YESTERDAY would have been your birthday. January 24. Six months older than me for six months, I’d remind you. Normally I would have spent the weeks between Christmas and now trying to think of something original to buy you. And then, at the last moment, I’d just buy you another book.

Scotland’s golf courses have been urged to close in the wake of the Government’s latest measures to combat the coronavirus.

Dumbarton police station has temporarily closed after a member of staff showed symptoms of Covid-19.

E-learning may help some schools keep instruction flowing but major gaps in access and resources mean not all schools are ready to offer virtual classes, and not all students are equipped to learn online.

Thanks to the coronavirus epidemic, America is facing a school shutdown of historic proportions, deepening learning divides among students and taking away the centers of communities. Can we ever make up the lost learning time?

Bernie Sanders' sweeping vision would establish a $60,000 minimum salary for teachers, while clamping down on charters and boosting efforts to desegregate schools. It's hard to see a lot of it becoming a reality.

Few districts have done as much as Wake County, N.C., to keep schools racially and socioeconomically diverse, but’s it’s a battle the school board says it has been losing. Can it reverse the trend?

Students who were chronically absent or at risk of dropping out before the coronavirus outbreak are even more at risk now that schools are closed, experts say.

Indiana's state Senate has approved a measure that would create access for middle-income families for private-school vouchers. As it stands, it's one of the most ambitious voucher proposals ever offered in the states.

Source: El tiempo - Una subida de 2°C altera la metilación del ADN y la expresión de genes claves para la supervivencia y el desarrollo. Este estudio ofrece una nueva visión sobre las consecuencias del cambio climático en los peces a través de modificaciones epigenéticas en todo el genoma

Source: Infobae - El cambio climático es probablemente el mayor desafío ambiental y social que enfrenta la humanidad, y que fue generado por el ser humano. Es un problema global que se resuelve en forma global, en donde existen muchos matices que hacen difícil el consenso entre los países respecto a las decisiones que deben tomarse. Sin embargo, todos reconocen el siguiente principio como marco de discusión: principio de responsabilidades comunes pero diferenciadas. Este principio reconoce que todos los países tienen responsabilidad común de solucionar el problema, aunque no todos en el mismo nivel y grado, ya que históricamente los países desarrollados han contaminado más a efecto de construir sus economías que aquellos que están en vías de desarrollo. Y no todos los países tienen la misma capacidad y recursos para enfrentar la problemática.

Autism has been associated with pregnancy and birth complications that may indicate a suboptimal prenatal environment. Although the interpregnancy interval (IPI) may affect the prenatal environment, the association between the IPI and risk for autism is not known.

Using full-sibling pairs from a large population, the authors examined the association between autism and IPIs. Second-born children conceived after an IPI of <12 months had more than threefold increased odds of autism relative to those with IPIs of ≥36 months. (Read the full article)

Macroglossia is a clinical feature of several disorders and a common reason for additional diagnostic investigations during infancy. Limited research has been done on the evaluation of macroglossia when other features are not suggestive of Beckwith-Wiedemann syndrome.

All patients with apparently isolated macroglossia should have at least initial evaluation with abdominal ultrasounds and molecular studies for Beckwith-Wiedemann syndrome before a final diagnosis is given. Other common diagnoses included isolated macroglossia, chromosomal abnormalities, hypothyroidism, and mucopolysaccharidoses. (Read the full article)

Because most childhood tuberculosis cases are sputum smear-negative, diagnosis relies largely upon clinical presentation, tuberculin skin testing, and chest radiograph. Diagnostic limitations contribute to treatment delays and high mortality. However, childhood tuberculosis (TB) mortality risk factors are not well documented.

This study demonstrates that false-negative TST is common in children with active TB and is associated with increased risk of death. A negative TST should not delay anti-TB therapy. Improved diagnostic modalities are urgently needed in resource-limited settings. (Read the full article)

Foreign-born children and adolescents in the United States experience higher tuberculosis (TB) morbidity rates than US-born children and adolescents. Pediatric risk assessment should account for country of birth, contact with a known TB case, or travel to TB-endemic countries.

Our study reports national data on parental/guardian countries of origin and international residence of pediatric patients with TB. Two-thirds of US-born children with TB have international family connections, and many have lived in countries with increased risk for TB acquisition. (Read the full article)

Pediatric tuberculosis is significant for public health professionals because it is an indicator of the recent transmission of tuberculosis in the community. Data on incidence and clinical features of pediatric tuberculosis from China are scarce.

We conducted this study to describe the patient characteristics, clinical–epidemiological profile, and treatment outcomes for pediatric tuberculosis in a referral hospital setting in China. (Read the full article)

Studies have linked bullying with BMI, with overweight and obese youth vulnerable to bullying and its negative psychological and health consequences. However, there has been little comprehensive assessment of weight-based victimization, especially in weight loss treatment–seeking samples of youth.

WBV is prevalent in treatment-seeking youth, who report victimization from peers (92%), friends (70%), parents (37%), and teachers (27%). Providers should discuss WBV in their assessment and treatment of pediatric patients who are overweight or obese. (Read the full article)

The incidence of permanent hearing loss doubles between birth and school age. Otoacoustic emissions screening has been used successfully in early childhood educational settings to identify children with losses not found through newborn screening.

