IP-10 is a novel immunologic marker for tuberculosis (TB) infection. It has been suggested that IP-10 may perform better in children compared with the QuantiFERON test, but only a few studies have investigated IP-10 for diagnosing active TB in children.

This study is the first to investigate IP-10 and QuantiFERON for diagnosing TB in children by using consensus classifications. Both IP-10 and QuantiFERON exhibited poor performance in children from a high-burden setting, and performance was especially compromised in young children. (Read the full article)

Light and intermittent smoking are harmful, but increasingly common, smoking patterns. It is unknown how adolescents perceive these smoking patterns, and whether these views differ by sociodemographic characteristics, and exposure to and use of tobacco.

US adolescents perceive light and intermittent smoking as significantly less dangerous than heavier smoking. One in 4 adolescents believes intermittent smoking causes little to no harm. Perceptions of relative safety were common among smokers. (Read the full article)

Early first sexual intercourse (FSI) is a risk factor for unplanned teenage pregnancy, sexually transmitted infection, and adverse health outcomes in adolescence and into adulthood. In girls, externalizing behaviors are more strongly associated with earlier FSI than internalizing behaviors.

Externalizing behavior from as early as 5 in boys and 10 in girls is a significant risk factor for earlier age at FSI. Internalizing behavior at ages 8 and 10 was associated with early FSI for boys but not girls. (Read the full article)

Adolescent obesity is characterized by endothelial dysfunction at the macrovascular and microvascular level; high endothelial microparticle (EMP) and low endothelial progenitor cell (EPC) counts contribute to these processes. Although reversal of macrovascular endothelial dysfunction is feasible, clinical evidence regarding microvascular endothelial dysfunction is scarce.

Ten months of diet and exercise training improves microvascular endothelial function (peak response) in obese adolescents. EPC and EMP displayed a biphasic response, with an increase in EPC at 5 months and a decrease in EMP at the end of the treatment. (Read the full article)

Fifteen percent of tuberculosis cases globally are resistant to the drug isoniazid. Isoniazid resistance puts patients with tuberculosis at risk for poor treatment outcomes and threatens the effectiveness of isoniazid preventive therapy in people with latent tuberculosis infection.

We present the first global and regional estimates of the proportion of children with tuberculosis who have isoniazid-resistant disease, showing large geographic variations in risk of resistance. We estimate the number of annual incident cases of isoniazid-resistant tuberculosis in children. (Read the full article)

Infant screening is valued by members of the lay public, but how different benefits are independently valued, and whether harms are disvalued, is not known. Public expectations of screening can inform decisions about what diseases to screen for.

The public values clinical benefits of screening and disvalues harms, with tolerance for harm proportional to clinical benefit. These findings support newborn screening policies prioritizing clinical benefits over solely informational benefits, coupled with concerted efforts to avoid or minimize harms. (Read the full article)

Central nervous system (CNS) tuberculosis has high morbidity and mortality, and it frequently affects children aged <5 years.

In California, children who were US-born, Hispanic, and aged <5 years were at increased risk of CNS tuberculosis. Children with CNS tuberculosis were more likely to die. Specific populations of US-born infants might benefit from additional prevention measures. (Read the full article)

Amid coronavirus-related school closures, advocates worry Education Secretary Betsy DeVos may waive requirements of special education law if Congress signs off. Schools say it's difficult to meet some requirements during the pandemic.

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We analyse how Latvia secured a point against Germany at UEFA EURO 2004.

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.

