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Inhibition of SARS-CoV-2 infection by the cyclophilin inhibitor Alisporivir (Debio 025) [Antiviral Agents]

Cyclophilins play a key role in the lifecycle of coronaviruses. Alisporivir (Debio 025) is a non-immunosuppressive analogue of cyclosporin A with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in VeroE6 cell line, with an EC50 of 0.46±0.04 μM. Alisporivir inhibited a post-entry step of the SARS-CoV-2 lifecycle. These results justify that a proof-of-concept Phase 2 trial be rapidly conducted with alisporivir in patients with SARS-CoV-2 infection.




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Google's Advanced Protection Expands to Phone-Only Users

Google has made it easier to join the company's Advanced Protection Program, which is designed to stop the most sophisticated hackers from breaking into your Gmail account. Before you needed two security keys to enroll. Now you just need a smartphone.




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Bad Flaw in Windows 10 Also Affects Chrome Browser

Security researchers are demonstrating how you can use the Windows 10 flaw, CVE-2020-0601, to spoof the trusted digital certificates for official website domains on Google's Chrome browser. These same certificates can warn you about hacking attempts.




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Feds Seize WeLeakInfo.com for Selling Access to Stolen Data

The FBI seizes the internet domain to WeLeakInfo.com, a site that was cataloging billions of records, such as email addresses and passwords, from more than 10,300 data breaches at various companies and service providers.




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Report: Apple Dropped Plans for Fully-Encrypted iCloud Backups

Six sources confirmed Apple changed its mind on end-to-end encrypted backups two years ago following an FBI complaint and concerns users could lose access to their own data.




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Report: Hack of Amazon's CEO Phone Tied to Saudi Prince

The stunning allegation reportedly comes from a forensic analysis Amazon CEO Jeff Bezos commissioned to determine the culprit behind the hack, which resulted in his private photos ending up in the hands of the National Enquirer.




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After Bezos Phone Hack, UN Points Finger at Saudis, Calls for Probe

According to a recent forensic analysis, a WhatsApp account from the Saudi Crown Prince Mohammed bin Salman allegedly sent government-bought spyware to Bezos' phone in May 2018, two UN human rights experts said on Wednesday.




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Oops! Microsoft Briefly Leaked 250M Customer Support Records

The records involved conversation logs between Microsoft support agents and customers across the globe, dating back to 2005. Most of the records were redacted of customer contact information, but not all.




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The Cost of Avast's Free Antivirus: Companies Can Spy on Your Clicks

Avast is harvesting users' browser histories on the pretext that the data has been 'de-identified,' thus protecting your privacy. But the data, which is being sold to third parties, can be linked back to people's real identities, exposing every click and search they've made.




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Save 30 Percent on Keeper, Never Click 'Forgot Password' Again

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.




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New Coronavirus Strain? Nope, Just Hackers Trying to Spread Malware

The hackers have been using files and emails that warn about a new coronavirus strain to trick users into opening them. Doing so can secretly deliver malware to the victim's machine.




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Hackers Pose as Wall Street Journal Reporter to Phish Victims

Watch out for suspicious interview requests. 'The main focus of this phishing campaign was stealing email account information of the victims, and finding information about their contacts/networks,' the cybersecurity experts at Certfa Lab warned on Wednesday.




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Malware Steals Data By Adjusting Screen Brightness

Malware on an air-gapped computer can transmit data like Morse code by changing screen brightness in a way that's invisible to the naked eye but easily recorded with a camera.




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The Best Parental Control Software for 2020

Parenting styles run the gamut and so do the features in parental control and monitoring utilities. We've tested the top hardware- and software-based services to help you choose the right one for your family.




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The Best Free Antivirus Protection for 2020

Windows Defender is improving, but you still shouldn't rely on Windows 10's security tools as your sole means of protection. Many free third-party security apps are more effective at keeping you safe. We've tested 17 no-cost services to help you find the best free antivirus for protecting your PC.




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Fin24.com | JSE wrap | Oil price drop drives further stock pessimism

The JSE fell on Tuesday as global markets tumbled on the back of a rout in crude oil prices.




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Fin24.com | Brent crude oil drops to 21-year low as selling pressure intensifies

"The entire energy market is still on a knife edge," says an economist.




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Fin24.com | JSE wrap | Local stocks firmer as inflation slows

The local bourse inched higher on Wednesday as global stocks took a breather following consecutive sessions of weakness.




