospitals and just one ventilator to assist the current population of around 160,000 people in the region,” the NGOs’ statement explained.

Iraq’s healthcare system, which has suffered for decades from the effects of sanctions and war, currently faces a critical shortage of doctors and medicine, according to a Reuters investigation. Hospitals in Iraq are already overcrowded and doctors overworked, while the healthcare situation is slightly better in the semi-autonomous Kurdistan Region of Iraq, which has its own health ministry.

There have been at least 1,600 cases of COVID-19 documented in Iraq, which is under pressure to reopen its border with Iran, which has had more than 85,000 confirmed coronavirus cases, according to Johns Hopkins University Coronavirus Resource Center.

Humanitarian workers have also had trouble reaching those in need due to movement restrictions, and have raised concerns about the risk of an outbreak in internally displaced persons (IDP) camps.

Social distancing is very difficult in these high-density IDP camps in Iraq, where 1.8 million people remain displaced due to insecurity and reconstruction needs, according to the UN.

The 25 NGOs called for the government of Iraq and the United Nations to provide testing capacity in the IDP camps in Sinjar, Tel Afar and the Nineveh Plains.

“At present, it is impossible to apprehend the extent of the spread of the virus because no testing for the disease is taking place in the camps, while restrictions of movement impede the work of humanitarian actors who provide basic essentials such as food, water and medicine,” they stated.

Psychological risk for trauma survivors

Genocide survivors with trauma also face increased personal risk of psychological harm amid isolation imposed by coronavirus measures.

As in much of the world, authorities in Iraqi Kurdistan have ordered people to stay home, imposed a curfew, and have closed places of worship, schools, restaurants, and most businesses. 

“Another alarming corollary of the COVID-19 pandemic in Iraq is the psychological impact on at-risk communities, including Yazidis, Turkmen and Christians, such as Assyrians,” it said.

This is a particular concern for the Yazidi communities in which thousands of women were victims of sexual violence by the Islamic State.

“Prior to the outbreak, Médecins Sans Frontières reported on a debilitating mental health crisis among Yazidis in Iraq, including a rising number of suicides,” it stated.

Suicides in this community have already been reported since social distancing measures were put into place, the NGOs reported. They called on the World Health Organization to address this “acute mental health crisis.”

In their appeal to the WHO and Iraqi government, the NGOs insisted that the stakes were high: 

“COVID-19 is a pandemic the likes of which we have not seen before. Survivors of genocide and other mass atrocity crimes are now waiting for this silent death to pass through the camps and their homes, unable to fight back.”



  • Middle East - Africa

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Latinos on the move: from Brazil to South Asia

"Going into overseas ministry made me face reality", says 28-year old Vanilda Vaz from Brazil. She has been travelling through Latin America to tell as many people as possible about her work in South Asia.




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Fin24.com | Ominous issues loom over firms

Land ownership, nationalisation and press regulation could have a negative effect on business in the next 10 years, says a scenario strategist.




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Nikon Introduces the Binocular Telescope 20x120 IV/25x120




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Nikon introduces the ACULON T02 binoculars




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Nikon introduces the Sportstar Zoom 8-24x25 binoculars




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Minor Gas Leak In LPG Container Of Goods Train At Bhopal: Rail Official

Gas leak was detected on a goods train transporting LPG on Saturday at Bhopal railway station in Madhya Pradesh, a Railways official said.




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Flags to Remain at Half-Staff in Honor of Sen. Inouye

Flags will remain at half-staff until Monday, December 24, in honor of the late Senator Daniel K. Inouye.




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Gouvènè Carney Deklare COVID-19 la yon Pwen Cho nan Konte Sussex, Anonse Agrandisman Sit Kominotè pou Tès yo

WILMINGTON, Del. – Gouvènè John Carney te deklare nan madi a ke Konte Sussex la se yon plas cho pou COVID-19 nan Delaware epi li te anonse orè inisyal pou Kowòdinasyon ak Swen nan Eta Delaware la ak sit kominotè pou tès yo.   Yo pral fè tès ak kontak sansibilizasyon yo nan plizyè kominote Sussex yo nan sant ki […]



  • Governor John Carney
  • Office of the Governor
  • Coronavirus

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Tata Consumer Products ties up with Domino’s Pizza, Zomato to deliver essential goods

These channel partnerships have been done in a phased manner, with Flipkart being the first e-commerce platform to enable the availability of its essential products in Mumbai, Bengaluru and Delhi.




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Vinod Kothari Consultants (P) Ltd

We are into consulting on non-banking financial services. The candidate must have strong drafting skills for business agreements involving complicated financial transactions. Very strong understanding of the law of secured lending - mortgages, assignment, transfer of security interests, pledges, NBFC regulations, etc - will be essentialNo phone calls please. Only emails.




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Cerebrino Solutions

We are hiring 'Assistant / Deputy Manager - Litigation' for our client, a leading insurance company. Position: Assistant Manager / Deputy Manager - Litigation Job location: Ahmedabad Experience: Minimum 4 years in litigation Roles and responsibilities - AM / DM for litigation: Managing West & Central Zone (Gujarat, MP, Maharashtra, Goa, Daman & Diu) who shall work from Ahmedabad office.  Manage the entire litigation for the said zone; Manage the criminal matters, Ombudsman, FIR, recoveries; Handle the Litigation Management Tool; Participate in POSH complaints in his/her zone; The candidate should have at least 4 years of litigation experience, either in practice, law firm or corporate Candidates with acquaintance in the Gujarathi language The interested candidates should share their CVs to jobs@cerebrino.com along with the mention of - Current location Total experience: Experience in litigation: Current CTC Expected CTC Notice period




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Australia consults on restrictions for isothiazolinones

Applies to rinse-off cosmetics and other preparations




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'Clear evidence' of PFOA carcinogenic activity, according to NTP report

Effects observed in male rats