There is an urgent need for new, potent anti-tuberculosis (TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3, 4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent anti-tuberculosis activity. The minimum inhibitory concentrations of the compound for Mycobacterium tuberculosis ranged from 0.00024 to 0.002 μg/mL. It had bactericidal activity against both growing and intracellular bacilli, and the frequency of spontaneous resistance for Mycobacterium tuberculosis H37Rv was less than 1.91 x 10^-7. It did not show antagonistic effects with other anti-TB agents in an in vitro checkerboard assay. Whole genome and targeted sequencing of resistant isolates to OPC-167832 identified the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1), an essential enzyme for cell wall biosynthesis, as the target of this compound, and further studies demonstrated inhibition of the DprE1 enzymatic activity by OPC-167832. In a mouse model of chronic TB, OPC-167832 showed potent bactericidal activities starting at a dose of 0.625 mg/kg. Further, it exhibited significant combination effects in 2-drug combinations with delamanid, bedaquiline, or levofloxacin. Finally, 3-4 drug regimens comprised of delamanid and OPC-167832 as the core along with bedaquiline, moxifloxacin, or linezolid showed superior efficacy in reducing bacterial burden and preventing relapse compared to the standard treatment regimen. In summary, these results suggest that OPC-167832 is a novel and potent anti-TB agent and regimens containing OPC-167832 and new or repurposed anti-TB drugs may have the potential to shorten the duration of treatment for TB.

Globally, mutations in the katG gene account for the majority of isoniazid-resistant strains of Mycobacterium tuberculosis. Buyankhishig et al analyzed a limited number of Mycobacterium tuberculosis strains in Mongolia and found that isoniazid resistance was mainly attributable to inhA mutations. The GenoType® MTBDRplus assay was performed for isolates collected in the First National Tuberculosis Prevalence Survey and the Third Anti-Tuberculosis Drug Resistance Survey to investigate genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis in Mongolia. Of the 409 isoniazid-resistant isolates detected by the GenoType® MTBDRplus assay, 127 (31.1%) were resistant to rifampicin, 294 (71.9%) had inhA mutations without katG mutations, 113 (27.6%) had katG mutations without inhA mutations, and two (0.5%) strains had mutations in both the inhA and katG genes. Of the 115 strains with any katG mutation, 114 (99.1%) had mutations in codon 315 (S315T). Of the 296 trains with any inhA mutation, 290 (98.0%) had a C–15T mutation. The proportion of isoniazid-resistant strains with katG mutations was 25.3% among new cases and 36.2% among retreatment cases (p=0.03), as well as 17.0% among rifampicin-susceptible strains and 52.8% among rifampicin-resistant strains (p<0.01). Rifampicin resistance was significantly associated with the katG mutation (adjusted odds ratio 5.36, 95% CI 3.3–8.67, p<0.001). Mutations in inhA predominated in isoniazid-resistant tuberculosis in Mongolia. However, the proportion of katG mutations in isolates from previously treated cases was higher than that among new cases, and that in cases with rifampicin resistance was higher than that in cases without rifampicin resistance.

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficult to treat non-multiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our pre-clinical drug development pipeline. In most available dormancy models it takes a long time to create a dormant state and it is difficult to identify and quantify this non-multiplying condition.

The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes non-multiplying after 10 days of streptomycin starvation, but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetic model to assess the difference in the activity of isoniazid, rifampicin, moxifloxacin and bedaquiline against log-phase growth compared to the non-multiplying M. tuberculosis subpopulation by CFU counting including a novel AUC-based approach as well as time-to-positivity (TTP) measurements.

We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampicin and high dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value as it identifies a specific mycobacterial subpopulation that is non-culturable on solid media.

In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

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

Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study is to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography–tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, 14.08 ± 10.61 mg/L, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t =-2.810, p = 0.015; t =-4.901, p = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB infected tissues in patients with spinal MDR-TB.

Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC₅₀ value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.

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

The password-fatigued masses will be pleased to find Keeper's new 30 percent off deal, which brings it down to $20.99 per year from its typical $29.99.

During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

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During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

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Amid coronavirus-related school closures, advocates worry Education Secretary Betsy DeVos may waive requirements of special education law if Congress signs off. Schools say it's difficult to meet some requirements during the pandemic.

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Graham A. Colditz
Jul 1, 1995; 96:29-35
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Yong Y. Han
Dec 1, 2005; 116:1506-1512
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Start your new year off right by getting some new customized items for your business, or just treat yourself to a unique 2020 calendar of your own design, all for a fantastic price.