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Fin24.com | JSE wrap | Surge as global sentiment remains optimistic

Local stocks advanced for a second consecutive session on Thursday as global markets remained resurgent.




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Fin24.com | Oil prices roar back on US-Iran tensions

Oil prices made a spectacular comeback Thursday as fresh US-Iran tensions erupted, also helping equities advance after US labour market figures provided a glimmer of hope for the world's top economy.




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Fin24.com | Stocks struggle as antiviral drug hopes fade

Stock markets struggled on Friday as hopes of quickly finding a treatment for coronavirus were dashed, analysts said, and more crushing economic data delivered a body blow to confidence.




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Fin24.com | Stock markets rally on virus hopes, but oil tanks

Equity markets have rallied Monday as countries eased coronavirus lockdown measures, but oil prices tumbled as a supply glut offset output cuts.




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Fin24.com | Gold falls as moves to reopen economies erode appetite for havens

The precious metal eased for a third day after US equities hit the highest in almost seven weeks as states including Florida took steps toward easing restrictions.




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Fin24.com | Local bourse firms as global economies gear for partial reopening

Global markets rallied on the back of optimism that most governments were gearing up to at least partially reopen their economies following lockdowns to prevent the spread of the coronavirus.




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Fin24.com | Positive virus drug trial news spurs stocks

The surge in stocks was on the back of positive news from trials being conducted on a potential treatment for the coronavirus. With most economies looking to partially reopen their economies, this brought a jump across most asset classes including commodities.




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Fin24.com | SA stocks are on track for a record month

Unprecedented demand for online services and entertainment during the Covid-19 pandemic lockdowns, along with a scramble for haven investments, have helped set South African stocks on course for a record month.




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Fin24.com | JSE erases earlier gains as global economy exhibits more strain

The local bourse had managed to open firmer following a rally in Asian stocks in earlier trading.




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Fin24.com | Stock markets plunge on devastating growth data

Stock markets plunged on Thursday after economic growth data confirmed fears of Covid-19's bruising impact on the world economy.




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Fin24.com | Gold bars fight coronavirus kits for space on the plane

Swiss refiner Valcambi SA tried for five straight days last month to move a shipment of gold out of Hong Kong. Twice the metal was packed carefully onto a plane, only to be offloaded again.




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Fin24.com | Markets wrap | JSE retreats as global markets fret over economic growth

Deep losses were recorded across most European benchmarks except the FTSE 100 which managed to trade relatively flat on the day.




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Fin24.com | Oil rises for a fifth day with output cuts easing glut concern

Oil was headed for the longest run of daily gains in more than nine months on signs the worst of the supply glut may be over as production cuts start to take effect.




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Fin24.com | Markets wrap | Firmer close in Asia lifts JSE All-Share Index

On the currency market, the rand traded softer against the greenback as it slipped to a session low of R18.77/$.




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Fin24.com | Markets wrap | Local stocks edge higher as optimism remains

Still, there was disappointment in terms of economic data following the release of the SACCI Business Confidence index data for April which came in at 77.8, compared to a forecast of 89.2.




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Fin24.com | Oil set for second weekly gain with market starting to rebalance

Oil headed for its first back-to-back weekly gain since February as output cuts from the biggest producers and a nascent recovery in demand began to rebalance a market awash with crude.




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Fin24.com | Stocks rise despite record US job losses

The rand strengthened against the greenback as it peaked at a session high of R18.30 before it was recorded trading 1.41% firmer at R18.32/$ at 17.00




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Philanthropies Want to Fund Civics Education. But How?

A new paper sketches out the landscape and tensions in civic education as philanthropies look for ways to support the field.




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RHSU Classic: How Education Philanthropy Can Accidentally Promote Groupthink and Bandwagonism

In number 10 in our countdown, I tried to offer a few thoughts to funders as they embraced new agendas and looked to avoid repeating yesterday's missteps.




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Education Is the Darling of Wealthy Philanthropists, But K-12 Is Losing Its Luster

Around the world, education is the largest recipient of philanthropic giving by a large margin, but in the United States, funders are moving away from investing in K-12 schools in favor of early childhood and higher education.




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Grantmakers for Education Chief on Philanthropy's Response to Coronavirus

Funders have been both fast and thoughtful about how to work with national and local partners to listen to needs from the field, identify best practices, and deploy resources quickly, says Celine Coggins.