Using otoacoustic emissions to screen the hearing of young children during routine health care visits is feasible and can lead to the identification of permanent hearing loss overlooked by providers relying solely on subjective methods. (Read the full article)

In preterm infants receiving supplemental oxygen, manual control of the inspired oxygen fraction is often difficult and time consuming, which may increase the risk of complications. We developed a system for automatic oxygen control and proved its efficacy in the past.

A multicenter study adds evidence for the proposed automatic oxygen control system to significantly improve oxygen administration to preterm infants receiving mechanical ventilation or nasal continuous positive airway pressure while reducing workload compared with routine manual oxygen control. (Read the full article)

More than 60% of all US tuberculosis cases occur among foreign-born persons, but ~90% of cases in young children occur among US-born; many of these children have foreign-born parents, suggesting that this is an important population for prevention.

This is the first study to calculate tuberculosis rates in US-born children by parental nativity. Compared with US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. (Read the full article)

Little is known about the epidemiology and pathogenicity of Clostridium difficile infection among children, particularly those aged ≤3 years in whom colonization is common and pathogenicity uncertain.

Young children, 1 to 3 years of age, had the highest Clostridium difficile infection incidence. Considering that clinical presentation, outcomes, and disease severity were similar across age groups, C difficile infection in the youngest age group likely represents true disease and not asymptomatic colonization. (Read the full article)

Animal studies document dose-dependent and duration-of-therapy-dependent fluoroquinolone cartilage toxicity in weight-bearing joints. Preliminary pediatric data collected after fluoroquinolone treatment and up to 1 year posttreatment in blinded and unblinded studies suggest the possibility of cartilage toxicity in children.

These are the first prospectively collected data on fluoroquinolone musculoskeletal safety collected posttherapy from randomized, comparative studies of respiratory tract infections and analyzed at 5 years. Long-term musculoskeletal adverse events occurred with equal frequency in both levofloxacin and comparator groups. (Read the full article)

Allostatic load (AL), a biomarker of cardiometabolic risk, predicts the onset of the chronic diseases of aging including cardiac disease, diabetes, hypertension, and stroke. Socioeconomic-related stressors, such as low family income, are associated with AL.

African American youth who grow up in neighborhoods in which poverty levels increase across adolescence evince high AL. The study also highlights the benefits of emotional support in ameliorating this association. (Read the full article)

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)

Exclusively breastfed newborns lose weight daily in the first few days after birth. The amount of weight lost varies substantially between newborns, with higher amounts of weight loss increasing risk for morbidity.

This study presents nomograms demonstrating percentiles for weight loss by delivery mode for those who are exclusively breastfed. The nomograms have potential to be used for early identification of neonates on a trajectory for greater weight loss and related morbidities. (Read the full article)

Immune-related bioactive proteins are highly concentrated in the colostrum of mothers who deliver preterm infants. Oropharyngeal administration was proposed as a safe and feasible alternative method of providing colostrum to immunocompromised premature infants.

Oropharyngeally administered colostrum during the first few days of life increased urinary secretory immunoglobulin A and lactoferrin, decreased urinary interleukin-1β, reduced salivary transforming growth factor-β1 and interleukin-8, and reduced the occurrence of clinical sepsis in extremely premature infants. (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)

Prior studies have found a positive relationship between macro-level indicators of home foreclosure and child maltreatment rates. The extent to which home foreclosure may be associated with child protective services involvement at the micro level is largely unknown.

Foreclosure filings are positively associated with child protective services involvement. However, this is true of the periods before and after a filing, which are characterized by economic and other stress, which may drive this association more than the filing itself. (Read the full article)

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)

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)

Summer programs that use multimedia may improve student literacy, numeracy, phonics skills, and math vocabulary, according to a study released by WestEd, a nonprofit education research organization. The report examines the Electric Company's Summer Learning Program, which is sponsored by the Sesame

Track where schools are closed and their status for reopening.

Professor of Chemistry Paul Cremer is developing a biosensor platform that could be used to perform real-time, continuous detection of SARS-CoV-2, the virus that causes COVID-19.

Ya paso otro año así que le daremos otro vistazo a nuestra busca perpetua por el ISP mas veloz en México

To help ease the transition to remote instruction, educators have launched virtual professional learning communities to share resources, ask questions, and give advice.

Burundi escapó de una guerra civil y años de terror. Hoy se supone que vive en democracia, pero eso está por verse. Ante las próximas elecciones de mayo, y con el panorama de violencia política que asuela el país, parece imposible que éstas se celebren pacíficamente y bajo el paraguas de la democracia.

The fight against entrenched armed groups in eastern Congo such as the ADF-Nalu needs to switch from a military to an intelligence-based approach.

The deteriorating situation in Burundi is a perfect storm of much that undermines stability in Africa today — presidents seeking impunity and power through dubious new terms, authoritarian regimes muzzling opposition and independent media, regional rivalries stalemating efforts to bring peace and outside powers unwilling or unable to act.

β-lactam resistance in Staphylococcus aureus limits treatment options. Stp1 and Stk1, a serine-threonine phosphatase and kinase respectively, mediate serine-threonine kinase (STK) signaling. Loss of function point mutations in stp1 were detected among laboratory passaged, β-lactam resistant S. aureus strains lacking mecA and blaZ, the major determinants of β-lactam resistance in the bacteria. Loss of Stp1 function facilitates β-lactam resistance of the bacteria.

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

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.

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.

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.

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