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From the creepy scales to the gaping wheel arches, the Vision Avtr is not particularly attractive, but it is environmentally friendly, from its vegan leather interior to its compostable battery.

During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

A new supercapacitor based on manganese oxide could combine the storage capacity of batteries with the high power and fast charging of other supercapacitors, according to researchers at Penn State and two universities in China.

During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

During special Easter outreaches to women in red light areas, outreach workers go in the knowledge that Jesus is with them and His resurrection power gives hope, strength and life.

One cabin on the Riverboat was specially set aside as a prayer room to encourage intercessory prayer at all times.

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The Wicked Lasers LaserCube is a portable, battery-powered laser projector that can deliver light shows, play games, and even etch wood.

Gunnar's Work-Play gaming glasses react to sunlight, shifting from a blue-ray-reducing amber tint indoors to full-on sunglasses outside.

As currently funded, $278 million project would unfairly burden electric ratepayers on Delmarva WILMINGTON, Del. – Delaware Governor John Carney and Maryland Governor Larry Hogan on Tuesday sent a letter to members of the Federal Energy Regulatory Commission, urging commissioners to expedite their review of the $278 million Artificial Island transmission line project and consider a […]

THE MEZZANINE GALLERY TO EXHIBIT HUGH PHIBB’S “WHAT THE WATER SAID…” WATERCOLORS Wilmington, Del. (January 24, 2018) – What the Water Said…Flowers, Places & Faces will be on view in the Mezzanine Gallery from February 2-23, 2018. A free opening reception to meet the artist will be held on Friday, February 2 from 5-7 p.m. […]

During the COVID-19 pandemic, however, the daily work routine for tailors and apprentices looks a bit different than usual: for several weeks, they have been producing hand-crafted masks for use of...

Conversational commerce, as it is more popularly known, is any form of online communication that takes place during an e-commerce purchase.

An Indian-origin man has pleaded guilty to an arson attack on a commercial centre in UK's Leicester in central England and is scheduled to get sentenced for the crime at a hearing in June.

Agency: DOT Closing Date: 6/4/2020

Agency: TRE Closing Date: 5/29/2020

The Division of Public Health (DPH) will host a two-day, exercise on Tuesday, June 19, and Wednesday, June 20, at Sussex Central High School, Georgetown. The purpose is to test the division’s ability to operate a shelter for residents who may be displaced or unable to occupy their homes in the event of a disaster.

The Division of Public Health (DPH) is looking for volunteers to participate in an emergency preparedness exercise on Saturday, September 28, 2019, at two Delaware Technical Community College (Delaware Tech) campuses. The purpose of the exercise is to evaluate the state’s ability to set up Points of Dispensing and simulate the dispersal of life-saving medication in an emergency situation.

Newport --

Traffic Information: The Delaware Department of Transportation (DelDOT) announces to motorists that the following ramps will be closed for reconstruction of the guardrails and the installation of detection system.



Sunday, March 15, 2020 from 8:00 p.m. until 5:00 a.m. on Monday, March 16, 2020

Location: Exit 5B/I-95 northbound to Route 141 northbound

Monday, March 16, 2020 starting at 8:00 p.m. until 5:00 a.m. on Tuesday, March 17, 2020

Tuesday, March 17, 2020 at 8:00 p.m. until 5:00 a.m. on Wednesday, March 18, 2020

Location: Exit 3A/Route 141 northbound to I-95 northbound

Location: Exit 3A/Route 141 southbound to I-95 northbound

Detour Routes for Exits:

Exit 5B/I-95 northbound to Route 141 northbound

For traffic on I-95 northbound, south of Route 141 interchange, motorists will take the decel/accel lane to the ramp to I-295 northbound, take the ramp to US 13 southbound and take the ramp to Route 141 northbound.

Exit 3A/Route 141 northbound to I-95 northbound

Motorist traveling northeast on Airport Road will follow detour signs, taking Route 141 southbound to US 13 to I-295 to I-95 northbound. [More]

DEPARTMENT OF NATURAL RESOURCES AND ENVIRONMENTAL CONTROL: Division of Fish and Wildlife