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Philanthropy Roundtable K-12 Chief on Funders' Response to Coronavirus

"This pandemic has given us an opportunity to think boldly about students' educational needs and how to creatively respond to them," says Katherine Haley.




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NewSchools Venture Fund CEO on Education Philanthropy During Coronavirus

"Folks in some foundations are quietly expressing frustration that they've been cautioned to stay in their lane and only fund things aligned with their pre-COVID strategy," says Stacey Childress.




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Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

METHODS:

We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture).

RESULTS:

We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively.

CONCLUSIONS:

The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.




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Antibiotic Use and Outcomes in Children in the Emergency Department With Suspected Pneumonia

BACKGROUND AND OBJECTIVES:

Antibiotic therapy is often prescribed for suspected community-acquired pneumonia (CAP) in children despite a lack of knowledge of causative pathogen. Our objective in this study was to investigate the association between antibiotic prescription and treatment failure in children with suspected CAP who are discharged from the hospital emergency department (ED).

METHODS:

We performed a prospective cohort study of children (ages 3 months–18 years) who were discharged from the ED with suspected CAP. The primary exposure was antibiotic receipt or prescription. The primary outcome was treatment failure (ie, hospitalization after being discharged from the ED, return visit with antibiotic initiation or change, or antibiotic change within 7–15 days from the ED visit). The secondary outcomes included parent-reported quality-of-life measures. Propensity score matching was used to limit potential bias attributable to treatment selection between children who did and did not receive an antibiotic prescription.

RESULTS:

Of 337 eligible children, 294 were matched on the basis of propensity score. There was no statistical difference in treatment failure between children who received antibiotics and those who did not (odds ratio 1.0; 95% confidence interval 0.45–2.2). There was no difference in the proportion of children with return visits with hospitalization (3.4% with antibiotics versus 3.4% without), initiation and/or change of antibiotics (4.8% vs 6.1%), or parent-reported quality-of-life measures.

CONCLUSIONS:

Among children with suspected CAP, the outcomes were not statistically different between those who did and did not receive an antibiotic prescription.




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Pediatric Orphan Drug Indications: 2010-2018

BACKGROUND:

Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan indications.

METHODS:

We classified the 402 orphan indications the US Food and Drug Administration approved between 2010 and 2018 as "pediatric" if they were approved for children only or targeted pediatric diseases. We determined the number of unique diseases targeted by pediatric orphan indications and calculated the proportion that were for (1) novel drugs, (2) non-novel drugs approved to treat ≥1 common disease, and (3) non-novel drugs approved only to treat rare diseases. Among pediatric orphan indications eligible for US Food and Drug Administration breakthrough designation (granted to drugs potentially representing major therapeutic advances), we calculated the proportion receiving this designation.

RESULTS:

Of the 402 orphan indications, 136 (33.8%) were pediatric. These 136 indications targeted 87 unique diseases; 21 diseases were targeted by ≥1 indication. Of the 136 pediatric orphan indications, 60 (44.1%) were for novel drugs, 45 (33.1%) were for non-novel drugs approved to treat ≥1 common disease, and 31 (22.8%) were for non-novel drugs approved only to treat rare diseases. Among 97 indications eligible for breakthrough designation, 20 (20.6%) received this designation.

CONCLUSIONS:

Recent orphan drug development has increased the availability of treatments for pediatric rare diseases. Most pediatric orphan indications expanded use of existing drugs, and many targeted the same disease. Some indications may represent breakthroughs, but substantial unmet need for treatments remains for most pediatric rare diseases.




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Body Dissatisfaction and Mental Health Outcomes of Youth on Gender-Affirming Hormone Therapy

OBJECTIVES:

Our first aim was to examine baseline differences in body dissatisfaction, depression, and anxiety symptoms by gender, age, and Tanner (ie, pubertal) stage. Our second aim was to test for changes in youth symptoms over the first year of receiving gender-affirming hormone therapy. Our third aim was to examine potential differences in change over time by demographic and treatment characteristics. Youth experiences of suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) are also reported.

METHODS:

Participants (n = 148; ages 9–18 years; mean age 14.9 years) were receiving gender-affirming hormone therapy at a multidisciplinary program in Dallas, Texas (n = 25 puberty suppression only; n = 123 feminizing or masculinizing hormone therapy). Participants completed surveys assessing body dissatisfaction (Body Image Scale), depression (Quick Inventory of Depressive Symptoms), and anxiety (Screen for Child Anxiety Related Emotional Disorders) at initial presentation to the clinic and at follow-up. Clinicians completed the Quick Inventory of Depressive Symptoms and collected information on youth experiences of suicidal ideation, suicide attempt, and NSSI.

RESULTS:

Affirmed males reported greater depression and anxiety at baseline, but these differences were small (P < .01). Youth reported large improvements in body dissatisfaction (P < .001), small to moderate improvements in self-report of depressive symptoms (P < .001), and small improvements in total anxiety symptoms (P < .01). No demographic or treatment-related characteristics were associated with change over time. Lifetime and follow-up rates were 81% and 39% for suicidal ideation, 16% and 4% for suicide attempt, and 52% and 18% for NSSI, respectively.

CONCLUSIONS:

Results provide further evidence of the critical role of gender-affirming hormone therapy in reducing body dissatisfaction. Modest initial improvements in mental health were also evident.




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Trends in Regionalization of Emergency Care for Common Pediatric Conditions

BACKGROUND:

For children who cannot be discharged from the emergency department, definitive care has become less frequent at most hospitals. It is uncertain whether this is true for common conditions that do not require specialty care. We sought to determine how the likelihood of definitive care has changed for 3 common pediatric conditions: asthma, croup, and gastroenteritis.

METHODS:

We used the Nationwide Emergency Department Sample database to study children <18 years old presenting to emergency departments in the United States from 2008 to 2016 with a primary diagnosis of asthma, croup, or gastroenteritis, excluding critically ill patients. The primary outcome was referral rate: the number of patients transferred among all patients who could not be discharged. Analyses were stratified by quartile of annual pediatric volume. We used logistic regression to determine if changes over time in demographics or comorbidities could account for referral rate changes.

RESULTS:

Referral rates increased for each condition in all volume quartiles. Referral rates were greatest in the lowest pediatric volume quartile. Referral rates in the lowest pediatric volume quartile increased for asthma (13.6% per year; 95% confidence interval [CI] 5.6%–22.2%), croup (14.8% per year; 95% CI 2.6%–28.3%), and gastroenteritis (16.4% per year; 95% CI 3.5%–31.0%). Changes over time in patient age, sex, comorbidities, weekend presentation, payer mix, urban-rural location of presentation, or area income did not account for these findings.

CONCLUSIONS:

Increasing referral rates over time suggest decreasing provision of definitive care and regionalization of inpatient care for 3 common, generally straightforward conditions.




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Efficacy of Melatonin in Children With Postconcussive Symptoms: A Randomized Clinical Trial

BACKGROUND:

Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo.

METHODS:

We conducted a randomized, double-blind trial of 3 or 10 mg of melatonin compared with a placebo (NCT01874847). We included youth (ages 8–18 years) with PPCS at 4 to 6 weeks after mild traumatic brain injury. Those with significant medical or psychiatric histories or a previous concussion within the last 3 months were excluded. The primary outcome was change in the total youth self-reported Post-Concussion Symptom Inventory score measured after 28 days of treatment. Secondary outcomes included change in health-related quality of life, cognition, and sleep.

RESULTS:

Ninety-nine children (mean age: 13.8 years; SD = 2.6 years; 58% girls) were randomly assigned. Symptoms improved over time with a median Post-Concussion Symptom Inventory change score of –21 (95% confidence interval [CI]: –16 to –27). There was no significant effect of melatonin when compared with a placebo in the intention-to-treat analysis (3 mg melatonin, –2 [95% CI: –13 to 6]; 10 mg melatonin, 4 [95% CI: –7 to 14]). No significant group differences in secondary outcomes were observed. Side effects were mild and similar to the placebo.

CONCLUSIONS:

Children with PPCS had significant impairment in their quality of life. Seventy-eight percent demonstrated significant recovery between 1 and 3 months postinjury. This clinical trial does not support the use of melatonin for the treatment of pediatric PPCS.




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Dietary Fats and Atherosclerosis From Childhood to Adulthood

BACKGROUND:

The association of dietary fat distribution with markers of subclinical atherosclerosis during early life is unknown. We examined whether success in achieving the main target of an infancy-onset dietary intervention based on the distribution of dietary fat was associated with aortic and carotid intima-media thickness (IMT) and distensibility from childhood to young adulthood.

METHODS:

In the prospective randomized controlled Special Turku Coronary Risk Factor Intervention Project trial, personalized dietary counseling was given biannually to healthy children from infancy to young adulthood. The counseling was based on Nordic Nutrition Recommendations, with the main aim of improving the distribution of dietary fat in children’s diets. IMT and distensibility of the abdominal aorta and common carotid artery were measured repeatedly at ages 11 (n = 439), 13 (n = 499), 15 (n = 506), 17 (n = 477), and 19 years (n = 429). The targeted distribution of dietary fat was defined as a ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids of <1:2 and as an intake of saturated fatty acids of <10% of energy intake. Participants who met ≥1 of these 2 criteria were defined to achieve the main intervention target.

RESULTS:

Individuals who achieved the main intervention target had lower aortic IMT (age- and sex-adjusted mean difference 10.4 µm; 95% confidence interval: 0.3 to 20.5 µm) and better aortic distensibility (0.13% per 10 mm Hg; 95% confidence interval: 0.00% to 0.26% per10 mm Hg) compared with their peers who did not meet the target.

CONCLUSIONS:

Achieving the main target of an infancy-onset dietary intervention, reflecting dietary guidelines, was favorably associated with aortic IMT and distensibility during the early life course. These data support the recommendation of favoring unsaturated fat to enhance arterial health.




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Breastfeeding Initiation, Duration, and Supplementation Among Mexican-Origin Women in Texas

BACKGROUND:

Mexican-origin women breastfeed at similar rates as white women in the United States, yet they usually breastfeed for less time. In our study, we seek to identify differences in Mexican-origin women’s breastfeeding intentions, initiation, continuation, and supplementation across nativity and country-of-education groups.

METHODS:

The data are from a prospective cohort study of postpartum women ages 18 to 44 recruited from 8 Texas hospitals. We included 1235 Mexican-origin women who were born and educated in either Texas or Mexico. Women were interviewed at delivery and at 3, 6, 12, 18, and 24 months post partum. Breastfeeding intentions and initiation were reported at baseline, continuation was collected at each interview, and weeks until supplementation was assessed for both solids and formula. Women were classified into 3 categories: born and educated in Mexico, born and educated in the United States, and born in Mexico and educated in the United States.

RESULTS:

Breastfeeding initiation and continuation varied by nativity and country of birth, although all women reported similar breastfeeding intentions. Women born and educated in Mexico initiated and continued breastfeeding in higher proportions than women born and educated in the United States. Mexican-born and US-educated women formed an intermediate group. Early supplementation with formula and solid foods was similar across groups, and early supplementation with formula negatively impacted duration across all groups.

CONCLUSIONS:

Nativity and country of education are important predictors of breastfeeding and should be assessed in pediatric and postpartum settings to tailor breastfeeding support. Support is especially warranted among US-born women, and additional educational interventions should be developed to forestall early supplementation with formula across all acculturation groups.




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Mental Health Outcomes Among Homeless, Runaway, and Stably Housed Youth

BACKGROUND AND OBJECTIVES:

Runaway youth and homeless youth are at risk for adverse mental health outcomes. These 2 populations are frequently pooled together in both research and interventions yet may have unique health needs. We sought to assess differences in mental health outcomes among these populations.

METHODS:

We conducted a secondary data analysis of ninth- and 11th-graders in the 2016 minnesota Student Survey (n = 68 785). We categorized youth into 4 subgroups based on housing status in the previous year: (1) unaccompanied homeless youth (0.5%), (2) runaway youth (4%), (3) youth who had both run away and been homeless (0.6%), and (4) stably housed youth (95%). We performed multivariable logistic regression to compare 4 mental health outcomes (self-injury, suicidal ideation, suicide attempts, and depressive symptoms) across groups, controlling for demographics and abuse history.

RESULTS:

Unstably housed youth had poorer mental health outcomes when compared with their stably housed peers (P < .05). For example, 11% of homeless youth, 20% of runaways, and 33% of youth who had experienced both had attempted suicide in the previous year compared with 2% of stably housed youth (adjusted odds ratios 2.4, 4.9, and 7.1, respectively). Other outcomes showed a similar pattern.

CONCLUSIONS:

Our findings suggest that runaway and homeless youth represent unique populations with high levels of mental health needs who would benefit from targeted clinical and community interventions. Pediatric clinicians represent one potential point of screening and intervention.